80 research outputs found

    Taking care of systemic sclerosis patients during COVID-19 pandemic : rethink the clinical activity

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    COVID-19 outbreak has quickly spread worldwide, causing a high pressure on the health-care system. In Italy, from March 8, 2020, all the deferrable clinical activities have been suspended to increase the health care offer for COVID-19 patients. The hospital organization has been modified also in order to assure non-COVID-19 patients assistance. The Scleroderma Unit of ASST Pini-CTO Hospital, in Milan, in the region mostly hit by SARS-CoV-2 in Italy, follows more than 600 patients affected by systemic sclerosis (SSc). Patients with SSc need a close follow-up with a regular screening of organ involvement and frequent intravenous treatments. All SSc patients have been educated about ministerial directives to limit COVID-19 spread. The organization of our Scleroderma Unit has been quickly rethought to assure SSc patients assistance in safety for them and for health-care workers during urgent visits or infusion therapies. Using electronic way of communication with frequent virtual contact and guarantying home deliveries of some therapies, we allowed a continuity of care also outside the Hospital

    Correlation of HER2 status between primary tumors and corresponding circulating tumor cells in advanced breast cancer patients

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    International audienceBiocharacterization of circulating tumor cells (CTCs) in the peripheral blood of advanced breast cancer (ABC) patients may represent a real-time tumor biopsy. We assessed HER2 status on CTCs from blood samples of ABC patients. CTCs were separated and stained using the CellSearch System. HER2 status was assessed by immunofluorescence and, when technically feasible, by fluorescence in situ hybridization. Blood samples were obtained from 66 ABC patients. Forty patients had a positive CTC sample (61%) and of these, 15 (37%) had HER2 + CTCs. We found non-concordant results in 32% of cases: 29% (8/28) of HER2-negative primary tumors had HER2-positive CTCs and 42% (5/12) of HER2-positive primary tumors had HER2-negative CTCs ( = 0.278). Our study suggests that a subset of patients with HER2-negative primary tumors develops HER2-positive CTCs during disease progression

    Current challenges in software solutions for mass spectrometry-based quantitative proteomics

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    This work was in part supported by the PRIME-XS project, grant agreement number 262067, funded by the European Union seventh Framework Programme; The Netherlands Proteomics Centre, embedded in The Netherlands Genomics Initiative; The Netherlands Bioinformatics Centre; and the Centre for Biomedical Genetics (to S.C., B.B. and A.J.R.H); by NIH grants NCRR RR001614 and RR019934 (to the UCSF Mass Spectrometry Facility, director: A.L. Burlingame, P.B.); and by grants from the MRC, CR-UK, BBSRC and Barts and the London Charity (to P.C.

    Statistical quality assessment and outlier detection for liquid chromatography-mass spectrometry experiments

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    <p>Abstract</p> <p>Background</p> <p>Quality assessment methods, that are common place in engineering and industrial production, are not widely spread in large-scale proteomics experiments. But modern technologies such as Multi-Dimensional Liquid Chromatography coupled to Mass Spectrometry (LC-MS) produce large quantities of proteomic data. These data are prone to measurement errors and reproducibility problems such that an automatic quality assessment and control become increasingly important.</p> <p>Results</p> <p>We propose a methodology to assess the quality and reproducibility of data generated in quantitative LC-MS experiments. We introduce quality descriptors that capture different aspects of the quality and reproducibility of LC-MS data sets. Our method is based on the Mahalanobis distance and a robust Principal Component Analysis.</p> <p>Conclusion</p> <p>We evaluate our approach on several data sets of different complexities and show that we are able to precisely detect LC-MS runs of poor signal quality in large-scale studies.</p

    The coding and non-coding RNA single-cell atlas of the human fetal striatum

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    peer reviewedDeciphering how the human striatum develops is paramount to understand diseases affecting this region. To decode the transcriptional modules that regulate this structure during development we first catalogued 1116, de novo identified, lincRNAs and then profiled 96,789 single-cells from the early human fetal striatum. We found that D1 and D2 medium spiny neurons (MSNs) arise from a common progenitor and that lineage commitment is established during the post-mitotic transition, across a pre-MSN phase that exhibits a continuous spectrum of fate determinants. We then uncovered cell type-specific gene regulatory networks that we validated through in silico perturbation. Finally, we identified human-specific lincRNAs that contribute to the phylogenetic divergence of this structure in humans. In conclusion, our study has delineated the cellular hierarchies governing MSN lineage commitment

    Endothelial Cell Capture of Heparin-Binding Growth Factors under Flow

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    Circulation is an important delivery method for both natural and synthetic molecules, but microenvironment interactions, regulated by endothelial cells and critical to the molecule's fate, are difficult to interpret using traditional approaches. In this work, we analyzed and predicted growth factor capture under flow using computer modeling and a three-dimensional experimental approach that includes pertinent circulation characteristics such as pulsatile flow, competing binding interactions, and limited bioavailability. An understanding of the controlling features of this process was desired. The experimental module consisted of a bioreactor with synthetic endothelial-lined hollow fibers under flow. The physical design of the system was incorporated into the model parameters. The heparin-binding growth factor fibroblast growth factor-2 (FGF-2) was used for both the experiments and simulations. Our computational model was composed of three parts: (1) media flow equations, (2) mass transport equations and (3) cell surface reaction equations. The model is based on the flow and reactions within a single hollow fiber and was scaled linearly by the total number of fibers for comparison with experimental results. Our model predicted, and experiments confirmed, that removal of heparan sulfate (HS) from the system would result in a dramatic loss of binding by heparin-binding proteins, but not by proteins that do not bind heparin. The model further predicted a significant loss of bound protein at flow rates only slightly higher than average capillary flow rates, corroborated experimentally, suggesting that the probability of capture in a single pass at high flow rates is extremely low. Several other key parameters were investigated with the coupling between receptors and proteoglycans shown to have a critical impact on successful capture. The combined system offers opportunities to examine circulation capture in a straightforward quantitative manner that should prove advantageous for biologicals or drug delivery investigations
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