bluuebunny/crossref_metadata_2025_split huggingface dataset:
A Systematic Review on Extracellular Vesicles-Enriched Fat Grafting: A Shifting Paradigm
Authors: Ghiasloo Mohammad , De Wilde Laura , Singh Kashika , Tonnard Patrick , Verpaele Alexis , De Wever Olivier , Blondeel Phillip 
Published: December 2020

Abstract

Background
Recent evidence confirms that mesenchymal stem cells (MSCs) facilitate angiogenesis mainly through paracrine function. Extracellular vesicles (EVs) are regarded as key components of the cell secretome, possessing functional properties of their source cells. Subsequently, MSC-EVs have emerged as a novel cell-free approach to improve fat graft retention rate.

Objectives
The authors sought to provide a systematic review of all studies reporting the utilization of MSC-EVs to improve graft retention rate.

Methods
A systematic search was undertaken employing the Embase, PubMed, and Cochrane Central Register of Controlled Trials databases. Outcome measures included donor/receptor organism of the fat graft, study model, intervention groups, evaluation intervals, EV research data, and in vitro and in vivo results.

Results
Of the total 1717 articles, 62 full texts were screened. Seven studies reporting on 294 mice were included. Overall, EV-treated groups showed higher graft retention rates compared with untreated groups. Notably, retention rate was similar following EV and MSC treatment. In addition to reduced inflammation, graft enrichment with EVs resulted in early revascularization and better graft integrity. Interestingly, hypoxic preconditioning of MSCs improved their beneficial paracrine effects and led to a more proangiogenic EV population, as observed by both in vitro and in vivo results.

Conclusions
MSC-EVs appear to offer an interesting cell-free alternative to improve fat graft survival. Although their clinical relevance remains to be determined, it is clear that not the cells but rather their secretome is essential for graft survival. Thus, a paradigm shift from cell-assisted lipotransfer towards “secretome-assisted lipotransfer” is well on its way.

Level of Evidence: 4
Computational resources for identifying and describing proteins driving liquid–liquid phase separation
Authors: Pancsa Rita , Vranken Wim , Mészáros Bálint 
Published: December 2020

AbstractOne of the most intriguing fields emerging in current molecular biology is the study of membraneless organelles formed via liquid–liquid phase separation (LLPS). These organelles perform crucial functions in cell regulation and signalling, and recent years have also brought about the understanding of the molecular mechanism of their formation. The LLPS field is continuously developing and optimizing dedicated in vitro and in vivo methods to identify and characterize these non-stoichiometric molecular condensates and the proteins able to drive or contribute to LLPS. Building on these observations, several computational tools and resources have emerged in parallel to serve as platforms for the collection, annotation and prediction of membraneless organelle-linked proteins. In this survey, we showcase recent advancements in LLPS bioinformatics, focusing on (i) available databases and ontologies that are necessary to describe the studied phenomena and the experimental results in an unambiguous way and (ii) prediction methods to assess the potential LLPS involvement of proteins. Through hands-on application of these resources on example proteins and representative datasets, we give a practical guide to show how they can be used in conjunction to provide in silico information on LLPS.
Hypergraph-based persistent cohomology (HPC) for molecular representations in drug design
Authors: Liu Xiang , Wang Xiangjun , Wu Jie , Xia Kelin 
Published: December 2020

AbstractArtificial intelligence (AI) based drug design has demonstrated great potential to fundamentally change the pharmaceutical industries. Currently, a key issue in AI-based drug design is efficient transferable molecular descriptors or fingerprints. Here, we present hypergraph-based molecular topological representation, hypergraph-based (weighted) persistent cohomology (HPC/HWPC) and HPC/HWPC-based molecular fingerprints for machine learning models in drug design. Molecular structures and their atomic interactions are highly complicated and pose great challenges for efficient mathematical representations. We develop the first hypergraph-based topological framework to characterize detailed molecular structures and interactions at atomic level. Inspired by the elegant path complex model, hypergraph-based embedded homology and persistent homology have been proposed recently. Based on them, we construct HPC/HWPC, and use them to generate molecular descriptors for learning models in protein–ligand binding affinity prediction, one of the key step in drug design. Our models are tested on three most commonly-used databases, including PDBbind-v2007, PDBbind-v2013 and PDBbind-v2016, and outperform all existing machine learning models with traditional molecular descriptors. Our HPC/HWPC models have demonstrated great potential in AI-based drug design.
Assessment and Simplification of Treatment Eligibility Among Patients With Chronic Hepatitis B Infection in Vietnam
Authors: Vu Hai Vinh , Shimakawa Yusuke , Kim Jin , Do Ngoc Hai , Le Minh Quang , Laureillard Didier , Lemoine Maud 
Published: December 2020

Abstract

Background
Treatment eligibility and the accuracy of its simplified criteria have been poorly documented in patients with chronic hepatitis B virus (HBV) infection worldwide, especially in low- and middle-income countries.

Methods
From a cohort of HBV-infected patients in Vietnam, we assessed the proportion of patients eligible for treatment using the national guidelines based on reference tests (HBV DNA quantification and FibroScan); and the accuracy of simplified treatment criteria free from HBV DNA and FibroScan (Treatment Eligibility in Africa for the Hepatitis B Virus [TREAT-B] score and simplified World Health Organization [WHO] criteria) to select patients for antiviral therapy using the national guidelines as a reference.

Results
We analyzed 400 consecutive treatment-naïve HBV-monoinfected patients: 49% males, median age 38 years (range, 18–86), 32% hepatitis B e antigen-positive, median HBV DNA 4.8 log10 IU/mL (undetectable −8.4), median FibroScan 5.3 kPa (3.0–67.8), and 25% having significant liver fibrosis including 12% with cirrhosis. Of these, 167 (42%) fulfilled treatment criteria according to national guidelines. Using the national criteria as a reference, the performance of TREAT-B to select patients for treatment was high (area under the receiver operating characteristic [AUROC], 0.89 [95% confidence interval 0.87-0.92]) with a sensitivity of 74.3% and a specificity of 88.4%. In a subset of patients with 2 alanine aminotransferase measurements over a 6-month period (n = 89), the AUROC of TREAT-B was significantly higher than that of the simplified WHO criteria (P &lt; .001).

Conclusions
Our study suggests that a large proportion of patients with chronic HBV infection require antiviral therapy in Vietnam. Compared with the simplified WHO criteria free from HBV DNA quantification, TREAT-B is a better alternative to easily indicate treatment eligibility and might help scale up treatment intervention in Vietnam.
Evaluating the Efficacy of Coronavirus Disease 2019 Vaccines
Authors: Lin Dan-Yu , Zeng Donglin , Mehrotra Devan V , Corey Lawrence , Gilbert Peter B 
Published: December 2020

Abstract
A large number of studies are being conducted to evaluate the efficacy and safety of candidate vaccines against coronavirus disease 2019 (COVID-19). Most phase 3 trials have adopted virologically confirmed symptomatic COVID-19 as the primary efficacy end point, although laboratory-confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is also of interest. In addition, it is important to evaluate the effect of vaccination on disease severity. To provide a full picture of vaccine efficacy and make efficient use of available data, we propose using SARS-CoV-2 infection, symptomatic COVID-19, and severe COVID-19 as dual or triple primary end points. We demonstrate the advantages of this strategy through realistic simulation studies. Finally, we show how this approach can provide rigorous interim monitoring of the trials and efficient assessment of the durability of vaccine efficacy.
Steroid hormones in Pacific walrus bones collected over three millennia indicate physiological responses to changes in estimated population size and the environment
Authors: Charapata Patrick , Horstmann Lara , Misarti Nicole 
Published: December 2020

Abstract
The Pacific walrus (Odobenus rosmarus divergens) is an iconic Arctic marine mammal and an important resource to many Alaska Natives. A decrease in sea ice habitat and unknown population numbers has led to concern of the long-term future health of the walrus population. There is currently no clear understanding of how walrus physiology might be affected by a changing Arctic ecosystem. In this study, steroid hormone concentrations (progesterone, testosterone, cortisol and estradiol) were analysed in walrus bones collected during archaeological [3585–200 calendar years before present (BP)], historical [1880–2006 common era (CE)] and modern (2014–2016 CE) time periods, representing ~ 3651 years, to track changes in reproductive activity and cortisol concentrations (biomarker of stress) over time. Our results show that modern walrus samples have similar cortisol concentrations (median = 43.97 ± standard deviation 904.38 ng/g lipid) to archaeological walruses (38.94 ± 296.17 ng/g lipid, P = 0.75). Cortisol concentrations were weakly correlated with a 15-year average September Chukchi Sea ice cover (P = 0.002, 0.02, r2 = 0.09, 0.04, for females and males, respectively), indicating a possible physiological resiliency to sea ice recession in the Arctic. All steroid hormones had significant negative correlations with mean walrus population estimates from 1960 to 2016 (P &lt; 0.001). Progesterone in females and testosterone in males exhibited significant correlations with average September Chukchi Sea ice cover for years 1880–2016 (P &lt; 0.001 for both, r2 = 0.34, 0.22, respectively). Modern walruses had significantly lower (P = &lt; 0.001) reproductive hormone concentrations compared with historic walruses during times of rapid population increase, indicative of a population possibly at carrying capacity. This is the first study to apply bone as a tool to monitor long-term changes in hormones that may be associated with changes in walrus population size and sea ice cover.
The cardiovascular–dialysis nexus: the transition to dialysis is a treacherous time for the heart
Authors: Chan Kevin , Moe Sharon M , Saran Rajiv , Libby Peter 
Published: December 2020

Abstract
Chronic kidney disease (CKD) patients require dialysis to manage the progressive complications of uraemia. Yet, many physicians and patients do not recognize that dialysis initiation, although often necessary, subjects patients to substantial risk for cardiovascular (CV) death. While most recognize CV mortality risk approximately doubles with CKD the new data presented here show that this risk spikes to &gt;20 times higher than the US population average at the initiation of chronic renal replacement therapy, and this elevated CV risk continues through the first 4 months of dialysis. Moreover, this peak reflects how dialysis itself changes the pathophysiology of CV disease and transforms its presentation, progression, and prognosis. This article reviews how dialysis initiation modifies the interpretation of circulating biomarkers, alters the accuracy of CV imaging, and worsens prognosis. We advocate a multidisciplinary approach and outline the issues practitioners should consider to optimize CV care for this unique and vulnerable population during a perilous passage.
Lipoprotein(a), LDL-cholesterol, and hypertension: predictors of the need for aortic valve replacement in familial hypercholesterolaemia
Authors: Pérez de Isla Leopoldo , Watts Gerald F , Alonso Rodrigo , Díaz-Díaz José Luis , Muñiz-Grijalvo Ovidio , Zambón Daniel , Fuentes Francisco , de Andrés Raimundo , Padró Teresa , López-Miranda José , Mata Pedro 
Published: December 2020

Abstract

Aims
Familial hypercholesterolaemia (FH) and elevated lipoprotein(a) [Lp(a)] are inherited disorders associated with premature atherosclerotic cardiovascular disease (ASCVD). Aortic valve stenosis (AVS) is the most prevalent valvular heart disease and low-density lipoprotein cholesterol (LDL-C) and Lp(a) may be involved in its pathobiology. We investigated the frequency and predictors of severe AVS requiring aortic valve replacement (AVR) in molecularly defined patients with FH.

Methods and results
SAFEHEART is a long-term prospective cohort study of a population with FH and non-affected relatives (NAR). We analysed the frequency and predictors of the need for AVR due to AVS in this cohort. Five thousand and twenty-two subjects were enrolled (3712 with FH; 1310 NAR). Fifty patients with FH (1.48%) and 3 NAR (0.27%) required AVR [odds ratio 5.71; 95% confidence interval (CI): 1.78–18.4; P = 0.003] after a mean follow-up of 7.48 (3.75) years. The incidence of AVR was significantly higher in patients with FH (log-rank 5.93; P = 0.015). Cox regression analysis demonstrated an association between FH and AVR (hazard ratio: 3.89; 95% CI: 1.20–12.63; P = 0.024), with older age, previous ASCVD, hypertension, increased LDL-CLp(a)-years, and elevated Lp(a) being independently predictive of an event.

Conclusion
The need for AVR due to AVS is significantly increased in FH patients, particularly in those who are older and have previous ASCVD, hypertension, increased LDL-CLp(a)-years and elevated Lp(a). Reduction in LDL-C and Lp(a) together with control of hypertension could retard the progression of AVS in FH, but this needs testing in clinical trials.
ClinicalTrials.gov number NCT02693548.
Using machine learning to identify local cellular properties that support re-entrant activation in patient-specific models of atrial fibrillation
Authors: Corrado Cesare , Williams Steven , Roney Caroline , Plank Gernot , O’Neill Mark , Niederer Steven 
Published: December 2020

AbstractAimsAtrial fibrillation (AF) is sustained by re-entrant activation patterns. Ablation strategies have been proposed that target regions of tissue that may support re-entrant activation patterns. We aimed to characterize the tissue properties associated with regions that tether re-entrant activation patterns in a validated virtual patient cohort.Methods and resultsAtrial fibrillation patient-specific models (seven paroxysmal and three persistent) were generated and validated against local activation time (LAT) measurements during an S1–S2 pacing protocol from the coronary sinus and high right atrium, respectively. Atrial models were stimulated with burst pacing from three locations in the proximity of each pulmonary vein to initiate re-entrant activation patterns. Five atria exhibited sustained activation patterns for at least 80 s. Models with short maximum action potential durations (APDs) were associated with sustained activation. Phase singularities were mapped across the atria sustained activation patterns. Regions with a low maximum conduction velocity (CV) were associated with tethering of phase singularities. A support vector machine (SVM) was trained on maximum local conduction velocity and action potential duration to identify regions that tether phase singularities. The SVM identified regions of tissue that could support tethering with 91% accuracy. This accuracy increased to 95% when the SVM was also trained on surface area.ConclusionIn a virtual patient cohort, local tissue properties, that can be measured (CV) or estimated (APD; using effective refractory period as a surrogate) clinically, identified regions of tissue that tether phase singularities. Combing CV and APD with atrial surface area further improved the accuracy in identifying regions that tether phase singularities.
Genetic and functional diversity of PsyI/PsyR quorum-sensing system in the Pseudomonas syringae complex
Authors: Morohoshi Tomohiro , Oshima Akinori , Xie Xiaonan , Someya Nobutaka 
Published: December 2020

ABSTRACT
Strains belonging to the Pseudomonas syringae complex often possess quorum-sensing systems that comprise N-acyl-l-homoserine lactone (AHL) synthases (PsyI) and AHL receptors (PsyR). Here, we investigated the diversity of PsyI/PsyR quorum-sensing systems in 630 strains of the P. syringae complex. AHL production was observed in most strains of Pseudomonas amygdali and Pseudomonas meliae, and a few strains of Pseudomonas coronafaciens and P. syringae. The DNA sequences of psyIR and their upstream and downstream regions were categorized into eight types. P. amygdali pv. myricae, Pseudomonas savastanoi, and P. syringae pv. solidagae, maculicola, broussonetiae, and tomato encoded psyI, but did not produce detectable amounts of AHL. In P. savastanoi, an amino acid substitution (R27S) in PsyI caused defective AHL production. The psyI gene of P. syringae pv. tomato was converted to pseudogenes by frameshift mutations. Escherichia coli harboring psyI genes from P. amygdali pv. myricae, P. syringae pv. solidagae and broussonetiae showed high levels of AHL production. Forced expression of functional psyR restored AHL production in P. amygdali pv. myricae and P. syringae pv. solidagae. In conclusion, our study indicates that the PsyI/PsyR quorum-sensing systems in P. syringae strains are genetically and functionally diverse, with diversity being linked to phylogenetic and pathovar classifications.
Identification of a differentiation stall in epithelial mesenchymal transition in histone H3–mutant diffuse midline glioma
Authors: Sanders Lauren M , Cheney Allison , Seninge Lucas , van den Bout Anouk , Chen Marissa , Beale Holly C , Kephart Ellen Towle , Pfeil Jacob , Learned Katrina , Lyle A Geoffrey , Bjork Isabel , Haussler David , Salama Sofie R , Vaske Olena M 
Published: December 2020

Abstract

Background
Diffuse midline gliomas with histone H3 K27M (H3K27M) mutations occur in early childhood and are marked by an invasive phenotype and global decrease in H3K27me3, an epigenetic mark that regulates differentiation and development. H3K27M mutation timing and effect on early embryonic brain development are not fully characterized.

Results
We analyzed multiple publicly available RNA sequencing datasets to identify differentially expressed genes between H3K27M and non-K27M pediatric gliomas. We found that genes involved in the epithelial-mesenchymal transition (EMT) were significantly overrepresented among differentially expressed genes. Overall, the expression of pre-EMT genes was increased in the H3K27M tumors as compared to non-K27M tumors, while the expression of post-EMT genes was decreased. We hypothesized that H3K27M may contribute to gliomagenesis by stalling an EMT required for early brain development, and evaluated this hypothesis by using another publicly available dataset of single-cell and bulk RNA sequencing data from developing cerebral organoids. This analysis revealed similarities between H3K27M tumors and pre-EMT normal brain cells. Finally, a previously published single-cell RNA sequencing dataset of H3K27M and non-K27M gliomas revealed subgroups of cells at different stages of EMT. In particular, H3.1K27M tumors resemble a later EMT stage compared to H3.3K27M tumors.

Conclusions
Our data analyses indicate that this mutation may be associated with a differentiation stall evident from the failure to proceed through the EMT-like developmental processes, and that H3K27M cells preferentially exist in a pre-EMT cell phenotype. This study demonstrates how novel biological insights could be derived from combined analysis of several previously published datasets, highlighting the importance of making genomic data available to the community in a timely manner.
Long-read assembly of the Brassica napus reference genome Darmor-bzh
Authors: Rousseau-Gueutin Mathieu , Belser Caroline , Da Silva Corinne , Richard Gautier , Istace Benjamin , Cruaud Corinne , Falentin Cyril , Boideau Franz , Boutte Julien , Delourme Regine , Deniot Gwenaëlle , Engelen Stefan , de Carvalho Julie Ferreira , Lemainque Arnaud , Maillet Loeiz , Morice Jérôme , Wincker Patrick , Denoeud France , Chèvre Anne-Marie , Aury Jean-Marc 
Published: December 2020

Abstract

Background
The combination of long reads and long-range information to produce genome assemblies is now accepted as a common standard. This strategy not only allows access to the gene catalogue of a given species but also reveals the architecture and organization of chromosomes, including complex regions such as telomeres and centromeres. The Brassica genus is not exempt, and many assemblies based on long reads are now available. The reference genome for Brassica napus, Darmor-bzh, which was published in 2014, was produced using short reads and its contiguity was extremely low compared with current assemblies of the Brassica genus.

Findings
Herein, we report the new long-read assembly of Darmor-bzh genome (Brassica napus) generated by combining long-read sequencing data and optical and genetic maps. Using the PromethION device and 6 flowcells, we generated ∼16 million long reads representing 93× coverage and, more importantly, 6× with reads longer than 100 kb. This ultralong-read dataset allows us to generate one of the most contiguous and complete assemblies of a Brassica genome to date (contig N50 &gt; 10 Mb). In addition, we exploited all the advantages of the nanopore technology to detect modified bases and sequence transcriptomic data using direct RNA to annotate the genome and focus on resistance genes.

Conclusion
Using these cutting-edge technologies, and in particular by relying on all the advantages of the nanopore technology, we provide the most contiguous Brassica napus assembly, a resource that will be valuable to the Brassica community for crop improvement and will facilitate the rapid selection of agronomically important traits.
Aortic remodelling effect of the frozen elephant trunk technique on Stanford type A acute aortic dissection
Authors: Kuroda Yoshinori , Uchida Tetsuro , Ohba Eiichi , Yamashita Atsushi , Nakai Shingo , Kobayashi Kimihiro , Ochiai Tomonori , Sadahiro Mitsuaki 
Published: December 2020

Abstract
Total arch replacement using the frozen elephant trunk procedure is performed for true lumen expansion of the descending aorta in patients with type A acute aortic dissection. However, the remodelling effect of the frozen elephant trunk on the dissected descending aorta is unclear. We aimed to evaluate the effect of the frozen elephant trunk on postoperative descending aortic remodelling after surgery. Between December 2012 and January 2020, we retrospectively investigated 24 patients who underwent total arch replacement using the frozen elephant trunk for type A acute aortic dissection. Remodelling of the descending aorta was evaluated using computed tomography. The aortic remodelling effect, based on aortic true lumen ratio, was determined for (i) DeBakey type (type I versus type III retrograde); (ii) thoracic endovascular aneurysm repair reintervention status (reintervention versus no reintervention); and (iii) stent length of the frozen elephant trunk (60 vs 90 mm). Postoperative true lumen ratio significantly increased in the type I dissection group. The true lumen ratio in the no-reintervention group, which had many patients with the type I dissection, significantly increased after the frozen elephant trunk. Aortic remodelling due to the frozen elephant trunk can be expected after type I acute aortic dissections.