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Song, Lei, Jiaqi Liang, Wenting Wang, Jie Gao, Hua Chai, Yu Tan, Liying Zheng, Mei Xue, and Dazhuo Shi. "Global Trends in Research of Mitochondrial Biogenesis over past 20 Years: A Bibliometric Analysis." Oxidative Medicine and Cellular Longevity 2023 (January 4, 2023): 1–17. http://dx.doi.org/10.1155/2023/7291284.
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Background. Mitochondrial biogenesis-related studies have increased rapidly within the last 20 years, whereas there has been no bibliometric analysis on this topic to reveal relevant progress and development trends. Objectives. In this study, a bibliometric approach was adopted to summarize and analyze the published literature in this field of mitochondrial biogenesis over the past 20 years to reveal the major countries/regions, institutions and authors, core literature and journal, research hotspots and frontiers in this field. Methods. The Web of Science Core Collection database was used for literature retrieval and dataset export. The CiteSpace and VOSviewer visual mapping software were used to explore research collaboration between countries/regions, institutions and authors, distribution of subject categories, core journals, research hotspots, and frontiers in this field. Results. In the last 20 years, the annual number of publications has shown an increasing trend yearly. The USA, China, and South Korea have achieved fruitful research results in this field, among which Duke University and Chinese Academy of Sciences are the main research institutions. Rick G Schnellmann, Claude A Piantadosi, and Hagir B Suliman are the top three authors in terms of number of publications, while RC Scarpulla, ZD Wu, and P Puigserver are the top three authors in terms of cocitation frequency. PLOS One, Biochemical and Biophysical Research Communications, and Journal of Biological Chemistry are the top three journals in terms of number of articles published. Three papers published by Richard C Scarpulla have advanced this field and are important literature for understanding the field. Mechanistic studies on mitochondrial biosynthesis have been a long-standing hot topic; the main keywords include skeletal muscle, oxidative stress, gene expression, activation, and nitric oxide, and autophagy and apoptosis have been important research directions in recent years. Conclusion. These results summarize the major research findings in the field of mitochondrial biogenesis over the past 20 years in various aspects, highlighting the major research hotspots and possible future research directions and helping researchers to quickly grasp the overview of the developments in this field.
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SEMUKHINA, ELENA. "ON THE CULTURAL-ETHIC CATEGORIES TRANSFORMATION IN EUROPE OF THE XIX CENTURY: SEARCH FOR THE BASIC FOUNDATIONS." Культурный код, no. 2023-1 (2023): 38–49. http://dx.doi.org/10.36945/2658-3852-2023-1-38-49.
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The article aims at discussing the XIX century’s European studies which influenced the new ethically-themed performance, viewed as the source of the main meaningful (or subject-to-subject) cultural categories. Social and scientific changes, which led to the “cultural upheaval”, made the scientists consider the value system newly and define the existence of the dynamic cultural-ethic elements as a system. Further this approach provided the basis for the division of the cultural categories into fundamental and meaningful. The vectors of ethic norms’ transformation are also under discussion, i.e. the development of philosophical ideas of the following researchers A. Schopenhauer, F. Nietzsche, Ch. Darwin, A. Bergson: voluntaristic (built on the philosophy of the will), evolutionist (based on the Ch. Darwin’s theory of biological evolution) and vital (designed on the metaphysics of Bergson’s Elan Vital). Viewed as a whole, both “philosophy of living” and Ch. Darwin’s theory of the origin of species seem to ground cultural categories of a moral and ethical value. Thanks to them, life turned out to be not only of irrational creative philosophical principle but also of the ultimate value; while the concept struggle for existence moved to Biology. Life as an ultimate value acknowledgment did not mean the full refusal from the morality with the social degradation, it was only associated with relativization of traditional (Christian, primarily) values. This acknowledgment did not involve the recognition of the human being’s unlimited selfishness which in practice had to give way to the “instinct” of solidarity found in animality.
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Kulkarni, Roshni, Amy D. Shapiro, Jerzy Windyga, Margaret V. Ragni, K. John Pasi, Margareth Castro Ozelo, Elisa Tsao, and Baisong Mei. "Low Bleeding Rates with Increase or Maintenance of Physical Activity in Patients Treated with Recombinant Factor IX Fc Fusion Protein (rFIXFc) in the B-LONG and Kids B-LONG Studies." Blood 126, no. 23 (December 3, 2015): 2307. http://dx.doi.org/10.1182/blood.v126.23.2307.2307.
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Abstract Background: The phase 3 B-LONG and Kids B-LONG studies demonstrated low annualized bleeding rates (ABRs) with rFIXFc prophylaxis in subjects with severe hemophilia B. Compared with prestudy FIX treatment, rFIXFc prophylaxis reduced weekly factor consumption and infusion frequency. Aims: To evaluate the effect of rFIXFc on subjects' physical activity across age groups using a subject-reported assessment and to examine ABRs with respect to change in physical activity and prestudy treatment regimen (prophylaxis or episodic) in B-LONG and Kids B-LONG. Methods: Previously treated males with severe haemophilia B (≤ 2 IU/dL endogenous FIX activity) were eligible for B-LONG (≥ 12 years of age) and Kids B-LONG (<12 years of age). Subjects in B-LONG were enrolled into 1 of 4 treatment arms: Arm 1, weekly prophylaxis; Arm 2, individualized interval prophylaxis; Arm 3, episodic treatment; or Arm 4, perioperative management (not included in this analysis). All subjects in Kids B-LONG started on weekly rFIXFc prophylaxis. There were no restrictions on physical activity in either study. Physical activity assessments were conducted at Weeks 4, 16, 26, 39, and 52 (B-LONG) and Weeks 3, 12, 24, 36, and 50 (Kids B-LONG). At each visit after their first rFIXFc dose, subjects were asked to report activity levels relative to their prior study visit as: more (or more intensive), fewer (or less intensive), or about the same amount of physical activities. To summarize each subject's change in physical activity during the study compared with baseline, subjects were classified into one of 4 groups: more, the same, less, or undetermined. Within each treatment group, prestudy and on-study ABRs were analyzed according to change in physical activity category and prestudy regimen. Analyses included all subjects who received ≥ 1 dose of rFIXFc during the efficacy period and who completed ≥ 1 physical activity assessment. Results: This analysis included 112 subjects from B-LONG and 30 subjects from Kids B-LONG. The majority of subjects in both studies reported more or the same amount of physical activity during the study; few subjects reported less physical activity. Percent of subjects with changes in physical activity levels (more, same, less, undetermined) in B-LONG were: Arm 1 (n = 60), 35%, 42%, 7%, 17%; Arm 2 (n = 25), 48%, 28%, 16%, 8%; Arm 3 (n = 27), 30%, 26%, 15%, 30%; and in Kids B-LONG (n = 30) were: 57%, 20%, 10%, 13%, respectively. Similar physical activity results were observed in subjects with and without target joints at baseline. Median on-study ABRs with rFIXFc prophylaxis were low in B-LONG and Kids B-LONG for all categories of change in physical activity; for subjects on prestudy prophylaxis who reported more or similar physical activity during B-LONG/Kids B-LONG, median ABRs with rFIXFc were similar or lower compared with prestudy ABR (Table). Summary/Conclusion: The majority of subjects in B-LONG (71%) and Kids B-LONG (77%) maintained or increased physical activity levels during the study. ABRs were low in both studies, regardless of change in physical activity. These results suggest that people with severe hemophilia B across age groups may maintain or increase their physical activity levels with rFIXFc while also maintaining low bleeding rates with reduced infusion frequency. Table 1. Prestudy and On-study Median (IQR) ABR by Physical Activity Level in B-LONG and Kids B-LONG Parent study: B-LONG Kids B-LONG On-study rFIXFc prophylaxis: Arm 1 (weekly) Arm 2 (individualized interval) Weekly Prestudy FIX regimen: Prophylaxis (n = 30) Episodic (n = 28) Prophylaxis (n = 13) Episodic (n = 13) Prophylaxis (n = 30) Median (IQR) ABR by physical activity category More n = 6 n = 11 n = 5 n = 5 n = 17 Prestudy 6.00 (1.00, 15.00) 14.00(11.00, 28.00) 1.00(0, 1.00) 25.00(22.00, 25.00) 2.00(0, 3.00) On-study 4.76 (3.09, 5.62) 3.13(1.14, 4.34) 0(0, 0.72) 2.19(1.66, 2.61) 2.09(0, 3.13) Same n = 15 n = 10 n = 2 n = 5 n = 6 Prestudy 1.00(1.00, 6.00) 26.00(20.00, 40.00) 4.00(1.00, 7.00) 33.00(27.00, 39.00) 2.50(0, 3.00) On-study 1.13(0, 2.30) 2.62(0.99, 5.23) 1.15(0, 2.30) 1.09(0, 4.43) 0.53(0, 2.90) Less n = 3 n = 0 n = 2 n = 1 n = 3 Prestudy 0(0,0) -- 3.00(2.00, 4.00) 22.00 5.00(2.00, 6.00) On-study 0(0,0) -- 3.78(0, 7.56) 0 1.85(1.06, 5.43) Undetermined n = 4 n = 5 n = 1 n = 1 n = 4 Prestudy 4.50(2.50, 8.00) 25.00(20.00, 40.00) 4.00 12.00 7.00(3.50, 13.00) On-study 3.76(1.76, 5.35) 1.04(0, 1.16) 0 3.12 2.21(1.09, 3.92) ABR, annualized bleeding rate; IQR, interquartile range. Disclosures Kulkarni: Baxter: Membership on an entity's Board of Directors or advisory committees, Research Funding; Bayer: Membership on an entity's Board of Directors or advisory committees, Research Funding; Novo Nordisk: Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Pfizer: Membership on an entity's Board of Directors or advisory committees; Kedrion: Membership on an entity's Board of Directors or advisory committees; BPL: Membership on an entity's Board of Directors or advisory committees; Biogen: Research Funding, Speakers Bureau. Shapiro:Baxalta, Novo Nordisk, Biogen, ProMetic Life Sciences, and Kedrion Biopharma: Consultancy; Biogen: Speakers Bureau; Bayer Healthcare, Baxalta, Biogen, CSL Behring, Daiichi Sankyo, Kedrion Biopharma, Octapharma, OPKO, ProMetic Life Sciences, PTC Therapeutics, and Selexys: Research Funding; Baxalta, Novo Nordisk, Biogen,: Membership on an entity's Board of Directors or advisory committees. Windyga:Baxalta, Novo Nordisk, and Biogen: Research Funding; Baxalta, Novo Nordisk, Sanofi, CSL Behring, Bayer, and Pfizer: Honoraria; Baxalta, Novo Nordisk, Sanofi, Biogen, CSL Behring, Bayer, and Pfizer: Membership on an entity's Board of Directors or advisory committees. Ragni:SPARK: Research Funding; Alnylam: Research Funding; Bristol Myers Squibb: Research Funding; Biomarin: Research Funding; Shire: Membership on an entity's Board of Directors or advisory committees, Research Funding; Bayer: Research Funding; Genentech Roche: Research Funding; Pfizer: Research Funding; CSL Behring: Research Funding; Vascular Medicine Institute: Research Funding; Dimension: Research Funding; Baxalta: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Biogen: Research Funding; Tacere Benitec: Membership on an entity's Board of Directors or advisory committees. Pasi:Octapharma: Research Funding; Biogen, Octapharma, Genzyme, and Pfizer: Consultancy, Honoraria. Ozelo:Baxter: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Biogen: Research Funding; Novo Nordisk: Research Funding, Speakers Bureau. Tsao:Biogen: Employment, Equity Ownership. Mei:Biogen: Employment, Equity Ownership.
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Eckstein, Olive S., Nitya Gulati, Lisa Forbes, Erin Peckham-Gregory, Nmazuo Wudo Ozuah, M. Cecilia Poli, Tiphanie Vogel, et al. "Genomic Characterization of a Pediatric Cohort with Non-Malignant Lymphoproliferative Disorders." Blood 134, Supplement_1 (November 13, 2019): 83. http://dx.doi.org/10.1182/blood-2019-131884.
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Introduction: Pediatric non-malignant lymphoproliferative disorders (LPDs) are a clinically and genetically heterogeneous. While transient lymphadenopathy is extremely common and rarely dangerous, long-standing immune dysregulation and lymphoproliferation in children may be life-threatening. Data to guide evaluation and treatment of children with benign LPD are lacking. The primary objective of this study was to define the genomic spectrum and clinical characteristics of a cohort of children with nonmalignant LPD. Identification of the underlying pathogenic mechanisms may facilitate timely interventions and potentially guide optimal therapeutic strategies. Method s: Patients at Texas Children's Hospital and collaborating referral centers who met criteria for non-malignant LPD were offered participation in this study, approved by the Baylor College of Medicine Institutional Review Board. LPD was defined as persistent lymphadenopathy, lymph organ involvement, or lymphocytic infiltration for more than 3 months, with or without chronic or significant EBV infection. Chronic or significant EBV infection was defined as recurrent or persistent EBV viremia more than 3 months, invasive EBV disease, or EBV PCR copies >100,000. All subjects and/or family members provided written informed consent to have their clinical and genetic information published. Genetic testing was performed clinically or through research-based whole-exome sequencing (WES). Results : Fifty-one subjects from 47 different families with non-malignant LPD were identified. Median age at disease presentation was 3.3 years (range 3.9 weeks - 21 years) with nearly equal proportions of males (n = 26) and females (n = 25). Almost half of subjects were Hispanic (49%), and 29% were non-Hispanic white. Fifteen subjects (29%) met HLH-2004 diagnostic criteria for HLH. Twenty-one patients had EBV-associated lymphoproliferative disorders (EBV-LPD) and 6 of the 51 ultimately developed malignancy. Clinical genetic testing was performed in 29 patients, and research-based WES was performed in 44 patients. Potential disease-causing genetic defects were identified in 62% of families. Of these pathogenic variants, targeted therapies may be effective for treatment in at least 10 of the conditions (17 subjects, 33%). Furthermore, genetic results supported potential for curative HSCT in 35% of the patients. Mechanistically, all of the LPD-associated genes could be placed into 1 of 3 categories: 1) defective control of lymphocyte activity; 2) impaired lymphocyte activation, cytoskeletal organization, and apoptosis; and 3) dysregulated inflammation. Ten-year survival for the entire cohort was 72.4% with a median 5.6 years of follow-up (range 0.10 - 26.6). Patients without evidence of a genetic explanation had a lower ten-year survival compared to those patients for whom a genetic explanation was identified (48% versus 82%, respectively, p=0.03). When both EBV-LPD and genetic explanation were considered, the ten-year survival estimate for those with EBV-associated disease and no genetic explanation was significantly worse than those with EBV-associated disease and a genetic explanation (17% vs. 90%; p =0.002). Patients without EBV-associated disease were at lower risk of death than those with EBV-LPD. Evaluating outcomes associated with maximum treatment received, ten-year survival was lowest (25% survival) among those who underwent HSCT. Conclusion s: Pediatric non-malignant LPD represents a group of conditions with high risk of death. WES identified actionable mutations in the majority of LPD cases in this cohort. Early identification of these mutations can guide therapy by confirming diagnosis, revealing molecular targets and/or supporting definitive therapy with stem cell transplant. Disclosures Forbes: Takeda: Consultancy. Jolles:CSL Behring: Consultancy, Honoraria, Research Funding, Speakers Bureau; LFB: Consultancy, Honoraria, Research Funding, Speakers Bureau; UCB Pharma: Consultancy, Other: Drug Safety Committee; Shire/Takeda: Consultancy, Honoraria, Research Funding, Speakers Bureau; Pharming: Consultancy, Honoraria, Research Funding, Speakers Bureau; Octapharma: Consultancy, Honoraria, Research Funding, Speakers Bureau. Heslop:Marker Therapeutics: Equity Ownership, Membership on an entity's Board of Directors or advisory committees; Allovir: Equity Ownership; Gilead Biosciences: Membership on an entity's Board of Directors or advisory committees; Kiadis: Membership on an entity's Board of Directors or advisory committees; Tessa Therapeutics: Membership on an entity's Board of Directors or advisory committees, Research Funding; Cell Medica: Research Funding. Rouce:Novartis: Consultancy, Honoraria; Tessa Therapeutics: Research Funding; Kite, a Gilead Company: Consultancy, Honoraria.
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Muzyka, Logan, Nicolas K. Goff, Nikita Choudhary, and Michael T. Koltz. "Systematic Review of Molecular Targeted Therapies for Adult-Type Diffuse Glioma: An Analysis of Clinical and Laboratory Studies." International Journal of Molecular Sciences 24, no. 13 (June 21, 2023): 10456. http://dx.doi.org/10.3390/ijms241310456.
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Gliomas are the most common brain tumor in adults, and molecularly targeted therapies to treat gliomas are becoming a frequent topic of investigation. The current state of molecular targeted therapy research for adult-type diffuse gliomas has yet to be characterized, particularly following the 2021 WHO guideline changes for classifying gliomas using molecular subtypes. This systematic review sought to characterize the current state of molecular target therapy research for adult-type diffuse glioma to better inform scientific progress and guide next steps in this field of study. A systematic review was conducted in accordance with PRISMA guidelines. Studies meeting inclusion criteria were queried for study design, subject (patients, human cell lines, mice, etc.), type of tumor studied, molecular target, respective molecular pathway, and details pertaining to the molecular targeted therapy—namely the modality, dose, and duration of treatment. A total of 350 studies met the inclusion criteria. A total of 52 of these were clinical studies, 190 were laboratory studies investigating existing molecular therapies, and 108 were laboratory studies investigating new molecular targets. Further, a total of 119 ongoing clinical trials are also underway, per a detailed query on clinicaltrials.gov. GBM was the predominant tumor studied in both ongoing and published clinical studies as well as in laboratory analyses. A few studies mentioned IDH-mutant astrocytomas or oligodendrogliomas. The most common molecular targets in published clinical studies and clinical trials were protein kinase pathways, followed by microenvironmental targets, immunotherapy, and cell cycle/apoptosis pathways. The most common molecular targets in laboratory studies were also protein kinase pathways; however, cell cycle/apoptosis pathways were the next most frequent target, followed by microenvironmental targets, then immunotherapy pathways, with the wnt/β-catenin pathway arising in the cohort of novel targets. In this systematic review, we examined the current evidence on molecular targeted therapy for adult-type diffuse glioma and discussed its implications for clinical practice and future research. Ultimately, published research falls broadly into three categories—clinical studies, laboratory testing of existing therapies, and laboratory identification of novel targets—and heavily centers on GBM rather than IDH-mutant astrocytoma or oligodendroglioma. Ongoing clinical trials are numerous in this area of research as well and follow a similar pattern in tumor type and targeted pathways as published clinical studies. The most common molecular targets in all study types were protein kinase pathways. Microenvironmental targets were more numerous in clinical studies, whereas cell cycle/apoptosis were more numerous in laboratory studies. Immunotherapy pathways are on the rise in all study types, and the wnt/β-catenin pathway is increasingly identified as a novel target.
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Talalaeva, Galina. "Dynamics of Representations Concerning Mechanisms of Formation of Social Identity of Youth: a Review of Publications of the RSCI." DEMIS. Demographic Research 2, no. 3 (October 7, 2022): 89–103. http://dx.doi.org/10.19181/demis.2022.2.3.7.
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The subject of the research is the phenomenon of dissipation of the social identity of young people in modern Russian society. Purpose: to compare the reflection of this phenomenon in the academic and public consciousness. Hypothesis: the dynamics and structure of the idea of the social identity of young people at the present stage of Russia's development is not the same in the academic and public consciousness. The hypothesis was tested on the example of publications included in the RSCI database. There are two categories of publications: 1) scientific journals, dissertations, 2) conference materials. The first reflects ideas about social phenomena in the minds of the academic community; the second is in the mass consciousness of the general scientific community. Search depth 11 years (2012–2021). It included the annexation of Crimea to Russia, pension reform, the C0VID-19 pandemic, and the merger of two social support funds for the population (PF and FSS). The volume of empirical data amounted to 86341 titles of publications. The views of the authors of publications on the phenomenon under study were recorded according to five search queries: “social identity of young people”, “social security”, “social protection”, “social assistance”, “social support”. The algorithm of the relationship between these topics was studied using paired correlation analysis. It was found that the peak of publications for these requests coincided with the three-year period 2016–2018. The reflection of the problem of the social identity of young people in academic publications preceded its active discussion in conference proceedings by 4–6 years. Fundamental differences are found in the ideas about the social identity of young people in the academic and public consciousness. In scientific articles and dissertations, the social identity of young people is considered as a special case of self-organization of complex social systems, in conference materials – as a separate element of a hierarchically built deterministic financial system. The results obtained are regarded by us as proof of the correctness of the null hypothesis put forward. Possible areas of application of the results of the study: youth, social and demographic policy of the state at a new stage of socio-economic reforms. The limitation for the implementation of the research results in the practice of social management may be the effect of inertial public opinion and mass consciousness, as well as the financial interests of individual lobbies currently involved in the implementation of social projects. Directions for future research – targeted monitoring of the transformation of the mass in accordance with the requirements of the modern technological revolution.
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Zhou, Yifan, Minwen Zhou, Min Gao, Haiyun Liu, and Xiaodong Sun. "Factors Affecting the Foveal Avascular Zone Area in Healthy Eyes among Young Chinese Adults." BioMed Research International 2020 (March 24, 2020): 1–8. http://dx.doi.org/10.1155/2020/7361492.
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Purpose. To evaluate the influence of systemic and ocular factors on the foveal avascular zone (FAZ) area in young Chinese subjects’ healthy eyes. Methods. The current observational, cross-sectional study included 344 eyes from 172 healthy individuals (103 women, 69 men). Optical coherence tomography angiography realized with the split-spectrum amplitude-decorrelation angiography (SSADA) algorithm was used to assess the area of superficial FAZ. To determine the related factors and to reveal their potential correlations with the FAZ area, comprehensive examinations including both systemic and ocular ones were executed. Systemic examination involved factors including age, gender, and body mass index, while ocular examination involved factors including BCVA, refractive error, intraocular pressure, axial length (AL), anterior chamber depth, and central corneal thickness. Especially for fundus examination, central macular thickness (CMT), retinal volume, mean retinal thickness, macular blood flow area/vessel density in the superficial retinal layer (SRL) and deep retinal layer (DRL), mean retinal nerve fiber layer (RNFL) thickness, ganglion cell layer (GCL) thickness, C/D rate, rim area, and subfoveal choroid thickness were assessed, using mixed-effects regression models to appropriately account for intereye correlation. Subgroup analyses were performed based on gender and high myopia categories. Results. The mean FAZ area was 0.30±0.11 mm2 and varied significantly across gender (P=0.0024). AL, CMT, and RNFL thickness were found significantly correlated with the FAZ area in the univariate regression analysis (AL, P=0.0005; CMT, P<0.0001; and RNFL thickness, P=0.0461). According to the multivariate results, CMT and macular blood flow in SRL were negatively correlated with FAZ (CMT: P<0.0001; macular blood flow in SRL: P=0.00223). Mean retinal thickness, mean GCL thickness, and macular blood flow in DRL were positively correlated with FAZ (mean retinal thickness: P=0.0005; mean GCL thickness: P<0.0001; and macular blood flow in DRL: P=0.0099). Correlation results among these filtered factors and FAZ were more pronounced in non-high-myopic eyes than in high-myopic eyes and had a significant difference when data of male and female subjects were processed separately from each other. Conclusion. The present cross-sectional study performed comprehensive systemic and ocular examinations in young Chinese adults and filtered factors affecting FAZ. We indicated that among all the assessed candidate factors, gender, AL, retinal thickness, macular blood flow, RNFL, and GCL thickness affected the FAZ area most significantly. Such findings would facilitate future research concerning the role of FAZ variation in fundus diseases.
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Fink-Puches, Regina, Paulus Zenahlik, Barbara Bäck, Josef Smolle, Helmut Kerl, and Lorenzo Cerroni. "Primary cutaneous lymphomas: applicability of current classification schemes (European Organization for Research and Treatment of Cancer, World Health Organization) based on clinicopathologic features observed in a large group of patients." Blood 99, no. 3 (February 1, 2002): 800–805. http://dx.doi.org/10.1182/blood.v99.3.800.
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Abstract Classification of primary cutaneous lymphomas (PCLs) is the subject of ongoing controversy. Based on a series of 556 patients, the applicability of the European Organization for Research and Treatment of Cancer (EORTC) classification for PCLs was assessed and compared to the proposed World Health Organization (WHO) classification of hematologic malignancies. The large majority of patients could be properly classified according to the scheme proposed by the EORTC. Comparison of estimated 5-year survival for specific diagnostic categories of PCLs demonstrated nearly complete concordance of the present results with those of the EORTC study for most of the indolent cutaneous T-cell lymphomas and cutaneous B-cell lymphomas, whereas differences were found for mycosis fungoides-associated follicular mucinosis and Sezary syndrome. A few patients with newly described entities (CD8+ epidermotropic cytotoxic T-cell lymphoma, primary cutaneous natural killer/T-cell lymphoma) could not be classified according to the EORTC scheme. Comparison of the EORTC with the WHO classification showed that the EORTC scheme allows a more precise categorization of the patients, especially for cutaneous B-cell lymphoma. In conclusion, the study confirmed that the EORTC classification allows a better management of patients with PCL. Small amendments to that classification should be carried out to account for recently described entities and to unify some of the diagnostic categories.
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Farooq, Muhammad, Aman Ullah Khan, Hosny El-Adawy, Katja Mertens-Scholz, Iahtasham Khan, Heinrich Neubauer, and Yuh-Shan Ho. "Research Trends and Hotspots of Q Fever Research: A Bibliometric Analysis 1990-2019." BioMed Research International 2022 (January 15, 2022): 1–14. http://dx.doi.org/10.1155/2022/9324471.
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Q fever is a worldwide distributed zoonosis caused by Coxiella burnetii, a Gram-negative bacterium. Despite existence of large amount of research data on the developments related to Q fever, no bibliometric analysis of this subject is available to our knowledge. Bibliometric studies are an essential resource to track scholarly trends and research output in a subject. This study is aimed at reporting a bibliometric analysis of publications related to Q fever (2,840 articles published in the period 1990-2019) retrieved from Science Citation Index Expanded, an online database of Clarivate Analytics Web of Science Core Collection. Data was retrieved using keywords “Q fever” or “Coxiella burnetii” in title, abstract, and author keywords to describe important research indicators such as the kind and language of articles, the most important publications, research journals and categories, authors, institutions, and the countries having the most significant contribution to this subject. Finally, the emerging areas in field of diagnosis, host range, and clinical presentation were identified. Word cluster analysis of research related to Q fever revealed that major focus of research has been on zoonosis, seroprevalence, laboratory diagnosis (mainly using ELISA and PCR), clinical manifestations (abortion and endocarditis), vectors (ticks), and hosts (sheep, goat, and cattle). This bibliometric study is intended to visualize the existing research landscape and future trends in Q fever to assist in future knowledge exchange and research collaborations.
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Boyle, Molly H., Bindu Bennet, Karyn Colman, Anna-Lena Frisk, Begonya Garcia, Christopher D. Houle, Annette Romeike, Radhakrishna Sura, Jonathan Werner, and Susan A. Elmore. "Publication Categories in Toxicologic Pathology." Toxicologic Pathology 49, no. 5 (February 12, 2021): 1042–47. http://dx.doi.org/10.1177/0192623321992305.
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Toxicologic Pathology is the official journal of the Society of Toxicologic Pathology (STP), the British Society of Toxicological Pathology, and the European STP (ESTP). Toxicologic Pathology publishes articles related to topics in various aspects of toxicologic pathology such as anatomic pathology, clinical pathology, experimental pathology, and biomarker research. Publications include society-endorsed Best Practice/Position and Points to Consider publications and ESTP Expert Workshop articles that are relevant to toxicologic pathology and scientific regulatory processes, Opinion articles under the banner of the STP Toxicologic Pathology Forum, Original Articles, Review Articles (unsolicited/contributed, mini, and invited), Brief Communications, Letters to the Editor, Meeting Reports, and Book Reviews. This article provides details on the various publication categories in Toxicologic Pathology and will serve as a reference for authors and readers.
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Kim, Joonhee. "Analysis on Music Meditation Research Papers and Critical Review: Focused on Research Papers from 2000 to 2021." Korean Society of Culture and Convergence 44, no. 7 (July 31, 2022): 623–32. http://dx.doi.org/10.33645/cnc.2022.7.44.7.623.
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One of the most noteworthy keywords in the 21th century is undoubtedly ‘meditation’. Also, along with meditation, 'music' began to attract attention, and music meditation became a trend. In this paper, academic papers published from 2000 to 2021 were divided into five categories and some major papers were reviewed. As a result, the papers lacked specific references to meditation music compared to the research process, or the distinction between music meditation and music appreciation was ambiguous, and the concept of music therapy was mixed. In addition, the setting of meditation music and control of experimental groups remained. In order to systematically practice meditation through music and to conduct more fundamental research, accurate understanding of music meditation and meditation music, establishment of terminology, understanding of instrumental functions of music, separation of music meditation and music therapy, and creation of meditation music to enhance the effectiveness of meditation. I suggest that we explore how to use music as a preliminary stage before meditation. It is also hoped that more music experts will participate in the study of music meditation.
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Pratiwi, Essy Dian, Mohammad Masykuri, and Murni Ramli. "Active Learning Strategy on Higher Education Biology Learning: A Systematic Review." Tadris: Jurnal Keguruan dan Ilmu Tarbiyah 6, no. 1 (June 29, 2021): 75–86. http://dx.doi.org/10.24042/tadris.v6i1.7345.
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Student-centered learning intends to increase student participation. Biology subject is a broad scope and has a level of abstract concepts. Active learning has the potential to maximize the learning process of biology subjects. The purpose of the research is to describe the implementation and strategies of active learning applied to biology learning in higher education. The method used descriptive and systematic review. Selecting articles used the ERIC database. The search was carried out with predetermined categories, then a manual selection of the article to ensure the selected one. There are nine journals with nineteen articles analyzed at the higher education level of biology subject matter. This study's results, the implementation of active learning strategies, require support from lecturers and university stakeholders so that active learning runs effectively. An Active learning strategy used in biology material in higher education consists of the use of low-cost technology (virtual cell learning module) to high cost (SCALE-UP, clicker), low-cost learning without involving technology (card games, card organisms, kinesthetic physical models, 5E lesson plan, and pre-class reading guide) to outside the classroom (field training). The university's role and the understanding of lecturers in implementing active learning strategies have a crucial role in determining student learning outcomes. Lecturers and university stakeholders need to build cooperation, including a learning policy system and classroom implementation.
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Hwang, Eunji. "A Study on Vocal Education in Applied Music Analysis of Research Trends in Korea." Korean Society of Culture and Convergence 44, no. 7 (July 31, 2022): 351–59. http://dx.doi.org/10.33645/cnc.2022.7.44.7.351.
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The purpose of this study is to present the direction of future related research by analyzing domestic degree papers and papers related to vocal education published in academic journals. To this end, 175 papers (37 academic papers and 138 degree papers) that meet the conditions were collected and analyzed by year of publication, research method, research subject, and research content. The results of the study are as follows. First, vocal education research has shown a gradual increase since 2003 By 2018, it was found that the individual reached its peak. Second, as a result of analysis by research method, ‘literary research’ was found to have been conducted the most. Third, as a result of analysis by research subject, ‘literature and analysis theory’ was the highest. Fourth, as a result of analysis by research content, ‘case study’ was found to be the most common. Fifth, as a result of analyzing the trends by publishing journal, it was confirmed that the most studies were published in ‘popular music content’. Sixth, as a result of classification by registered information, the largest number of studies were published in the ‘registered place’. Based on the contents of the analysis results, the direction and direction of future related research were presented.
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Marko, Nicholas F., and Robert J. Weil. "The molecular biology of WHO Grade II gliomas." Neurosurgical Focus 34, no. 2 (February 2013): E1. http://dx.doi.org/10.3171/2012.12.focus12283.
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The WHO grading scheme for glial neoplasms assigns Grade II to 5 distinct tumors of astrocytic or oligodendroglial lineage: diffuse astrocytoma, oligodendroglioma, oligoastrocytoma, pleomorphic xanthoastrocytoma, and pilomyxoid astrocytoma. Although commonly referred to collectively as among the “low-grade gliomas,” these 5 tumors represent molecularly and clinically unique entities. Each is the subject of active basic research aimed at developing a more complete understanding of its molecular biology, and the pace of such research continues to accelerate. Additionally, because managing and predicting the course of these tumors has historically proven challenging, translational research regarding Grade II gliomas continues in the hopes of identifying novel molecular features that can better inform diagnostic, prognostic, and therapeutic strategies. Unfortunately, the basic and translational literature regarding the molecular biology of WHO Grade II gliomas remains nebulous. The authors' goal for this review was to present a comprehensive discussion of current knowledge regarding the molecular characteristics of these 5 WHO Grade II tumors on the chromosomal, genomic, and epigenomic levels. Additionally, they discuss the emerging evidence suggesting molecular differences between adult and pediatric Grade II gliomas. Finally, they present an overview of current strategies for using molecular data to classify low-grade gliomas into clinically relevant categories based on tumor biology.
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Benton, Christopher B., Koichi Takahashi, Prithviraj Bose, Feng Wang, Hsiang-Chun Chen, Xiaofeng Zheng, Jianhua Zhang, et al. "Archetypes of AML Defined Using Whole Exome Sequencing and Clinical Characteristics in a Diverse Group of Patients." Blood 128, no. 22 (December 2, 2016): 597. http://dx.doi.org/10.1182/blood.v128.22.597.597.
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Abstract Background: Acute myeloid leukemia (AML) comprises a heterogeneous collection of morphologically related diseases. The identification and study of somatic mutations in AML using next-generation sequencing has led to insights into the pathogenesis of AML. Constellations of specific mutations may correlate with clinical phenotype and reveal the most relevant cooperating molecular pathways. Understanding AML biological pathways will contribute to more personalized, directed therapies and improve outcomes. Most sequencing efforts have focused on select groups of AML patients or select gene panels. Characterization of mutations identified by whole exome sequencing for AML patients from a variety of clinical scenarios has not been the subject of one study. Methods: Whole exome sequencing (WES) was performed, in addition to complete clinical molecular diagnostics, on leukemia samples from a diverse group of 141 consecutive AML patients who underwent complete clinical evaluation at a single quaternary leukemia care institution (MD Anderson Cancer Center, MDACC). The cohort included adults of all ages, treatment histories (treated/untreated), and ontogenies (de novo/secondary/therapy-related). To facilitate the identification of driver mutations from WES data, an automatic pipeline was developed to filter and annotate raw variants, and then select non-polymorphism, protein-coding changing mutations. A relational mutation/clinical database was created to analyze gene mutations and gene categories in the context of well-annotated mutations and complete clinical indices including treatments and outcomes. Results: We characterized the landscape of driver mutations in an unselected group of AML patients, and classified mutations by 9 predefined functional categories of known aberrant pathways implicated in AML (Figure 1). The frequency and distribution of gene mutations and gene categories were determined and compared to TCGA AML whole exome sequencing mutation data, derived from a de novo, untreated AML cohort. Forty-six separate genes/fusions were mutated in the MDACC cohort, including 326 mutations. The MDACC cohort included 23 cases (16%) with a TP53 mutation. Overall, a mean of 2.3+/-1.4 mutations-of-interest were identified per patient. For the MDACC dataset, the likelihood of co-occurrence and mutual exclusivity was determined for each gene (mutated in greater than 2 cases, n=34) and each gene category (n=9) versus every other gene, gene category, as well as each individual annotated clinical characteristic (n=30). 156 statistically significant co-occurring pairs and 71 statistically significant mutually exclusive pairs were found. We analyzed hierarchically clustered, strength-of-association correlograms to identify likely mutational frameworks with similarly associated clinical/molecular characteristics. We identified patterns of predominant genetic alterations that defined 4 distinct AML archetypes: 1) Transcription factor [TRNSXN] (16% of cases), 2) Nucleolar/Methylation/Signaling [NMS] (40%), 3) Spliceosome [SPLICE] (21%), and 4) TP53-mutated [TP53] (16%). Ten cases had no identifiable mutation-of-interest, compared to 4 cases without mutation in TCGA data. The defining mutational characteristics of each AML archetype, and select associated characteristics are shown in Table 1. Conclusions: Analysis of whole exome sequencing data along with clinical information from all-comer AML patients identifies archetypal classes of the disease, each with particular tendencies for specific mutational, clinical, and outcome characteristics. Our approach demonstrates that genomic characterization of mutations in a variety of diverse clinical scenarios has the potential to identify representative mechanisms of AML development across the spectrum of disease presentations. Disclosures Daver: Otsuka: Consultancy, Honoraria; Sunesis: Consultancy, Research Funding; Pfizer: Consultancy, Research Funding; Karyopharm: Honoraria, Research Funding; Ariad: Research Funding; Kiromic: Research Funding; BMS: Research Funding. Jabbour:ARIAD: Consultancy, Research Funding; Pfizer: Consultancy, Research Funding; Novartis: Research Funding; BMS: Consultancy. DiNardo:Agios: Other: advisory board, Research Funding; Celgene: Research Funding; Novartis: Other: advisory board, Research Funding; Daiichi Sankyo: Other: advisory board, Research Funding; Abbvie: Research Funding. Konopleva:Reata Pharmaceuticals: Equity Ownership; Abbvie: Consultancy, Research Funding; Genentech: Consultancy, Research Funding; Stemline: Consultancy, Research Funding; Eli Lilly: Research Funding; Cellectis: Research Funding; Calithera: Research Funding. Cortes:ARIAD: Consultancy, Research Funding; BMS: Consultancy, Research Funding; Novartis: Consultancy, Research Funding; Pfizer: Consultancy, Research Funding; Teva: Research Funding.
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Jankowski, Maurycy, Ana Angelova Volponi, Rafael Shinoske Siroma, Nelson Pinto, Marcelo A. Melo, Kornelia Krajnik, Jamil A. Shibli, Paul Mozdziak, Mariusz T. Skowroński, and Marta Dyszkiewicz-Konwińska. "Current application of exosomes in medicine." Medical Journal of Cell Biology 10, no. 1 (March 1, 2022): 18–22. http://dx.doi.org/10.2478/acb-2022-0003.
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Abstract Exosomes are a distinct type of extracellular vesicles that play a major role in intracellular transport and communication. Depending on the cell of origin, exosomes can contain diverse constituents of a cell, including DNA, RNA, lipids, metabolites, cytosolic and cell-surface proteins, playing important roles in a wide range of physiological and pathological processes. Due to these facts, they are subject of extensive research aiming at translating the knowledge into clinical approaches that are at the interface between nanomedicine and biopharmaceuticals. Their potential clinical use mostly revolves around the fields of diagnostics and drug delivery, especially important in treatment of cancer. The conventional and emerging methods of exosome isolation are either based on their physical properties (such as density and/or size) or their functions. However, the isolation approaches are still characterised by significant downsides, lacking standardisation, and ensuring purity. The review gives a critical overview on exosomes characteristics, isolation approaches and the potential that exosomes hold in developing new clinical approaches of modern medicine, highlighting the need for further research to fully grasp their potential and translate the knowledge into future therapeutic solutions.
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Perangin-Angin, Erbina Selvia Br, Z. K. A. Baizal, and Donni Richasdy. "Question Answering using Ontology for Sumedang Larang History with Support Vector Machine Based on Telegram Bot." JURNAL MEDIA INFORMATIKA BUDIDARMA 6, no. 4 (October 25, 2022): 2438. http://dx.doi.org/10.30865/mib.v6i4.4574.
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Technological developments affect many aspects, one of which is historical education. History lessons can shape students' personalities and encourage an interest in historical knowledge. There are many stories from Indonesian history, one of which is the Sumedang Larang Kingdom. The Sumedang Larang Kingdom is one of the Islamic kingdoms in Pasundan. However, not many people know about this kingdom. The millennial generation is technologically advanced, so they can take advantage of technological advances to quickly introduce the history of Sumedang Larang. One of them utilizes the telegram bot using the Application Programming Interface (API), which can connect the system to the telegram platform. In addition, this technology can be used as a history learning attraction using the question answering system (QA). Our research aims to build a QA system that can introduce the history of Sumedang Larang to the millennial generation. Because this system uses ontology knowledge with concepts related to the Sumedang Larang domain, it can focus on the history of Sumedang Larang. Applying the support vector machine (SVM) algorithm to process classification text can make it easier to search for text categories. The test results show the performance of the SVM method with a test size parameter of 0.5, such as 74% and 78%. The performance test results are accuracy scores in the subject category and object classification.
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Samiha, Yulia Tri, Syarifah Syarifah, and Puput Maryati. "PENGARUH MODEL PEMBELAJARAN COURSE REVIEW HORAY TERHADAP HASIL BELAJAR SISWA PADA MATA PELAJARAN BIOLOGI DI MA SABILULHASANAH." Edubiotik : Jurnal Pendidikan, Biologi dan Terapan 4, no. 01 (July 5, 2019): 29–37. http://dx.doi.org/10.33503/ebio.v4i01.410.
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The problem that we need to be solved in the world of our education is the weak learning process. The learning process in the classroom is still directed at the child's ability to memorize information. While biology requires logical and reasonable learning to be accepted and absorbed by the brain so that it can last long. The aim of the research is to know the influence of course review horay learning toward student’s of cognitive learning class ten in the subject matter cell in MA Sabilul Hasanah Kecamatan Sembawa Kabupaten Banyuasin. This research method used quasi-experimental design with a quantitative approach research pretest-posttest control group design. The sample is taken by using purposive sampling techniques. The sample was grade XI MIA 2 as an experimental class and class XI MIA 1 as the control class. The instrument used in this research is a test to measure student’s cognitive learning about the cognitive categories C1-C4. Data analysis use the t-test, data on the calculation difference average posttest both groups earned value t-test much as 4,806 while value t-table with significant level5% with degrees of freedom (dk) 42 is equal to1,684, it can be said that t-test > t-table means the alternative hypothesis (Ha) be accepted and the null hypothesis (H0) rejected. It can be concluded that there is a significant influence of course review horay learning toward student’s of cognitive learning class eleven in the subject matter cell inMA Sabilul Hasanah.
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Kane, Chikako, Kenshi Takechi, Masayuki Chuma, Hiroshi Nokihara, Tomoko Takagai, and Hiroaki Yanagawa. "Perspectives of non-specialists on the potential to serve as ethics committee members." Journal of International Medical Research 47, no. 5 (January 24, 2019): 1868–76. http://dx.doi.org/10.1177/0300060518823941.
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Objective In Japan, under the new Clinical Trials Act pertaining to investigator-initiated clinical trials that came into effect on 1 April 2018, review boards should review proposed clinical trials while considering written opinions from specialists. Additionally, involvement of non-specialists is mandatory, and attention is being placed on their effective contributions. This study was performed to determine representative key issues with which to promote these contributions. Methods This qualitative study was conducted in 2018 using a focus group interview of six non-specialists regarding perspectives on clinical research itself and research ethics committees. Results For perspectives on clinical research itself, 33 codes were established and sorted into 2 categories and 6 subcategories relating to ambivalence toward clinical research. For perspectives on research ethics committees, 54 codes were established and sorted into 3 categories and 10 subcategories relating to the theme “knowledge and an environment that promotes non-specialist members’ participation.” One notable result was the willingness of participants to obtain details about a study should they be selected. Conclusions The results suggest that detailed explanation of a particular study would encourage non-specialist members to participate in a clinical research review committee. Education aimed at non-specialist participation should therefore be considered in future studies.
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Hasanah, Rafiatul, and Winda Dwi Kusumawati. "DEVELOPMENT OF ETHNOSCIENCE-BASED DIGITAL TEACHING MATERIALS IN AUTHENTIC JEMBER PATROL MUSIC IN SOUND SUB MATERIALS FOR STUDENTS IN JUNIOR HIGH SCHOOL." INSECTA: Integrative Science Education and Teaching Activity Journal 3, no. 1 (May 30, 2022): 56–69. http://dx.doi.org/10.21154/insecta.v3i1.3976.
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Culture is the wealth of the Indonesian nation while education is an intermediary for forming the character of the nation's successor. Learning in schools is an interaction that helps students understand learning materials, especially conceptual and factual learning. One of them is in learning Natural Sciences (IPA), in the field of Physics. Noise material is a conceptual material with a discussion of sound waves produced by vibrating objects (sound sources). Based on the needs analysis obtained, the development of appropriate teaching materials to explain the material is a digital book. The purpose of this study is to describe the level of validation of teaching materials and describe student responses to ethnoscience-based digital teaching materials in Authentic Jember Patrol music on sound sub-materials in class VIII SMP/MTs students. The type of research used is the development of a 4-D model. The subject of validity in this study involved material experts and media experts and science teachers, with the results of material validation being 91.03%, media experts 89, 41%, and user experts (teachers) 88, 23% very valid categories. While the student response test in this study was divided into 2, namely, small-scale test and large-scale test with an average percentage result of 80.76% with a valid category, and large-scale trials obtained an average percentage of 87.28% with a category very, without any revisions to the developed teaching material products.
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Berko, Andriy, Dmytro Polivenok, and Tetiana Shestakevych. "Information systems for automating work flows: a comparative analysis." Vìsnik Nacìonalʹnogo unìversitetu "Lʹvìvsʹka polìtehnìka". Serìâ Ìnformacìjnì sistemi ta merežì 13 (July 15, 2023): 243–50. http://dx.doi.org/10.23939/sisn2023.13.243.
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Workflow is a sequence of repeated and controlled steps aimed at completing a specific task or work. The urgency of the task of optimizing such works contributed to the development of methods and means of operations research to optimize such processes for the needs of various subject areas. Information technologies to support such workflow are workflow engines that enable faster automation, ensure compliance with norms and standards, formalize business processes, improve communication, etc. The workflow management systems are divided into the following categories: automation using robotics, intelligent integration platforms, intelligent business process management systems, open-source engines, the cloud-supported, as well as data flow processing systems. For a more detailed analysis, it is advisable to choose the following engines and services: built-in, cloud-oriented, and those to support both scenarios (jBPM, Camunda, Zeebe, Amazon Step Functions). It is appropriate to define evaluation criteria and compare such workflow automation systems to form further recommendations regarding their selection and application. Such criteria are development activity, stability and history of commercial use, versioning support, standards support, support for timers and asynchronous execution, support for human-oriented and manual tasks, integration with other solutions, monitoring and logging, scaling, cloud support, the possibility of scanning in private infrastructure, the presence of a visual interface, the convenience of local development and testing, open source code, the necessary programming for implementation and cost. A comparison of advantages and disadvantages can be used to decide on a workflow automation system.
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Hu, Xinfeng, Congzhu Tan, and Guodong Zhu. "Clinical Characteristics of Molecularly Defined Renal Cell Carcinomas." Current Issues in Molecular Biology 45, no. 6 (May 31, 2023): 4763–77. http://dx.doi.org/10.3390/cimb45060303.
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Kidney tumors comprise a broad spectrum of different histopathological entities, with more than 0.4 million newly diagnosed cases each year, mostly in middle-aged and older men. Based on the description of the 2022 World Health Organization (WHO) classification of renal cell carcinoma (RCC), some new categories of tumor types have been added according to their specific molecular typing. However, studies on these types of RCC are still superficial, many types of these RCC currently lack accurate diagnostic standards in the clinic, and treatment protocols are largely consistent with the treatment guidelines for clear cell RCC (ccRCC), which might result in worse treatment outcomes for patients with these types of molecularly defined RCC. In this article, we conduct a narrative review of the literature published in the last 15 years on molecularly defined RCC. The purpose of this review is to summarize the clinical features and the current status of research on the detection and treatment of molecularly defined RCC.
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Cavada, Benildo Sousa, Vinicius Jose Silva Osterne, Vanir Reis Pinto-Junior, and Kyria Santiago Nascimento. "ConBr, the Lectin from Canavalia brasiliensis Mart. Seeds: Forty Years of Research." Current Protein & Peptide Science 20, no. 6 (May 20, 2019): 600–613. http://dx.doi.org/10.2174/1389203720666190104123210.
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Lectins are defined as proteins or glycoproteins capable of specific and reversible binding to carbohydrates. Inside this group of proteins, the most well-studied lectins belong to the Leguminosae family, and inside this family, the Diocleinae subtribe includes the most characterized lectin Concanavalin A (ConA), as well as ConBr, the lectin from Canavalia brasiliensis, the subject of this review. Since 1979, several studies have been published in the literature regarding this lectin, from its isolation and characterization to its several biological activities. This year, 2019, will mark 40 years since researchers have begun to study ConBr and 100 years since the discovery of ConA, making 2019 a momentous year for lectinology. Owing to the abundance of studies involving ConBr, this review will focus on ConBr’s purification, physicochemical properties, functional and structural analyses, biological activities and biotechnological applications. This will give researchers a broad glimpse into the potential of this lectin, as well as it characteristics, as we look ahead to its expanding applications in glycomics and biotechnology.
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Zhang, Hanrui, and Muredach P. Reilly. "Human Induced Pluripotent Stem Cell–Derived Macrophages for Unraveling Human Macrophage Biology." Arteriosclerosis, Thrombosis, and Vascular Biology 37, no. 11 (November 2017): 2000–2006. http://dx.doi.org/10.1161/atvbaha.117.309195.
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Despite a substantial appreciation for the critical role of macrophages in cardiometabolic diseases, understanding of human macrophage biology has been hampered by the lack of reliable and scalable models for cellular and genetic studies. Human induced pluripotent stem cell (iPSC)–derived macrophages (IPSDM), as an unlimited source of subject genotype-specific cells, will undoubtedly play an important role in advancing our understanding of the role of macrophages in human diseases. In this review, we summarize current literature in the differentiation and characterization of IPSDM at phenotypic, functional, and transcriptomic levels. We emphasize the progress in differentiating iPSC to tissue resident macrophages, and in understanding the ontogeny of in vitro differentiated IPSDM that resembles primitive hematopoiesis, rather than adult definitive hematopoiesis. We review the application of IPSDM in modeling both Mendelian genetic disorders and host–pathogen interactions. Finally, we highlighted the potential areas of research using IPSDM in functional validation of coronary artery disease loci in genome-wide association studies, functional genomic analyses, drug testing, and cell therapeutics in cardiovascular diseases.
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Kadyrov, F. N. "Issues of taxation of compensation payments for treatment of COVID-19 with personal income tax." Manager Zdravoochranenia, no. 10 (January 17, 2023): 97–100. http://dx.doi.org/10.21045/1811-0185-2022-10-97-100.
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Previously existing payments for the treatment of coronavirus infection (incentive payments, special social benefits) were not taxed on personal income. Therefore, the question naturally arises whether compensation payments to certain categories of persons at risk of contracting a new coronavirus infection are subject to taxation with this income. This problem is all the more urgent because, in accordance with the Tax Code, a number of types of compensation payments are exempt from taxation. The article analyzes the positions of the tax authorities on the problem under consideration, taking into account judicial practice, and concludes that compensation payments related to the treatment of COVID‑19 are an element of remuneration, act as a form of compensation surcharges for work in harmful working conditions, and therefore are subject to personal income tax in a general manner.
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Abel, Gregory A., Donnie Hebert, Cecilia Lee, James M. Foran, Steven D. Gore, Wael Saber, Dana Elise Rollison, et al. "Patient-Reported Outcomes and Frailty Among Participants in the NHLBI MDS Natural History Study." Blood 136, Supplement 1 (November 5, 2020): 15–16. http://dx.doi.org/10.1182/blood-2020-136992.
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Introduction: Patient-reported outcomes (PROs) such as quality of life (QOL) are variably affected in patients with myelodysplastic syndromes (MDS), but the heterogeneous composition of disease states grouped together as "MDS" increases the difficulty of assessing and understanding these outcomes. Moreover, little is known about the potential relationship between QOL and frailty in this population. Methods: The NHLBI MDS Natural History Study (NCT02775383) is a prospective cohort enrolling patients undergoing diagnostic work up for suspected MDS or MDS/myeloproliferative neoplasms (MPNs) in the setting of cytopenias. Untreated participants undergo bone marrow assessment with centralized histopathology review at enrollment for assignment into subcategories for longitudinal follow-up: MDS, MDS/MPN, ICUS, AML (<30% blasts), and "At-Risk" (cases with sub-threshold dysplasia or select karyotypic or genetic mutations). PRO and frailty data are collected at enrollment and every six months thereafter. PRO instruments include MDS-specific (QUALMS) and general (FACT-G, PROMIS Fatigue Short Form 7a, EQ-5D-5L) instruments, and a measure of frailty (VES-13). While no frailty instrument alone has been shown to be a substitute for comprehensive geriatric assessment, VES-13 has been successfully used in cancer-related studies for basic screening, where a score of 3 or more is considered frail (vulnerable). An analysis of variance (ANOVA) was used for the overall comparisons of mean baseline scores between diagnostic categories. Pairwise comparisons of scores between diagnostic categories and vulnerability subgroups were performed via two-sample t-tests. Results : Of 835 participants assessed for eligibility, 369 (44%) were classified as MDS, MDS/MPN, AML, ICUS or At-Risk, and further evaluated. Mean age was 72 years (standard deviation (SD)=10.7) and 68% were male. Mean baseline scores on the PRO measures are compared between diagnostic categories in the Table; scores did not differ significantly across categories. In particular, no significant differences were found between MDS and the other diagnostic categories. ICUS had similar QOL scores to MDS and MDS/MPN (e.g., means (SD) on EQ-5D-5L of 74.1 (17.8) in ICUS and 70.8 (19.4) in MDS, p=0.348) but had significantly higher scores than those for AML on EQ-5D-5L (60.7 (28.4), p=0.031). For the 216 participants with diagnostically-confirmed MDS, QOL impairment was similar to that routinely seen in other cancers; for example, the mean total FACT-G was 81.8 (SD=15.9), similar to localized breast cancer (82.4, SD=16.2), localized colorectal cancer (79.6, SD=16.1), and lung cancer with no current evidence of disease (82.6, SD=15.5; comparison means from Pearlman, Cancer, 2014). For frail/vulnerable participants with MDS or MDS/MPN (N=87), the most common reasons for vulnerability were age ≥75 years (68%), overall rating of health as poor or fair (62%), and difficulty with prolonged physical activity (90%) such as walking a quarter mile (75%) or doing heavy housework (70%). A minority also were vulnerable due to requiring help with instrumental activities of daily living (iADLS) such as shopping (28%) or managing money (16%). Mean QOL scores were compared between vulnerability subgroups (Figure). Vulnerable participants pooled over all diagnostic categories had significantly worse PROs than non-vulnerable participants for all measures (p<0.001). In particular, vulnerable MDS participants scored significantly worse on the QUALMS (mean 64.4, SD=13.4) vs. non-vulnerable MDS participants (mean 72.7, SD=13.3), p<0.001. Conclusions: Participants in our cohort with histologically-confirmed MDS-even low-grade MDS-had similar impairments in PROs as those with other cancers. Among those with histologically-confirmed MDS, vulnerable participants had significantly worse QOL on many measures compared to non-vulnerable participants, suggesting that this domain of function be specifically assessed in clinic. Moreover, while a "gestalt" of frailty may be inferred by observing how patients present and move in the office, these data suggest that other contributing domains, such as difficulty with prolonged physical activity and iADLs, should be evaluated explicitly. Disclosures Foran: H3Biosciences: Research Funding; Aptose: Research Funding; Kura Oncology: Research Funding; Takeda: Research Funding; Servier: Membership on an entity's Board of Directors or advisory committees; Xencor: Research Funding; Agios: Honoraria, Research Funding; Boehringer Ingelheim: Research Funding; Actinium: Research Funding; Aprea: Research Funding; BMS: Membership on an entity's Board of Directors or advisory committees; Novartis: Membership on an entity's Board of Directors or advisory committees; Trillium: Research Funding; Revolution Medicine: Consultancy; Pfizer: Membership on an entity's Board of Directors or advisory committees; Abbvie: Research Funding. Gore:Abbvie: Consultancy, Honoraria, Research Funding. Padron:Incyte: Research Funding; Kura: Research Funding; Novartis: Honoraria; BMS: Research Funding. Sekeres:BMS: Consultancy, Membership on an entity's Board of Directors or advisory committees; Pfizer: Consultancy, Membership on an entity's Board of Directors or advisory committees; Takeda/Millenium: Consultancy, Membership on an entity's Board of Directors or advisory committees.
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Schutgens, Frans, and Hans Clevers. "Human Organoids: Tools for Understanding Biology and Treating Diseases." Annual Review of Pathology: Mechanisms of Disease 15, no. 1 (January 24, 2020): 211–34. http://dx.doi.org/10.1146/annurev-pathmechdis-012419-032611.
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Organoids are in vitro–cultured three-dimensional structures that recapitulate key aspects of in vivo organs. They can be established from pluripotent stem cells and from adult stem cells, the latter being the subject of this review. Organoids derived from adult stem cells exploit the tissue regeneration process that is driven by these cells, and they can be established directly from the healthy or diseased epithelium of many organs. Organoids are amenable to any experimental approach that has been developed for cell lines. Applications in experimental biology involve the modeling of tissue physiology and disease, including malignant, hereditary, and infectious diseases. Biobanks of patient-derived tumor organoids are used in drug development research, and they hold promise for developing personalized and regenerative medicine. In this review, we discuss the applications of adult stem cell–derived organoids in the laboratory and the clinic.
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Sri Ranjani, Tallam, and Ch Ramadevi. "Evaluation of Cell Biology and Genetics using VIKOR Method." Agricultural, Biologicals and Food Science 2, no. 1 (May 1, 2023): 01–05. http://dx.doi.org/10.46632/abfs/2/1/1.
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Cell biology and genetics are fields of heredity research. They enable experts to examine indigenous people's genetic data to identify their current state of health. By taking necessary precautions, one can protect their health using this technology. Cell biology has quickly expanded in the medical field and has emerged as the only treatment for issues with human reproduction. Genetics, or the science of genes and heredity, is all about the study of features that are passed down from one generation to the next. The subject of cell biology is the smallest units of life, cells, and their structures and functions. Understanding the structure and physiological functioning of single cells, and how cells interact and work together in great numbers to generate tissues and organisms, is a goal of cell biology. Cell biology is based on the notion that a cell is the basic unit of all life. Understanding the tissues and organisms that make up cells in great detail is made possible by concentrating on the cell. If you want to teach in a classroom, you can look into botany or zoology. If you're interested in biological or industrial sciences or medical research, you can choose from genetics, microbiology, or biotechnology. Cell biology encompasses both eukaryotic and prokaryotic cells and has a wide range of subtopics, including the research of cellular metabolism, cell communication, cell cycle, chemistry, and cell composition. Cells can be examined using a variety of microscopy techniques, cell culturing, and cell fractionation. There are two different cell types: prokaryotic and eukaryotic ones. Despite having differing morphologies (see Prokaryote, Eukaryote), eukaryotic organisms are remarkably comparable in terms of underlying molecular make-up and functions. Over the past 50 years, cell biology has seen remarkable expansion as a key area of basic science (1). Medicine makes use of information from basic science domains such as cell biology for the benefit of patients (2-4). A subfield of biology known as cell biology focuses on the cell, including its different types, structures, functions, and interactions with other cells. The subfields of cell biology include cell composition, cell cycle, cell communication, and cell metabolism. Research in several domains, including genetics, biochemistry, neuroscience, plant biology, molecular biology, microbiology, and immunology, is tied to those in cell biology. The VIKOR (VIšekriterijumsko Compromising Rangiranje) Optimal Replacement Select method is used in the evaluation of Epidermal Growth Factor Receptor, Fibroblast Growth Factor Receptors, Discoidin Domain Receptor, Mitogen-Activated Protein Kinase, and Nuclear Receptor-Binding SET Domain Protein alternatives for skin, lung, head/neck, and cervical cancer. Fibroblast Growth Factor Receptors have the highest rank, whereas Nuclear Receptor-Binding SET Domain Protein has the lowest rank.
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Opondo, Philip R., Anthony A. Olashore, Keneilwe Molebatsi, Caleb J. Othieno, and James O. Ayugi. "Mental health research in Botswana: a semi-systematic scoping review." Journal of International Medical Research 48, no. 10 (October 2020): 030006052096645. http://dx.doi.org/10.1177/0300060520966458.
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Mental and substance use disorders are a leading cause of disability worldwide. Despite this, there is a paucity of mental health research in low- and middle-income countries, especially in sub-Saharan Africa. We carried out a semi-systematic scoping review to determine the extent of mental health research in Botswana. Using a predetermined search strategy, we searched the databases Web of Science, PubMed, and EBSCOhost (Academic Search Complete, CINAHL with Full Text, MEDLINE, MEDLINE with Full Text, MLA International Bibliography, Open Dissertations) for articles written in English from inception to June 2020. We identified 58 studies for inclusion. The most researched subject was mental health aspects of HIV/AIDS, followed by research on neurotic and stress-related disorders. Most studies were cross-sectional and the earliest published study was from 1983. The majority of the studies were carried out by researchers affiliated to the University of Botswana, followed by academic institutions in the USA. There seems to be limited mental health research in Botswana, and there is a need to increase research capacity.
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Aguilar-Alonso, P., O. Vera-López, E. Brambila-Colombres, O. Segura-Badilla, R. Avalos-López, M. Lazcano-Hernández, and A. R. Navarro-Cruz. "Evaluation of Oxidative Stress in Cardiomyocytes during the Aging Process in Rats Treated with Resveratrol." Oxidative Medicine and Cellular Longevity 2018 (2018): 1–9. http://dx.doi.org/10.1155/2018/1390483.
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The substantial increase in the number of elderly people in our societies represents a challenge for biology and medicine. The societies of the industrialized countries are subject to a progressive aging process that translates into an increase in the cardiovascular risk of the population. In the present work, the activity of catalase and superoxide dismutase was evaluated, as well as markers of oxidative stress (concentration of nitric oxide and total lipoperoxidation in its main components: malondialdehyde and 4-hydroxyalkene) in cardiomyocytes during the aging process in rats treated with resveratrol. Rats were divided into 4 groups according to the following categories: control (without treatment), negative control group (administered with physiological solution with 10% ethanol), positive control group (administered with vitamin E, 2 mg/kg/day), and group administered with resveratrol (10 mg/kg/day); these groups in turn were divided into 2, 4, 6, and 8 months of treatment. The analysis of nitric oxide showed a decreased level in the cardiac tissue in the groups treated with resveratrol; the same occurs when total lipoperoxidation is analyzed. The enzymatic activity studied (catalase and superoxide dismutase) did not present significant changes with respect to the controls. It is concluded that the cardioprotective effect of resveratrol is due to the antioxidant effect and other antiaging effects and not to the activation of the enzymes catalase and superoxide dismutase.
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Wang, Michael, Michael Recht, Neeraj Iyer, David L. Cooper, and John Michael Soucie. "The Relationship of Joint Range of Motion to Factor Activity in Patients with Hemophilia A and B without Prophylaxis: A Longitudinal Assessment of the CDC-UDC Hemophilia Dataset." Blood 130, Suppl_1 (December 7, 2017): 756. http://dx.doi.org/10.1182/blood.v130.suppl_1.756.756.
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Abstract Background: Recurrent joint bleeding in severe congenital hemophilia results in arthropathy and functional impairment. Clinical and epidemiologic evidence suggest that patients with moderate and mild hemophilia also experience joint bleeding, particularly with factor activity (FA) levels below 15-20%. While arthropathy and joint interventions have been reported in mild-moderate hemophilia, the longitudinal assessment of arthropathy development and relationship to FA has not been reported. Methods: During the Centers for Disease Control and Prevention (CDC) Universal Data Collection (UDC) surveillance initiative (1998-2011), joint range of motion (ROM) measurements were taken on each of 10 joints (shoulders, elbows, hips, knees and ankles) by trained care providers using standardized methods at each comprehensive visit. Data were extracted from male patients with hemophilia (PWH) age ≥2 years with baseline FA levels ≤ 40%, excluding those who had been prescribed prophylaxis or had evidence of an inhibitor at any time. ROM measures from all 10 joints combined for each subject and data collected similarly on a population without bleeding or joint disorders (Soucie JM, Haemophilia 2012) age 12-20 males) were used to calculate a proportion of normal ROM (PN-ROM) measure for each study subject and each normal male using the 12-20 year old normals as the reference. Because very young subjects have greater ROM than 12 - 20 year olds, the PN-ROM value for these subjects could exceed 100%. Least square means of the PN-ROM values for subjects in categories of these characteristics were compared using general linear regression. Data collected from 2 to 14 UDC visits for each subject were analyzed using mixed model repeated measures linear regression to evaluate the effects of patient characteristics on the rate of ROM loss over time. Results: There were 6,703 (4,807 hemophilia A) eligible PWH with 30,102 UDC visits (mean 4.5 per patient). Of these, 26% had severe and 31% moderate hemophilia, 52% were youth or teens, 10% were either black or Hispanic, and 45% were overweight or obese. PN-ROM declined with age (106% for youngest to 85% for oldest subjects), and was associated with hemophilia severity, race/ethnicity, obesity, and viral illnesses. The relationship between PN-ROM and the combination of age and baseline FA level (Table) showed values for most PWH were within 10 percent of similarly aged normals. Only PWH ≥30 years old with FA ≤2% and those ≥50 years old with FA ≤5% had mean PN-ROM values >10% less than controls; those ≥40 years old with FA <1% had PN-ROM values >20% less than controls. The figures demonstrate that the loss in PN-ROM is linear with the steepest decline among subjects with severe disease, and the overall magnitude of the decline appears to be greater for subjects with hemophilia A than B. In the multivariate analysis subjects with <1% FA had a 0.428 percent greater decrease in PN-ROM each year relative to those with 16% - 40% FA and this excess decrease was highly statistically significant (p < 0.001). A similar significant effect was seen among subjects with either 1% - 5% or 6% - 9% FA, however, the magnitude of the decrease in the PN-ROM (0.126 for both) was about one-fourth that seen among those with severe hemophilia. FA levels from 10% to 15% did not significantly influence the rate of PN-ROM change over time relative to those with FA >15%. Those with hemophilia B lost PN-ROM at a 0.05 percent slower rate than those with hemophilia A (p < 0.001). Conclusion: The effect of FA level on ROM loss is far greater than that of any of the other characteristics, but only for patients with FA levels less than 10%. This emphasizes the need to maintain a high index of suspicion in individuals with moderate and low-mild hemophilia and of older age. The effect of hemophilia type (A vs B) on rate of ROM loss is about one-tenth that of having severe disease, and may be one reason for the difficulty in proving that hemophilia B has a less severe phenotype. Figure Figure. Disclosures Wang: Acerta Pharma: Consultancy, Research Funding; Asana Biosciences: Research Funding; BeiGene: Research Funding; Celgene: Honoraria, Research Funding; Dava Oncology: Honoraria; Janssen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; June Therapeutics: Research Funding; Kite Pharma: Research Funding; Onyx: Research Funding; Pharmacyclics: Research Funding; Proteolix: Honoraria, Research Funding. Recht: Biogen: Membership on an entity's Board of Directors or advisory committees, Research Funding; CSL Behring: Membership on an entity's Board of Directors or advisory committees; Genentech: Research Funding; Kedrion: Membership on an entity's Board of Directors or advisory committees; NovoNordisk: Research Funding; Pfizer: Membership on an entity's Board of Directors or advisory committees; Shire: Membership on an entity's Board of Directors or advisory committees, Research Funding. Iyer: Novo Nordisk Inc.: Employment. Cooper: Novo Nordisk Inc.: Employment.
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Dong, Xueting, Yaochong Tan, Donglin Zhuang, Tingting Hu, and Mingyi Zhao. "Global Characteristics and Trends in Research on Ferroptosis: A Data-Driven Bibliometric Study." Oxidative Medicine and Cellular Longevity 2022 (January 17, 2022): 1–12. http://dx.doi.org/10.1155/2022/8661864.
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Ferroptosis, an iron-dependent form of regulated cell death, has drawn an increasing amount of attention since it was first mentioned in 2012 and is found to play a significant role in the treatment of certain diseases. Our study is aimed at analysing the scientific output of ferroptosis research and at driving future research into novel publications. Publications focused on ferroptosis were retrieved from the SCI-EXPANDED database of the Web of Science Core Collection and were screened according to inclusion criteria. CiteSpace V and Microsoft Excel 2016 were used to evaluate and visualize the results, including generating network maps and analysing annual publications, country, category, references and cocited references, and keywords. As of October 1, 2021, a total of 1690 original articles related to ferroptosis were included, and the overall trend of the number of publications rapidly increased. Among the common categories in the field of ferroptosis, the most common category was biochemistry and molecular biology. Worldwide, China and the United States were the leading countries for research production. The retrieved 1690 publications received 44,650 citations, with an average of 26.42 citations per paper (October 1, 2021). By citation analysis, Scott J Dixon’s article in 2012 was the most symbolic reference and the earliest publication in the field of ferroptosis, with the highest citation rate (2709 times). Among the most common keywords, most were related to the mechanisms and regulatory networks of ferroptosis. Furthermore, with accumulating evidence demonstrating the role of ferroptosis in cancers and other diseases, inducing ferroptosis in clinical treatment is becoming a new research focus that should be closely monitored.
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Kim, Bohyun, Minsun Jung, and Kyung Chul Moon. "The Prognostic Significance of Protein Expression of CASZ1 in Clear Cell Renal Cell Carcinoma." Disease Markers 2019 (August 6, 2019): 1–6. http://dx.doi.org/10.1155/2019/1342161.
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Backgrounds. Clear cell renal cell carcinoma (ccRCC) is the most common histologic subtype of renal cell carcinoma (RCC) and shows a relatively poor prognosis among RCCs. Castor zinc finger 1 (CASZ1) is a transcription factor, prominently known for its tumor suppression role in neuroblastoma and other cancers. However, there has been no research about the prognostic significance of CASZ1 in ccRCC. In this study, we investigated CASZ1 expression in ccRCC and analyzed its prognostic implications. Methods. A total of 896 ccRCC patients, who underwent surgical resection from 1995 to 2008, were included. We prepared tissue microarray blocks, evaluated CASZ1 nuclear expression by immunohistochemistry, and classified the cases into low or high expression categories. Results. A low expression of CASZ1 was observed in 320 cases (35.7%) and was significantly associated with large tumor size, high World Health Organization/International Society of Urological Pathology (WHO/ISUP) grade, and high T category and M category. In survival analysis, a low expression of CASZ1 was significantly correlated with unfavorable progression-free survival (PFS) (p<0.001), overall survival (OS) (p<0.001), and cancer-specific survival (CSS) (p<0.001) and was an independent prognostic factor for PFS and CSS in multivariate analysis adjusted for tumor size, WHO/ISUP grade, T category, N category, and M category. Conclusions. Our study is the first to show the prognostic significance of CASZ1 expression in ccRCC. Our results revealed that low expression of CASZ1 is associated with poor prognosis and may serve as a new prognostic indicator.
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Robotti, Suzanne. "The heritable legacy of diethylstilbestrol: a bellwether for endocrine disruption in humans." Biology of Reproduction 105, no. 3 (August 17, 2021): 687–89. http://dx.doi.org/10.1093/biolre/ioab146.
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Abstract Millions of women and their fetuses were exposed to the toxic pregnancy drug diethylstilbestrol (DES) from the 1940s into the 1970s, a time when the medical profession had little knowledge about potential developmental consequences of fetal drug exposures. Pathological consequences of DES exposure to the pregnant mothers and their offspring are well documented, but now generational research is finding that the grandchildren of women given DES in pregnancy are also at risk. This commentary summarizes presentations on this subject from the Beyond Genes panel “Heritable Impacts of Diethylstilbestrol (DES).”
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Niu, Qin, Qiannan Sun, Rushui Bai, Yunfan Zhang, Zimeng Zhuang, Xin Zhang, Tianyi Xin, Si Chen, and Bing Han. "Progress of Nanomaterials-Based Photothermal Therapy for Oral Squamous Cell Carcinoma." International Journal of Molecular Sciences 23, no. 18 (September 9, 2022): 10428. http://dx.doi.org/10.3390/ijms231810428.
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Oral squamous cell carcinoma (OSCC) is one of the top 15 most prevalent cancers worldwide. However, the current treatment models for OSCC (e.g., surgery, chemotherapy, radiotherapy, and combination therapy) present several limitations: damage to adjacent healthy tissue, possible recurrence, low efficiency, and severe side effects. In this context, nanomaterial-based photothermal therapy (PTT) has attracted extensive research attention. This paper reviews the latest progress in the application of biological nanomaterials for PTT in OSCC. We divide photothermal nanomaterials into four categories (noble metal nanomaterials, carbon-based nanomaterials, metal compounds, and organic nanomaterials) and introduce each category in detail. We also mention in detail the drug delivery systems for PTT of OSCC and briefly summarize the applications of hydrogels, liposomes, and micelles. Finally, we note the challenges faced by the clinical application of PTT nanomaterials and the possibility of further improvement, providing direction for the future research of PTT in OSCC treatment.
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Wilkins, Anna, Elisa Fontana, Gift Nyamundanda, Chanthirika Ragulan, Yatish Patil, David Mansfield, Jennifer Kingston, et al. "Differential and longitudinal immune gene patterns associated with reprogrammed microenvironment and viral mimicry in response to neoadjuvant radiotherapy in rectal cancer." Journal for ImmunoTherapy of Cancer 9, no. 3 (March 2021): e001717. http://dx.doi.org/10.1136/jitc-2020-001717.
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BackgroundRectal cancers show a highly varied response to neoadjuvant radiotherapy/chemoradiation (RT/CRT) and the impact of the tumor immune microenvironment on this response is poorly understood. Current clinical tumor regression grading systems attempt to measure radiotherapy response but are subject to interobserver variation. An unbiased and unique histopathological quantification method (change in tumor cell density (ΔTCD)) may improve classification of RT/CRT response. Furthermore, immune gene expression profiling (GEP) may identify differences in expression levels of genes relevant to different radiotherapy responses: (1) at baseline between poor and good responders, and (2) longitudinally from preradiotherapy to postradiotherapy samples. Overall, this may inform novel therapeutic RT/CRT combination strategies in rectal cancer.MethodsWe generated GEPs for 53 patients from biopsies taken prior to preoperative radiotherapy. TCD was used to assess rectal tumor response to neoadjuvant RT/CRT and ΔTCD was subjected to k-means clustering to classify patients into different response categories. Differential gene expression analysis was performed using statistical analysis of microarrays, pathway enrichment analysis and immune cell type analysis using single sample gene set enrichment analysis. Immunohistochemistry was performed to validate specific results. The results were validated using 220 pretreatment samples from publicly available datasets at metalevel of pathway and survival analyses.ResultsΔTCD scores ranged from 12.4% to −47.7% and stratified patients into three response categories. At baseline, 40 genes were significantly upregulated in poor (n=12) versus good responders (n=21), including myeloid and stromal cell genes. Of several pathways showing significant enrichment at baseline in poor responders, epithelial to mesenchymal transition, coagulation, complement activation and apical junction pathways were validated in external cohorts. Unlike poor responders, good responders showed longitudinal (preradiotherapy vs postradiotherapy samples) upregulation of 198 immune genes, reflecting an increased T-cell-inflamed GEP, type-I interferon and macrophage populations. Longitudinal pathway analysis suggested viral-like pathogen responses occurred in post-treatment resected samples compared with pretreatment biopsies in good responders.ConclusionThis study suggests potentially druggable immune targets in poor responders at baseline and indicates that tumors with a good RT/CRT response reprogrammed from immune “cold” towards an immunologically “hot” phenotype on treatment with radiotherapy.
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Machnicka, Beata, Renata Grochowalska, Dżamila M. Bogusławska, and Aleksander F. Sikorski. "The role of spectrin in cell adhesion and cell–cell contact." Experimental Biology and Medicine 244, no. 15 (June 21, 2019): 1303–12. http://dx.doi.org/10.1177/1535370219859003.
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Spectrins are proteins that are responsible for many aspects of cell function and adaptation to changing environments. Primarily the spectrin-based membrane skeleton maintains cell membrane integrity and its mechanical properties, together with the cytoskeletal network a support cell shape. The occurrence of a variety of spectrin isoforms in diverse cellular environments indicates that it is a multifunctional protein involved in numerous physiological pathways. Participation of spectrin in cell–cell and cell–extracellular matrix adhesion and formation of dynamic plasma membrane protrusions and associated signaling events is a subject of interest for researchers in the fields of cell biology and molecular medicine. In this mini-review, we focus on data concerning the role of spectrins in cell surface activities such as adhesion, cell–cell contact, and invadosome formation. We discuss data on different adhesion proteins that directly or indirectly interact with spectrin repeats. New findings support the involvement of spectrin in cell adhesion and spreading, formation of lamellipodia, and also the participation in morphogenetic processes, such as eye development, oogenesis, and angiogenesis. Here, we review the role of spectrin in cell adhesion and cell–cell contact.Impact statementThis article reviews properties of spectrins as a group of proteins involved in cell surface activities such as, adhesion and cell–cell contact, and their contribution to morphogenesis. We show a new area of research and discuss the involvement of spectrin in regulation of cell–cell contact leading to immunological synapse formation and in shaping synapse architecture during myoblast fusion. Data indicate involvement of spectrins in adhesion and cell–cell or cell–extracellular matrix interactions and therefore in signaling pathways. There is evidence of spectrin’s contribution to the processes of morphogenesis which are connected to its interactions with adhesion molecules, membrane proteins (and perhaps lipids), and actin. Our aim was to highlight the essential role of spectrin in cell–cell contact and cell adhesion.
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Hidayat, Tomi, Nasral Nasral, Santoso Santoso, and Pariyanto Pariyanto. "Molekuler Method of Portofolio Resume Assignment to Improving Students Concept Comprehension Towards Molecular Cellular Biology Class." Jurnal Penelitian Pendidikan IPA 9, no. 4 (April 30, 2023): 1881–85. http://dx.doi.org/10.29303/jppipa.v9i4.3403.
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Cell and molecular biology are among the topics that have led to the application of molecular technology. Problems arise when learners lack understanding of concepts or even frequent misconceptions due to many abstract concepts. This study aims to determine the level of student understanding through a resume in the form of a portfolio. The research method used descriptive approach. The population of the study is the students of Biology Education study program which has taken the subject of cell Biology and molecular number of 102 students, and the sample determination using random cluster so that 40 students are obtained. Data were analyzed descriptively-quantitative. Based on the findings in the field, it is known that the average value of the resume portfolio of 71.60 and categorized high. Thus, the students' concept of understanding is in the high category so that the assignment method makes the resume in the form of portfolio able to give better understanding of the concept of lecture material of Cell and Molecular Biology, with the average value of concept understanding through portfolio is in high category
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Li, Yan, Lungen Lu, and Xiaobo Cai. "Liver Regeneration and Cell Transplantation for End-Stage Liver Disease." Biomolecules 11, no. 12 (December 20, 2021): 1907. http://dx.doi.org/10.3390/biom11121907.
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Liver transplantation is the only curative option for end-stage liver disease; however, the limitations of liver transplantation require further research into other alternatives. Considering that liver regeneration is prevalent in liver injury settings, regenerative medicine is suggested as a promising therapeutic strategy for end-stage liver disease. Upon the source of regenerating hepatocytes, liver regeneration could be divided into two categories: hepatocyte-driven liver regeneration (typical regeneration) and liver progenitor cell-driven liver regeneration (alternative regeneration). Due to the massive loss of hepatocytes, the alternative regeneration plays a vital role in end-stage liver disease. Advances in knowledge of liver regeneration and tissue engineering have accelerated the progress of regenerative medicine strategies for end-stage liver disease. In this article, we generally reviewed the recent findings and current knowledge of liver regeneration, mainly regarding aspects of the histological basis of regeneration, histogenesis and mechanisms of hepatocytes’ regeneration. In addition, this review provides an update on the regenerative medicine strategies for end-stage liver disease. We conclude that regenerative medicine is a promising therapeutic strategy for end-stage liver disease. However, further studies are still required.
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Halpern, Anna B., Megan Othus, Kelda Gardner, Genevieve Alcorn, Mary-Elizabeth M. Percival, Emily M. Huebner, Bart L. Scott, et al. "Mini- Vs. Regular-Dose CLAG-M (Cladribine, Cytarabine, G-CSF, and Mitoxantrone) in Medically Less Fit Adults with Newly-Diagnosed Acute Myeloid Leukemia (AML) and Other High-Grade Myeloid Neoplasms." Blood 134, Supplement_1 (November 13, 2019): 1364. http://dx.doi.org/10.1182/blood-2019-123542.
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Background: Optimal treatment for medically less fit adults with acute myeloid leukemia (AML) remains uncertain. Retrospective data suggest intensive therapy may lead to better outcomes in these patients. However, these findings must be interpreted cautiously because of the possibility of selection bias and other confounders. Ideally, the optimal treatment intensity is defined via randomized trial but whether patients and their physicians are amenable to such a study is unknown. We therefore designed a trial (NCT03012672) to 1) evaluate the feasibility of randomization between intensive and non-intensive therapy in this population and 2) examine the impact of treatment intensity on response rate and survival. We used CLAG-M as high-dose cytarabine-based intensive induction therapy. Rather than selecting different classes of drugs in the 2 treatment arms- which may have different modes of action and therefore confound the question of treatment intensity - we used reduced-dose ("mini") CLAG-M as the non-intensive comparator. Methods: Adults ≥18 years were eligible if they had untreated AML or high-grade myeloid neoplasms (≥10% blasts in blood or marrow) and were medically less fit as defined by having a "treatment related mortality" (TRM) score of ≥13.1, corresponding to a >10-15% 28-day mortality with intensive chemotherapy. Left ventricular ejection fraction ≤45% was the only organ function exclusion. Patient-physician pairs were first asked if they were amenable to randomized treatment allocation. If so, they were randomized 1:1 to mini- vs. regular-dose CLAG-M. If not, in order to evaluate our secondary endpoints, the patient or physician could choose the treatment arm and still enroll on study. Patients and physicians then completed surveys elucidating their decision-making processes. Up to 2 induction courses were given with mini- vs. regular-dose CLAG-M: cladribine 2 or 5 mg/m2/day (days 1-5), cytarabine 100 or 2,000 mg/m2/day (days 1-5), G-CSF 300 or 480µcg/day for weight </≥76kg in both arms (days 0-5), and mitoxantrone 6 or 18 mg/m2/day (days 1-3). CLAG at identical doses was used for post-remission therapy for up to 4 (regular-dose CLAG) or 12 (mini-CLAG) cycles. The primary endpoint was feasibility of randomization, defined as ≥26/50 of patient-physician pairs agreeing to randomization. Secondary outcomes included rate of complete remission (CR) negative for measurable ("minimal") residual disease (MRD), rate of CR plus CR with incomplete hematologic recovery (CR+CRi), and overall survival (OS). Results: This trial enrolled 33 patients. Only 3 (9%) patient/physician pairs agreed to randomization and thus randomization was deemed infeasible (primary endpoint). Eighteen pairs chose mini-CLAG-M and 12 regular-dose CLAG-M for a total of 19 subjects in the lower dose and 14 subjects in the higher dose arms. The decision favoring lower dose treatment was made largely by the physician in 5/18 (28%) cases, the patient in 11/18 (61%) cases and both in 2/18 (11%). The decision favoring the higher dose arm was made by the patient in most cases 9/12 (75%), both physician and patient in 2/12 (16%) and the physician in only 1/12 (8%) cases. Despite the limitations of lack of randomization, patients' baseline characteristics were well balanced with regard to age, performance status, TRM score, lab values and cytogenetic/mutational risk categories (Table 1). One patient was not yet evaluable for response or TRM at data cutoff. Rates of MRDneg CR were comparable: 6/19 (32%) in the lower and 3/14 (21%) in the higher dose groups (p=0.70). CR+CRi rates were also similar in both arms (43% vs. 56% in lower vs. higher dose arms; p=0.47). Three (16%) patients experienced early death in the lower dose arm vs. 1 (7%) in the higher dose arm (p=0.43). With a median follow up of 4.2 months, there was no survival difference between the two groups (median OS of 6.1 months in the lower vs. 4.7 months in the higher dose arm; p=0.81; Figure 1). Conclusions: Randomization of medically unfit patients to lower- vs. higher-intensity therapy was not feasible, and physicians rarely chose higher intensity therapy in this patient group. Acknowledging the limitation of short follow-up time and small sample size, our trial did not identify significant differences in outcomes between intensive and non-intensive chemotherapy. Analysis of differences in QOL and healthcare resource utilization between groups is ongoing. Disclosures Halpern: Pfizer Pharmaceuticals: Research Funding; Bayer Pharmaceuticals: Research Funding. Othus:Celgene: Other: Data Safety and Monitoring Committee. Gardner:Abbvie: Speakers Bureau. Percival:Genentech: Membership on an entity's Board of Directors or advisory committees; Pfizer Inc.: Research Funding; Nohla Therapeutics: Research Funding. Scott:Incyte: Consultancy; Novartis: Consultancy; Agios: Consultancy; Celgene: Consultancy. Becker:AbbVie, Amgen, Bristol-Myers Squibb, Glycomimetics, Invivoscribe, JW Pharmaceuticals, Novartis, Trovagene: Research Funding; Accordant Health Services/Caremark: Consultancy; The France Foundation: Honoraria. Oehler:Pfizer Inc.: Research Funding; Blueprint Medicines: Consultancy. Walter:BioLineRx: Consultancy; Astellas: Consultancy; Argenx BVBA: Consultancy; BiVictriX: Consultancy; Agios: Consultancy; Amgen: Consultancy; Amphivena Therapeutics: Consultancy, Equity Ownership; Boehringer Ingelheim: Consultancy; Boston Biomedical: Consultancy; Covagen: Consultancy; Daiichi Sankyo: Consultancy; Jazz Pharmaceuticals: Consultancy; Seattle Genetics: Research Funding; Race Oncology: Consultancy; Aptevo Therapeutics: Consultancy, Research Funding; Kite Pharma: Consultancy; New Link Genetics: Consultancy; Pfizer: Consultancy, Research Funding. OffLabel Disclosure: Cladribine is FDA-approved for Hairy Cell Leukemia. Here we describe its use for AML, where is is also widely used with prior publications supporting its use
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Carton, Flavia, and Manuela Malatesta. "In Vitro Models of Biological Barriers for Nanomedical Research." International Journal of Molecular Sciences 23, no. 16 (August 10, 2022): 8910. http://dx.doi.org/10.3390/ijms23168910.
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Nanoconstructs developed for biomedical purposes must overcome diverse biological barriers before reaching the target where playing their therapeutic or diagnostic function. In vivo models are very complex and unsuitable to distinguish the roles plaid by the multiple biological barriers on nanoparticle biodistribution and effect; in addition, they are costly, time-consuming and subject to strict ethical regulation. For these reasons, simplified in vitro models are preferred, at least for the earlier phases of the nanoconstruct development. Many in vitro models have therefore been set up. Each model has its own pros and cons: conventional 2D cell cultures are simple and cost-effective, but the information remains limited to single cells; cell monolayers allow the formation of cell–cell junctions and the assessment of nanoparticle translocation across structured barriers but they lack three-dimensionality; 3D cell culture systems are more appropriate to test in vitro nanoparticle biodistribution but they are static; finally, bioreactors and microfluidic devices can mimicking the physiological flow occurring in vivo thus providing in vitro biological barrier models suitable to reliably assess nanoparticles relocation. In this evolving context, the present review provides an overview of the most representative and performing in vitro models of biological barriers set up for nanomedical research.
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Bose, Prithviraj, Naval Daver, Elias J. Jabbour, Allison Pike, Kate J. Newberry, Lingsha Zhou, Sherry Pierce, Xuemei Wang, Hagop M. Kantarjian, and Srdan Verstovsek. "Phase-2 Study of Sotatercept (ACE-011) in Myeloproliferative Neoplasm-Associated Myelofibrosis and Anemia." Blood 128, no. 22 (December 2, 2016): 478. http://dx.doi.org/10.1182/blood.v128.22.478.478.
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Abstract Introduction: Anemia is common in MPN-associated myelofibrosis (MF), and current therapies (e.g., erythropoiesis stimulating agents, androgens, danazol, immune modulatory drugs and corticosteroids) are unsatisfactory. Furthermore, anemia is not improved and initially worsened by ruxolitinib, an important MF therapy. New drugs with novel mechanisms of action are needed. Sotatercept is a first-in-class activin receptor type IIA (ActRIIA) ligand trap consisting of the extracellular domain of ActIIRA linked to the human IgG1 Fc domain. Sotatercept binds to and sequesters ligands of the transforming growth factor beta (TGF-ß) superfamily, thus relieving their blockade of terminal erythroid differentiation. Pre-clinically, sotatercept corrects ineffective erythropoiesis in ß-thalassemia (Dussiot, M. et al. Nat Med 2014) and its murine ortholog RAP-011 improves erythropoiesis in Diamond Blackfan anemia (Ear, J. et al. Blood 2015). Clinical trials in persons with lower risk myelodysplastic syndromes (Komrokji, R. et al. ASH 2014) and chemotherapy-induced anemia (Raftopoulos, H. et al. Support Care Cancer 2016) have shown promising results. Methods: This is an ongoing phase-2 study of sotatercept, 0.75 or 1 mg/kg subcutaneously every 3 weeks (1 cycle), in subjects with MF, whether primary (PMF) or post-polycythemia vera/essential thrombocythemia (post-PV/ET MF). Subjects must be RBC-transfusion-dependent (Gale, R.P. et al. Leuk Res 2011), have hemoglobin <10 g/dL on every determination during the 84 days preceding study entry without RBC transfusions, or have hemoglobin <10 g/dL despite intermittent RBC transfusions without fulfilling the criteria for transfusion dependence. Primary endpoints include anemia response and safety. Secondary endpoints include time to and duration of anemia response. Anemia response is a composite of RBC-transfusion-independence and hemoglobin response (increase of ≥1.5 g/dL from baseline on every determination consecutively over ≥84 days without RBC transfusions). Subjects must have received ≥5 cycles of sotatercept to be evaluable for response. Results: 18 subjects are enrolled to date. 1 subject received 6 cycles at a sub-therapeutic dose of 0.3 mg/kg and was not considered for efficacy evaluation, but was evaluable for safety. Of the remaining 17 subjects, 11 received 0.75 mg/kg and 6, 1 mg/kg. Median age was 67 years (range, 47-84 years); 10 were male and 7 female. 14 had PMF and 3, post-ET MF. 12 subjects had JAK2 V617F, 1 had MPLW515L and 2 had CALR exon 9 mutations. 1 subject was triple negative and 1 subject had no JAK2 or MPL mutation but was not tested for CALR mutations. All 17 subjects had intermediate-2 or high risk disease by the Dynamic International Prognostic Scoring System. Table 1 summarizes baseline variables for these 17 subjects. Median number of cycles of sotatercept received is 5 (range, 1-13). 14 of the 17 subjects received ≥5 cycles and were evaluable for response. The 3 other subjects received 1, 2 and 2 cycles and discontinued due to unrelated medical problems, hypertension and stem cell transplant (SCT), respectively. 5 of 14 (36%) evaluable subjects have responded; 4 of whom continue on study in ongoing response. All responders are female and all female subjects evaluable for response responded. Responses occurred across phenotypic driver mutation categories and in both transfusion-dependent (n=3) and -independent (n=2) subjects. 40% and 25% of evaluable patients responded in the 0.75 mg/kg and 1 mg/kg dose cohorts, respectively. Most adverse events (AEs) were grades 1 or 2. The only AEs possibly attributable to sotatercept include grade 3 hypertension leading to discontinuation, and grade 1 myalgia, bone pain, pain in extremity and injection site reaction. 5 subjects remain on study. 12 have discontinued because of no response (5), SCT (2), unrelated medical problems (1), hypertension (1), disease progression (1), transformation to AML (1) and withdrawal of consent (1). Conclusion: Sotatercept improves anemia and RBC-transfusion-dependence in persons with MF and is well-tolerated. Enrollment to the trial is ongoing; updated results will be presented. A separate cohort of subjects receiving ruxolitinib has been added and will also be discussed. Based on the preponderance of responses at the 0.75 mg/kg dose, this dose has been selected for the combination cohort. Disclosures Daver: Incyte: Consultancy, Other: Advisory board, Research Funding. Jabbour:ARIAD: Consultancy, Research Funding; Pfizer: Consultancy, Research Funding; Novartis: Research Funding; BMS: Consultancy.
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Fink, Marc Y., Hanna Pincas, Soon Gang Choi, German Nudelman, and Stuart C. Sealfon. "Research Resource: Gonadotropin-Releasing Hormone Receptor-Mediated Signaling Network in LβT2 Cells: A Pathway-Based Web-Accessible Knowledgebase." Molecular Endocrinology 24, no. 9 (September 1, 2010): 1863–71. http://dx.doi.org/10.1210/me.2009-0530.
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Abstract The GnRH receptor (GnRHR), expressed at the cell surface of the anterior pituitary gonadotrope, is critical for normal secretion of gonadotropins LH and FSH, pubertal development, and reproduction. The signaling network downstream of the GnRHR and the molecular bases of the regulation of gonadotropin expression have been the subject of intense research. The murine LβT2 cell line represents a mature gonadotrope and therefore is an important model for the study of GnRHR-signaling pathways and modulation of the gonadotrope cell by physiological regulators. In order to facilitate access to the information contained in this complex and evolving literature, we have developed a pathway-based knowledgebase that is web hosted. At present, using 106 relevant primary publications, we curated a comprehensive knowledgebase of the GnRHR signaling in the LβT2 cell in the form of a process diagram. Positive and negative controls of gonadotropin gene expression, which included GnRH itself, hypothalamic factors, gonadal steroids and peptides, as well as other hormones, were illustrated. The knowledgebase contains 187 entities and 206 reactions. It was assembled using CellDesigner software, which provides an annotated graphic representation of interactions, stored in Systems Biology Mark-up Language. We then utilized Biological Pathway Publisher, a software suite previously developed in our laboratory, to host the knowledgebase in a web-accessible format as a public resource. In addition, the network entities were linked to a public wiki, providing a forum for discussion, updating, and error correction. The GnRHR-signaling network is openly accessible at http://tsb.mssm.edu/pathwayPublisher/GnRHR_Pathway/GnRHR_Pathway_ index.html.
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Zhang, Jun, Albert F. DeFelice, Joseph P. Hanig, and Thomas Colatsky. "Biomarkers of Endothelial Cell Activation Serve as Potential Surrogate Markers for Drug-induced Vascular Injury." Toxicologic Pathology 38, no. 6 (August 17, 2010): 856–71. http://dx.doi.org/10.1177/0192623310378866.
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Drug-induced vascular injury (DIVI) is a nonclinical finding that often confounds the toxicological evaluation of investigational drugs, but there is an absence of qualified biomarkers that can be used to detect and monitor its appearance in animals and patients during drug development and clinical use. It is well known that endothelial cell (EC) activation plays a key role in the expression and evolution of DIVI, and the various immunological and inflammatory factors involved in its expression may serve as potential biomarker candidates. Activated ECs change their morphology and gene expression, generating endothelial adhesion molecules, pro-coagulant molecules, cytokines, chemokines, vasodilators, nitric oxide, and acute-phase reactants. This review provides a brief historical background of EC activation and the search for biomarkers of early EC activation for monitoring DIVI. At present, no biomarkers of EC activation have been qualified to predict DIVI in the nonclinical or clinical context, and a robust pathologic foundation for their use is still lacking. We propose three categories of EC activation biomarkers: recommended surrogate markers, potentially useful markers, and emerging candidate markers. This review alerts pharmaceutical companies, research institutions, and regulatory agencies to the continuing need for reliable biomarkers of EC activation in drug development.
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Yang, Gisuk. "Analysis on Doping Mindset and Propensity of Domestic Athletes: Focusing on Whether to Have Doping Education and Punishment Perception." Korean Society of Culture and Convergence 44, no. 7 (July 31, 2022): 587–96. http://dx.doi.org/10.33645/cnc.2022.7.44.7.587.
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This study is designed to confirm differences on doping mindset and propensity considering demographic characteristic, whether to have doping education, whether to have doping punishment perception of domestic athletes. For this purpose, we selected 955 athletes as subject of study, and investigated doping mindset and propensity of athletes by using Performance Enhancement Attitude Scale as a research tool. As a result, first, it was found that there was a statistically significant difference in doping education depending on age, career, national team experience, and winning experience. Second, it was found that there was a statistically significant difference in punishment perception depending on age, career, national team experience, winning experience, and doping education. Third, it was found that there was a statistically significant difference in PEAS depending on age and doping education. It is judged that this result can be used as useful basic data in carrying out doping prevention of domestic athletes.
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Patel, Sharvil Piyush, Andrew Harkins, Michelle J. Lee, and Christopher R. Flowers. "Using Informatics Tools to Characterize Precision Medicine Treatments for Diffuse Large B-Cell Lymphoma (DLBCL)." Blood 132, Supplement 1 (November 29, 2018): 4801. http://dx.doi.org/10.1182/blood-2018-99-119917.
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Abstract Diffuse large B-cell lymphoma (DLBCL) is genetically and clinically heterogeneous. Despite immunohistochemical and genomic subtyping, standard firstline DLBCL treatment remains rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP). As genetic profiling becomes more accessible and pervasive, studies identifying specific drug-gene interactions in DLBCL are needed to develop future patient-specific DLBCL treatment strategies that improve the delivery of effective and cost-effective, patient-centered care. Methods: We performed a systematic literature review using PubMed Medical Subject Heading and text word terms for DLBCL/genetics and exome sequencing and recorded DLBCL mutations, associated mutation frequencies, pathways, and implications for overall survival (OS) with a focus on recent publications from Reddy et al 2017, Chapuy et al 2018, and Schmitz et al 2018 and related articles. Data for mutation frequencies and OS were extracted from Reddy et al (2017; https://dlbcl.davelab.org/). Mutations were categorized as either favorable or unfavorable. Favorable mutations were associated with 3-year OS ≥ OS for patients equivalent or better than IPI score ≤1 in this dataset (≥90.1%), whereas unfavorable mutations were associated with 3-year OS ≤ OS for patients with an IPI score ≥2 from this dataset (≤64.0%). Potential mutation-specific treatments were identified from the initial literature review, using the Drug-Gene Interaction database (DGIdb, http://www.dgidb.org/, Cotto et al, 2017) and the Open Targets Platform (OTP, https://www.targetvalidation.org/, Koscielny et al, 2017). DLBCL therapeutic groups were defined for mutations/mutation groups that affected ≥5% of DLBCL patients and were associated with targeted therapies based on DGIdb and OTP. Specific drug-gene interactions were characterized using a series of PubMed searches. Results: The analysis identified 32 articles with 55 total therapeutic clusters. 3 mutations were associated with favorable outcomes with an expected 3-year OS of 90.1% (95% CI: 81.1%-95.0%], and 7 mutations were associated with unfavorable outcomes with an expected 3-year OS of 64.0% (95% CI: 56.3%-70.7%) (Figure). The intersection of mutations associated with unfavorable outcomes and mutations associated with targeted therapies yielded 16 therapeutic clusters and revealed a predicted population of 17.6% of DLBCL with poor risk disease and potentially targetable mutations (Table). Drug-gene interaction characterizations identified 267 pertinent studies that included: in vitro studies, mouse models, or clinical trials of the interactions' roles in any cancer. Of these, 7 studies (1 clinical trial, 6 in vitro studies, and 1 mouse model) directly investigated DLBCL specific effects for fostamatinib, ibrutinib, and crizotinib. Conclusions: Linking systematic review with informatics tools identified DLBCL populations, DLBCL specific gene-drug interactions, and potential therapies for trials for patients who relapse and frontline combinations with R-CHOP that can be used in precision medicine strategies for improving outcomes in this disease. Disclosures Flowers: Genentech/Roche (unpaid): Consultancy; Pharmacyclics/ Janssen: Consultancy; Gilead: Research Funding; Millennium/Takeda: Research Funding; TG Therapeutics: Research Funding; Janssen Pharmaceutical: Research Funding; Karyopharm: Consultancy; Denovo Biopharma: Consultancy; Abbvie: Consultancy; Genentech/Roche: Research Funding; Gilead: Consultancy; Bayer: Consultancy; Celgene: Research Funding; Abbvie: Research Funding; Acerta: Consultancy; Beigene: Consultancy; Pharmacyclics: Research Funding.
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Hexner, Elizabeth. "The Role of T Cells in Hematopoietic Stem Cell Engraftment." Scientific World JOURNAL 6 (2006): 246–53. http://dx.doi.org/10.1100/tsw.2006.47.
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Much attention has focused on the immune recovery of donor T cells following hematopoietic stem cell transplantation (HSCT). Termed immune reconstitution, a better understanding of the dynamics of the functional recovery of immune cells following HSCT has important implications both for fighting infections and, in the allogeneic setting, for providing antitumor activity while controlling graft-vs.-host disease (GVHD). The immune cells involved in immune reconstitution include antigen-presenting cells, B lymphocytes, natural killer cells, and, in particular, T lymphocytes, the immune cell that will be the subject of this review. In addition, T cells can play an important role in the process of engraftment of hematopoietic stem cells. The evidence for a T cell tropic effect on hematopoietic engraftment is both direct and indirect, and comes from the clinic as well as the research lab. Animal models have provided useful clues, but the molecular mechanisms that govern the interaction between donor stem cells, donor T cells, the host immune system, and the stem cell niche remain obscure. This review will describe the current published clinical and basic evidence related to T cells and stem cell engraftment, and will identify future directions for translational research in this area.
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Libkind, A. N., V. A. Markusova, and L. E. Mindeli. "Bibliometric Indicators of Russian Journals by JCR-Science Edition, 1995-2010." Acta Naturae 5, no. 3 (September 15, 2013): 6–12. http://dx.doi.org/10.32607/20758251-2013-5-3-6-12.
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A representative empirical bibliometric analysis of Russian journals included in the Journal Citation Reports-Science Edition (JCR-SE) for the time period 19952010 was conducted at the macro level (excluding the subject categories). It was found that the growth in the number of articles covered by JCR (a 1.8-fold increase compared to 1995) is ahead of the growth rates of Russian publications (1.2-fold increase). Hence, the share of Russian articles covered by JCR-SE was down from 2.5% in 1995 to 1.7% in 2010. It was determined that the number of articles published in an average Russian journal reduced by 20% as compared to the number of articles in an average journal of the full data set. These facts could partly shed light on the question why Russian research performance is staggering (approximately 30,000 articles per year), although the coverage of Russian journals has expanded to 150 titles. Over the past 15 years, a twofold increase in the impact factor of the Russian journals has been observed, which is higher than that for the full data set of journals (a 1.4-fold increase). Measures to improve the quality of Russian journals are proposed.
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Mattfeldt, Torsten, Danilo Trijic, Hans‐Werner Gottfried, and Hans A. Kestler. "Classification of Incidental Carcinoma of the Prostate Using Learning Vector Quantization and Support Vector Machines." Analytical Cellular Pathology 26, no. 1-2 (January 1, 2004): 45–55. http://dx.doi.org/10.1155/2004/982809.
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The subclassification of incidental prostatic carcinoma into the categories T1a and T1b is of major prognostic and therapeutic relevance. In this paper an attempt was made to find out which properties mainly predispose to these two tumor categories, and whether it is possible to predict the category from a battery of clinical and histopathological variables using newer methods of multivariate data analysis. The incidental prostatic carcinomas of the decade 1990–99 diagnosed at our department were reexamined. Besides acquisition of routine clinical and pathological data, the tumours were scored by immunohistochemistry for proliferative activity and p53‐overexpression. Tumour vascularization (angiogenesis) and epithelial texture were investigated by quantitative stereology. Learning vector quantization (LVQ) and support vector machines (SVM) were used for the purpose of prediction of tumour category from a set of 10 input variables (age, Gleason score, preoperative PSA value, immunohistochemical scores for proliferation and p53‐overexpression, 3 stereological parameters of angiogenesis, 2 stereological parameters of epithelial texture). In a stepwise logistic regression analysis with the tumour categories T1a and T1b as dependent variables, only the Gleason score and the volume fraction of epithelial cells proved to be significant as independent predictor variables of the tumour category. Using LVQ and SVM with the information from all 10 input variables, more than 80 of the cases could be correctly predicted as T1a or T1b category with specificity, sensitivity, negative and positive predictive value from 74–92%. Using only the two significant input variables Gleason score and epithelial volume fraction, the accuracy of prediction was not worse. Thus, descriptive and quantitative texture parameters of tumour cells are of major importance for the extent of propagation in the prostate gland in incidental prostatic adenocarcinomas. Classical statistical tools and neuronal approaches led to consistent conclusions.
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Malik, Arif, Misbah Sultana, Aamer Qazi, Mahmood Husain Qazi, Gulshan Parveen, Sulayman Waquar, Abdul Basit Ashraf, and Mahmood Rasool. "Role of Natural Radiosensitizers and Cancer Cell Radioresistance: An Update." Analytical Cellular Pathology 2016 (2016): 1–8. http://dx.doi.org/10.1155/2016/6146595.
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Cancer originates from genetic mutations accumulation. Cancer stem cells have been depicted as tumorigenic cells that can differentiate and self-renew. Cancer stem cells are thought to be resistant to conventional therapy like chemotherapy and radiation therapy. Radiation therapy and chemotherapy damage carcinomic DNA cells. Because of the ability of cancer stem cells to self-renew and reproduce malignant tumors, they are the subject of intensive research. In this review, CSCs radioresistant mechanisms which include DNA damage response and natural radiosensitizers have been summed up. Reactive oxygen species play an important role in different physiological processes. ROS scavenging is responsible for regulation of reactive oxygen species generation. A researcher has proved that microRNAs regulate tumor radiation resistance. Ionizing radiation does not kill the cancer cells; rather, IR just slows down the signs and symptoms. Ionizing radiation damages DNA directly/indirectly. IR is given mostly in combination with other chemo/radiotherapies. We briefly described here the behavior of cancer stem cells and radioresistance therapies in cancer treatment. To overcome radioresistance in treatment of cancer, strategies like fractionation modification, treatment in combination, inflammation modification, and overcoming hypoxic tumor have been practiced. Natural radiosensitizers, for example, curcumin, genistein, and quercetin, are more beneficial than synthetic compounds.