bluuebunny/crossref_metadata_2025_split huggingface dataset:
Prevention and contrast of child abuse and neglect in the practice of European paediatricians: a multi-national pilot study
Authors: Nigri Paola , Corsello Giovanni , Nigri Luigi , Bali Donjeta , Kuli-Lito Giorgina , Plesca Doina , Pop Tudor Lucian , Carrasco-Sanz Angel , Namazova-Baranova Leyla , Mestrovic Julije , Vural Mehmet , Giardino Ida , Losonczi Laszlo , Somekh Eli , Balducci Maria Teresa , Pettoello-Mantovani Massimo , Ferrara Pietro 
Published: May 2021

AbstractBackgroundChild abuse and neglect, or maltreatment, is a serious public health problem, which may cause long-term effects on children’s health and wellbeing and expose them to further adulthood vulnerabilities. Studies on child maltreatment performed in Europe are scarce, and the number of participants enrolled relatively small. The aim of this multi-national European pilot study, was to evaluate the level of understanding and perception of the concepts of child abuse and neglect by European paediatricians working in different medical settings, and the attitude toward these forms of maltreatment in their practice.MethodsThe study was performed by a cross-sectional, descriptive, online survey, made available online to European paediatricians members of 50 national paediatric, who belonged to four different medical settings: hospital, family care, university centres and private practice.The questionnaire, designed as a multiple choice questions survey, with a single answer option consisted of 22 questions/statements. Frequency analyses were applied. Most of the data were described using univariate analysis and Chi-squared tests were used to compare the respondents and answers and a significance level ofp ≤ 0.05 applied.ResultsFindings show that European paediatricians consider the training on child maltreatment currently provided by medical school curricula and paediatric residency courses to be largely insufficient and continuing education courses were considered of great importance to cover educational gaps. Physical violence was recognized by paediatricians mostly during occasional visits with a significant correlation between detecting abuse during an occasional visit and being a primary care paediatrician. Results also showed a reluctance by paediatricians to report cases of maltreatment to the competent judicial authorities.ConclusionsData of this study may provide useful contribution to the current limited knowledge about the familiarity of European paediatricians with child maltreatment and their skills to recognize, manage and contrast abusive childhood experiences in their practice. Finally, they could provide local legislators and health authorities with information useful to further improve public health approaches and rules able to effectively address shared risk and protective factors, which could prevent child abuse and neglect from ever occurring.
What are the risk factors for admission to the pediatric intensive unit among pediatric patients with COVID-19?
Authors: Esposito Susanna , Caramelli Fabio , Principi Nicola 
Published: May 2021

AbstractBackgroundAlthough with exceptions, evidence seems to indicate that children have lower susceptibility than adults to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. When infected, children generally remain asymptomatic or develop mild disease. A small number of pediatric cases required admission to the pediatric intensive care unit (PICU), respiratory support with a mechanical ventilation and additional life-saving interventions. Even if rarely, death can occur. Aim of this manuscript is to highlight the risk factors associated with severe outcome among pediatric patients with COVID-19.Main findingsEarly identification of SARS-CoV-2-infected children at risk of developing severe COVID-19 is vital for service planning, as severely affected pediatric patients require high-quality care and should be followed only where an adequately structured PICU is available. However, early identification of children who must be carefully monitored for substantial risk of severe COVID-19 remains difficult. An underlying comorbidity and heart involvement are frequently observed in severe paediatric cases. Reduced left ventricular systolic function with an ejection fraction < 60%; diastolic dysfunction; and arrhythmias, including ST segment changes, QTc prolongation, and premature atrial or ventricular beat, are the earliest manifestations of heart involvement. Inclusion of heart enzyme serum levels and evaluation of ventricular function among predictive markers could lead to a more effective evaluation of children at risk with proper selection of those to admit to the PICU and with more adequate treatment in case of more severe clinical manifestations.ConclusionsTo appropriately manage severe pediatric COVID-19 cases, greater attention should be paid to risk factors in children and adolescents, especially to cardiovascular alterations (e.g., heart enzyme serum levels and evaluation of ventricular function). Further studies are needed and the development of a validated score based on all the most common presumed markers of disease severity seems essential.
Functional consequences of a rare missense BARD1 c.403G>A germline mutation identified in a triple-negative breast cancer patient
Authors: Zheng Yuanting , Li Bingying , Pan Dejing , Cao Jun , Zhang Jian , Wang Xiaolin , Li Xiangnan , Hou Wanwan , Bao Ding , Ren Luyao , Yang Jingcheng , Wang Shangzi , Qiu Yangyang , Zhou Fei , Liu Zhiwei , Zhu Sibo , Zhang Lei , Qing Tao , Wang Yi , Yu Ying , Wu Jiaxue , Hu Xichun , Shi Leming 
Published: May 2021

AbstractWe identified a rare missense germline mutation in BARD1 (c.403G>A or p.Asp135Asn) as pathogenic using integrated genomics and transcriptomics profiling of germline and tumor samples from an early-onset triple-negative breast cancer patient who later was administrated with a PARP inhibitor for 2 months. We demonstrated in cell and mouse models that, compared to the wild-type, (1) c.403G>A mutant cell lines were more sensitive to irradiation, a DNA damage agent, and a PARP inhibitor; (2) c.403G>A mutation inhibited interaction between BARD1 and RAD51 (but not BRCA1); and (3) c.403G>A mutant mice were hypersensitive to ionizing radiation. Our study shed lights on the clinical interpretation of rare germline mutations of BARD1.
Deep sequencing of pre-translational mRNPs reveals hidden flux through evolutionarily conserved alternative splicing nonsense-mediated decay pathways
Authors: Kovalak Carrie , Donovan Scott , Bicknell Alicia A. , Metkar Mihir , Moore Melissa J. 
Published: May 2021

AbstractBackgroundAlternative splicing, which generates multiple mRNA isoforms from single genes, is crucial for the regulation of eukaryotic gene expression. The flux through competing splicing pathways cannot be determined by traditional RNA-Seq, however, because different mRNA isoforms can have widely differing decay rates. Indeed, some mRNA isoforms with extremely short half-lives, such as those subject to translation-dependent nonsense-mediated decay (AS-NMD), may be completely overlooked in even the most extensive RNA-Seq analyses.ResultsRNA immunoprecipitation in tandem (RIPiT) of exon junction complex components allows for purification of post-splicing mRNA-protein particles (mRNPs) not yet subject to translation (pre-translational mRNPs) and, therefore, translation-dependent mRNA decay. Here we compare exon junction complex RIPiT-Seq to whole cell RNA-Seq data from HEK293 cells. Consistent with expectation, the flux through known AS-NMD pathways is substantially higher than that captured by RNA-Seq. Our RIPiT-Seq also definitively demonstrates that the splicing machinery itself has no ability to detect reading frame. We identify thousands of previously unannotated splicing events; while many can be attributed to splicing noise, others are evolutionarily conserved events that produce new AS-NMD isoforms likely involved in maintenance of protein homeostasis. Several of these occur in genes whose overexpression has been linked to poor cancer prognosis.ConclusionsDeep sequencing of RNAs in post-splicing, pre-translational mRNPs provides a means to identify and quantify splicing events without the confounding influence of differential mRNA decay. For many known AS-NMD targets, the nonsense-mediated decay-linked alternative splicing pathway predominates. Exon junction complex RIPiT-Seq also revealed numerous conserved but previously unannotated AS-NMD events.
Schema: metric learning enables interpretable synthesis of heterogeneous single-cell modalities
Authors: Singh Rohit , Hie Brian L. , Narayan Ashwin , Berger Bonnie 
Published: May 2021

AbstractA complete understanding of biological processes requires synthesizing information across heterogeneous modalities, such as age, disease status, or gene expression. Technological advances in single-cell profiling have enabled researchers to assay multiple modalities simultaneously. We present Schema, which uses a principled metric learning strategy that identifies informative features in a modality to synthesize disparate modalities into a single coherent interpretation. We use Schema to infer cell types by integrating gene expression and chromatin accessibility data; demonstrate informative data visualizations that synthesize multiple modalities; perform differential gene expression analysis in the context of spatial variability; and estimate evolutionary pressure on peptide sequences.
A generalization of t-SNE and UMAP to single-cell multimodal omics
Authors: Do Van Hoan , Canzar Stefan 
Published: May 2021

AbstractEmerging single-cell technologies profile multiple types of molecules within individual cells. A fundamental step in the analysis of the produced high-dimensional data is their visualization using dimensionality reduction techniques such as t-SNE and UMAP. We introduce j-SNE and j-UMAP as their natural generalizations to the joint visualization of multimodal omics data. Our approach automatically learns the relative contribution of each modality to a concise representation of cellular identity that promotes discriminative features but suppresses noise. On eight datasets, j-SNE and j-UMAP produce unified embeddings that better agree with known cell types and that harmonize RNA and protein velocity landscapes.
Serum proteomic profiling in patients with advanced Schistosoma japonicum-induced hepatic fibrosis
Authors: Huang Jing , Yin Xinguang , Zhang Lifang , Yao Ming , Wei Dahai , Wu Yiming 
Published: May 2021

Abstract
Background
Schistosoma japonicum is a parasitic flatworm that is the aetiological agent of human schistosomiasis, an important cause of hepatic fibrosis. Schistosomiasis-induced hepatic fibrosis is a consequence of the highly fibrogenic nature of egg-induced granulomatous lesions, which are the main pathogenic features of schistosomiasis. Although global awareness of the association between schistosomiasis-induced hepatic fibrosis and S. japonicum infection is increasing, little is known about the molecular differences associated with rapid progression to schistosomiasis in cirrhotic patients.

Methods
We systematically used data-independent acquisition (DIA)-based liquid chromatography-mass spectrometry to identify differentially expressed proteins in serum samples from patients with advanced S. japonicum-induced hepatic fibrosis.

Results
Our analysis identified 1144 proteins, among which 66 were differentially expressed between the healthy control group and the group of patients with advanced S. japonicum-induced hepatic fibrosis stage F2 (SHF-F2) and 214 were differentially expressed between the SHF-F2 and SHF-F4 groups (up- or downregulation of at least 1.5-fold in serum samples). The results also indicated that two selected proteins (C1QA and CFD) are potential biomarkers for distinguishing between patients with SHF-F2 and those with SHF-F4 due to S. japonicum infection.

Conclusions
We provide here the first global proteomic profile of serum samples from patients with advanced S. japonicum-induced hepatic fibrosis. The proteins C1QA and CFD are potential diagnostic markers for patients with SHF-F2 and SHF-F4 due to S. japonicum infection, although further large-scale studies are needed. Our DIA-based quantitative proteomic analysis revealed molecular differences among individuals at different stages of advanced S. japonicum-induced hepatic fibrosis and may provide fundamental information for further detailed investigations.

Graphical Abstract
DNA methylation profiling for molecular classification of adult diffuse lower-grade gliomas
Authors: Ferreyra Vega Sandra , Olsson Bontell Thomas , Corell Alba , Smits Anja , Jakola Asgeir Store , Carén Helena 
Published: May 2021

AbstractBackgroundDNA methylation profiling has facilitated and improved the classification of a wide variety of tumors of the central nervous system. In this study, we investigated the potential utility of DNA methylation profiling to achieve molecular diagnosis in adult primary diffuse lower-grade glioma (dLGG) according to WHO 2016 classification system. We also evaluated whether methylation profiling could provide improved molecular characterization and identify prognostic differences beyond the classical histological WHO grade together withIDHmutation status and 1p/19q codeletion status. All patients diagnosed with dLGG in the period 2007–2016 from the Västra Götaland region in Sweden were assessed for inclusion in the study.ResultsA total of 166 dLGG cases were subjected for genome-wide DNA methylation analysis. Of these, 126 (76%) were assigned a defined diagnostic methylation class with a class prediction score ≥ 0.84 and subclass score ≥ 0.50. The assigned methylation classes were highly associated with theirIDHmutation status and 1p/19q codeletion status.IDH-wildtype gliomas were further divided into subgroups with distinct molecular features.ConclusionThe stratification of the patients by methylation profiling was as effective as the integrated WHO 2016 molecular reclassification at predicting the clinical outcome of the patients. Our study shows that DNA methylation profiling is a reliable and robust approach for the classification of dLGG into molecular defined subgroups, providing accurate detection of molecular markers according to WHO 2016 classification.
TRPC7 regulates the electrophysiological functions of embryonic stem cell-derived cardiomyocytes
Authors: Liu Xianji , Zhao Rui , Ding Qianqian , Yao Xiaoqiang , Tsang Suk Ying 
Published: May 2021

AbstractBackgroundBiological pacemakers consisting of pluripotent stem cell-derived cardiomyocytes are potentially useful for treating bradycardia. However, tachyarrhythmia caused by derived cardiomyocytes themselves is one of main barriers hampering their clinical translation. An in-depth understanding of the mechanisms underlying the spontaneous action potential (a.k.a. automaticity) might provide potential approaches to solve this problem. The aim of this project is to study the role of canonical transient receptor potential isoform 7 (TRPC7) channels in regulating the automaticity of embryonic stem cell-derived cardiomyocytes (ESC-CMs).Methods and resultsBy Western blotting, the expression of TRPC7 was found to be increased during the differentiation of mouse ESC-CMs (mESC-CMs). Adenovirus-mediated TRPC7 knockdown decreased while overexpression increased the frequency of Ca2+transients (CaTs), local Ca2+releases (LCRs), and action potentials (APs) as detected by confocal microscopy and whole-cell patch-clamping. TRPC7 was found to be positively associated with the activity of ryanodine receptor 2 (RyR2), sarco/endoplasmic reticulum Ca2+-ATPase (SERCA), and sodium-calcium exchanger (NCX) but not hyperpolarization-activated, cyclic nucleotide-gated channel (HCN), and inositol trisphosphate receptor (IP3R). Knockdown or overexpression of TRPC7 did not alter the expression of HCN4, Cav1.3, Cav3.1, Cav3.2, IP3R1, RyR2, and SERCA but positively regulated the phosphorylation of RyR2 at S2814 and phospholamban (PLN) at T17. Moreover, the positive regulation of APs by TRPC7 was Ca2+-dependent, as overexpression of N-terminus of TRPC7 (dominant negative of TRPC7) which diminished the Ca2+permeability of TRPC7 decreased the AP frequency.ConclusionsTRPC7 regulates the automaticity of mESC-CMs through two mechanisms. On the one hand, TRPC7 positively regulates the intracellular Ca2+clock through the regulation of activities of both RyR2 and SERCA; on the other hand, TRPC7 also positively regulates the membrane clock via its influence on NCX activity. Altogether, our study reveals that TRPC7 is a potential drug target to manipulate the action potential firing rate of pluripotent stem cell-derived cardiomyocyte-based biological pacemakers to prevent tachyarrhythmia, a condition that might be encountered after transplantation.
Small extracellular vesicles from human adipose-derived mesenchymal stromal cells: a potential promoter of fat graft survival
Authors: Chen Aizhen , Tang Shijie , He Jiawei , Li Xiangyu , Peng Guohao , Zhang Haoruo , Chen Jinghua , Chen Liangwan , Chen Xiaosong 
Published: May 2021

Abstract
Background
Small extracellular vesicles (sEVs) with genetic information secreted by cells play a crucial role in the cellular microenvironment. In this study, our purpose is to explore the characteristics of the small extracellular vesicles of human adipose-derived mesenchymal stromal cells (hADMSC-sEVs) and studied the role of hADMSC-sEVs in improving the survival rate of grafted fat.

Methods
In the present study, we used the transmission electron microscopy, nano-tracking analysis, nanoflow surface protein analysis, and zeta potential value to identify sEVs. SEVs’ trajectory was traced dynamically to verify whether hADMSC-sEVs can be internalized into human umbilical vein endothelial cells (HUVECs) in vitro at different times. The angiogenic property of hADMSC-sEVs was observed by measuring the volume, weight, and histological analysis of the grafted fats in nude mouse models.

Results
Our research showed that the hADMSC-sEVs were sEVs with double-layer membrane structure and the diameter of which is within 30–150 nm. hADMSC-sEVs exert biological influence mainly through internalization into cells. Compared with the control group, the hADMSC-sEVs group had a significantly higher survival rate of grafted fat, morphological integrity, and a lower degree of inflammation and fibrosis. And immunohistochemistry showed that hADMSC-sEVs significantly increased the neovascularisation and the expression of CD34, VEGFR2, and Ki-67 in the graft tissue.

Conclusions
As a potential nanomaterial, hADMSC-sEVs have been explored in the field of cell-free application of stem cell technology. hADMSC-sEVs promoted the survival of grafted fats by promoting the formation of new blood vessels, which is another promising progress in the field of regenerative medicine. We believe that hADMSC-sEVs will have a broad application prospect in the field of regenerative medicine in the future.
Consecutive daily administration of intratracheal surfactant and human umbilical cord-derived mesenchymal stem cells attenuates hyperoxia-induced lung injury in neonatal rats
Authors: Chou Hsiu-Chu , Chang Chien-Hsiang , Chen Chien-Han , Lin Willie , Chen Chung-Ming 
Published: May 2021

Abstract
Background
Surfactant therapy is a standard of care for preterm infants with respiratory distress and reduces the incidence of death and bronchopulmonary dysplasia in these patients. Our previous study found that mesenchymal stem cells (MSCs) attenuated hyperoxia-induced lung injury and the combination therapy of surfactant and human umbilical cord-derived MSCs (hUC-MSCs) did not have additive effects on hyperoxia-induced lung injury in neonatal rats. The aim is to evaluate the effects of 2 consecutive days of intratracheal administration of surfactant and hUC-MSCs on hyperoxia-induced lung injury.

Methods
Neonatal Sprague Dawley rats were reared in either room air (RA) or hyperoxia (85% O2) from postnatal days 1 to 14. On postnatal day 4, the rats received intratracheal injections of either 20 μL of normal saline (NS) or 20 μL of surfactant. On postnatal day 5, the rats reared in RA received intratracheal NS, and the rats reared in O2 received intratracheal NS or hUC-MSCs (3 × 104 or 3 × 105 cells). Six study groups were examined: RA + NS + NS, RA + surfactant + NS, O2 + NS + NS, O2 + surfactant + NS, O2 + surfactant + hUC-MSCs (3 × 104 cells), and O2 + surfactant + hUC-MSCs (3 × 105 cells). The lungs were excised for histological, western blot, and cytokine analyses.

Results
The rats reared in hyperoxia and treated with NS yielded significantly higher mean linear intercepts (MLIs) and interleukin (IL)-1β and IL-6 levels and significantly lower vascular endothelial growth factors (VEGFs), platelet-derived growth factor protein expression, and vascular density than did those reared in RA and treated with NS or surfactant. The lowered MLIs and cytokines and the increased VEGF expression and vascular density indicated that the surfactant and surfactant + hUC-MSCs (3 × 104 cells) treatment attenuated hyperoxia-induced lung injury. The surfactant + hUC-MSCs (3 × 105 cells) group exhibited a significantly lower MLI and significantly higher VEGF expression and vascular density than the surfactant + hUC-MSCs (3 × 104 cells) group did.

Conclusions
Consecutive daily administration of intratracheal surfactant and hUC-MSCs can be an effective regimen for treating hyperoxia-induced lung injury in neonates.
Conversion of stem cells from apical papilla into endothelial cells by small molecules and growth factors
Authors: Yi Baicheng , Ding Tian , Jiang Shan , Gong Ting , Chopra Hitesh , Sha Ou , Dissanayaka Waruna Lakmal , Ge Shaohua , Zhang Chengfei 
Published: May 2021

Abstract
Objectives
Recently, a new strategy has been developed to directly reprogram one cell type towards another targeted cell type using small molecule compounds. Human fibroblasts have been chemically reprogrammed into neuronal cells, Schwann cells and cardiomyocyte-like cells by different small molecule combinations. This study aimed to explore whether stem cells from apical papilla (SCAP) could be reprogrammed into endothelial cells (ECs) using the same strategy.

Materials and methods
The expression level of endothelial-specific genes and proteins after chemical induction of SCAP was assessed by RT-PCR, western blotting, flow cytometry and immunofluorescence. The in vitro functions of SCAP-derived chemical-induced endothelial cells (SCAP-ECs) were evaluated by tube-like structure formation assay, acetylated low-density lipoprotein (ac-LDL) uptake and NO secretion detection. The proliferation and the migration ability of SCAP-ECs were evaluated by CCK-8 and Transwell assay. LPS stimulation was used to mimic the inflammatory environment in demonstrating the ability of SCAP-ECs to express adhesion molecules. The in vivo Matrigel plug angiogenesis assay was performed to assess the function of SCAP-ECs in generating vascular structures using the immune-deficient mouse model.

Results
SCAP-ECs expressed upregulated endothelial-specific genes and proteins; displayed endothelial transcriptional networks; exhibited the ability to form functional tubular-like structures, uptake ac-LDL and secrete NO in vitro; and contributed to generate blood vessels in vivo. The SCAP-ECs could also express adhesion molecules in the pro-inflammatory environment and have a similar migration and proliferation ability as HUVECs.

Conclusions
Our study demonstrates that the set of small molecules and growth factors could significantly promote endothelial transdifferentiation of SCAP, which provides a promising candidate cell source for vascular engineering and treatment of ischemic diseases.