bluuebunny/crossref_metadata_2025_split huggingface dataset:
Mixed type of total anomalous pulmonary venous connection: diagnosis, surgical approach and outcomes
Authors: Xiang Ming , Wu Chun , Pan Zhengxia , Wang Quan , Xi Linyun 
Published: October 2020

Abstract
Purpose
To summarize the diagnosis and treatment of 13 patients with mixed-type total anomalous pulmonary venous connection (TAPVC) and propose another classification for mixed TAPVC.

Methods
A retrospective review of 13 patients with mixed TAPVC undergoing repair at a single institution was conducted between January 2010 and November 2019. The diagnosis of mixed-type TAPVC was made in all patients using echocardiography combined with computed tomography angiography. According to the mixed TAPVC anatomy, there were 3 patients with type I TAPVC (2 + 2 veins), 10 patients with type II TAPVC (3 + 1 veins) and no patients with type III TAPVC. Correspondingly, there was 1 patient with the “SVC + VV” subtype, 2 patients with the “CS + C” subtype, 8 patients with the “CS + VV” subtype, 1 patient with the “CS + SVC” subtype and 1 patient with the “RA + SVC” subtype according to our classification system. All patients underwent cardiopulmonary bypass surgery.

Results
The median weight at surgery was 4.6 ± 1.0 kg (3.4–7.3 kg), and the median age at surgery was 96.2 ± 81.2 days (10–242 days). The median cardiopulmonary bypass time was 132.7 ± 25.1 min (range, 100 to 190 min). The cross-clamping time was 69.2 ± 14.4 min (range, 45 to 88 min). The hospital mortality rate was 7.7% (1 of 13), with late mortality occurring in 1 patient because of pulmonary venous obstruction (PVO) 7 months after surgery. The average follow-up after surgery was 3.4 ± 2.2 years (range, 5 months to 8 years). The survival rates at 3 and 5 years were both 90.9% ± 8.7% (95% CI: 73.8–108%). All remaining surviving patients were asymptomatic.

Conclusion
Mixed TAPVC can be repaired with good results in children and can be correctly diagnosed with echocardiography combined with computed tomography angiography. The classification system we propose is pragmatic and can guide the surgical approach.
Effect of dexmedetomidine on intraoperative Surgical Pleth Index in patients undergoing video-assisted thoracoscopic lung lobectomy
Authors: Wang Yu-Lan , Kong Xiao-Qi , Ji Fu-Hai 
Published: October 2020

Abstract
Background
The Surgical Pleth Index (SPI) is a monitoring method that reflects painful stimuli during general anesthesia, and dexmedetomidine is an analgesic adjuvant with an opioid-sparing effect. But up to now, it is still unclear whether dexmedetomidine has any influence on SPI. To investigate whether dexmedetomidine has an effect on SPI during video-assisted thoracoscopic surgery.

Methods
We enrolled 94 patients who underwent video-assisted thoracoscopic lung lobectomy. Patients were randomly assigned to a dexmedetomidine group (dexmedetomidine: 0.8 μg/kg administered for 10 min before anesthesia) or normal saline group (equal volume of normal saline). SPI and vital signs were recorded. The number rating scale (NRS) pain score was also evaluated.

Results
SPI values were significantly lower in the dexmedetomidine group than in the normal saline group at intubation and at discharge from the postanesthesia care unit. Compared with the normal saline group, mean arterial pressure and heart rate were both significantly lower in the dexmedetomidine group at intubation. Heart rate was lower at skin incision in the dexmedetomidine group. The NRS score in the normal saline group was noticeably higher vs. the dexmedetomidine group at discharge from the postanesthesia care unit.

Conclusions
Dexmedetomidine decreased intraoperative SPI and NRS scores. Our results showed that dexmedetomidine attenuated noxious stimuli.

Trial registration
Chinese Clinical Trial Registry (ChiCTR): ChiCTR-OOC-16009450, Registered 16 October, 2016.
Children at risk: A nation-wide, cross-sectional study examining post-traumatic stress symptoms in refugee minors from Syria, Iraq and Afghanistan resettled in Sweden between 2014 and 2018
Authors: Solberg Øivind , Nissen Alexander , Vaez Marjan , Cauley Prue , Eriksson Anna-Karin , Saboonchi Fredrik 
Published: October 2020

Abstract
Background
The objective of the present study was to assess nation-wide, representative prevalence estimates for symptom-defined posttraumatic stress disorder (PTSD) within populations of refugee minors from Afghanistan, Syria and Iraq resettled in Sweden.

Methods
A nation-wide, cross-sectional, questionnaire study with a stratified sample of refugee minors, aged 16–18 years, from Afghanistan, Iraq and Syria, resettled in Sweden between 2014 and 2018 (N = 5071) was conducted. The response rate was 22.3%, leaving n = 1129 refugee minors (boys 53.1% / girls 46.9%) in the final sample. Symptom-defined prevalences of PTSD were measured using CRIES-8 with ≥17 as cut-off. Data were analyzed using frequency distributions, and strata-specific PTSD prevalences with 95% confidence intervals (95% CIs), were estimated. The association between migratory status on arrival (unaccompanied vs. accompanied) and PTSD was estimated using crude and adjusted odds ratios (OR) utilizing logistic regression analyses with 95% CIs.

Results
Overall, the weighted PTSD prevalence was 42% (95% CI 38.9–45.1), with minors from Afghanistan presenting the highest prevalence (56.9, 95% CI 51.5–62.2), compared to minors from Iraq (36.8, 95% CI 28.9–45.4) and Syria (33.4, 95% CI 29.4–37.6). Unaccompanied minors from Afghanistan had higher odds of PTSD compared to accompanied minors from Afghanistan (OR = 1.92, 95% CI 1.08–3.40). Gender differences were non-significant.

Conclusions
High prevalences of symptom-defined PTSD among refugee minors in general and in unaccompanied minors from Afghanistan in particular, were revealed. Findings calls for continued efforts to support this especially vulnerable group.
Severe COVID-19 virus reactivation following treatment for B cell acute lymphoblastic leukemia
Authors: Lancman Guido , Mascarenhas John , Bar-Natan Michal 
Published: October 2020

AbstractSARS-CoV-2 has infected millions of people worldwide, but little is known at this time about second infections or reactivation. Here, we report a case of a 55-year-old female undergoing treatment for CD20+ B cell acute lymphoblastic leukemia who experienced a viral reactivation after receiving rituximab, cytarabine, and dasatinib. She was initially hospitalized with COVID-19 in April and developed a high antibody titer with two negative nasal polymerase chain reaction (PCR) swabs for SARS-CoV-2 on discharge. After recovery, she resumed treatment in June for her leukemia, which included rituximab, cytarabine, and dasatinib. She promptly lost her COVID-19 antibodies, and her nasal PCR turned positive in June. She developed a severe COVID-19 pneumonia with lymphopenia, high inflammatory markers, and characteristic bilateral ground-glass opacities on chest CT, requiring high-flow nasal cannula and transfer to the intensive care unit. She received steroids, anticoagulation, and convalescent plasma, and within 48 h she was off oxygen. She was discharged home in stable condition several days later. Given the short time frame from leukemia treatment to PCR positivity and the low case rate in mid-June in New York City, reinfection appears to have been unlikely and SARS-CoV-2 reactivation is a possible explanation. This case illustrates the risks of treating recently recovered COVID-19 patients with immunosuppressive therapy, particularly lymphocyte- and antibody-depleting therapy, and raises new questions about the potential of SARS-CoV-2 reactivation.
Long non-coding RNA LPP-AS2 promotes glioma tumorigenesis via miR-7-5p/EGFR/PI3K/AKT/c-MYC feedback loop
Authors: Zhang Xiaoming , Niu Wanxiang , Mu Maolin , Hu Shanshan , Niu Chaoshi 
Published: October 2020

Abstract
Background
Glioblastoma is the most common primary malignant intracranial tumor with poor clinical prognosis in adults. Accumulating evidence indicates that long non-coding RNAs (lncRNAs) function as important regulators in cancer progression, including glioblastoma. Here, we identified a new lncRNA LPP antisense RNA-2 (LPP-AS2) and investigated its function and mechanism in the development of glioma.

Methods
High-throughput RNA sequencing was performed to discriminate differentially expressed lncRNAs and mRNAs between glioma tissues and normal brain tissues. Expression of LPP-AS2, epidermal growth factor receptor (EGFR) and miR-7-5p in glioma tissues and cell lines was detected by real-time quantitative PCR (RT-qPCR), and the functions of lncRNA LPP-AS2 in glioma were assessed by in vivo and in vitro assays. Insight into the underlying mechanism of competitive endogenous RNAs (ceRNAs) was obtained via bioinformatic analysis, dual luciferase reporter assays, RNA pulldown assays, RNA immunoprecipitation (RIP) and rescue experiments.

Results
The results of high-throughput RNA-seq indicated lncRNA LPP-AS2 was upregulated in glioma tissues and further confirmed by RT-qPCR. Higher LPP-AS2 expression was related to a poor prognosis in glioma patients. Based on functional studies, LPP-AS2 depletion inhibited glioma cell proliferation, invasion and promoted apoptosis in vitro and restrained tumor growth in vivo, overexpression of LPP-AS2 resulted in the opposite effects. In addition, LPP-AS2 and EGFR were observed in co-expression networks. LPP-AS2 was found to function as a ceRNA to regulate EGFR expression by sponging miR-7-5p in glioma cells. The result of chromatin immunoprecipitation (ChIP) assays validated that c-MYC binds directly to the promoter region of LPP-AS2. As a downstream protein of EGFR, c-MYC was modulated by LPP-AS2 and in turn enhanced LPP-AS2 expression. Thus, lncRNA LPP-AS2 promoted glioma tumorigenesis via a miR-7-5p/EGFR/PI3K/AKT/c-MYC feedback loop.

Conclusions
Our study elucidated that LPP-AS2 acted as an oncogene through a novel molecular pathway in glioma and might be a potential therapeutic approach for glioma diagnosis, therapy and prognosis.
Characterization of universal features of partially methylated domains across tissues and species
Authors: Decato Benjamin E. , Qu Jianghan , Ji Xiaojing , Wagenblast Elvin , Knott Simon R. V. , Hannon Gregory J. , Smith Andrew D. 
Published: October 2020

AbstractBackgroundPartially methylated domains (PMDs) are a hallmark of epigenomes in reproducible and specific biological contexts, including cancer cells, the placenta, and cultured cell lines. Existing methods for deciding whether PMDs exist in a sample, as well as their identification, are few, often tailored to specific biological questions, and require high coverage samples for accurate identification.ResultsIn this study, we outline a set of axioms that take a step towards a functional definition for PMDs, describe an improved method for comparable PMD detection across samples with substantially differing sequencing depths, and refine the decision criteria for whether a sample contains PMDs using a data-driven approach. Applying our method to 267 methylomes from 7 species, we corroborated recent results regarding the general association between replication timing and PMD state, and report identification of several reproducibly “escapee” genes within late-replicating domains that escape the reduced expression and hypomethylation of their immediate genomic neighborhood. We also explored the discordant PMD state of orthologous genes between human and mouse, and observed a directional association of PMD state with gene expression and local gene density.ConclusionsOur improved method makes low sequencing depth, population-level studies of PMD variation possible and our results further refine the model of PMD formation as one where sequence context and regional epigenomic features both play a role in gradual genome-wide hypomethylation.
Generation of cortical neurons through large-scale expanding neuroepithelial stem cell from human pluripotent stem cells
Authors: Zhao Shumei , Duan Kui , Ai Zongyong , Niu Baohua , Chen Yanying , Kong Ruize , Li Tianqing 
Published: October 2020

AbstractBackgroundConsiderable progress has been made in converting human pluripotent stem cells (hPSCs) into cortical neurons for disease modeling and regenerative medicine. However, these procedures are hard to provide sufficient cells for their applications. Using a combination of small-molecules and growth factors, we previously identified one condition which can rapidly induce hPSCs into neuroepithelial stem cells (NESCs). Here, we developed a scalable suspension culture system, which largely yields high-quality NESC-spheres and subsequent cortical neurons.MethodsThe NESC medium was first optimized, and the suspension culture system was then enlarged from plates to stirred bioreactors for large-scale production of NESC-spheres by a stirring speed of 60 rpm. During the expansion, the quality of NESC-spheres was evaluated. The differentiation potential of NESC-spheres into cortical neurons was demonstrated by removing bFGF and two pathway inhibitors from the NESC medium. Cellular immunofluorescence staining, global transcriptome, and single-cell RNA sequencing analysis were used to identify the characteristics, identities, purities, or homogeneities of NESC-spheres or their differentiated cells, respectively.ResultsThe optimized culture system is more conducive to large-scale suspension production of NESCs. These largely expanded NESC-spheres maintain unlimited self-renewal ability and NESC state by retaining their uniform sizes, high cell vitalities, and robust expansion abilities. After long-term expansion, NESC-spheres preserve high purity, homogeneity, and normal diploid karyotype. These expanded NESC-spheres on a large scale have strong differentiation potential and effectively produce mature cortical neurons.ConclusionsWe developed a serum-free, defined, and low-cost culture system for large-scale expansion of NESCs in stirred suspension bioreactors. The stable and controllable 3D system supports long-term expansion of high-quality and homogeneous NESC-spheres. These NESC-spheres can be used to efficiently give rise to cortical neurons for cell therapy, disease modeling, and drug screening in future.
UBA2 activates Wnt/β-catenin signaling pathway during protection of R28 retinal precursor cells from hypoxia by extracellular vesicles derived from placental mesenchymal stem cells
Authors: Koh Kyungmin , Park Mira , Bae Eun Soo , Duong Van-An , Park Jong-Moon , Lee Hookeun , Lew Helen 
Published: October 2020

Abstract
Background
Stem cell transplantation has been proposed as an alternative treatment for intractable optic nerve disorders characterized by irrecoverable loss of cells. Mesenchymal stem cells, with varying tissue regeneration and recovery capabilities, are being considered for potential cell therapies. To overcome the limitations of cell therapy, we isolated exosomes from human placenta-derived mesenchymal stem cells (hPMSCs) and investigated their therapeutic effects in R28 cells (retinal precursor cells) exposed to CoCl2.

Method
After 9 h of exposure to CoCl2, the hypoxic damaged R28 cells were divided into the non-treatment group (CoCl2 + R28 cells) and treatment group (CoCl2 + R28 cells treated with exosome). Immunoblot analysis was performed for Pcna, Hif-1α, Vegf, Vimentin, Thy-1, Gap43, Ermn, Neuroflament, Wnt3a, β-catenin, phospo-GSK3β, Lef-1, UBA2, Skp1, βTrcp, and ubiquitin. The proteomes of each group were analyzed by liquid chromatography/tandem mass (LC-MS/MS) spectrometry. Differentially expressed proteins (DEPs) were detected by label-free quantification, and the interactions of the proteins were examined through signal transduction pathway and gene ontology analysis.

Result
We observed that exosome could significantly recover proliferation damaged by CoCl2 treatment. In addition, the treatment group presented the decreased expression of Hif-1α protein (P < 0.05) and increased expression of proliferation marker, Pcna, and nerve regeneration-related factors such as Vimentin, Thy-1, and Neuroflament (P < 0.05) compared with the non-treatment group. In total, 200 DEPs were identified in the non-treatment group and treatment group (fold change ≥ 2, p < 0.05). Catenin and ubiquitin systems (UBA2, UBE2E3, UBE2I) were found in both the DEP lists of downregulated proteins from the non-treatment group and upregulated proteins from the treatment group. The mRNA expressions of ubiquitin systems were significantly decreased under hypoxic conditions. Moreover, UBA2 and Wnt/β-catenin protein were associated with the rescue of the hypoxic damaged R28 cells. Using a siRNA system, we could find it out that hPMSC exosomes could not repair altered expressions of target proteins by CoCl2 in lacking UBA2 R28 cells.

Conclusion
This study reported that hypoxic damaged expression of regeneration markers in R28 cells was significantly recovered by hPMSC exosomes. We could also demonstrate that UBA2 played a key role in activating the Wnt/β-catenin signaling pathway during protection of hypoxic damaged R28 cells, induced by hPMSC exosomes.
Acquisition of cancer stem cell properties in osteosarcoma cells by defined factors
Authors: Fujiwara Shuichi , Kawamoto Teruya , Kawakami Yohei , Koterazawa Yasufumi , Hara Hitomi , Takemori Toshiyuki , Kitayama Kazumichi , Yahiro Shunsuke , Kakutani Kenichiro , Matsumoto Tomoyuki , Matsushita Takehiko , Niikura Takahiro , Koyanagi-Aoi Michiyo , Aoi Takashi , Kuroda Ryosuke , Akisue Toshihiro 
Published: October 2020

AbstractBackgroundCancer stem cells (CSCs) are considered to be responsible for tumor initiation, formation, and poor prognosis of cancer patients. However, the rarity of CSCs in clinical samples makes it difficult to elucidate characteristics of CSCs, especially in osteosarcoma (OS). The aim of this study is to verify whether it is possible to generate CSC-like cells by transducing defined factors into an OS cell line.MethodsWe retrovirally transduced the Octamer-binding transcription factor 3/4 (OCT3/4), Kruppel-like factor 4 (KLF4), and SRY-box transcription factor 2 (SOX2) genes into the MG-63 human OS cell line (MG-OKS). Parental and GFP-transduced MG-63 cells were used as negative control. We assessed the properties of the generated cells in vitro and in vivo. Multiple comparisons among groups were made using a one-way analysis of variance (ANOVA) followed by post hoc testing with Tukey’s procedure.ResultsMG-OKS cells in vitro exhibited the significantly increased mRNA expression levels of CSC markers (CD24,CD26, andCD133), decreased cell growth, increased chemoresistance and cell migration, and enhanced sphere formation. Notably, MG-OKS cells cultured under osteogenic differentiation conditions showed strongly positive staining for both Alizarin Red S and alkaline phosphatase, indicating osteogenesis of the cells. Gene ontology analysis of microarray data revealed significant upregulation of epidermal-related genes. Tumors derived from MG-OKS cells in vivo were significantly larger than those from other cells in μCT analysis, and immunohistochemical staining showed that Ki-67, osteocalcin, and HIF-1α-positive cells were more frequently detected in the MG-OKS-derived tumors.ConclusionsIn this study, we successfully generated OS CSC-like cells with significantly enhanced CSC properties following transduction of defined factors.
Bronchioalveolar stem cells derived from mouse-induced pluripotent stem cells promote airway epithelium regeneration
Authors: Kawakita Naoya , Toba Hiroaki , Miyoshi Keiko , Sakamoto Shinichi , Matsumoto Daisuke , Takashima Mika , Aoyama Mariko , Inoue Seiya , Morimoto Masami , Nishino Takeshi , Takizawa Hiromitsu , Tangoku Akira 
Published: October 2020

Abstract
Background
Bronchioalveolar stem cells (BASCs) located at the bronchioalveolar-duct junction (BADJ) are stem cells residing in alveoli and terminal bronchioles that can self-renew and differentiate into alveolar type (AT)-1 cells, AT-2 cells, club cells, and ciliated cells. Following terminal-bronchiole injury, BASCs increase in number and promote repair. However, whether BASCs can be differentiated from mouse-induced pluripotent stem cells (iPSCs) remains unreported, and the therapeutic potential of such cells is unclear. We therefore sought to differentiate BASCs from iPSCs and examine their potential for use in the treatment of epithelial injury in terminal bronchioles.

Methods
BASCs were induced using a modified protocol for differentiating mouse iPSCs into AT-2 cells. Differentiated iPSCs were intratracheally transplanted into naphthalene-treated mice. The engraftment of BASCs into the BADJ and their subsequent ability to promote repair of injury to the airway epithelium were evaluated.

Results
Flow cytometric analysis revealed that BASCs represented ~ 7% of the cells obtained. Additionally, ultrastructural analysis of these iPSC-derived BASCs via transmission electron microscopy showed that the cells containing secretory granules harboured microvilli, as well as small and immature lamellar body-like structures. When the differentiated iPSCs were intratracheally transplanted in naphthalene-induced airway epithelium injury, transplanted BASCs were found to be engrafted in the BADJ epithelium and alveolar spaces for 14 days after transplantation and to maintain the BASC phenotype. Notably, repair of the terminal-bronchiole epithelium was markedly promoted after transplantation of the differentiated iPSCs.

Conclusions
Mouse iPSCs could be differentiated in vitro into cells that display a similar phenotype to BASCs. Given that the differentiated iPSCs promoted epithelial repair in the mouse model of naphthalene-induced airway epithelium injury, this method may serve as a basis for the development of treatments for terminal-bronchiole/alveolar-region disorders.
In vivo glucose metabolism and glutamate levels in mGluR5 knockout mice: a multimodal neuroimaging study using [18F]FDG microPET and MRS
Authors: Joo Yo-Han , Kim Yun-Kwan , Choi In-Gyu , Kim Hyeon-Jin , Son Young-Don , Kim Hang-Keun , Cumming Paul , Kim Jong-Hoon 
Published: October 2020

AbstractBackgroundPerturbed functional coupling between the metabotropic glutamate receptor-5 (mGluR5) and N-methyl-d-aspartate (NMDA) receptor-mediated excitatory glutamatergic neurotransmission may contribute to the pathophysiology of psychiatric disorders such as schizophrenia. We aimed to establish the functional interaction between mGluR5 and NMDA receptors in brain of mice with genetic ablation of the mGluR5.MethodsWe first measured the brain glutamate levels with magnetic resonance spectroscopy (MRS) in mGluR5 knockout (KO) and wild-type (WT) mice. Then, we assessed brain glucose metabolism with [18F]fluorodeoxyglucose ([18F]FDG) positron emission tomography before and after the acute administration of an NMDA antagonist, MK-801 (0.5 mg/kg), in the same mGluR5 KO and WT mice.ResultsBetween-group comparisons showed no significant differences in [18F]FDG standardized uptake values (SUVs) in brain of mGluR5 KO and WT mice at baseline, but widespread reductions in mGluR5 KO mice compared to WT mice after MK-801 administration (p < 0.05). The baseline glutamate levels did not differ significantly between the two groups. However, there were significant negative correlations between baseline prefrontal glutamate levels and regional [18F]FDG SUVs in mGluR5 KO mice (p < 0.05), but no such correlations in WT mice. Fisher’s Z-transformation analysis revealed significant between-group differences in these correlations (p < 0.05).ConclusionsThis is the first multimodal neuroimaging study in mGluR5 KO mice and the first report on the association between cerebral glucose metabolism and glutamate levels in living rodents. The results indicate that mGluR5 KO mice respond to NMDA antagonism with reduced cerebral glucose metabolism, suggesting that mGluR5 transmission normally moderates the net effects of NMDA receptor antagonism on neuronal activity. The negative correlation between glutamate levels and glucose metabolism in mGluR5 KO mice at baseline may suggest an unmasking of an inhibitory component of the glutamatergic regulation of neuronal energy metabolism.