bluuebunny/crossref_metadata_2025_split huggingface dataset:
Potential of resveratrol in enrichment of neural progenitor-like cells induction of human stem cells from apical papilla
Authors: Songsaad Anupong , Gonmanee Thanasup , Ruangsawasdi Nisarat , Phruksaniyom Chareerut , Thonabulsombat Charoensri 
Published: May 2020

Abstract
Introduction: Stem cell transplantation of exogenous neural progenitor cells (NPCs) derived from mesenchymal stem cells (MSCs) has emerged as a promising approach of neurodegenerative disease. Human stem cells from apical papilla (hSCAPs) are derived from migratory neural crest stem cells, and exhibit a potential of neuronal differentiation. However, their neuronal differentiation is low and unpredictable. Resveratrol has been described as a sirtuin 1 ( SIRT1 ) activator which plays an important role in enhancing neuronal differentiation. In this study, we investigate the potential of resveratrol as an enhancer on neuronal differentiation through NPCs induction of hSCAPs. Methods: Stem cells were isolated from human apical papilla, and characterized as MSCs. The cellular toxicity of resveratrol treatment to the characterized hSCAPs was investigated by MTT assay. The non-cellular toxicity concentrations of resveratrol were assessed with various pre-treatment times to select the optimal condition that highly expressed the neural progenitor gene, NES . Consequently, the optimal condition of resveratrol pre-treatment was synergistically performed with a neuronal induction medium to trigger neuronal differentiation. The differentiated cells were visualized, the genes profiling was quantified, and the percentage of neuronal differentiation was calculated. Results: The cellular toxicity of resveratrol was not observed for up to 50 µM for 12 hours. Interestingly, hSCAPs pre-treated with 10 µM resveratrol for 12 hours (RSV-hSCAPs) significantly expressed NES , which is determined as the optimal condition. Under neuronal induction, both of hSCAPs and RSV-hSCAPs were differentiated (d-hSCAPs, and RSV-d-hSCAPs) as they exhibited neuronal-like appearances. Additionally, the neuronal induction medium actively promotes neural progenitor marker expression in both d-hSCAPs, and RSV-d-hSCAPs . The highest expression of NES was observed in RSV-d-hSCAPs. Importantly, the neuronal differentiation of RSV-d-hSCAPs was significantly increased for 4 times. Conclusion: This study demonstrated that pre-treatment of resveratrol strongly induces neural progenitor marker gene expression which synergistically enhances neural progenitor-like cells’ induction with neuronal induction medium.
Comparison of the properties of bone marrow-derived dedifferentiated fat cells and mesenchymal stem cells in humans
Authors: Lu Wei , Yu Yehua , Yang Shaoxin , Zhai Yuanmei , Zhao Chong , Wei Yanyu , Shi Jun 
Published: May 2020

Abstract
Background

Dedifferentiated fat (DFAT) cells have been studied as a potential tool for various aspects of tissue engineering. However, the understanding of DFAT cells is mainly derived from studies of inguinal subcutaneous or visceral white adipose tissues rather than human bone marrow (BM). Here, we focused on DFAT cells dedifferentiated from bone marrow adipocytes.
Methods

A plate ceiling culture method and light microscope were used to observe the morphological changes in bone marrow adipocytes. RT-qPCR analysis, immunofluorescence and immunocytochemistry were used to compare gene and protein expression before and after the adipogenic and osteogenic differentiation of BM-DFAT cells and mesenchymal stem cells from bone marrow (BM-MSCs). CCK8 assays and annexin V-PI staining were used to assess the effect of BM-DFAT cells on the proliferation and chemoresistance of leukaemic cells.
Results

We found that bone marrow adipocytes can dedifferentiate into fibroblast-like multipotent cells, and BM-DFAT cells exhibited similar a morphology, immunophenotype, multipotent gene expression, proliferation ability and osteogenic differentiation in comparison with BM-MSCs. Interestingly, BM-DFAT cells possessed a higher potential for adipogenic differentiation than BM-MSCs, since they expressed a lower level of Pref-1, an inhibitor of adipogenesis. Meanwhile, our results revealed the significantly enhanced proliferation of leukaemic cell lines in the BM-DFAT cell group compared with that in the BM-MSC group. However, the effects of BM-DFAT cells were not as obvious as those of BM-MSCs on the chemoresistance of leukaemic cells.
Conclusions

This is the first study to illustrate the properties of BM-DFAT cells. We determined that BM-DFAT cells may be a useful cell source to study the role of bone marrow adipocytes and might be utilized for clinical applications in regenerative medicine.
Induced neural stem cell grafts exert neuroprotection through an interaction between Crry and Akt in a mouse model of closed head injury
Authors: Gao Mou , Dong Qin , Wang Wenjia , Yang Zhijun , Lu Yingzhou , Ding Boyun , Chen Lihua , Zhang Jianning , Xu Ruxiang 
Published: May 2020

Abstract
Background
Recently, growing evidence has indicated an important role of the complement system, a crucial component of immunity, in mediating neuroinflammation and promoting neuronal apoptosis following closed head injury (CHI). We previously reported that transplanted induced neural stem cells (iNSCs) pre-treated with CHI mouse serum could enhance complement receptor type 1-related protein y (Crry) expression and ameliorate complement-mediated damage in mouse CHI models. However, the mechanism underlying the elevated levels of Crry expression remains elusive.
Methods
CHI models were established using a standardized weight-drop device and CHI mouse serum was collected at 12 h post-trauma. Complement deposition assay, Akt inhibition assay, cell viability assay, functional assay, cell transplantation, morphological and molecular biological analyses were performed.
Results
In the present study, we observed dramatic increases in the levels of Crry expression and Akt activation in iNSCs receiving CHI mouse serum treatment. Remarkably, Akt inhibition led to the reduction of Crry expression in iNSCs. Intriguingly, the treatment of iNSC-derived neurons with recombinant complement receptor 2-conjugated Crry (CR2-Crry), which inhibits all complement pathways, substantially enhanced Crry expression and Akt activation in neurons after CHI mouse serum treatment. In subsequent in vitro experiments of pre-treatment of iNSCs with CR2-Crry, we observed significant increases in the levels of Crry expression and Akt activation in iNSCs, iNSC-derived astrocytes and neurons post-treatment with CHI mouse serum. Additionally, an in vivo study showed that intracerebral-transplanted iNSCs pre-treated with CR2-Crry markedly enhanced Crry expression in neurons and protected neurons from complement-dependent damage in the brains of CHI mice.
Conclusions
In summary, iNSCs receiving CR2-Crry pre-treatment increased the levels of Crry expression in iNSCs, iNSC-derived astrocytes and neurons and attenuated complement-mediated injury following CHI.
Differential transcriptomics in sarcoidosis lung and lymph node granulomas with comparisons to pathogen-specific granulomas
Authors: Casanova Nancy G. , Gonzalez-Garay Manuel L , Sun Belinda , Bime Christian , Knox Kenneth S. , Crouser Elliot , Sun Xiaoguang , Sammani Nora , Gregory Taylor , Natt Bhupinder , Chaudhary Sachin , Lussier Yves , Garcia Joe G. N. 
Published: May 2020

Abstract
Rationale: Despite the availability of multi-“omics” strategies, insights into the etiology and pathogenesis of sarcoidosis have been elusive. This is partly due to the lack of reliable preclinical models and a paucity of validated biomarkers. As granulomas are a key feature of sarcoidosis, we speculate that direct genomic interrogation of sarcoid tissues, may lead to identification of dysregulated gene pathways or biomarker signatures.Objective: To facilitate the development sarcoidosis genomic biomarkers by gene expression profiling of sarcoidosis granulomas in lung and lymph node tissues (most commonly affected organs) and comparison to infectious granulomas (coccidiodomycosis and tuberculosis). Methods: Transcriptomic profiles of immune-related gene from micro-dissected lungs and mediastinal lymph nodes sarcoidosis granulomas was compared to infectious granulomas. Differentially-expressed genes (DEGs) were profiled, compared among the three granulomatous diseases and analyzed for functional enrichment pathways. Results: Despite histologic similarities, DEGs and pathway enrichment markedly differed in sarcoidosis granulomas from lymph nodes and lung. Lymph nodes showed a clear immunological response, whereas a structural regenerative response was observed in lung. Sarcoidosis granuloma gene expression data corroborated previously reported genomic biomarkers, excluded others and identified new genomic markers present in lung and lymph nodes, ADAMTS1, CXCL2, FABP4. Comparisons between sarcoidosis and pathogen granulomas identified pathway divergences and commonalities at gene expression level.Conclusion: These findings suggest the importance of tissue and disease-specificity evaluation when exploring sarcoidosis genomic markers. This relevant translational information in two commonly affected tissue in sarcoidosis and other two histopathological similar infections provides meaningful specific genomic-derived biomarkers for sarcoidosis diagnosis and prognosis.
Noninvasive KRAS mutation estimation in colorectal cancer using a deep learning method based on CT imaging
Authors: He kan , Liu Xiaoming , Li Mingyang , Li Xueyan , Yang Hualin , Zhang Huimao 
Published: May 2020

Abstract
ABSTRACT
Background: The detection of Kirsten rat sarcoma viral oncogene homolog ( KRAS )gene mutations in colorectal cancer (CRC) is key to the optimal design of individualized therapeutic strategies. The noninvasive prediction of the KRAS status in CRC is challenging. Deep learning (DL) in medical imaging has shown its high performance in diagnosis, classification, and prediction in recent years. In this paper, we investigated predictive performance by using a DL method with a residual neural network ( ResNet ) to estimate the KRAS mutation status in CRC patients based on pre-treatment contrast-enhanced CT imaging.
Methods: We have collected a dataset consisting of 157 patients with pathology-confirmed CRC who were divided into a training cohort (n = 117) and a testing cohort (n = 40). We developed an ResNet model that used portal venous phase CT images to estimate KRAS mutations in the axial, coronal, and sagittal directions of the training cohort and evaluated the model in the testing cohort. Several groups of expended region of interest （ROI）patches were generated for the ResNet model，to explore whether tissues around the tumor can contribute to cancer assessment. We also explored a radiomics model with the random forest classifier (RFC) to predict KRAS mutations and compared it with the DL model.
Results: The ResNet model in the axial direction achieved the higher area under the curve (AUC) value (0.90) in the testing cohort and peaked at 0.93 with an input of “ROI and 20-pixel” surrounding area. AUC of radiomics model in testing cohorts were 0.818. In comparison, the ResNet model showed better predictive ability .
Conclusions: Our experiments reveal that the computerized assessment of the pre-treatment CT images of CRC patients using a DL model has the potential to precisely predict KRAS mutations. This new model has the potential to assist in noninvasive KRAS mutation estimation.
Keywords: Colorectal Neoplasm, Mutation, Deep Learning
Airway managed by emergency physicians or anaesthesiologists in trauma patients: A retrospective cohort analysis of outcomes
Authors: Tang Cathy , Yang Marc L.C. , Chan Annie , Ho Paul H.F. 
Published: May 2020

Abstract
Objectives In some trauma centres, anaesthesiologists (AN) has the primary responsibility of managing airway in trauma resuscitation. However, as emergency physicians(EP) establishes a separate specialty with airway management and endotracheal intubation being one of the core skills, role delineation within trauma members may vary. In this cohort study, we aim to determine the difference in mortality of trauma patients requiring intubation in the Emergency Department between EP and AN. Methods We screened all 1588 patients in the hospital trauma registry from 2015 to 2018. We included all patients requiring endotracheal intubation and aged 18 or above but excluded those with pregnancy, presented with cardiac arrest and secondarily transferred from other hospitals. 349 eligible patients were sorted into two cohorts according to the physicians who performed intubations (AN 205 patients, EP 144 patients). Patients' baseline demographics, 30-day all-cause mortality, and other predefined secondary outcomes were compared by statistical tests. Stepwise logistic regression of 30-day all-cause mortality were performed. Results Our study has shown that intubation by emergency physicians was not associated with higher 30-day all-cause mortality after potential confounders were controlled by logistic regression. (adjusted OR 1.253, p = 0.607) Both group also did not differ in other clinical important secondary outcomes, including proportion of successful intubations, use of surgical airway or rescue manoeuvres, respiratory and airway complications , mortality in intensive care or high-dependency unit, post-intubation cardiac arrest , post-intubation hypotension and post-intubation hypoxia. Conclusion Endotracheal intubation by EP is not associated with increased 30-day all-cause mortality when compared to AN after accounting for confounders.
Quantitative CT-based Image Registration Metrics Provide Different Ventilation and Lung Motion Patterns in Prone and Supine Positions in Healthy Subjects
Authors: Shin Kyung Min , Choi Jiwoong , Chae Kum Ju , Jin Gong Yong , Eskandari Ali , Hoffman Eric A. , Hall Chase , Castro Mario , Lee Chang Hyun 
Published: May 2020

Abstract
Background Previous studies suggested that the prone position (PP) improves oxygenation and reduces mortality among patients with acute respiratory distress syndrome (ARDS). However, the mechanism of this clinical benefit of PP is not completely understood. The aim of the present study was to quantitatively compare regional characteristics of lung functions in the PP with those in the supine position (SP) using inspiratory and expiratory computed tomography (CT) scans.Methods 90 subjects with normal pulmonary function and inspiration and expiration CT images were included in the study. Thirty-four subjects were scanned in PP, and 56 subjects were scanned in SP. Non-rigid image registration-based inspiratory-expiratory image matching assessment was used for regional lung function analysis. Tissue fractions (TF) were computed based on the CT density and compared on a lobar basis. Three registration-derived functional variables, relative regional air volume change (RRAVC), volumetric expansion ratio (J), and three-dimensional relative regional displacement (s*) were used to evaluate regional ventilation and deformation characteristics. Results J was greater in PP than in SP in the right middle lobe (P = 0.025), and RRAVC was increased in the upper and right middle lobes (P < 0.001). The ratio of the TF on inspiratory and expiratory scans, J, and RRAVC at the upper lobes to those at the middle and lower lobes and that ratio at the upper and middle lobes to those at the lower lobes of were all near unity in PP, and significantly higher than those in SP (0.98-1.06 vs 0.61-0.94, P < 0.001).Conclusion We visually and quantitatively observed that PP not only induced more uniform contributions of regional lung ventilation along the ventral-dorsal axis but also minimized the lobar differences of lung functions in comparison with SP. These findings may help clarify the benefits of applying PP to the patients with ARDS or other gravitationally dependent pathologic lung diseases.Trial registration Retrospectively registered.
Clustering and superspreading potential of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections in Hong Kong
Authors: Adam Dillon , Wu Peng , Wong Jessica , Lau Eric , Tsang Tim , Cauchemez Simon , Leung Gabriel , Cowling Benjamin 
Published: May 2020

Abstract
Superspreading events have characterised previous epidemics of severe acute respiratory syndrome coronavirus (SARS-CoV) and Middle East respiratory syndrome coronavirus (MERS-CoV) infections. Using contact tracing data, we identified and characterized SARS-CoV-2 clusters in Hong Kong. Given a superspreading threshold of 6-8 secondary cases, we identified 5-7 probable superspreading events and evidence of substantial overdispersion in transmissibility, and estimated that 20% of cases were responsible for 80% of local transmission. Among terminal cluster cases, 27% (45/167) ended in quarantine. Social exposures produced a greater number of secondary cases compared to family or work exposures (p<0.001) while delays between symptom onset and isolation did not reliably predict the number of individual secondary cases or resulting cluster sizes. Public health authorities should focus on rapid tracing and quarantine of contacts, along with physical distancing to prevent superspreading events in high-risk social environments.
Gross tumor volume determines toxicity and quality of life for patients with nasopharyngeal carcinoma treated by concurrent chemoradiotherapy with simultaneously integrated boost technique
Authors: Huang Tai-Lin , Chuang Hui-Ching , Huang Chun-Chieh , Chien Chih-Yen , Li Shau-Hsuan , Tsai Wen-Ling , Lee Tsair-Fwu , FANG FU-MIN 
Published: May 2020

Abstract
Background: To evaluate the impact of gross tumor volume (GTV) on toxicities and quality of life (QoL) for patients with nasopharyngeal carcinoma (NPC) treated by concurrent chemoradiotherapy with simultaneously integrated boost technique (chemo-SIB-IMRT). Methods: A total of 278 NPC patients with stage II-IVb treated by chemo-SIB-IMRT were enrolled. Toxicities were evaluated according to CTCAE version 4.03. QoL outcomes (n=219) were measured by using the EORTC QLQ-C30 and HN35 questionnaires at the time point of 12 months after chemo-SIB-IMRT. Results: A higher GTV was observed to be significantly associated with a higher mean or maximal dose in most organs at risk, together with more severe acute (mucositis, dermatitis, weight loss, and use of analgesic) and late toxicities (xerostomia, neck fibrosis, and radiation neuropathy). A linear regression model revealed that a higher GTV was significantly associated with a decline in role functioning and an increment in taste/smell, speech, social eating, opening mouth, dry mouth, and sticky saliva. Conclusion: GTV is the determining factor of some acute and late toxicities and QoL scales for NPC patients treated by chemo-SIB-IMRT.
A non-invasive ultrasound imaging method to measure acute radiation-induced bladder wall thickening in rats
Authors: Spinelli Antonello Enrico , Bresolin Andrea , Zuppone Stefania , Perani Laura , Fallara Giuseppe , Muzio Nadia Di , Vago Riccardo , Fiorino Claudio , Cozzarini Cesare 
Published: May 2020

Abstract
Background. Methods for the non-invasive quantification of changes in bladder wall thickness (BWT) as potential predictors of radiation cystitis (RC) in pre-clinical research would be desirable. The use of ultrasound (US) for this aim seems promising, but is still relatively unexplored. A method using US for BWT quantification in rats was developed and applied to measure early radiation-induced BWT changes.
Methods. Two groups (n=9 each) of female Fischer rats were treated with a single radiation dose of 25-30 and 35-40Gy respectively, using an image-guided micro-irradiator; six untreated rats were monitored as a control group. Empty, half-filled and fully-filled bladder volumes were determined for four non-irradiated rats by measuring axes from US 3D-images and applying the ellipsoid formula. Mean BWT was estimated for both ventral and dorsal bladder sides through the measurement of the bladder wall area along a segment of 4mm in the central sagittal scan, in order to minimize operator-dependence on the measurement position. US acquisitions of all fully-filled rat bladders were also acquired immediately before, and 4 and 28 days after irradiation. Mean BWTs normalized to the baseline value and corrected for filling were then used to evaluate acute bladder wall thickening and to quantify the dose-effect.
Results. The relationship between mean BWT and bladder volume in unirradiated rats showed that for a bladder volume >1.5mL the BWT is almost constant and equal to 0.30mm with variations within ±15%. The average ratios between BWT-post and BWT-pre irradiation showed a dose-effect relationship. Bladder wall thickening was observed for the 25-30 Gy and 35-40 Gy groups in 2/9 (22%) and 5/9 (56%) cases at day 4 and in 4/9 (44%) and 8/9 (89%) cases at day 28, respectively. The two groups showed significantly different BWTs both relative to the control group (p<0.0001) and between them (p=0.022). The BWT increment was on average 1.32±0.41, and was 1.30±0.21 after 25-30Gy and 1.47±0.29 and 1.90±0.83 after 35-40Gy at days 4 and 28 respectively.
Conclusions. The feasibility of using US on a preclinical rat model to detect BWT changes after bladder irradiation was demonstrated, and a clear dose-effect relationship was quantified. Although preliminary, these results are promising in addressing the potential role of this non-invasive approach in quantifying RC.
Non-synonymous Mutations of SARS-Cov-2 Leads Epitope Loss and Segregates its Varaints
Authors: Gupta Aayatti Mallick , Mandal Sukhendu 
Published: May 2020

Abstract
The non-synonymous mutations of SARS-Cov-2 isolated from across the world have been identified during the last few months. The surface glycoprotein spike of SARS-Cov-2 forms the most important hotspot for amino acid alterations followed by the ORF1a/ORF1ab poly-proteins. It is evident that the D614G mutation in spike glycoprotein and P4715L in RdRp is the important determinant of SARS-Cov-2 evolution since its emergence. P4715L in RdRp, G251V in ORF3a and S1498F of Nsp3 is associated with the epitope loss that may influence pathogenesis caused by antibody escape variants. Phylogenomics distinguished the ancestral viral samples from China and most part of Asia, isolated between Dec, 2019 to Feb, 2020 and the evolved variants isolated from Europe and Americas from Mar, 2020 to April, 2020. The evolved variants have been found to predominant globally with the loss of epitopes from its proteins. These have implications for SARS-Cov-2 transmission, pathogenesis and immune interventions.