bluuebunny/crossref_metadata_2025_split huggingface dataset:
Circular RNA hsa_circ_0014130 Inhibits Apoptosis in Non–Small Cell Lung Cancer by Sponging miR-136-5p and Upregulating BCL2
Authors: Geng Ying , Bao Yongxia , Deng Lili , Su Dongju , Zheng Hongyan , Zhang Wei 
Published: February 2020

Abstract

Previous studies indicated that circular RNAs (circRNA) played vital roles in the development of non–small cell lung cancer (NSCLC). Although hsa_circ_0014130 might be a potential NSCLC biomarker, its function in NSCLC remains unknown. Thus, this study aimed to investigate the role of hsa_circ_0014130 in the progression of NSCLC. The levels of hsa_circ_0014130 in NSCLC tissues and adjacent normal tissues were determined by qRT-PCR. In addition, the expressions of Bcl-2 and cleaved caspase-3 in A549 cells were detected with Western blot analysis. Meanwhile, the dual luciferase reporter system assay was used to determine the interaction of hsa_circ_0014130 and miR-136-5p or Bcl-2 and miR-136-5p in NSCLC, respectively. The level of hsa_circ_0014130 was significantly upregulated in NSCLC tissues. Downregulation of hsa_circ_0014130 markedly inhibited the proliferation and invasion of A549 cells via inducing apoptosis. In addition, downregulation of hsa_circ_0014130 inhibited the tumorigenesis of subcutaneous A549 xenograft in mice in vivo. Meanwhile, mechanistic analysis indicated that downregulation of hsa_circ_0014130 decreased the expression of miR-136-5p–targeted gene Bcl-2 via acting as a competitive “sponge” of miR-136-5p. In this study, we found that hsa_circ_0014130 was upregulated in NSCLC tissues. In addition, hsa_circ_0014130 functions as a tumor promoter in NSCLC to promote tumor growth through upregulating Bcl-2 partially via “sponging” miR-136-5p.

Implications:
In conclusion, hsa_circ_0014130 might function as a prognostic factor for patients with NSCLC and might be a therapeutic target for the treatment of NSCLC in future.
Psychometric Properties of the Polish version of the Drug-Use Disorders Identification Test
Authors: Klimkiewicz Anna , Jakubczyk Andrzej , Mach Anna , Abramowska Małgorzata , Serafin Piotr , Szczypiński Jan , Demkow Marta , Wojnar Marcin 
Published: February 2020

<b><i>Background:</i></b> Substance use is a growing problem worldwide, and there is a great need to develop national policies addressing prevention and treatment of substance-use disorders (SUD). However, the lack of a commonly used, valuable diagnostic tool to assess the symptoms of SUDs precludes comparison of the prevalence of drug-use problems as well as the efficacy of policy strategies applied in different countries. This study was conducted to validate one of the commonly used scales the Drug Use Disorders Identification Test (the DUDIT) for use in Polish condition. <b><i>Objectives:</i></b> The aims of this study were to test the reliability of the DUDIT in the Polish population, to confirm the comparative stability of the factor structure of the instrument, and to verify previously proposed DUDIT cutoff scoring. <b><i>Methods:</i></b> The group of drug users comprised 127 patients aged 19–40 years (mean age 30.37, SD 6.36) with a diagnosis of SUD, while the control group consisted of 533 students aged 19–25 years (mean age 20.72, SD 1.88). All participants completed the Polish version of the DUDIT. Internal consistency of the Polish version of the DUDIT was determined, and subsequently external validation was performed. <b><i>Results:</i></b> Analysis showed that the Polish version of the DUDIT was characterized by a good reliability based on Cronbach’s α, with a value of 0.92. The between-group comparison revealed a significant difference between the control group and substance-dependent patients corresponding to a large effect size (Cohen’s d = 3.27). The receiver-operating characteristic analysis, comparing the DUDIT score to the ICD-10 diagnosis of SUD, showed an optimal cutoff value of 7 points, with a sensitivity of 0.929 and a specificity of 0.974. <b><i>Conclusion:</i></b> These results constitute preliminary evidence that the Polish version of the DUDIT may be a valid and reliable screening tool for drug-use disorders in the Polish population.
Regional Variation in the Management and Outcomes of Acute Myocardial Infarction With Cardiogenic Shock in the United States
Authors: Vallabhajosyula Saraschandra , Patlolla Sri Harsha , Dunlay Shannon M. , Prasad Abhiram , Bell Malcolm R. , Jaffe Allan S. , Gersh Bernard J. , Rihal Charanjit S. , Holmes David R. , Barsness Gregory W. 
Published: February 2020

Background:
There are few studies evaluating regional disparities in the care of acute myocardial infarction-cardiogenic shock (AMI-CS).

Methods and Results:

Using the National Inpatient Sample from 2000 to 2016, we identified adults with a primary diagnosis of AMI and concomitant CS admitted to the United States census regions of Northeast, Midwest, South, and West. Interhospital transfers were excluded. End points of interest included in-hospital mortality, use of coronary angiography, percutaneous coronary intervention, mechanical circulatory support, hospitalization costs, length of stay, and discharge disposition. Multivariable regression was used to adjust for potential confounding. Of the 402 825 AMI-CS admissions, 16.8%, 22.5%, 39.3%, and 21.4% were admitted to the Northeast, Midwest, South, and West, respectively. Higher rates of ST-elevation AMI-CS were noted in the Midwest and West. Admissions to the Northeast were on average characterized by a higher frequency of whites, Medicare beneficiaries, and lower rates of cardiac arrest. Admissions to the Northeast were less likely to receive coronary angiography, percutaneous coronary intervention, and mechanical circulatory support, despite the highest rates of extracorporeal membrane oxygenation use. Compared with the Northeast, in-hospital mortality was lower in the Midwest (adjusted odds ratio [aOR], 0.96 [95% CI, 0.93–0.98];
P
<0.001) and West (aOR, 0.96 [95% CI, 0.94–0.98];
P
=0.001) but higher in the South (aOR, 1.04 [95% CI, 1.01–1.06];
P
=0.002). The Midwest (aOR, 1.68 [95% CI, 1.62–1.74];
P
<0.001), South (aOR, 1.86 [95% CI, 1.80–1.92];
P
<0.001), and West (aOR, 1.93 [95% CI, 1.86–2.00];
P
<0.001) had higher discharges to home.

Conclusions:
There remain significant regional disparities in the management and outcomes of AMI-CS.
Plasma Estradiol and Testosterone Levels and Ischemic Stroke in Postmenopausal Women
Authors: Hu Jie , Lin Jennifer H. , Jiménez Monik C. , Manson JoAnn E. , Hankinson Susan E. , Rexrode Kathryn M. 
Published: February 2020

Background and Purpose—
Although exogenous hormone therapy (HT) use has been associated with increased risk of ischemic stroke in postmenopausal women, it remains unknown whether sex hormone levels contribute to ischemic stroke risk. We aimed to estimate associations between plasma sex hormone levels and ischemic stroke risk, by HT status, in a nested case-control study of postmenopausal women from the NHS (Nurses’ Health Study).

Methods—
Women with confirmed incident ischemic stroke (n=419) were matched with controls (n=419) by age, HT use, and other factors. Plasma estradiol and testosterone levels were measured using liquid chromatography tandem mass spectrometry; SHBG (sex hormone-binding globulin) was assayed by electrochemiluminescence immunoassay. Associations of total and free estradiol and testosterone, the estradiol/testosterone ratio, and SHBG with ischemic stroke were estimated using conditional logistic regressions stratified by HT status with adjustment for matching and cardiovascular risk factors.

Results—

Current HT users had different hormone profiles from never/past users. No clear linear trends were observed between estradiol (total or free) levels or the estradiol/testosterone ratio and ischemic stroke risk among either current users (
P
trend
>0.1) or never/past users (
P
trend
>0.6). For both current and never/past users, the associations between some of the sex hormones and ischemic stroke differed by body mass index categories (
P
interaction
≤0.04). For women with a body mass index <25 kg/m
2
, a higher estradiol/testosterone ratio was associated with significantly elevated ischemic stroke risk among current users (
P
trend
=0.01), and higher levels of total and free estradiol were significantly associated with higher ischemic stroke risk among never/past users (
P
trend
≤0.04). Testosterone and SHBG were not associated with ischemic stroke in either current or never/past users.

Conclusions—
Our findings do not support a role of sex hormone levels in mediating ischemic stroke risk among postmenopausal women. Replications in additional larger studies are required.
Corporate governance and turnaround: Evidence from Australia
Authors: Miglani Seema , Ahmed Kamran , Henry Darren 
Published: February 2020

We examine the relationship between ownership and outside director attributes and corporate turnaround outcomes using matched samples of 99 turnaround and 99 non-turnaround listed Australian firms during the 2004–2015 period. Based on agency theory principles, we propose that key shareholder groups (block ownership, director ownership, institutional ownership) and outside directors are related to firm-level turnaround outcomes, and particularly changes in these attributes across decline to turnaround periods. Our results provide evidence that turnaround and non-turnaround firms differ in terms of their ownership and board composition structures, and that changes in director ownership and the degree of board independence are important in determining the likelihood of turnaround success. JEL Classification: G33, G34, M40
Combined Single Cell Lineage and Transcriptome Sequencing Unveils Cell-Autonomous Regulators of Hematopoietic Stem Cell Fate
Authors: Rodriguez-Fraticelli Alejo E , Weinreb Caleb S , Klein Allon Moshe , Wang Shou-Wen , Camargo Fernando D 
Published: February 2020

Blood regeneration upon transplantation relies on the activity of long-term repopulating hematopoietic stem cells (LT-HSCs). One of the major controversies in hematopoiesis relates to the apparently different properties that HSCs have in transplantation versus unperturbed settings. In unperturbed steady state hematopoiesis, the most potent HSCs appear to be mostly dormant, and only producing platelet-lineage cells. In turn, upon transplant, even a single transplanted HSC can actively divide and regenerate hundreds of millions of blood progenitors of all lineages. It would thus appear that HSCs have different fundamental properties in each study system.
However, most transplantation studies have only tracked the lineage output of the transplanted HSC clones, and rarely the regeneration of the HSC compartment itself. In addition, clonal assays have not been performed at sufficient resolution to fully capture the diversity and clonal complexity of the regenerated HSC compartment. Here, we have used expressible barcodes, which can be sequenced in conventional single cell RNAseq assays, to simultaneously record the functional outcomes and transcriptional states of thousands of HSCs.
Our analysis revealed multiple clonal HSC behaviors following transplantation that drastically differ in their differentiation activity, lineage-bias and self-renewal. Surprisingly, we witnessed a large fraction of clones that efficiently repopulate the HSC compartment but show limited contribution to differentiated progeny. Furthermore, these inactive clones have increased competitive multilineage serial repopulating capacity, implying that shortly after transplant a subset of clones reestablishes the native-like LT-HSC behaviors. Our results also argue that this clonal distribution of labor is controlled by cell autonomous, heritable properties (i.e. the epigenetic cell state).
Then, using only our clonal readouts to segregate single HSC transcriptomes, we unveiled the transcriptional signatures that associated with unique HSC outcomes (platelet bias, clonal expansion, dormancy, etc.) and unraveled, for the first time, a gene signature for functional long-term serially repopulating clones. We interrogated the drivers of this cell state using an in vivo inducible CRISPR screening and identified 5 novel regulators that are required to regenerate the HSC compartment in a cell autonomous fashion.
In conclusion, we demonstrate that functional LT-HSCs share more similar properties in native and transplantation hematopoiesis than previously expected. Consequently, we unveil a definition of the essential, common functional properties of HSCs and the molecular programs that control them.
Figure 1

Disclosures
No relevant conflicts of interest to declare.
Bach1 Inhibitors Reduce Stasis in Townes Sickle Cell Mouse Model
Authors: Belcher John D , Biddle Margaret , Stickens Domi , Olson Lyndsay , Bell Eric , Chen Chunsheng , Abdulla Fuad , Nguyen Julia , Kiser Zachary Monroe , Lloyd Jacob , Vercellotti Gregory M 
Published: February 2020

In sickle cell disease (SCD) excessive release of Hb and heme into the vasculature can activate innate immune toll-like receptor 4 (TLR4) signaling in the vasculature leading to inflammation and vaso-occlusion. Heme-mediated TLR4 signaling can be interrupted by inducing heme oxygenase 1 (HO-1) to degrade heme or ferritin heavy chain (FTH1) to sequester iron. Globin synthesis, HO-1 expression, heme/iron homeostasis, and antioxidant levels are regulated in part by antioxidant response genes, which is a set of hundreds of genes that possess antioxidant response elements (ARE) in their promoter regions. Bach1 complexes bind to ARE sites and dominantly repress Nrf2 transcriptional activity. This transcriptional repression can be inactivated by heme binding to Bach1. We have discovered small molecule BACH1 inhibitors that increase HO-1 and FTH1 mRNA in HepG2 cells. Additionally, they restore glutathione levels and inhibit VCAM-1 expression in human primary aortic endothelial cells upon hemin or TNFα challenge. To investigate if Bach1 inhibitors could have an effect on vaso-occlusion in vivo, microvascular stasis was examined in Townes-SS mice with implanted dorsal skin-fold chambers. Townes-SS mice were orally gavaged with vehicle or Bach1 inhibitors at different doses once daily for 8 days. Microvascular stasis was determined in 20-25 preselected flowing subcutaneous venules in response to intravenous infusion of hemin (3.2 μmol/kg). Stasis was significantly inhibited by Bach1 inhibitors in a dose responsive manner. After stasis measurement, blood was collected and the F-cells were stained using the Kleihauer-Betke Test. F-cell % was significantly increased by Bach1 inhibitor treatment at all doses tested.

Disclosures
Belcher: Mitobridge, an Astellas Company: Consultancy, Research Funding. Biddle:Mitobrige, an Astellas Company: Employment, Membership on an entity's Board of Directors or advisory committees, Patents & Royalties. Stickens:Mitobridge, an Astellas Company: Employment, Membership on an entity's Board of Directors or advisory committees, Patents & Royalties. Olson:Mitobridge, an Astellas Company: Employment. Bell:Mitobridge, an Astellas Company: Employment. Vercellotti:Mitobridge, an Astellas Company: Consultancy, Research Funding.
A Busulfan Following Cyclophosphamide and Constant Cell Dose Protocol Improved Results in Alternative Donor Hematologic Stem Cell Transplantation in Thalassemia Major: A Result from Long-Term Large-Size Multi-Center Study
Authors: He Yuelin , Jiang Hua , Li Changgang , Zhu Yiping , Wu Xuedong , Sixi Liu , Yuhua Qu , Liao Jiangyu , Feng Xiaoqin , Liu Huaying , Peng Zhiyong , He Lan , Bu Chaoke , Mandeen Gautam , Wing Leung , Li Chunfu 
Published: February 2020

Sibling donor transplantation (SDT) is a proven curative therapy for patients with thalassemia major (TM), NF-08-TM protocol improved the outcomes of unrelated donor transplantation (UDT) in single-center. This study aim was to determine whether outcomes of NF-08-TM protocol could be proved in multicenter and long-term follow-up and to compare the outcomes of full-matched (FM) and one-locus mismatch (WM) UDT. 586 patients from 4 pediatric BMT centers in China from Dec. 2008 to Jun. 2016 received NF-08-TM protocol, a newly designed Busulfan following Cyclophosphamide and constant cell dose protocol. With a median follow-up of 57 months (range, 21-116), the 9-year OS, TFS, GR, and TRM were 94.4%, 92.8%, 2.7%, and 5.6%, respectively, in total. The corresponding rates for SDTs (n=224) were 95.9%, 95.5%, 1.4% and 4.1%; for UDTs (n=275) were 92.4%, 89.9%, 4.3% and 7.6%; for parental donor transplantation (PDT, n=40) were 95.0%, 95.0%, 0% and 5.0%; and for cord blood transplantation (CBT, n=47) were 97.9%, 95.4%, 2.6% and 2.1%, respectively.The incidence of grade II-IV aGVHD, III-IV aGVHD, mild cGVHD and moderate/severe cGVHD of the entire cohort was 8.9%, 4.6%, 3.7%, and 1.4%, respectively. There was no statistically significant difference (SSD) in OS, TFS, TRM, and GR when comparing FM-SDTs with those of FM-PDTs, FM-UDTs or FM-CBTs. Among PDTs, no SSD was found in OS, TFS, TRM, GR, and GVHD in comparison of FM-PDTs and WM-PDTs. More moderate/severe cGVHD occurred in WM-UDTs than FM-UDTs. Compared FM-SDTs, WM-UDTs had worse OS, TFS, TRM, and a higher rate of grade II-IV aGVHD and cGVHD. Current study proved that Good outcomes of NF-08-TM protocol in single-center be proved in multicenter and long-term follow-up. Compared to the outcomes of FM-UDT) those of well-UDT was worse and was not recommended to thalassemia patients.

Disclosures
Wing: Miltenyi Biotec: Employment.
Multilocus phylogeny and cryptic diversity of white-toothed shrews (Mammalia, Eulipotyphla, Crocidura) in China
Authors: Chen Shunde , Qing Jiao , Liu Zhu , Liu Yang , Tang Mingkun , Murphy Robert W. , Pu Yingting , Wang Xuming , Tang Keyi , Guo Keji , Jiang Xuelong , Liu Shaoying 
Published: February 2020

AbstractBackgroundCrocidura, the most speciose mammalian genus, occurs across much of Asia, Europe and Africa. The taxonomy of Chinese representatives has been studied primarily based on cursory morphological comparisons and their molecular phylogenetic analyses remain unexplored. In order to understand the phylogeny of this group in China, we estimated the first multilocus phylogeny and conducted species delimitation, including taxon sampling throughout their distribution range.ResultsWe obtained one mitochondrial gene (cytb) (~ 1, 134 bp) and three nuclear genes (ApoB,BRCA1,RAG1) (~ 2, 170 bp) for 132 samples from 57 localities. Molecular analyses identified at least 14 putative species that occur within two major well-supported groups in China. PolyphyleticC. wuchihensisappears to be composed of two putative species. Two subspecies,C. rapax rapaxandC. rapax kurodaishould be elevated to full species status. A phylogenetic tree based on mitochondrial gene from AsianCrociduraspecies showed that theC. rapax rapaxis embedded withinC. attenuata, making the latter a paraphyletic group. Three strongly supported undescribed species (C.sp.1,C.sp.2 andC.sp.3) are revealed from Zada County of Tibet (Western China), Hongjiang County of Hunan Province (Central China) and Dongyang County of Zhejiang Province (Eastern China), Motuo County of Tibet, respectively. The divergence time estimation suggested that China’sCrociduraspecies began to diversify during the late Pliocene (3.66 Ma) and the Early Pleistocene (2.29 Ma), followed by a series of diversifications through the Pleistocene.ConclusionsThe cryptic diversity found in this study indicated that the number of species is strongly underestimated under the current taxonomy. We propose that the three undescribed species should be evaluated using extensive taxon sampling and comprehensive morphological and morphometric approaches. Climate change since the late Pliocene and the uplift of the Qinghai-Tibet Plateau may result in the diversification and speciation of China’sCrociduraspecies. In short, the underestimated diversity underlines the need for a taxonomic revision of ChineseCrociduraspecies.
Cost-effectiveness analysis of chromosomal microarray as a primary test for prenatal diagnosis in Hong Kong
Authors: Chung Claudia Ching Yan , Chan Kelvin Yuen Kwong , Hui Pui Wah , Au Patrick Kwok Cheung , Tam Wai Keung , Li Samuel Kai Man , Leung Gordon Ka Chun , Fung Jasmine Lee Fong , Chan Marcus Chun Yin , Luk Ho Ming , Mak Annisa Shui Lam , Leung Kwok Yin , Tang Mary Hoi Yin , Chung Brian Hon Yin , Kan Anita Sik Yau 
Published: February 2020

Abstract
Background
Chromosomal microarray (CMA) has been shown to be cost-effective over karyotyping in invasive prenatal diagnosis for pregnancies with fetal ultrasound anomalies. Yet, information regarding preceding and subsequent tests must be considered as a whole before the true cost-effectiveness can emerge. Currently in Hong Kong, karyotyping is offered free as the standard prenatal test while genome-wide array comparative genome hybridization (aCGH), a form of CMA, is self-financed. A new algorithm was proposed to use aCGH following quantitative fluorescent polymerase chain reaction (QF-PCR) as primary test instead of karyotyping. This study aims to evaluate the cost-effectiveness of the proposed algorithm versus the current algorithm for prenatal diagnosis in Hong Kong.

Methods
Between November 2014 and February 2016, 129 pregnant women who required invasive prenatal diagnosis at two public hospitals in Hong Kong were prospectively recruited. The proposed algorithm was performed for all participants in this demonstration study. For the cost-effectiveness analysis, cost and outcome (diagnostic rate) data were compared with that of a hypothetical scenario representing the current algorithm. Further analysis was performed to incorporate women’s willingness-to-pay for the aCGH test. Impact of government subsidies on the aCGH test was explored as a sensitivity analysis.

Results
The proposed algorithm dominated the current algorithm for prenatal diagnosis. Both algorithms were equally effective but the proposed algorithm was significantly cheaper (p ≤ 0.05). Taking into account women’s willingness-to-pay for an aCGH test, the proposed algorithm was more effective and less costly than the current algorithm. When the government subsidy reaches 100%, the maximum number of diagnoses could be made.

Conclusion
By switching to the proposed algorithm, cost saving can be achieved whilst maximizing the diagnostic rate for invasive prenatal diagnosis. It is recommended to implement aCGH as a primary test following QF-PCR to replace the majority of karyotyping for prenatal diagnosis in Hong Kong.