bluuebunny/crossref_metadata_2025_split huggingface dataset:
Fully phased human genome assembly without parental data using single-cell strand sequencing and long reads
Authors:   Human Genome Structural Variation Consortium, Porubsky David , Ebert Peter , Audano Peter A. , Vollger Mitchell R. , Harvey William T. , Marijon Pierre , Ebler Jana , Munson Katherine M. , Sorensen Melanie , Sulovari Arvis , Haukness Marina , Ghareghani Maryam , Lansdorp Peter M. , Paten Benedict , Devine Scott E. , Sanders Ashley D. , Lee Charles , Chaisson Mark J. P. , Korbel Jan O. , Eichler Evan E. , Marschall Tobias 
Published: December 2020

AbstractHuman genomes are typically assembled as consensus sequences that lack information on parental haplotypes. Here we describe a reference-free workflow for diploid de novo genome assembly that combines the chromosome-wide phasing and scaffolding capabilities of single-cell strand sequencing1,2 with continuous long-read or high-fidelity3 sequencing data. Employing this strategy, we produced a completely phased de novo genome assembly for each haplotype of an individual of Puerto Rican descent (HG00733) in the absence of parental data. The assemblies are accurate (quality value > 40) and highly contiguous (contig N50 > 23 Mbp) with low switch error rates (0.17%), providing fully phased single-nucleotide variants, indels and structural variants. A comparison of Oxford Nanopore Technologies and Pacific Biosciences phased assemblies identified 154 regions that are preferential sites of contig breaks, irrespective of sequencing technology or phasing algorithms.
Using phidelta diagrams to discover relevant patterns in multilayer perceptrons
Authors: Armano Giuliano 
Published: December 2020

AbstractUnderstanding the inner behaviour of multilayer perceptrons during and after training is a goal of paramount importance for many researchers worldwide. This article experimentally shows that relevant patterns emerge upon training, which are typically related to the underlying problem difficulty. The occurrence of these patterns is highlighted by means of$$\langle \varphi ,\delta \rangle$$⟨φ,δ⟩diagrams, a 2D graphical tool originally devised to support the work of researchers on classifier performance evaluation and on feature assessment. The underlying assumption being that multilayer perceptrons are powerful engines for feature encoding, hidden layers have been inspected as they were in fact hosting new input features. Interestingly, there are problems that appear difficult if dealt with using a single hidden layer, whereas they turn out to be easier upon the addition of further layers. The experimental findings reported in this article give further support to the standpoint according to which implementing neural architectures with multiple layers may help to boost their generalisation ability. A generic training strategy inspired by some relevant recommendations of deep learning has also been devised. A basic implementation of this strategy has been thoroughly used during the experiments aimed at identifying relevant patterns inside multilayer perceptrons. Further experiments performed in a comparative setting have shown that it could be adopted as viable alternative to the classical backpropagation algorithm.
Targeting macrophage priming by polyphyllin VII triggers anti-tumor immunity via STING-governed cytotoxic T-cell infiltration in lung cancer
Authors: Yu Jinglu , Deng Haibin , Xu Zhenye 
Published: December 2020

AbstractStimulator of interferon genes (STING) controlled innate immune pathway is essential for host defense against pathogenic infection and effective anti-tumor adaptive immunity initiation. Although macrophages transformed across diverse phenotypes play crucial roles in anti-tumor immune response, events determining this transformation and the host-intrinsic role of STING in this process remain controversial. Here we report how STING signaling acts as a key switch to dominate the gene expression patterns of macrophage transformation for promoting priming and releasing immunosuppression. Furthermore, polyphyllin VII, a potential STING agonist, exerts anti-tumor efficacy upon macrophages priming and subsequent cytotoxic T lymphocytes intratumoral infiltration. Meanwhile, the simultaneous PD-L1 amplification on macrophages in response to PP VII is also ruled by STING, thus PP VII may benefit immune-checkpoint blockade therapy for combining. Moreover, PP VII suppresses carcinogenesis upon restraining the immunosuppressed macrophage transformation. This is due to the boosted STING that negatively regulates a STAT3 propagated crosstalk between immune cells and tumor cells. Overall, PP VII-stimulated STING in macrophages provides a paradigm for anti-tumor, and if possible, anti-infection immunotherapy.
Trends of low physical activity among Iranian adolescents across urban and rural areas during 2006–2011
Authors: Amiri Parisa , Naseri Parisa , Vahedi-Notash Golnaz , Jalali-Farahani Sara , Mehrabi Yadollah , Hamzavi-Zarghani Najmeh , Azizi Fereidoun , Hadaegh Farzad , Khalili Davood 
Published: December 2020

AbstractIt is well documented that physical inactivity is related to weight gain and a whole host of chronic diseases. This study investigated trends of low physical activity among Iranian adolescents in urban and rural areas between 2006–2011. A total of 12,178 adolescents, aged between 15 and 19 years, participated in National Surveys of Risk Factors for Non-Communicable Diseases. Data on physical activity was obtained using the global physical activity questionnaire. A complex sample survey and multinomial logistic regression were used to model physical activity levels. The percentage of adolescents who had low levels of physical activity increased from 2006 to 2011 in both urban and rural areas. Low and moderate levels of physical activity were lower in rural girls as compared with urban girls, with a prevalence ratio of 0.59 (95% CI 0.47–0.74) and 0.59 (95% CI 0.47–0.74), respectively. The corresponding values for boys residing in rural areas compared with boys in urban areas were 0.56 (95% CI 0.43–0.75) and 0.60 (95% CI 0.48–0.74), respectively. The adolescents' lifestyles showed an increasing trend for physical inactivity in both genders; however, in rural areas, only girls had a rising affinity for a sedentary lifestyle throughout the 2006–2011 years.
Linear infrastructure habitats increase landscape-scale diversity of plants but not of flower-visiting insects
Authors: Dániel-Ferreira Juliana , Bommarco Riccardo , Wissman Jörgen , Öckinger Erik 
Published: December 2020

AbstractHabitats along linear infrastructure, such as roads and electrical transmission lines, can have high local biodiversity. To determine whether these habitats also contribute to landscape-scale biodiversity, we estimated species richness, evenness and phylogenetic diversity of plant, butterfly and bumblebee communities in 32 4 km2 landscapes with or without power line corridors, and with contrasting areas of road verges. Landscapes with power line corridors had on average six more plant species than landscapes without power lines, but there was no such effect for butterflies and bumblebees. Plant communities displayed considerable evenness in species abundances both in landscapes with and without power lines and high and low road verge densities. We hypothesize that the higher number of plant species in landscapes with power line corridors is due to these landscapes having a higher extinction debt than the landscapes without power line corridors, such that plant diversity is declining slower in landscapes with power lines. This calls for targeted conservation actions in semi-natural grasslands within landscapes with power line corridors to maintain biodiversity and prevent imminent population extinctions.
Impedance analysis of adherent cells after in situ electroporation-mediated delivery of bioactive proteins, DNA and nanoparticles in µL-volumes
Authors: Stolwijk Judith A. , Wegener Joachim 
Published: December 2020

AbstractSpecific intracellular manipulation of animal cells is a persistent goal in experimental cell biology. Such manipulations allow precise and targeted interference with signaling cascades, metabolic pathways, or bi-molecular interactions for subsequent tracking of functional consequences. However, most biomolecules capable of molecular recognition are membrane impermeable. The ability to introduce these molecules into the cytoplasm and then to apply appropriate readouts to monitor the corresponding cell response could prove to be an important research tool. This study describes such an experimental approach combining in situ electroporation (ISE) as a means to efficiently deliver biomolecules to the cytoplasm with an impedance-based, time-resolved analysis of cell status using electric cell-substrate impedance sensing (ECIS). In this approach, gold-film electrodes, deposited on the bottom of regular culture dishes, are used for both electroporation and monitoring. The design of the electrode layout and measurement chamber allows working with sample volumes as small as 10 µL. A miniaturized setup for combined electroporation and impedance sensing (µISE-ECIS) was applied to load different adherent cells with bioactive macromolecules including enzymes, antibodies, nucleic acids and quantum dot nanoparticles. The cell response after loading the cytoplasm with RNase A or cytochrome c (in the presence or absence of caspase inhibitors) was tracked by non-invasive impedance readings in real-time.
Personalized quantification of facial normality: a machine learning approach
Authors: Boyaci Osman , Serpedin Erchin , Stotland Mitchell A. 
Published: December 2020

AbstractWhat is a normal face? A fundamental task for the facial reconstructive surgeon is to answer that question as it pertains to any given individual. Accordingly, it would be important to be able to place the facial appearance of a patient with congenital or acquired deformity numerically along their own continuum of normality, and to measure any surgical changes against such a personalized benchmark. This has not previously been possible. We have solved this problem by designing a computerized model that produces realistic, normalized versions of any given facial image, and objectively measures the perceptual distance between the raw and normalized facial image pair. The model is able to faithfully predict human scoring of facial normality. We believe this work represents a paradigm shift in the assessment of the human face, holding great promise for development as an objective tool for surgical planning, patient education, and as a means for clinical outcome measurement.
Post-operative fracture risk assessment following tumor curettage in the distal femur: a hybrid in vitro and in silico biomechanical approach
Authors: Ghouchani Azadeh , Rouhi Gholamreza , Ebrahimzadeh Mohammad Hosein 
Published: December 2020

AbstractThe distal femur is the predominant site for benign bone tumours and a common site for fracture following tumour removal or cementation. However, the lack of conclusive assessment criterion for post-operative fracture risk and appropriate devices for cement augmentation are serious concerns. Hence, a validated biomechanical tool was developed to assess bone strength, depending on the size and location of artificially created tumorous defects in the distal femora. The mechanics of the bone–cement interface was investigated to determine the main causes of reconstruction failure. Based on quantitative-CT images, non-linear and heterogeneous finite element (FE) models of human cadaveric distal femora with simulated tumourous defects were created and validated using in vitro mechanical tests from 14 cadaveric samples. Statistical analyses demonstrated a strong linear relationship (R2 = 0.95, slope = 1.12) with no significant difference between bone strengths predicted by in silico analyses and in vitro tests (P = 0.174). FE analyses showed little reduction in bone strength until the defect was 35% or more of epiphyseal volume, and reduction in bone strength was less pronounced for laterally located defects than medial side defects. Moreover, the proximal end of the cortical window and the most interior wall of the bone–cement interface were the most vulnerable sites for reconstruction failure.
The effect of acute exercise on interleukin-6 and hypothalamic–pituitary–adrenal axis responses in patients with coronary artery disease
Authors: Mahmood Zeid , Davidsson Anette , Olsson Eva , Leanderson Per , Lundberg Anna K. , Jonasson Lena 
Published: December 2020

AbstractVulnerability to stress-induced inflammation has been linked to a dysfunctional hypothalamus–pituitary–adrenal (HPA) axis. In the present study, patients with known or suspected coronary artery disease (CAD) were assessed with respect to inflammatory and HPA axis response to acute physical exercise. An exercise stress test was combined with SPECT myocardial perfusion imaging. Plasma and saliva samples were collected before and 30 min after exercise. Interleukin (IL)-6 and adrenocorticotropic hormone (ACTH) were measured in plasma, while cortisol was measured in both plasma and saliva. In total, 124 patients were included of whom 29% had a prior history of CAD and/or a myocardial perfusion deficit. The levels of exercise intensity and duration were comparable in CAD and non-CAD patients. However, in CAD patients, IL-6 increased after exercise (p = 0.019) while no differences were seen in HPA axis variables. Conversely, patients without CAD exhibited increased levels of ACTH (p = 0.003) and cortisol (p = 0.004 in plasma, p = 0.006 in saliva), but no change in IL-6. We conclude that the IL-6 response to acute physical exercise is exaggerated in CAD patients and may be out of balance due to HPA axis hypoactivity. It remains to be further investigated whether this imbalance is a potential diagnostic and therapeutic target in CAD.
Optimization of one-parameter family of integration formulae for solving stiff chemical-kinetic ODEs
Authors: Morii Youhi , Shima Eiji 
Published: December 2020

AbstractA fast and robust Jacobian-free time-integration method—called Minimum-error Adaptation of a Chemical-Kinetic ODE Solver (MACKS)—for solving stiff ODEs pertaining to chemical-kinetics is proposed herein. The MACKS formulation is based on optimization of the one-parameter family of integration formulae coupled with a dual time-stepping method to facilitate error minimization. The proposed method demonstrates higher accuracy compared to the method—Extended Robustness-enhanced numerical algorithm (ERENA)—previously proposed by the authors. Additionally, when this method is employed in homogeneous-ignition simulations, it facilitates realization of faster performance compared to CVODE.
Degree difference: a simple measure to characterize structural heterogeneity in complex networks
Authors: Farzam Amirhossein , Samal Areejit , Jost Jürgen 
Published: December 2020

AbstractDespite the growing interest in characterizing the local geometry leading to the global topology of networks, our understanding of the local structure of complex networks, especially real-world networks, is still incomplete. Here, we analyze a simple, elegant yet underexplored measure, ‘degree difference’ (DD) between vertices of an edge, to understand the local network geometry. We describe the connection between DD and global assortativity of the network from both formal and conceptual perspective, and show that DD can reveal structural properties that are not obtained from other such measures in network science. Typically, edges with different DD play different structural roles and the DD distribution is an important network signature. Notably, DD is the basic unit of assortativity. We provide an explanation as to why DD can characterize structural heterogeneity in mixing patterns unlike global assortativity and local node assortativity. By analyzing synthetic and real networks, we show that DD distribution can be used to distinguish between different types of networks including those networks that cannot be easily distinguished using degree sequence and global assortativity. Moreover, we show DD to be an indicator for topological robustness of scale-free networks. Overall, DD is a local measure that is simple to define, easy to evaluate, and that reveals structural properties of networks not readily seen from other measures.
Metabolism and pharmacokinetics of a novel polyphenol fatty acid ester phloridzin docosahexaenoate in Balb/c female mice
Authors: Fernando Wasundara , Goralski Kerry B. , Hoskin David W. , Rupasinghe H. P. Vasantha 
Published: December 2020

AbstractFlavonoids are known to undergo phase II metabolism and produce metabolites with similar or stronger biological effects compared to the parent flavonoids. However, the limited cellular uptake and bioavailability restrict their clinical use. We synthesized phloridzin docosahexaenoate (PZ-DHA), a novel fatty acid ester of polyphenol, through an acylation reaction with the aim of increasing the cellular availability and stability of the parent biomolecules, phloridzin (PZ) and docosahexaenoic acid (DHA). Here, we report metabolites and pharmacokinetic parameters of PZ-DHA, determined using ultra-high-performance liquid chromatography-electrospray ionization tandem mass spectrometry. PZ-DHA was taken-up by human (MDA-MB-231, MDA-MB-468, and MCF-7) and mouse (4T1) mammary carcinoma and human non-malignant mammary epithelial cells (MCF-10A) in cellular uptake assays. Our results suggested that the acylation improves the cellular uptake of PZ and stability of DHA within cells. In mouse hepatic microsomal assays, two major glucuronides of PZ-DHA, PZ-DHA-4-O-glucuronide and PZ-DHA-4′-O-glucuronide (MW = 923.02 g/mol), were detected. One tri-methylated- (4,4′,6′-O-trimethyl-PZ-DHA) (MW = 788.88 g/mol) and one di-sulphated- (PZ-DHA-4,4′-O-disulphide) PZ-DHA metabolite (MW = 906.20 g/mol) were also identified. Intraperitoneal injections of PZ-DHA (100 mg/kg) into Balb/c female mice was rapidly absorbed with a serum Cmax and Tmax of 23.7 µM and 60 min, respectively, and rapidly eliminated (t1/2 = 28.7 min). PZ-DHA and its metabolites are readily distributed throughout the body (Vd = 57 mL) into many organs. We identified in vitro and in vivo metabolites of PZ-DHA, which could be tested for potential use to treat diseases such as cancer in multiple organ systems.
Impact of bleeding during dual antiplatelet therapy in patients with coronary artery disease
Authors: Tung Ying-Chang , See Lai-Chu , Chang Shu-Hao , Liu Jia-Rou , Kuo Chi-Tai , Chang Chi-Jen 
Published: December 2020

AbstractThis nationwide retrospective cohort study used the National Health Insurance Research Database of Taiwan to compare the impact of bleeding on clinical outcomes in patients with acute myocardial infarction (AMI) versus chronic coronary syndrome (CCS). Between July 2007 and December 2010, patients with AMI (n = 15,391) and CCS (n = 19,724) who received dual antiplatelet therapy after coronary stenting were identified from the database. AMI was associated with increased risks of MI (AMI vs. CCS: 0.38 vs. 0.16 per 100 patient-months; p < 0.01), all-cause death (0.49 vs. 0.32 per 100 patient-months; p < 0.01), and BARC type 3 bleeding (0.22 vs. 0.13 per 100 patient-months; p < 0.01) at 1 year compared with CCS, while the risk of BARC type 2 bleeding was marginally higher in the CCS patients than in the AMI patients (1.32 vs. 1.4 per 100 person-months; p = 0.06). Bleeding was an independent predictor of MI, stroke, and all-cause death in this East Asian population, regardless of the initial presentation. Among the patients with bleeding, AMI was associated with a higher risk of ischemic events at 1 year after bleeding compared with CCS (MI: 0.34 vs. 0.25 per 100 patient-months; p = 0.06; ischemic stroke: 0.22 vs. 0.13 per 100 patient-months; p = 0.02). The 1-year mortality after bleeding was comparable between the two groups after propensity score weighting. In conclusion, bleeding conferred an increased risk of adverse outcomes in East Asian patients with AMI and CCS.
The Habc domain of syntaxin 3 is a ubiquitin binding domain
Authors: Giovannone Adrian J. , Reales Elena , Bhattaram Pallavi , Nackeeran Sirpi , Monahan Adam B. , Syed Rashid , Weimbs Thomas 
Published: December 2020

AbstractSyntaxins are a family of membrane-anchored SNARE proteins that are essential components required for membrane fusion in eukaryotic intracellular membrane trafficking pathways. Syntaxins contain an N-terminal regulatory domain, termed the Habc domain that is not highly conserved at the primary sequence level but folds into a three-helix bundle that is structurally conserved among family members. The syntaxin Habc domain has previously been found to be structurally very similar to the GAT domain present in GGA family members and related proteins that are otherwise completely unrelated to syntaxins. Because the GAT domain has been found to be a ubiquitin binding domain we hypothesized that the Habc domain of syntaxins may also bind to ubiquitin. Here, we report that the Habc domain of syntaxin 3 (Stx3) indeed binds to monomeric ubiquitin with low affinity. This domain binds efficiently to K63-linked poly-ubiquitin chains within a narrow range of chain lengths but not to K48-linked poly-ubiquitin chains. Other syntaxin family members also bind to K63-linked poly-ubiquitin chains but with different chain length specificities. Molecular modeling suggests that residues of the GGA3-GAT domain known to be important for ionic and hydrophobic interactions with ubiquitin may have equivalent, conserved residues within the Habc domain of Stx3. We conclude that the syntaxin Habc domain and the GAT domain are both structurally and functionally related, and likely share a common ancestry despite sequence divergence. Binding of Ubiquitin to the Habc domain may regulate the function of syntaxins in membrane fusion or may suggest additional functions of this protein family.
Menstrual blood-derived stromal cells modulate functional properties of mouse and human macrophages
Authors: Martínez-Aguilar Rocío , Romero-Pinedo Salvador , Ruiz-Magaña M. José , Olivares Enrique G. , Ruiz-Ruiz Carmen , Abadía-Molina Ana C. 
Published: December 2020

AbstractMenstrual blood-derived stromal cells (MenSCs) are emerging as a strong candidate for cell-based therapies due to their immunomodulatory properties. However, their direct impact on innate immune populations remains elusive. Since macrophages play a key role in the onset and development of inflammation, understanding MenSCs implication in the functional properties of these cells is required to refine their clinical effects during the treatment of inflammatory disorders. In this study, we assessed the effects that MenSCs had on the recruitment of macrophages and other innate immune cells in two mouse models of acute inflammation, a thioglycollate (TGC)-elicited peritonitis model and a monobacterial sepsis model. We found that, in the TGC model, MenSCs injection reduced the percentage of macrophages recruited to the peritoneum and promoted the generation of peritoneal immune cell aggregates. In the sepsis model, MenSCs exacerbated infection by diminishing the recruitment of macrophages and neutrophils to the site of infection and inducing defective bacterial clearance. Additional in vitro studies confirmed that co-culture with MenSCs impaired macrophage bactericidal properties, affecting bacterial killing and the production of reactive oxygen intermediates. Our findings suggest that MenSCs modulate the macrophage population and that this modulation must be taken into consideration when it comes to future clinical applications.