Background: The vast majority of cancer deaths can be attributed to tumor metastases. Disseminated tumor cells (DTCs) are thought to act as a reservoir of tumor clones which can lie dormant before causing overt metastases. Their presence has been shown to be a poor prognostic indicator in several tumor types. Despite their importance, the timing and source of DTCs is unclear across most solid cancers and even less is known about them in late-stage disease. The Posthumous Evaluation of the Advanced Cancer Environment (PEACE) post-mortem study enables extensive sampling of malignant lesions but also normal tissues, thereby allowing study of DTCs in patients with advanced cancer. Methods: We performed research autopsy sampling of macroscopically normal bone, lung and liver in 3 patients with advanced clear cell renal cell carcinoma (RCC). In addition, we performed bone marrow aspiration at autopsy from vertebral bodies and the ilium using an anterior approach. Mechanical disaggregation followed by collagenase digestion was used to generate single cell suspensions. Detection of tumor cells was carried out using antibodies against known tumor or epithelial markers carbonic anhydrase IX (CAIX). Epithelial cell adhesion molecule (EpCAM) was also used for bone marrow samples as native bone marrow cells do not express this marker. These sub-populations were then isolated using fluorescence activated cell sorting and DNA was extracted and amplified from single cells. Results: We performed and optimised collagenase-based digestion on all solid tissues collected. The percentage of viable cells generated varied significantly between subjects and tissues with bone marrow samples more viable than lung and liver. Rare and distinct populations of CAIX+ and EpCAM+ cells were detected in normal tissues between 0.5-2%. DNA amplification was successful on single cells isolated from normal lung and liver but not from bone tissue. Pilot shallow coverage whole genome sequencing revealed genomically aberrant cells ranging from single chromosome arm losses to widespread copy number aberrations. Conclusion: We demonstrate feasibility of sequencing single cells from autopsy study subjects. Rare populations of single cells with markers of clear cell RCC were detected and isolated both in normal tissues of patients with advanced disease. Genomic analyses of these cells will lead to insights into their relationship to the primary tumor and overt metastatic lesions. Citation Format: Haixi Yan, Cristina Cotobal Martin, Christie English, Annelien Verfaillie, Jonas Demeulemeester, Andrew Rowan, Annika Fendler, Anne-Laure Cattin, Sucheta Mahapatra, Lewis Au, Scott Shepherd, Ben Shum, Charlotte Spencer, Zayd Tippu, Ula Mahadeva, Anna Green, Eleanor Carlyle, Cristina Naceur-Lombardelli, PEACE consortium, Mariam Jamal-Hanjani, Charles Swanton, Samra Turajlic, Peter Van Loo. Detection of disseminated tumor cells in advanced clear cell renal cell carcinoma through research autopsy [abstract]. In: Proceedings of the AACR Special Conference: Cancer Metastasis; 2022 Nov 14-17; Portland, OR. Philadelphia (PA): AACR; Cancer Res 2022;83(2 Suppl_2):Abstract nr A011.
Elite female karatekas should have specific morphological characteristics suitable for their specializations. This study aimed to determine the differences in morphological characteristics and body composition of female karatekas according to different specializations. This study consisted of a total of 15 female karatekas divided according to specialization in kumite (fighting) and kata (form or movement pattern) disciplines. The subject sample included healthy, female senior karatekas, with no prior injuries divided into kumite (n-8, 22.75±4.65 years) and kata (n-7, 22.00±4.58 years) athletes. Morphological characteristics and body composition were evaluated by a battery of 11 variables: body height (BH), body mass (BM), triceps skinfold (TS), biceps skinfold (BiS), back skinfold (BS), abdominal skinfold (AS), upper leg skinfold (UlS), lower leg skinfold (LlS), body mass index (BMI), fat percentage (FP), and muscle mass percentages (MP). Based on the t-test for small independent samples, findings showed that female kata and kumite karatekas do not have different morphological characteristics. Although there was no difference in morphological characteristics, for more complete conclusions an analysis should be performed on a larger sample of elite female karate athletes.
We show that a subtle coupling between the thermal and solutal gradients driven by the thermodiffusion, cross-diffusion, and buoyancy force can lead to oscillatory dynamic behavior of a ternary mixture in the thermo-gravitational column. The potentially unstable stratification results from the interplay of mass fluxes of the two heaviest components where the leading role belongs to one of them. Our experiments and numerical analysis evidence not only the presence of oscillatory instability, but demonstrate the emergence of the secondary instability in the form of swinging pattern in addition to the large-scale standing wave. We suggest that the region, where oscillatory instability occurs, is characterized by opposite signs of Soret S'T1 and thermodiffusion D'T1 coefficients due to large cross-diffusion contribution.
Abstract D-dimer and fibrinogen are nonspecific diagnostic biomarkers for venous thromboembolism (VTE). The aim of this article was to present the values of D-dimer and fibrinogen in relation to the anatomical localization of deep vein thrombosis (DVT). This was an observational study, which included 1,142 patients hospitalized from 2010 to 2019 at the Department of Angiology, Clinical Center University of Sarajevo. Data on gender, age, and thrombosis location were collected of all patients. Fibrinogen and D-dimer values were available for 983 and 500 patients, respectively. Thrombosis location was classified as iliofemoral (521–45.6% patients), femoral–popliteal (486–42.6% patients), isolated calf DVT (63–5.5% patients), and upper extremity DVT (UEDVT in 72–6.3% patients). A majority, 448 (89.6%), of patients had high D-dimer (the cutoff is 0.55 mg/L) and 662 (67.3%) patients had high fibrinogen (reference range: 1.8–3.8 g/L). The highest D-dimer was detected in patients with iliofemoral DVT (mean: 10.48 mg/L), χ2 = 50.78, p = 0.00. The highest fibrinogen was detected in patients with iliofemoral DVT as well (mean 4.87 g/L), χ2 = 11.1, p = 0.01. D-dimer and fibrinogen values are significantly higher in patients iliofemoral DVT than femoral–popliteal and isolated calf DVT, and D-dimer values are significantly higher in lower extremity DVT than UEDVT, but these biomarkers cannot be used alone to discriminate between thrombosis locations. Further imaging is required.
This letter presents a measurement of the nuclear modification factor of large-radius jets in sqrt[s_{NN}]=5.02 TeV Pb+Pb collisions by the ATLAS experiment. The measurement is performed using 1.72 nb^{-1} and 257 pb^{-1} of Pb+Pb and pp data, respectively. The large-radius jets are reconstructed with the anti-k_{t} algorithm using a radius parameter of R=1.0, by reclustering anti-k_{t} R=0.2 jets, and are measured over the transverse momentum (p_{T}) kinematic range of 158<p_{T}<1000 GeV and absolute pseudorapidity |y|<2.0. The large-radius jet constituents are further reclustered using the k_{t} algorithm in order to obtain the splitting parameters, sqrt[d_{12}] and ΔR_{12}, which characterize the transverse momentum scale and angular separation for the hardest splitting in the jet, respectively. The nuclear modification factor, R_{AA}, obtained by comparing the Pb+Pb jet yields to those in pp collisions, is measured as a function of jet transverse momentum (p_{T}) and sqrt[d_{12}] or ΔR_{12}. A significant difference in the quenching of large-radius jets having single subjet and those with more complex substructure is observed. Systematic comparison of jet suppression in terms of R_{AA} for different jet definitions is also provided. Presented results support the hypothesis that jets with hard internal splittings lose more energy through quenching and provide a new perspective for understanding the role of jet structure in jet suppression.
Recent studies exploring the impact of methylation in tumor evolution suggest that while the methylation status of many of the CpG sites are preserved across distinct lineages, others are altered as the cancer progresses. Since changes in methylation status of a CpG site may be retained in mitosis, they could be used to infer the progression history of a tumor via single-cell lineage tree reconstruction. In this work, we introduce the first principled distance-based computational method, Sgootr, for inferring a tumor’s single-cell methylation lineage tree and jointly identifying lineage-informative CpG sites which harbor changes in methylation status that are retained along the lineage. We apply Sgootr on the single-cell bisulfite-treated whole genome sequencing data of multiregionally-sampled tumor cells from 9 metastatic colorectal cancer patients made available by Bian et al., as well as multiregionally-sampled single-cell reduced-representation bisulfite sequencing data from a glioblastoma patient made available by Chaligne et al.. We demonstrate that the tumor lineages constructed reveal a simple model underlying colorectal tumor progression and metastatic seeding. A comparison of Sgootr against alternative approaches shows that Sgootr can construct lineage trees with fewer migration events and more in concordance with the sequential-progression model of tumor evolution, in time a fraction of that used in prior studies. Interestingly, lineage-informative CpG sites identified by Sgootr are in inter-CpG island (CGI) regions, as opposed to CGI’s, which have been the main regions of interest in genomic methylation-related analyses. Sgootr is implemented as a Snakemake workflow, available at https://github.com/algo-cancer/Sgootr.
Food contaminated with bacterial pathogens is a great threat to human health and food spoilage, having an impact on public health and the food industry. Research in food safety seeks to develop a practical, rapid, and sensitive detection technique for food-borne pathogens. In the past few decades, real-time quantitative polymerase chain reaction (qPCR) has been developed, and multiplex qPCR is a preferred feature. Multiplex qPCR enables the simultaneous amplification of many targets of interest in one reaction by using more than one pair of primers. In this study, we have developed and evaluated a hydrolysis (TaqMan) probe-based system for simultaneous detection of eight of the most common food-borne pathogens in a single-step procedure by multiplex qPCR. A multicolor combinational probe coding (MCPC) strategy was utilized that allows multiple fluorophores to label different probes in combinatorial manner. This strategy enabled simultaneous detection, identification, and quantification of targeted genes. The efficiency of the individual qPCR reactions for each target gene had values comparable to those established for multiplex qPCR, with detection limits of approximately < 10 copies of DNA per reaction. Pathogen load helps to predict bacteriological quality status in food products and serves to validate the efficiency of procedures to minimize or eliminate their presence, so newly developed multiplex qPCR was quantitative for each pathogen. During sample preparation, a step to concentrate the target organism from a relatively large sample size, remove all potential PCR inhibitors, and yield samples in a volume suitable for qPCR was incorporated.
<p>The participation of deaf and hard of hearing people in sports activities contributes to the improvement of the quality of life in all its domains, and compared to people with some other types of disabilities, deaf and hard of hearing people achieve higher scores in sports activities. Practicing sports activities improves physical health, mental state, degree of independence and social relationships. Sports activities have a positive effect on building and strengthening the self-esteem of individuals. Subjective experience and individual perception have a great influence on the quality of an individual’s life, therefore, self-esteem is a very important factor that contributes to this. The aim of this paper is to review the literature from the period 2000–2021 on the impact of sports activities on the psychophysical health of deaf and hard of hearing people. The subject of interest was: to determine the role of sports activities in the quality of life of deaf and hard of hearing people, as well as how they affect their level of self-esteem. The following search engines were used for the literature search: Ebscohost, ScienceDirect, Wiley Inter Science and SpringerLink, KoBSON, Google Scholar. The results of the literature review showed that sports activities contributed to the preservation and development of the overall psychophysical health of deaf and hard of hearing people. Participation in sports activities, whether recreational or professional in nature, has proven to be a significant factor in raising the level of self-esteem, alleviating symptoms of anxiety and stress. Participation in sports activities leads to better social functioning among peers and building an inclusive society.</p>
Introduction This study aims to examine can sport protect children against loneliness and, if yes, whether this relationship depends on gender and/or sports-related variables. Methods The sample includes 762 10-year-old children (414 boys). The total score of The Children's Loneliness Scale is a dependent variable in the study, while sports participation (sports active—individual or team sports, or non-active) and level/duration of sports participation are independent variables. Results Obtained results indicate that the degree of loneliness differs depending on gender and whether the children are in sports activities or not. Unlike the level of sports participation, the duration of sports participation is relevant to the loneliness degree in both boys and girls. Discussion This research results could represent the right direction for educators and/or parents in their endeavor to preserve and develop school-age children's mental health.
Secure multiparty computation (MPC) is a cryptographic tool that allows computation on top of sensitive biomedical data without revealing private information to the involved entities. Here, we introduce Sequre, an easy-to-use, high-performance framework for developing performant MPC applications. Sequre offers a set of automatic compile-time optimizations that significantly improve the performance of MPC applications and incorporates the syntax of Python programming language to facilitate rapid application development. We demonstrate its usability and performance on various bioinformatics tasks showing up to 3–4 times increased speed over the existing pipelines with 7-fold reductions in codebase sizes.
This corrigendum corrects the authorship information to: Yipeng Xu, Gabriela Pachnikova, He Wang, Yaoyao Wu, Dorothea Przybilla, Zihao Chen, Shaoxing Zhu, Ulrich Keilholz. At the request of Dr. Reinhold Schäfer and with the agreement of all authors, Dr. Reinhold Schäfer is excluded from the list of authors. Dr. Schäfer expresses no doubts about the article's results and conclusion but was erroneously included on the list of authors. The authors sincerely apologize for the error and confirm that this correction does not change the conclusion of the article.
The purpose of this work is to show the development and evaluation of behavioural intentions of students by using mobile banking. The research goal is to explain determinants of students’ intentions towards the use of mobile banking. PLS SEM (partial least squares structural equation modeling) analysis was used for the model evaluation. The sample consists of 83 students from four higher education institutions operating in Bosnia and Herzegovina (B&H). Research results confirmed that subjective norm and attitude are significant predictors of the user’s attitude towards mobile banking acceptance, while the influence of self-efficacy was not determined. Attitudes related to mobile banking acceptance are primarily determined by perception of usefulness and self-efficacy, and to a lower degree by perception of privacy and security risk. Perception of mobile banking usefulness appeared to be the most significant predictor of attitudes, while simultaneously it influenced positively on acceptance of behavioral intention, including intervening effect of attitude variable. Digital literacy was proved to be a significant predictor for self-efficacy. From the perspective of banks, it is very important to see how a generation that a high potential for the use of modern technologies has perceives mobile banking, and what affects it to accept mobile banking. The results of this research are useful for banks to attract new younger users of mobile banking and increase their own benefits.
As sessile organisms, plants have evolved different strategies to defend themselves against various biotic stressors. An important aspect of the complex response of plants to biotic stress is the emission of volatile compounds (VOCs), which are involved in direct and indirect plant defence mechanisms. Indirect plant defences include a range of plant traits that mediate defence against herbivores and play an important ecological role by not only utilising plants-' own capabilities but also signalling and attracting natural enemies of herbivores. Often the combination of volatiles emitted is specific to herbivores; they are consequently recognised by parasites and other predators, providing a clear link between the volatile signature and the prey. In this review, we focus on indirect plant defence and summarise current knowledge and perspectives on relationships between plants, aphids, and parasitic wasps.
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