bluuebunny/crossref_metadata_2025_split huggingface dataset:
Comparison of Microfat, Nanofat, and Extracellular Matrix/Stromal Vascular Fraction Gel for Skin Rejuvenation: Basic Research and Clinical Applications
Authors: Yang Zhibin , Jin Shengyang , He Yu , Zhang Xinyu , Han Xuefeng , Li Facheng 
Published: January 2021

Abstract

Background
Over the past 2 decades, fat grafting has been extensively applied in the field of tissue regeneration.

Objectives
The aim of this study was to investigate the therapeutic potential of microfat, nanofat, and extracellular matrix/stromal vascular fraction gel (SVF-gel) in skin rejuvenation.

Methods
Microfat was harvested by a cannula with multiple 0.8-mm smooth side holes and processed with a fat stirrer to remove fibers. Nanofat and SVF-gel were prepared according to previously reported methods, and their structure and viability were evaluated. Then, SVF cells from the 3 types of samples were isolated and characterized, and the cell viability was compared.

Results
The microstructure of the 3 samples showed distinct differences. The microfat group showed a diameter of 100 to 120.0 μm under the microscope and presented a botryoid shape under calcein acetoxymethyl (calcein-AM)/propidium iodide staining. Scanning electron microscopy analysis showed that the microfat maintained an integral histologic structure. In the nanofat group, no viable adipocytes and no normal histologic structure were observed, but high levels of free lipids were noted. The SVF-gel group showed uniform dispersion of cells with different sizes and parts of the adipose histologic structure. Cell count and culture revealed that the number of viable SVF cells decreased distinctly in the nanofat group compared with the microfat group. In contrast, the number of viable SVF cells in the SVF-gel group increased moderately. Clinical applications with microfat showed marked improvements in skin wrinkles.

Conclusions
Microfat can preserve the integrity of the histologic structure and presents the advantages of subcutaneous volumetric restoration and improvement of skin quality in skin rejuvenation compared with the nanofat and SVF-gel.

Level of Evidence: 5
Machine learning for phytopathology: from the molecular scale towards the network scale
Authors: Wang Yansu , Zhou Murong , Zou Quan , Xu Lei 
Published: January 2021

Abstract
With the increasing volume of high-throughput sequencing data from a variety of omics techniques in the field of plant–pathogen interactions, sorting, retrieving, processing and visualizing biological information have become a great challenge. Within the explosion of data, machine learning offers powerful tools to process these complex omics data by various algorithms, such as Bayesian reasoning, support vector machine and random forest. Here, we introduce the basic frameworks of machine learning in dissecting plant–pathogen interactions and discuss the applications and advances of machine learning in plant–pathogen interactions from molecular to network biology, including the prediction of pathogen effectors, plant disease resistance protein monitoring and the discovery of protein–protein networks. The aim of this review is to provide a summary of advances in plant defense and pathogen infection and to indicate the important developments of machine learning in phytopathology.
Detecting high-scoring local alignments in pangenome graphs
Authors: Schulz Tizian , Wittler Roland , Rahmann Sven , Hach Faraz , Stoye Jens 
Published: January 2021

Abstract

Motivation
Increasing amounts of individual genomes sequenced per species motivate the usage of pangenomic approaches. Pangenomes may be represented as graphical structures, e.g. compacted colored de Bruijn graphs, which offer a low memory usage and facilitate reference-free sequence comparisons. While sequence-to-graph mapping to graphical pangenomes has been studied for some time, no local alignment search tool in the vein of BLAST has been proposed yet.

Results
We present a new heuristic method to find maximum scoring local alignments of a DNA query sequence to a pangenome represented as a compacted colored de Bruijn graph. Our approach additionally allows a comparison of similarity among sequences within the pangenome. We show that local alignment scores follow an exponential-tail distribution similar to BLAST scores, and we discuss how to estimate its parameters to separate local alignments representing sequence homology from spurious findings. An implementation of our method is presented, and its performance and usability are shown. Our approach scales sublinearly in running time and memory usage with respect to the number of genomes under consideration. This is an advantage over classical methods that do not make use of sequence similarity within the pangenome.

Availability and implementation
Source code and test data are available from https://gitlab.ub.uni-bielefeld.de/gi/plast.

Supplementary information
Supplementary data are available at Bioinformatics online.
Five Steps to Inject Transformative Change into the Post-2020 Global Biodiversity Framework
Authors: Grumbine R Edward , Xu Jianchu 
Published: January 2021

Abstract
Accelerating declines in biodiversity and unmet targets in the Convention on Biological Diversity's 2010–2020 Strategic Plan for Biodiversity are stimulating widespread calls for transformative change. Such change includes societal transitions toward sustainability, as well as in specific content of the CBD's draft Post-2020 Global Biodiversity Framework. We summarize research on transformative change and its links to biodiversity conservation, and discuss how it may influence the work of the CBD. We identify five steps to inject transformative change into the design and implementation of a new post-2020 framework: Pay attention to lessons learned from transitions research, plan for climate change, reframe area-based conservation, scale up biodiversity mainstreaming, and increase resources. These actions will transform the very nature of work under the CBD; a convention based on voluntary implementation by countries and facilitated by international administrators and experts must now accommodate a broader range of participants including businesses, Indigenous peoples, and multiple nonstate actors.
Information enhanced model selection for Gaussian graphical model with application to metabolomic data
Authors: Zhou Jie , Hoen Anne G , Mcritchie Susan , Pathmasiri Wimal , Viles Weston D , Nguyen Quang P , Madan Juliette C , Dade Erika , Karagas Margaret R , Gui Jiang 
Published: January 2021

SummaryIn light of the low signal-to-noise nature of many large biological data sets, we propose a novel method to learn the structure of association networks using Gaussian graphical models combined with prior knowledge. Our strategy includes two parts. In the first part, we propose a model selection criterion called structural Bayesian information criterion, in which the prior structure is modeled and incorporated into Bayesian information criterion. It is shown that the popular extended Bayesian information criterion is a special case of structural Bayesian information criterion. In the second part, we propose a two-step algorithm to construct the candidate model pool. The algorithm is data-driven and the prior structure is embedded into the candidate model automatically. Theoretical investigation shows that under some mild conditions structural Bayesian information criterion is a consistent model selection criterion for high-dimensional Gaussian graphical model. Simulation studies validate the superiority of the proposed algorithm over the existing ones and show the robustness to the model misspecification. Application to relative concentration data from infant feces collected from subjects enrolled in a large molecular epidemiological cohort study validates that metabolic pathway involvement is a statistically significant factor for the conditional dependence between metabolites. Furthermore, new relationships among metabolites are discovered which can not be identified by the conventional methods of pathway analysis. Some of them have been widely recognized in biological literature.
Detection of asymptomatic carotid stenosis in patients with lower-extremity arterial disease: development and external validations of a risk score
Authors: Poorthuis M H F , Morris D R , de Borst G J , Bots M L , Greving J P , Visseren F L J , Sherliker P , Clack R , Clarke R , Lewington S , Bulbulia R , Halliday A 
Published: January 2021

Abstract

Background
Recommendations for screening patients with lower-extremity arterial disease (LEAD) to detect asymptomatic carotid stenosis (ACS) are conflicting. Prediction models might identify patients at high risk of ACS, possibly allowing targeted screening to improve preventive therapy and compliance.

Methods
A systematic search for prediction models for at least 50 per cent ACS in patients with LEAD was conducted. A prediction model in screened patients from the USA with an ankle : brachial pressure index of 0.9 or less was subsequently developed, and assessed for discrimination and calibration. External validation was performed in two independent cohorts, from the UK and the Netherlands.

Results
After screening 4907 studies, no previously published prediction models were found. For development of a new model, data for 112 117 patients were used, of whom 6354 (5.7 per cent) had at least 50 per cent ACS and 2801 (2.5 per cent) had at least 70 per cent ACS. Age, sex, smoking status, history of hypercholesterolaemia, stroke/transient ischaemic attack, coronary heart disease and measured systolic BP were predictors of ACS. The model discrimination had an area under the receiver operating characteristic (AUROC) curve of 0.71 (95 per cent c.i. 0.71 to 0.72) for at least 50 per cent ACS and 0.73 (0.72 to 0.73) for at least 70 per cent ACS. Screening the 20 per cent of patients at greatest risk detected 12.4 per cent with at least 50 per cent ACS (number needed to screen (NNS) 8] and 5.8 per cent with at least 70 per cent ACS (NNS 17). This yielded 44.2 and 46.9 per cent of patients with at least 50 and 70 per cent ACS respectively. External validation showed reliable discrimination and adequate calibration.

Conclusion
The present risk score can predict significant ACS in patients with LEAD. This approach may inform targeted screening of high-risk individuals to enhance the detection of ACS.
An update on the role of anti-IL-12/IL23 agents in the management of inflammatory bowel disease
Authors: Nigam Gaurav B , Limdi Jimmy K 
Published: January 2021

AbstractIntroductionThe aim of treatment in inflammatory bowel disease (IBD) is to control symptoms and suppress gut inflammation with minimal systemic side effects. A large proportion of patients are either primary non-responders or lose response to currently licensed therapies. The development of monoclonal antibodies, blocking interleukin (IL)-12 and IL-23 pathways are a promising therapeutic advance. We review the data on IL12/23 inhibitors and emerging data on IL-23 inhibition in IBD treatment.Sources of dataThis review is based on data published in peer-reviewed journals and clinical trials registry.Areas of agreementUstekinumab is currently approved for managing corticosteroid and biologic refractory IBD patients with a favourable safety profile.Areas of controversyDespite a growing therapeutic armamentarium and convergence on the role of biological therapies in patients with greater disease severity, there remains considerable uncertainty with selection and positioning of treatment.Growing pointsEfficacy data from clinical trials and a growing body of real-world data have established a role for IL12/23 inhibitor Ustekinumab in IBD. There is resurgent interest in IL-23 specificity and the potential for incremental benefit. The potential for IL-22 to act as a biomarker for IL-23 inhibitors has exciting implications for personalized medicine.Areas timely for developing researchHead-to-head trials exploring efficacy and combination with other biologics with the potential for synergistic benefit are under investigation. Results of phase 3 trials with IL-23 inhibitors incorporating clinical, biochemical and endoscopic parameters and also exploring biomarkers as predictors of response are urgently needed.
Evidence that autosomal recessive spastic cerebral palsy-1 (CPSQ1) is caused by a missense variant in HPDL
Authors: Morgan Neil V , Yngvadottir Bryndis , O’Driscoll Mary , Clark Graeme R , Walsh Diana , Martin Ezequiel , Tee Louise , Reid Evan , Titheradge Hannah L , Maher Eamonn R 
Published: January 2021

Abstract
A subset of individuals diagnosed with cerebral palsy will have an underlying genetic diagnosis. Previously, a missense variant in GAD1 was described as a candidate mutation in a single family diagnosed with autosomal recessive spastic cerebral palsy-1 (CPSQ1; OMIM 603513). Following the ascertainment of a further branch of the CPSQ1 kindred, we found that the previously reported GAD1 variant did not segregate with the neurological disease phenotype in the recently ascertained branch of the kindred. Following genetic linkage studies to map autozygous regions and whole-exome sequencing, a missense variant (c.527 T &gt; C; p. Leu176Pro, rs773333490) in the HPDL gene was detected and found to segregate with disease status in both branches of the kindred. HPDL encodes a 371-amino acid protein (4-Hydroxyphenylpyruvate Dioxygenase Like) that localizes to mitochondria but whose function is uncertain. Recently, biallelic loss of function variants and missense substitution-causing variants in HPDL were reported to cause a childhood onset progressive spastic movement disorder with a variable presentation. These findings suggest that HPDL-related neurological disease may mimic spastic cerebral palsy and that GAD1 should not be included in diagnostic gene panels for inherited cerebral palsy.
Brain Gene Expression Pattern Correlated with the Differential Brain Activation by Pain and Touch in Humans
Authors: Tang Jie , Su Qian , Zhang Xue , Qin Wen , Liu Huaigui , Liang Meng , Yu Chunshui 
Published: January 2021

Abstract
Genes involved in pain and touch sensations have been studied extensively, but very few studies have tried to link them with neural activities in the brain. Here, we aimed to identify genes preferentially correlated to painful activation patterns by linking the spatial patterns of gene expression of Allen Human Brain Atlas with the pain-elicited neural responses in the human brain, with a parallel, control analysis for identification of genes preferentially correlated to tactile activation patterns. We identified 1828 genes whose expression patterns preferentially correlated to painful activation patterns and 411 genes whose expression patterns preferentially correlated to tactile activation pattern at the cortical level. In contrast to the enrichment for astrocyte and inhibitory synaptic transmission of genes preferentially correlated to tactile activation, the genes preferentially correlated to painful activation were mainly enriched for neuron and opioid- and addiction-related pathways and showed significant overlap with pain-related genes identified in previous studies. These findings not only provide important evidence for the differential genetic architectures of specific brain activation patterns elicited by painful and tactile stimuli but also validate a new approach to studying pain- and touch-related genes more directly from the perspective of neural responses in the human brain.
Spatial concentration of manufacturing industries in the United States: re-examination of long-run trends
Authors: Crafts Nicholas , Klein Alexander 
Published: January 2021

Abstract
We re-examine the long-run geographical development of US manufacturing industries using recent advances in spatial concentration measures. We construct spatially weighted indices of the geographical concentration between 1880 and 2007 taking into account industrial structure and checkerboard problem. New results emerge. Average spatial concentration was much lower in the late 20th than in the late 19th century, and it was the outcome of a continuing reduction over time. Spatial concentration did not increase in the early 20th century but declined, and we find no inverted-U shape pattern of long-run spatial concentration. The persistent tendency to greater spatial dispersion was characteristic of most industries.
Lipoprotein(a) is associated with large artery atherosclerosis stroke aetiology and stroke recurrence among patients below the age of 60 years: results from the BIOSIGNAL study
Authors: Arnold Markus , Schweizer Juliane , Nakas Christos T , Schütz Valerie , Westphal Laura P , Inauen Corinne , Pokorny Thomas , Luft Andreas , Leichtle Alexander , Arnold Marcel , Bicvic Antonela , Fischer Urs , De Marchis Gian Marco , Bonati Leo H , Müller Mandy D , Kahles Timo , Nedeltchev Krassen , Cereda Carlo W , Kägi Georg , Bustamante Alejandro , Montaner Joan , Ntaios George , Foerch Christian , Spanaus Katharina , von Eckardstein Arnold , Katan Mira 
Published: January 2021

Abstract

Aims
Lipoprotein(a) [Lp(a)] is a recognized causal risk factor for atherosclerotic cardiovascular disease but its role for acute ischaemic stroke (AIS) is controversial. In this study, we evaluated the association of Lp(a) with large artery atherosclerosis (LAA) stroke and risk of recurrent cerebrovascular events in AIS patients.

Methods and results
For this analysis of the prospective, observational, multicentre BIOSIGNAL cohort study we measured Lp(a) levels in plasma samples of 1733 primarily Caucasian (98.6%) AIS patients, collected within 24 h after symptom onset. Primary outcomes were LAA stroke aetiology and recurrent cerebrovascular events (ischaemic stroke or transient ischaemic attack) within 1 year. We showed that Lp(a) levels are independently associated with LAA stroke aetiology [adjusted odds ratio 1.48, 95% confidence interval (CI) 1.14-1.90, per unit log10Lp(a) increase] and identified age as a potent effect modifier (Pinteraction =0.031) of this association. The adjusted odds ratio for LAA stroke in patients aged &lt;60 years was 3.64 (95% CI 1.76–7.52) per unit log10Lp(a) increase and 4.04 (95% CI 1.73–9.43) using the established cut-off ≥100 nmol/l. For 152 recurrent cerebrovascular events, we did not find a significant association in the whole cohort. However, Lp(a) levels ≥100 nmol/l were associated with an increased risk for recurrent events among patients who were either &lt;60 years [adjusted hazard ratio (HR) 2.40, 95% CI 1.05–5.47], had evident LAA stroke aetiology (adjusted HR 2.18, 95% CI 1.08–4.40), or had no known atrial fibrillation (adjusted HR 1.60, 95% CI 1.03–2.48).

Conclusion
Elevated Lp(a) was independently associated with LAA stroke aetiology and risk of recurrent cerebrovascular events among primarily Caucasian individuals aged &lt;60 years or with evident arteriosclerotic disease.
Individual Tree and Stand Level Influences on the Growth, Vigor, and Decline of Red Oaks in the Ozarks
Authors: Voelker Steven L. , Muzika Rose-Marie , Guyette Richard P. 
Published: January 2021

Abstract
Repeated oak decline and mortality events have occurred in the Ozark region for decades and probably longer. We sampled an age sequence of 1,259 black and scarlet oaks (Quercus velutina Lam. and Quercus coccinea Muench.) to better describe the process of oak decline and mortality in the red oak group (subgenera Erythrobalanus). Trend in basal area increment (BAI) over the most recent 40 years was used to establish three vigor classes for trees with decreasing, stable, or increasing growth (Declining, Stable, or Healthy). We compared crown condition measures with absolute BAI and boundary line BAI, a measure of radial growth adjusted for tree size. A pulse of mortality was found to occur just subsequent to the most recent drought, although decline often started decades previously. Time series of individual tree BAI suggests that half of all oak decline events were incited by one or two drought-related step-changes in growth and variance. Predisposing factors to decline generally showed significant but weak relationships with crown conditions. Surviving oaks growing in high-mortality stands had poorer crown conditions and grew more slowly than trees in low-mortality stands. When recently dead trees were accounted for, the same high-mortality stands had significantly greater predecline basal area and stocking than low-mortality stands. Thus, a less competitive growth environment may afford some buffer to drought stress before oak decline but does not appear to help afflicted stands improve their growth and vigor.
A cohort ofCaenorhabditisspecies lacking the highly conservedlet-7microRNA
Authors: Nelson Charles , Ambros Victor 
Published: January 2021

AbstractThe let-7 gene encodes a highly conserved microRNA with critical functions integral to cell fate specification and developmental progression in diverse animals. In Caenorhabditis elegans, let-7 is a component of the heterochronic (developmental timing) gene regulatory network, and loss-of-function mutations of let-7 result in lethality during the larval to adult transition due to misregulation of the conserved let-7 target, lin-41. To date, no bilaterian animal lacking let-7 has been characterized. In this study, we identify a cohort of nematode species within the genus Caenorhabditis, closely related to C. elegans, that lack the let-7 microRNA, owing to absence of the let-7 gene. Using Caenorhabditis sulstoni as a representative let-7-lacking species to characterize normal larval development in the absence of let-7, we demonstrate that, except for the lack of let-7, the heterochronic gene network is otherwise functionally conserved. We also report that species lacking let-7 contain a group of divergent let-7 paralogs—also known as the let-7-family of microRNAs—that have apparently assumed the role of targeting the LIN-41 mRNA.
The fission yeast S-phase cyclin Cig2 can drive mitosis
Authors: Pickering Mary , Magner Mira , Keifenheim Dan , Rhind Nicholas 
Published: January 2021

AbstractCommitment to mitosis is regulated by cyclin-dependent kinase (CDK) activity. In the fission yeast Schizosaccharomyces pombe, the major B-type cyclin, Cdc13, is necessary and sufficient to drive mitotic entry. Furthermore, Cdc13 is also sufficient to drive S phase, demonstrating that a single cyclin can regulate alternating rounds of replication and mitosis, and providing the foundation of the quantitative model of CDK function. It has been assumed that Cig2, a B-type cyclin expressed only during S phase and incapable of driving mitosis in wild-type cells, was specialized for S-phase regulation. Here, we show that Cig2 is capable of driving mitosis. Cig2/CDK activity drives mitotic catastrophe—lethal mitosis in inviably small cells—in cells that lack CDK inhibition by tyrosine-phosphorylation. Moreover, Cig2/CDK can drive mitosis in the absence of Cdc13/CDK activity and constitutive expression of Cig2 can rescue loss of Cdc13 activity. These results demonstrate that in fission yeast, not only can the presumptive M-phase cyclin drive S phase, but the presumptive S-phase cyclin can drive M phase, further supporting the quantitative model of CDK function. Furthermore, these results provide an explanation, previously proposed on the basis of computational analyses, for the surprising observation that cells expressing a single-chain Cdc13-Cdc2 CDK do not require Y15 phosphorylation for viability. Their viability is due to the fact that in such cells, which lack Cig2/CDK complexes, Cdc13/CDK activity is unable to drive mitotic catastrophe.