dataesr/scientific-paragraphs-categorization huggingface dataset:
The expression of ACTC1 and TNNT2 in both types of hmMSCs exposed to 1 µM SAHA for 14 days was upregulated (Figure  4C, D ). HDAC inhibitor SAHA most significantly affected cardiac gene expression in pathological hmMSC. Data show that dilated myocardium-derived hmMSC still retained ability to differentiate to the cardio myogenic direction, which can be stimulated in vitro by epigenetic regulator SAHA. The effect of SAHA on HDAC activity during 3 days of incubation. Expression of cardiomyogenic differentiation-specific genes: alpha-cardiac actin (ACTC1) (C) and cardiac troponin T (TNNT2). (D) The relative cardiac gene expression is shown as 2 -∆Ctx 2,000,000 and was normalized to the ACTB gene. Data are shown as mean ± SD and are significant at * p ≤ 0. 05, ** p ≤ 0. 01 levels from not less than three repeats (n = 3) of three patients from each group as calculated using the GraphPad Prism 6 software.
Evaluation of hmMSC Morphology The size of healthy and pathological hmMSC was measured when cells reached a 50% confluence to better determine individual cell boundaries. Cell dimension was measured with the ImageJ software and analyzed using Microsoft Excel. The attachment area of individual hmMSC was marked and expressed as µm 2. The data are presented as cell size mean ± SD evaluating not less than 60 cells from three patients' biopsies of both types.
Identification of hmMSC Surface Markers The MSC origin of human healthy and dilated myocardium-derived MSC (hmMSC) has been investigated as described elsewhere  [43, 46]. Briefly, cell growth media was aspired, washed with PBS and exposed to 0. 25% trypsin-EDTA (Thermo Fisher Scientific, Waltham, MA, USA) for 1-2 min. After that, cells were suspended in 1% BSA (Sigma Aldrich, St. Louis, MO, USA) in PBS, counted, diluted to 0. 5 × 10 6 cells/mL, transferred into special flow cytometer tubes and incubated with specific fluorochromes-conjugated antibodies on ice for 30 min. Next, cells were washed with 1% BSA in PBS, centrifuged at 600 g for 5 min and resuspended in 1% BSA in PBS. Isotype controls were prepared. The cell samples were analyzed on BD FACSAriaTM IIU flow cytometer using the BD FACSDiva software (BD Biosciences, San Jose, CA, USA).
Statistical Analysis Statistical analysis was performed using Excel (Microsoft Corporation, Redmont, WA, USA) and the Graphpad Prism 6. 01 (GraphPad Software, San Diego, CA, USA) software. The differences between measurements were analyzed for their statistical significance using the independent-samples Student two-sided t-test. Results from three patients' cells of both types with not less than three-five repeats for each measurement were presented, unless indicated otherwise. Data were expressed as mean ± SD and were significant at * p ≤ 0. 05 comparing with corresponding control samples.
In relation with the highly compartmentalized Hippo pathway in cardiomyocytes, during cardiac stress, Mst1 and Lats2 are activated via a K-Ras-Rassf1Adependent mechanism in mitochondria or through a NF2-dependent mechanism in the nucleus, respectively, where Mst1 stimulates the mitochondrial mechanism of apoptosis by phosphorylating Bcl-xL and Lats2 induces nuclear exit of Yap  [13] [14] [15]. The activation of this canonical Hippo pathway leads to the stimulation of cell death and inhibition of compensatory hypertrophy by inhibition of Yap in cardiomyocytes  [16, 17]. Despite years of molecular biology-based cardiac research and circulatory understanding, several yet uncharacterized genes are expected to be associated with cardiomyopathies. Towards this end, we performed expressed sequence tags (EST)-based bioinformatic screening of genetic databases of heart and skeletal muscle and discovered several novel genes, one of which is SH3 domain-binding glutamic acid-rich (SH3BGR).
SH3BGR Regulates RhoA-SRF Signaling in NRVCMs The serum response factor (SRF) is one of the major transcription factors responsible for cardiomyocyte maturation, structural stability and pathological hypertrophy  [8, 27]. It plays a significant role in the transcriptional activation of natriuretic peptides and cardiac structural genes that form the core structure of the sarcomere, such as myosin heavy chain 6, 7 (myh 6, 7), myosin light chain 2 (myl2), cardiac alpha actin (ACTC1), etc. Interestingly, in terms of mechanistic relevance of our findings, we explored the Harmonizome, a collection of processed datasets gathered to serve and mine knowledge about genes and proteins, which revealed SRF as one of its transcription factors  [28]. Thus, we hypothesized that SH3BGR likely induces cardiomyocyte hypertrophy via SRF signaling in vitro.
On the other hand, a loss-of-function approach was followed to study the physiological function of SH3BGR. We observed alterations in SH3BGR levels in the heart of patients with cardiac hypertrophy as well as in the hearts of mouse model of cardiac hypertrophy due to biomechanical stress (TAC). Along these lines, hypertrophic induction and inhibition were observed on SH3BGR via gain-and loss-of-function approaches at in vitro level, respectively, suggesting overexpression, as well as knockdown, has an associated effect against the normal functioning of cells. Digging deeper to understand the mechanistic relevance of these experimental findings, through the Harmonizome database, we identified SH3BGR as one of the transcriptional targets of SRF, a major transcription factor governing the transcription of sarcomeric genes and cardiomyocyte hypertrophy.
Co-Localization Analysis of SH3BGR with α-Actinin The co-localization between SH3BGR and α-actinin was observed in NRVCMs using the LSM800 Zeiss laser-scanning microscope with the help of the ZEN-blue software package. The cells were seeded in a 12-well plate that had a collagen-coated coverslip in each well. Following the adenoviral infection and incubation phase, NRVCMs were first fixed with 4% PFA for 5 min and then, in one step, permeabilized and blocked with 0. 1% Triton X-100 in 2. 5% BSA in saline (PBS) for 1 h. The cells were then incubated for 1 h with primary antibodies using the following dilutions: polyclonal rabbit anti-SH3BGR (1:200) and monoclonal mouse antiα-actinin (1:200; Sigma) for co-localization observation. The respective secondary antibodies conjugated to either Alexa Fluor-546 (AF546) or Alexa Fluor-488 (AF488) (Thermo Fisher Scientific) were incubated for 1 h with the same dilution of 1:200 in 2.
45). Images were acquired using the BZ-II image viewer software (Keyence, Oaska, Japan version 2. 1) using a built-in camera at room temperature and were processed and analyzed by a BZ-II Analyzer (Keyence, version 2. 1) as detailed below. Cell size was measured using the HybridCellCount software module from Keyence with the fluorescence harvest kept at single-extraction mode. First, the fluorescence intensity thresholds were set for a moderately intense reference picture. Thereafter, α-actinin whole-cell staining was set as the target area and the blue DAPI-stained nuclei were then extracted from each green target area to determine the number of nuclei per target area, i. e. , cell. Then, MacroCellCount was performed, applying the settings from the reference picture to each target picture from one set of experiments.
RNA Isolation and qRT-PCR Total RNA was isolated from NRVCMs or human/mouse hearts or other mouse tissue samples using a cell-lysis reagent TriFast (Peqlab, Burladingen, Germany) and a Precellys homogenizer with coarse and fine plastic beads (only for mouse and human samples), following the manufacturer's instructions. A total of 1 µg of total RNA was transcribed into cDNA using the LunaScript RT supermix cDNA synthesis kit (New England Biolabs, Lpswich, MA, USA). For qRT-PCR, the EXPRESS SYBR Green ER reagent (Life Technologies, Inc. , Carlsbad, CA, USA) was used in a real-time PCR system CFX96 from Bio-Rad. Cycling conditions used for all the qRT-PCRs were 3 min at 95 • C followed by 40 cycles of 15 s at 95 • C and 45 s at 60 • C, a common step for annealing and extension, at which data were collected.
The overnight application of mono-or poly-clonal primary antibodies was followed by incubation with a suitable HRP-coupled secondary antibody (1:10,000; Santa Cruz Biotechnology, Dallas, TX, USA) or fluorescent antibody Alexa Fluor 546 (for Tubulin only). Finally, protein band visualization was achieved using a chemiluminescence kit (GE Healthcare) and was detected on an imaging system (FluorChem Q; Biozym). A quantitative densitometry analysis was performed using the ImageJ version 1. 46 software (National Institutes of Health) and plotted using Graphpad relative to control. All conditions were maintained in triplicates and repeated thrice.
Data Analysis The acquired force curves were analyzed using the JPK Data processing software. The first numerical treatment was the reduction of curve noise, followed by the baseline definition and the tilt correction. After these corrections, several adhesion parameters, identifiable on the retract force curve, were measured, exported, and analyzed (Figure  4B ): in particular (i) the total energy applied during the separation of 2 cells, represented by the area under the retracting force distance curve; (ii) the maximum force is the maximum value of the force applied during the separation step; (iii) the rupture pattern which illustrates interaction during short distance separation (0 to 5 µm of piezo withdraw). This pattern is characterized by jumps in the force retracting curve everyone preceded by a slope >20%.
These ruptures events were induced by broken adhesion protein link between two cells  [36, 50] ; (iv) nanotube pattern i. e. , nanotubes generated during long-distance separation (5 to 80 µm of piezo withdraw). In this latter case, this pattern of jumps in the retract force curve was preceded by a plateau with <15% derivation and persisting for > 1 µm, representing the force needed to break these plasma membranes, pulled out to form a nanotube between two cells after their contact  [35, 50, 51, 77]. The distribution of breaking forces was analyzed using OriginPro 9. 7 2020 software, and Gaussian function was fitted to highlight a specific population.
Statistics For all experiments, data was collected from at least three independent experiments. All data were first subjected to the Shapiro-Wilk normality test. The unpaired one-way ANOVA with Dunnet's or Tukey's correction for normal distributions or the Kruskal-Wallis with Dunn's correction test was employed. A confidence interval of 95% (p value of <0. 05) was used to identify significant differences among the samples. Data in the text are reported as mean of values ± standard deviation and graphically presented as scattered dot plots with mean (and median for those deviating from normality test) and standard deviation. Statistical analysis was performed using GraphPad Prism 7 software (San Diego, CA, USA).
Recent Ongoing Clinical Trials Currently, several ongoing clinical trials are investigating the effects of various gene therapies on cardiac regeneration in CVDs. According to the ClinicalTrials. gov (accessed on 12 July 2021), there are a total of seven gene therapy trials, including six studies that are actively recruiting (EXACT, ReGenHeart, Korean trial, NAN-CS101) or planning to recruit (AFFIRM, CUPID-3) and one active clinical trial (EPICCURE). The EXACT Trial is a phase I/II, first-in-human, multicenter, open-label, single arm dose escalation study recruiting 44 patients with refractory angina caused by CAD to evaluate the induction of therapeutic angiogenesis in ischemic myocardium by XC001 (AdVEGFXC1) [NCT04125732]. AdVEGFXC1 is an adenovirus type-5 vector expressing the hybrid VEGF with its three major isoforms  (121, 165, and 189)   [128].
In this trial, administration is at various doses by transthoracic epicardial procedure to 12 patients, followed by an increase in the maximum tolerated dose with 32 additional patients, and the main outcome measurements will be safety and side effect assessment. ReGenHeart is a randomized, double-blinded, placebo-controlled multicenter phase II study enrolling patients with refractory angina pectoris to evaluate safety and efficacy of AdVEGF-D gene transfer [NCT03039751]. The trial is recruiting 180 participants in six different centers to whom revascularization cannot be performed. AdVEGF-D will be injected into myocardium through a catheter at 10 different sites and compared with a similar placebo treatment. The primary endpoint is to assess improvement in exercise tolerance and relief of angina symptoms at six months after injection.
EPICCURE is a randomized, placebo-controlled, double-blind, multicenter, phase II clinical trial testing the effect of VEGF-A165 mRNA loaded in biocompatible citratebuffered saline (AZD8601) in patients with decreased LV function and undergoing CABG [NCT03370887]  [129]. AZD8601 will be injected during the surgery as 30 epicardial injections in a 10-min extension of cardioplegia under the control of quantitative 15O-water positron emission tomography (PET) imaging. At the moment, 11 patients are enrolled in the study, and the primary endpoint is to investigate safety and tolerability of the gene therapy up to six months after the surgery. MRNA-based technology used in the EPICCURE trial is a novel revolutionizing approach for gene delivery that can be utilized for a variety of purposes such as protein replacement, gene editing, infectious diseases, cancer vaccines, and others  [130].
Moreover, a recent study published in Nature found that the two mRNA vaccines induced a persistent and robust germinal center response indicating that these vaccines produced strong and efficient humoral immune responses  [133]. The benefits of mRNA-based technology have been utilized for cardiovascular gene therapy as well  [134]. Specifically, mRNA therapeutics using genes for VEGF, IGF-1, and other proteins for heart regeneration were shown to be safe and effective in various animal models. The AFFIRM study is a phase III clinical trial designed to determine the effect of intracoronary infusion of the human FGF-4 DNA sequence encoded in Ad5FGF-4 on ameliorating refractory angina symptoms and improving patient quality of life. This study will enroll 160 patients with refractory angina and the primary endpoint is the change of exercise tolerance test (ETT) duration over six months after intervention (NCT02928094).
However, previous clinical trials with Ad5FGF-4 have demonstrated specific beneficial effects of this gene therapy only in females, while no difference was observed between placebo and treatment groups among male patients  [68]. A phase II trial is ongoing in Korea to test the safety and efficacy of VM202RY, which is a DNA plasmid loaded with two isoforms of HGFs (723 and 728) (NCT03404024). A previous phase I trial demonstrated that VM202RY can improve cardiac perfusion and inhibit cardiac remodeling in patients with MI and angina  [135]. Now they are recruiting 108 patients with acute MI for transendocardial injection of VM202RY through catheter to evaluate its safety, tolerability, and efficacy compared with placebo. Primary outcome measurements are to determine the maximum tolerated dose and assess LV ejection fraction after six months.
Estimated study completion date was April, 2020, however, no results have yet been reported in English. The CUPID-3 study is a randomized, double-blind, placebo-controlled phase I/II trial investigating the effect of SRD-001, an adeno-associated virus serotype 1 vector expressing the transgene for sarcoplasmic/endoplasmic reticulum Ca 2+ ATPase 2a isoform (SERCA2a), on patients with cardiomyopathy and HF with reduced ejection fraction (NCT04703842). According to the authors, targeting SERCA2a enzyme expression by SRD-001 can correct defective intracellular Ca 2+ hemostasis, subsequently improving cardiac contractility. In addition, SRD-001 can also correct the impaired endothelium-dependent vasodilatation, improve coronary blood flow and prevent further progression of HF. To determine this, 56 participants will be enrolled in the study until June 2021 and SRD-001 will be delivered through one-time intracoronary infusion.
As a primary endpoint, change from baseline in symptomatic parameters (quality of life, HF severity), physical parameters, LV function/remodeling, and rate of recurrent and adverse events will be measured up to 12 months (NCT04703842). NAN-CS101 is a phase I, prospective, multi-center, open-label, sequential dose escalation study to test the safety and efficacy of one dose intracoronary infusion of BNP116. sc-CMV. I1c in patients with HF (NYHA class III) (NCT04179643). BNP116. sc-CMV. I1c is an AAV vector with a chimeric AAV2/AAV8 capsid containing an active inhibitor of protein phosphatase-1 (I-1) transgene. Previous preclinical studies on large animals demonstrated that chimeric AAV vectors can selectively target cardiac muscle, while I-1 inhibits expression of protein phosphatase-1 and increases cardiac expression of SERCA2a enzyme leading to the improvement of cardiac functions  [136, 137].
AC6 gene transfer safely increased LV function compared to a standard single-dose HF therapy and decreased admission rate in the treatment group  [138]. A larger phase III trial (FLOURISH) with the same drug was recently registered in clinicaltrials. gov (accessed on 12 July 2021); however, the current status of the study is withdrawn due to the reevaluation of "clinical development plans and strategy for RT-100" (NCT03360448). Therefore, despite its withdrawn status, a newly designed trial with Ad5. hAC6/RT100 can be conducted in the future. Table  1  summarizes the ongoing clinical trials. Overall, most ongoing trials related to cardiac regeneration are focused on gene therapy targeting the expression of different growth factors and their isoforms to improve angiogenesis. This might be justified by the fact that extended angiogenesis effectively improves vascular and cardiac tissue regeneration leading to the enhancement of cardiac functions.
Conceptualization, O. I. -G. and A. R. ; writing-original draft preparation, K. T. and O. I. -G. ; writing-review and editing, K. T. , O. I. -G. , M. M. M. , F. P. , and A. R. ; supervision, O. I. -G. and A. R. ; project administration, A. R. All authors have read and agreed to the published version of the manuscript. Funding: Research in the authors' laboratories on this topic is supported by the Spanish Ministry of Economy and Competitiveness-MINECO (RTI2018-095377-B-100), Instituto de Salud Carlos III-ISCIII/FEDER (Red de Terapia Celular-TerCel RD16/0011/0024 and RD16/0011/0005; PI 19/01350), Gobierno de Navarra Departamento de Salud (GNª8/2019), co-funded by FEDER funds, European Union's H2020 Program under grant agreement No 874827 (BRAV∃), AGAUR (2017-SGR-899), and CERCA Programme/Generalitat de Catalunya.
Author Contributions: Conceptualization, O. I. -G. and A. R. ; writing-original draft preparation, K. T. and O. I. -G. ; writing-review and editing, K. T. , O. I. -G. , M. M. M. , F. P. , and A. R. ; supervision, O. I. -G. and A. R. ; project administration, A. R. All authors have read and agreed to the published version of the manuscript. Funding: Research in the authors' laboratories on this topic is supported by the Spanish Ministry of Economy and Competitiveness-MINECO (RTI2018-095377-B-100), Instituto de Salud Carlos III-ISCIII/FEDER (Red de Terapia Celular-TerCel RD16/0011/0024 and RD16/0011/0005; PI 19/01350), Gobierno de Navarra Departamento de Salud (GNª8/2019), co-funded by FEDER funds, European Union's H2020 Program under grant agreement No 874827 (BRAV∃), AGAUR (2017-SGR-899), and CERCA Programme/Generalitat de Catalunya.
INTRODUCTION NoiseCapture 1  is an Android application developed by the Gustave Eiffel University 2  and the CNRS 3 as part of a participatory approach to environmental noise mapping. The application is open-source and all collected data are available under an Open Database License. The study presented here is the first exploratory analysis of the first three years of data collection, through the prism of sound sources. The analysis only focused on the tags checked by the users to qualify their environment and not on the sound spectrum of the measurements as it will be analyse in a further time. The first objective of the study was to control the quality of the tag data provided by the public, either by checking if some known temporal dynamics of sound sources are present in the dataset, or by checking the correspondence between some tags related to the acoustic measurement conditions (presence of rain or wind) with the records from the national meteorological service database.
As these exploratory works will be extended and consolidated thereafter to a more global exploration of the database, and with the will to include this study within the framework of the Open Science, an attention was brought on the reproductibility aspect of the analysis. It was entirely realized with Free and Open Source Software (FOSS) and literate programming techniques. The context of the study, the implemented methodology and the first results will be presented as well as the benefits of using literate programming in this type of exploratory work.
The collected data are freely accessible, in particular by the scientific community which would like to develop new tools for the evaluation and representation of sound environments. The beginning of this analysis was the release of a 3 years collection of environnemental acoustic samples. A first article presenting this dataset has been published in 2021  (Picaut et al. , 2021). It details the structure of the database and the data, the profile of the contributors and the contributions but does not analyze the content of the data. This is what this article proposes to begin.
Data The data used in this study are contributions made by the user of the application between August 29, 2017 and August 28, 2020. During this period, nearly 70,000 unique contributors allowed the collection of more than 260,000 tracks for a total of about 60 million seconds of measurement. A track (or trace) is a collected recording, it contains the record of the sound spectrum (1 second, third octave) recorded by the phone microphone coupled with its GPS positioning (1 second). Each track is timestamped too. The 3 years collection dataset is available with an Open Database License through the Gustave Eiffel university Dataverse 4. This information can be enriched by the contributor with labels. There are 18 predefined labels and the user can select one or more of them for each of the traces made.
The labels are detailed in  (Picaut et al. , 2021). The preliminary work presented here focuses on the analysis of the proportion of certain labels in the global sample at certain temporalities. In addition to data from the collaborative collection, some additional data were used to limit the study area. First we chose to limit the geographical scope of this preliminary study to metropolitan France because this area contains the largest number of recordings and having a single administrative area facilitates the collection of supplementary databases. Then we extended some analysis worldwide. The results presented here concern tracks recorded in the France metropolitan area. To facilitate the reproductibility of spatial filtering, it was decided to use open data sets from recognized sources: the Natural Earth database  (Patterson and Kelso, 2021)  and the Admin Express database from the French National Institute of Geographic and Forest Information (Institut Géographique National, 2021).