bluuebunny/crossref_metadata_2025_split huggingface dataset:
Developing Transient Gene Therapies to Decrease the Stability of Thrombi for Coagulopathy and Thrombosis
Authors: Strilchuk Amy W , Kastrup Christian , Palumbo Joseph S. , Cullis Pieter 
Published: November 2020

Thrombotic disorders are prevalent and dangerous. Thrombosis involves the formation of unwanted blood clots inside blood vessels, which can impair blood flow and lead to severe cardiovascular events, such as heart attack, stroke, and pulmonary embolism. Current therapies for thrombosis are unsatisfactory in that they require frequent re-administration, and are associated with a significant bleeding risk, a consequence of inhibiting the coagulation cascade upstream of fibrin generation. Coagulation proteins factor XIII (FXIII) and thrombin activatable fibrinolysis inhibitor (TAFI) are enzymes that act to stabilize clots, downstream of fibrin generation and polymerization. Though this makes them ideal targets to reduce the burden of thrombosis while maintaining hemostasis, no inhibitors for either protein are currently available in the clinic. As we have recently published (Strilchuk, et al. Blood. 2020), lipid nanoparticles can be used to deliver siRNA to knock-down FXIII-B and achieve depletion of FXIII-A from circulation in mice and rabbits. FXIII-A depletion causes less antiplasmin to be crosslinked to clots, resulting in clots that are more susceptible to fibrinolysis. In the current abstract, we have expanded on preliminary data showing that while clots are weaker, bleeding is not enhanced in mice or rabbits after minor or major injury. We have also leveraged the same biological tools to knock-down TAFI for days after a single administration. In the short term, these novel RNA agents will be valuable tools in investigating the biology of thrombotic disorders. The ultimate goal is to develop these agents into precise and long-acting prophylactic therapies for thrombotic disorders, that are safer and more effective than current standards of care.

Disclosures
No relevant conflicts of interest to declare.
B-lymphoblastic leukemia arising in a patient with chronic neutrophilic leukemia
Authors: Boddy Craig S. , Tan Brent T. , Aoki Joseph 
Published: November 2020

Key Points
We report the first identified case of chronic neutrophilic leukemia with transformation to B-lymphoblastic leukemia. Genetic alterations involving CSF3R, ASXL1, SRSF2, and RUNX1 contributed to the unusual progression and may drive B-cell leukemogenesis.
Anion-Regulated Synthesis of ZnO 1D Necklace-Like Nanostructures with High Photocatalytic Activity
Authors: Qin Xiaoyun , Shi Dongdong , Guo Bowen , Fu Cuicui , Zhang Jin , Xie Qingqing , Shi Xiangdong , Chen Fenghua , Qin Xiaomei , Yu Wei , Feng Xiangli , Liu Yan , Luo Dan 
Published: November 2020

Abstract
One-dimensional (1D) nanomaterials with specific architectures have received increasing attention for both scientific and technological interests for their applications in catalysis, sensing, and energy conversion, etc. However, the development of an operable and simple method for the fabrication of 1D nanostructures remains a challenge. In this work, we developed an “anion-regulated morphology” strategy, in which anions could regulate the dimensionally-restricted anisotropic growth of ZnO nanomaterials by adjusting the surface energy of different growth facets. ZnO 1D necklace-like nanostructures (NNS) could be prepared through a hydrothermal treatment of zinc acetate and urea mixture together with a subsequent calcination procedure at 400 °C. While replacing the acetate ions to nitrate, sulfate, and chlorion ions produced ZnO nanoflowers, nanosheets and hexagonal nanoplates, respectively. Density functional theory calculations were carried out to explain the mechanism behind the anions-regulating anisotropic crystal growth. The specified ZnO 1D NNS offered improved electron transport while the grain surface could supply enlarged specific surface area, thus providing advanced photocatalytic ability in the following photodegradation of methyl orange (MO). Among the four photocatalysts with different morphologies, ZnO 1D NNS, possessing the highest catalytic activity, degraded 57.29% MO in the photocatalytic reaction, which was 2 times, 10 times and 17 times higher than nanoflowers, nanosheets and hexagonal nanoplates, respectively. Our work provides new ideas for the construction and application of ZnO 1D nanomaterials.
A cost benefit model for high capacity transport in a comprehensive line-haul network
Authors: Lindqvist David , Salman Marwan , Bergqvist Rickard 
Published: November 2020

Abstract
The objective of the paper is to analyse the potential of introducing High Capacity Transport (HCT) within a comprehensive line-haul network. Barriers and enablers have been identified, and a cost benefit model has been developed. The model considers environmental performance, socio-economic costs and operational costs and has been applied to a Swedish context and case study. The findings reveal that HCT can contribute to the development of road transportation in the perspectives of energy consumption and emission releases. It can further strengthen the trade and competitiveness of Swedish hauliers, as the introduction can provide a more cost-efficient system for all actors, including the transporter. However, the potential is largest when longer vehicles are meticulously and scrupulously introduced on a designated network alone.
Differential responses in placenta and fetal thymus at 12 days post infection elucidate mechanisms of viral level and fetal compromise following PRRSV2 infection
Authors: Van Goor Angelica , Pasternak Alex , Walker Kristen , Hong Linjun , Malgarin Carolina , MacPhee Daniel J. , Harding John C. S. , Lunney Joan K. 
Published: November 2020

AbstractBackgroundA pregnant gilt infected with porcine reproductive and respiratory syndrome virus (PRRSV) can transmit the virus to her fetuses across the maternal-fetal-interface resulting in varying disease outcomes. However, the mechanisms leading to variation in fetal outcome in response to PRRSV infection are not fully understood. Our objective was to assess targeted immune-related gene expression patterns and pathways in the placenta and fetal thymus to elucidate the molecular mechanisms involved in the resistance/tolerance and susceptibility of fetuses to PRRSV2 infection. Fetuses were grouped by preservation status and PRRS viral load (VL): mock infected control (CTRL), no virus detected (UNINF), virus detected in the placenta only with viable (PLCO-VIA) or meconium-stained fetus (PLCO-MEC), low VL with viable (LVL-VIA) or meconium-stained fetus (LVL-MEC), and high VL with viable (HVL-VIA) or meconium-stained fetus (HVL-MEC).ResultsThe host immune response was initiated only in fetuses with detectable levels of PRRSV. No differentially expressed genes (DEG) in either the placenta or thymus were identified in UNINF, PLCO-VIA, and PLCO-MEC when compared to CTRL fetuses. Upon fetal infection, a set of core responsive IFN-inducible genes (CXCL10,IFIH1,IFIT1,IFIT3,ISG15, andMX1) were strongly upregulated in both tissues. Gene expression in the thymus is a better differentiator of fetal VL; the strong downregulation of several innate and adaptive immune pathways (e.g., B Cell Development) are indicative of HVL. Gene expression in the placenta may be a better differentiator of fetal demise than the thymus, based-on principle component analysis clustering, gene expression patterns, and dysregulation of the Apoptosis and Ubiquitination pathways.ConclusionOur data supports the concept that fetal outcome in response to PRRSV2 infection is determined by fetal, and more significantly placental response, which is initiated only after fetal infection. This conceptual model represents a significant step forward in understanding the mechanisms underpinning fetal susceptibility to the virus.
Whole genome analysis of the koa wilt pathogen (Fusarium oxysporum f. sp. koae) and the development of molecular tools for early detection and monitoring
Authors: Dobbs John T. , Kim Mee-Sook , Dudley Nicklos S. , Klopfenstein Ned B. , Yeh Aileen , Hauff Robert D. , Jones Tyler C. , Dumroese R. Kasten , Cannon Philip G. , Stewart Jane E. 
Published: November 2020

Abstract

Background
Development and application of DNA-based methods to distinguish highly virulent isolates of Fusarium oxysporum f. sp. koae [Fo koae; cause of koa wilt disease on Acacia koa (koa)] will help disease management through early detection, enhanced monitoring, and improved disease resistance-breeding programs.

Results
This study presents whole genome analyses of one highly virulent Fo koae isolate and one non-pathogenic F. oxysporum (Fo) isolate. These analyses allowed for the identification of putative lineage-specific DNA and predicted genes necessary for disease development on koa. Using putative chromosomes and predicted gene comparisons, Fo koae-exclusive, virulence genes were identified. The putative lineage-specific DNA included identified genes encoding products secreted in xylem (e. g., SIX1 and SIX6) that may be necessary for disease development on koa. Unique genes from Fo koae were used to develop pathogen-specific PCR primers. These diagnostic primers allowed target amplification in the characterized highly virulent Fo koae isolates but did not allow product amplification in low-virulence or non-pathogenic isolates of Fo. Thus, primers developed in this study will be useful for early detection and monitoring of highly virulent strains of Fo koae. Isolate verification is also important for disease resistance-breeding programs that require a diverse set of highly virulent Fo koae isolates for their disease-screening assays to develop disease-resistant koa.

Conclusions
These results provide the framework for understanding the pathogen genes necessary for koa wilt disease and the genetic variation of Fo koae populations across the Hawaiian Islands.
Analysis of splice variants of the human protein disulfide isomerase (P4HB) gene
Authors: Kajihara Daniela , Hon Chung-Chau , Abdullah Aimi Naim , Wosniak João , Moretti Ana Iochabel S. , Poloni Joice F. , Bonatto Diego , Hashimoto Kosuke , Carninci Piero , Laurindo Francisco R. M. 
Published: November 2020

AbstractBackgroundProtein Disulfide Isomerases are thiol oxidoreductase chaperones from thioredoxin superfamily with crucial roles in endoplasmic reticulum proteostasis, implicated in many diseases. The family prototype PDIA1 is also involved in vascular redox cell signaling. PDIA1 is coded by theP4HBgene. While forced changes inP4HBgene expression promote physiological effects, little is known about endogenousP4HBgene regulation and, in particular, gene modulation by alternative splicing. This study addressed theP4HBsplice variant landscape.ResultsTen protein coding sequences (Ensembl) of theP4HBgene originating from alternative splicing were characterized. Structural features suggest that except forP4HB-021, other splice variants are unlikely to exert thiol isomerase activity at the endoplasmic reticulum. Extensive analyses using FANTOM5, ENCODE Consortium and GTEx project databases as RNA-seq data sources were performed. These indicated widespread expression but significant variability in the degree of isoform expression among distinct tissues and even among distinct locations of the same cell, e.g., vascular smooth muscle cells from different origins.P4HB-02,P4HB-027 andP4HB-021 were relatively more expressed across each database, the latter particularly in vascular smooth muscle. Expression of such variants was validated by qRT-PCR in some cell types. The most consistently expressed splice variant wasP4HB-021 in human mammary artery vascular smooth muscle which, together with canonicalP4HBgene, had its expression enhanced by serum starvation.ConclusionsOur study details the splice variant landscape of theP4HBgene, indicating their potential role to diversify the functional reach of this crucial gene.P4HB-021 splice variant deserves further investigation in vascular smooth muscle cells.
Alternate recurrent coronary artery spasm and stress cardiomyopathy: a case report
Authors: Jin Yunpeng , Li Qiming , Guo Xiaogang 
Published: November 2020

Abstract

Background
Coronary artery spasm (CAS) and stress cardiomyopathy (SC) have different characteristic clinical manifestations in the case of suspicious myocardial infarction with nonobstructive coronary arteries. Established recurrence rates of both conditions have been reported, however, alternate recurrent CAS and SC in the same individual have not been described.

Case presentation
A 59-year-old man suffered from atypical chest pain in the first episode, acute heart attack in the second and third episodes (totally 3 times over a period of approximately 5 years). During the first episode, he visited our hospital with mild paroxysmal chest pain without obvious inducement for approximately 2 years. He was underdiagnosed at that time without other obvious findings except the poor R wave progression in V1–3 leads revealed in electrocardiogram. At 4 months after the first episode, he suffered from a heart attack (the second episode) and was diagnosed with SC based on the coronary angiography (CAG) and left ventriculography findings of nonobstructive coronary arteries combined with a classic apical ballooning shape. At 31 months after the second episode, he suffered another heart attack (the third episode) and was diagnosed with CAS based on the CAG results of recoverable severe multivessel stenoses. During the episodes, partial reversible nature of apical hypokinesis was observed in echocardiogram. In retrospect, the patient suffered silent CAS in the first episode, SC in the second episode, and severe multivessel CAS in the third episode.

Conclusion
The unusual presentations observed in this case have not been reported. This case suggests that cardiologists should be aware of the possibility of alternate recurrent CAS and SC in the same individual. Provocative tests for spasm and cardiac magnetic resonance imaging might help gain more insights into this issue.
Recruitment and retention of participants from socioeconomically deprived communities: lessons from the Awareness and Beliefs About Cancer (ABACus3) Randomised Controlled Trial
Authors: Kolovou Vasiliki , Moriarty Yvonne , Gilbert Stephanie , Quinn-Scoggins Harriet , Townson Julia , Padgett Louise , Owen Sioned , Buckle Peter , Edwards Adrian , Hepburn Julie , Lau Mandy , Matthews Maura , Mitchell Caroline , Neal Richard , Playle Rebecca , Robling Mike , Smits Stephanie , Trubey Rob , Wood Fiona , Brain Kate 
Published: November 2020

Abstract

Background
Recruitment of research participants poses challenges in socioeconomically deprived areas. The Awareness and Beliefs About Cancer (ABACus) phase 3 Randomised Control Trial recruited adult participants from socioeconomically deprived areas using a combined healthcare/community engagement model. We report the strategies used to successfully recruit and retain our trial participant sample.

Methods
Community and healthcare settings in areas of high socioeconomic deprivation were identified by lay advisors who recruited participants opportunistically or by appointment. Follow-up was done by telephone or post at 2-weeks and 6-months after recruitment, and all participants were offered financial incentives. Qualitative interviews were conducted with lay advisors regarding their experience and reflections.

Results
The lay advisors identified and contacted 107 potential recruitment venues across South and West Yorkshire and South East Wales of which 41.1% (n = 42) were opened for recruitment. A total of 234 participants were recruited, with 91% (n = 212) retention at 2-weeks and 85% (n = 199) at 6-months. Community settings yielded 75% (n = 176) of participants. Participants had a mean age of 61.3 years and 63.3% (n = 148) were female, with 66% (n = 154) resident in the most deprived geographical areas. Lay advisors described recruitment as intensive, although engaging participants was easier in community settings.

Conclusions
The ABACus3 trial achieved recruitment and high retention with a population that is often “hard to reach” or entirely missed in health research. Strategies were specifically tailored to engage the venues and adult residents of highly deprived areas. Future studies recruiting adults living in the most deprived areas might benefit from community recruitment and from collaborating with local gatekeepers who are key to engagement.
This study adheres to CONSORT guidelines.

Trial registration
Retrospectively registered with ISRCTN (http://www.isrctn.com/ISRCTN16872545) on 12.01.2018.
Non-invasive predictors of prognosis of Asian patients with histopathologically-confirmed lean nonalcoholic fatty liver disease
Authors: Iritani Soichi , Akuta Norio , Kawamura Yusuke , Kajiwara Akira , Kasuya Kayoko , Fujiyama Shunichiro , Sezaki Hitomi , Hosaka Tetsuya , Kobayashi Masahiro , Kobayashi Mariko , Saito Satoshi , Suzuki Fumitaka , Arase Yasuji , Ikeda Kenji , Suzuki Yoshiyuki , Kumada Hiromitsu 
Published: November 2020

Abstract

Background
The prognostic factors of morbidity and mortality in patients with lean NAFLD (body mass index < 25.0 kg/m2) are unknown.

Methods
In this retrospective study, 446 Japanese patients with histopathologically-confirmed NAFLD (lean NAFLD, n = 170) were followed for liver events, cardiovascular events, type 2 diabetes mellitus, and non-liver malignancies. The median observation period was 4.6 years. We also investigated the predictors of severe fibrosis (stage 3–4) and mortality in lean NAFLD patients.

Results
Glycolipid metabolic markers, liver function tests, NAFLD fibrosis score (NFS), and histological scoring were significantly lower in lean NAFLD patients than in non-lean NAFLD. The incidence of liver cancer was higher while that of T2DM was lower in lean NAFLD. Kaplan–Meier analysis showed no significant difference in overall survival between the lean and non-lean NAFLD. Multivariate analysis of data of lean NAFLD identified NFS ≥ − 1.455 as significant independent predictor of severe fibrosis, while history of liver cancer and NFS ≥ − 1.455 were predictors of overall survival.

Conclusions
Although patients with lean NAFLD have better histopathological and biochemical profile compared to patients with non-lean NAFLD, the prognosis is not different between the two groups. Lean NAFLD patients with NFS ≥ − 1.455 or history of liver cancer should be monitored carefully during follow-up.
Identification of ALDH3A2 as a novel prognostic biomarker in gastric adenocarcinoma using integrated bioinformatics analysis
Authors: Yin Zhenhua , Wu Dejun , Shi Jianping , Wei Xiyi , Jin Nuyun , Lu Xiaolan , Ren Xiaohan 
Published: November 2020

Abstract
Background
Extensive research has revealed that genes play a pivotal role in tumor development and growth. However, the underlying involvement of gene expression in gastric carcinoma (GC) remains to be investigated further.

Methods
In this study, we identified overlapping differentially expressed genes (DEGs) by comparing tumor tissue with adjacent normal tissue using the Gene Expression Omnibus (GEO) and the Cancer Genome Atlas (TCGA) database.

Results
Our analysis identified 79 up-regulated and ten down-regulated genes. Functional enrichment analysis and prognosis analysis were conducted on the identified genes, and the fatty aldehyde dehydrogenase (FALDH) gene, ALDH3A2, was chosen for more detailed analysis. We performed Gene Set Enrichment Analysis (GSEA) and immunocorrelation analysis (infiltration, copy number alterations, and checkpoints) to elucidate the mechanisms of action of ALDH3A2 in depth. The immunohistochemical (IHC) result based on 140 paraffin-embedded human GC samples indicated that ALDH3A2 was over-expressed in low-grade GC cases and the OS of patients with low expression of ALDH3A2 was significantly shorter than those with high ALDH3A2 expression. In vitro results indicated that the expression of ALDH3A2 was negatively correlated with PDCD1, PDCD1LG2, and CTLA-4.

Conclusion
We conclude that ALDH3A2 might be useful as a potential reference value for the relief and immunotherapy of GC, and also as an independent predictive marker for the prognosis of GC.
The DLC-1 tumor suppressor is involved in regulating immunomodulation of human mesenchymal stromal /stem cells through interacting with the Notch1 protein
Authors: Na Tao , Zhang Kehua , Yuan Bao-Zhu 
Published: November 2020

AbstractBackgroundImmunomodulatory activities of human mesenchymal stromal /stem cells (hMSCs) has been widely recognized as the most critical function of hMSCs for exerting its therapeutic effects. However, the detailed mechanisms responsible for regulating the immunomodulation of hMSCs still remain largely unknown. Previous studies revealed that the Notch1 protein exerted a pro-immunomodulatory function probably through interacting with the protein(s) subjective to proteasome-mediated protein degradation. The DLC-1 protein represents a well characterized tumor suppressor subjective to proteasome-mediated degradation. However, the detailed signaling pathway of Notch1 and the involvement of DLC-1 in regulating the immunomodulation of hMSCs have not been studied before.MethodsThe transfection with cDNA or siRNA into hMSCs assisted by co-culture of hMSCs with peripheral blood mononuclear cells and small molecule inhibitors of signaling proteins, followed by immunoprecipitation, Western blotting, RT-PCR, and flowcytometry, were employed to characterize the Notch1 signaling, to identify DLC-1 as a candidate proteasome-targeted protein, and to characterize DLC-1 signaling pathway and its interaction with the Notch1 signaling, in the regulation of immunomodulation of hMSCs, specifically, the inhibition of pro-inflammatory CD4+-Th1 lymphocytes, and the release of immunomodulatory molecule IDO1.Statistical analysisOne-way ANOVA was utilized as a statistical tool to analyze the data presented as means ± SEM of at least three separate experiments.ResultsThe present study revealed that the Notch1-Hey1 axis, but not the Notch1-Hes1 axis, was likely responsible for mediating the pro-immunomodulatory function of the Notch1 signaling. The DLC-1 protein was found subjective to proteasome-mediated protein degradation mediated by the DDB1 and FBXW5 E3 ligases and served as an inhibitor of the immunomodulation of hMSCs through inhibiting Rock1, but not Rock2, downstream the DLC-1 signaling. The Notch1 signaling in the Notch1-Hey1 pathway and the DLC-1 signaling in the DLC-1-Rock1-FBXW5 pathway exhibited a mutual exclusion interaction in the regulation of immunomodulation of hMSCs.ConclusionsThe present study uncovers a novel function of DLC-1 tumor suppressor in regulating the immunomodulation of hMSCs. It also proposes a novel mutual exclusion mechanism between the DLC-1 signaling and the Notch1 signaling that is possibly responsible for fine-tuning the immunomodulation of hMSCs with different clinical implications in hMSCs therapy.