bluuebunny/crossref_metadata_2025_split huggingface dataset:
Tumor Immunity Microenvironment-based classifications of bladder cancer for enhancing cancer immunotherapy
Authors: Meng Jialin , Lu Xiaofan , Zhou Yujie , Zhang Meng , Zhou Jun , Hao Zongyao , Du Yinan , Yan Fangrong , Liang Chaozhao 
Published: August 2020

ABSTRACTBackgroundBladder cancer is composed by a mass of heterogenetic characteristics, immunotherapy is a potential way to save the life of bladder cancer patients, but only benefit to about 20% patients.Methods and materialsA total of 4003 bladder cancer patients from 19 cohorts was enrolled in this study, collecting the clinical information and mRNA expression profile. The unsupervised non-negative matrix factorization (NMF) and nearest template prediction (NTP) algorithm was used to divide the patients to immune activated, immune exhausted and non-immune class. Verified gene sets of signatures were used to illustrate the characteristic of immunophenotypes. Clinical and genetic features were compared in different immunophenotypes.ResultsWe identified the immune class and non-immune classes in from TCGA-BLCA cohort. The 150 top different expression genes between these two classes was extracted as the input profile for the reappearing of the classification in the other 19 cohorts. As to the activated and exhausted subgroups, a stromal activation signature was conducted by NTP algorithm. Patients in the immune classes shown the highly enriched signatures of immunocytes, while the exhausted subgroup also shown an increased signature of TITR, WNT/TGF-β, TGF-β1 activated, and C-ECM signatures. Patients in the immune activated shown a lower CNA burden, better overall survival, and favorable response to anti-PD-1 therapy.ConclusionWe defined and validated a novel classifier among the 4003 bladder cancer patients. Anti-PD-1 immunotherapy could benefit more for the patients belong to immune activated subgroup, while ICB therapy plus TGF-β inhibitor or EP300 inhibitor might be more effectiveness for patients in immune exhausted subgroup.
Generative lesion pattern decomposition of cognitive impairment after stroke
Authors: Bonkhoff Anna K. , Lim Jae-Sung , Bae Hee-Joon , Weaver Nick A. , Kuijf Hugo J. , Biesbroek J. Matthijs , Rost Natalia S. , Bzdok Danilo 
Published: August 2020

SummaryCognitive impairment is a frequent and disabling sequela of stroke. There is however incomplete understanding of how lesion topographies in the left and right cerebral hemisphere brain interact to cause distinct cognitive deficits. We integrated machine learning and Bayesian hierarchical modeling to enable hemisphere-aware analysis of 1080 subacute ischemic stroke patients with deep profiling ∼3 months after stroke. We show relevance of the left hemisphere in the prediction of language and memory assessments, while global cognitive impairments were equally well predicted by lesion topographies from both sides. Damage to the hippocampal and occipital regions on the left were particularly informative about lost naming and memory function. Global cognitive impairment was predominantly linked to lesioned tissue in supramarginal and angular gyrus, the postcentral gyrus as well as the lateral occipital and opercular cortices of the left hemisphere. Hence, our analysis strategy uncovered that lesion patterns with unique hemispheric distributions are characteristic of how cognitive capacity is lost due to ischemic brain tissue damage.
Modular metabolite assembly inC. elegansdepends on carboxylesterases and formation of lysosome-related organelles
Authors: Le Henry H. , Wrobel Chester J. J. , Cohen Sarah M. , Yu Jingfang , Park Heenam , Helf Maximilian J. , Curtis Brian J. , Kruempel Joseph C. , Rodrigues Pedro R. , Hu Patrick J. , Sternberg Paul W. , Schroeder Frank C. 
Published: August 2020

AbstractSignaling molecules derived from attachment of diverse metabolic building blocks to ascarosides play a central role in the life history ofC. elegansand other nematodes; however, many aspects of their biogenesis remain unclear. Using comparative metabolomics, we show that a pathway mediating formation of intestinal lysosome-related organelles (LROs) is required for biosynthesis of most modular ascarosides as well as previously undescribed modular glucosides. Similar to modular ascarosides, the modular glucosides are derived from highly selective assembly of moieties from nucleoside, amino acid, neurotransmitter, and lipid metabolism, suggesting that modular glucosides, like the ascarosides, may serve signaling functions. We further show that carboxylesterases that localize to intestinal organelles are required for the assembly of both modular ascarosides and glucosides via ester and amide linkages. Further exploration of LRO function and carboxylesterase homologs inC. elegansand other animals may reveal additional new compound families and signaling paradigms.Abstract Figure
Intra-exon motif correlations as a proxy measure for mean per-tile sequence quality data in RNA-Seq
Authors: Alnasir Jamie J. , Shanahan Hugh P. 
Published: August 2020

AbstractGiven the wide variability in the quality of NGS data submitted to public repositories, it is essential to identify methods that can perform quality control on these datasets when additional quality control data, such as mean tile data, is missing. This is particularly important because such datasets are routinely deposited in public archives that now store data at an unprecedented scale. In this paper, we show that correlating counts of reads corresponding to pairs of motifs separated over specific distances on individual exons corresponds to mean tile data in the datasets we analysed, and can therefore be used when mean tile data is not available.As test datasets we use theH. sapiensIVT (in-vitrotranscribed) dataset of Lahens et al., and aD. melanogasterdataset comprising wild and mutant types from Aerts et al.Theintra-exonmotif correlations as a function of both GC content parameters are much higher in theIVT-PlasmidsmRNAselection freeRNA-Seq sample (control) than in the other RNA-Seq samples that did undergo mRNA selection: both ribosomal depletion (IVT-Only) and PolyA selection (IVT-polyA, wild-type, and mutant). There is considerable degradation of similar correlations in the mutant samples from theD. melanogasterdataset. This matches with the available mean tile data that has been gathered for these datasets. We observe that extremely low correlations are indicative of bias of technical origin, such as flowcell errors.
THE DYNAMICS OF HISTORICAL AND RECENT RANGE SHIFTS IN THE RUFFED GROUSE (Bonasa umbellus)
Authors: Perktaş Utku 
Published: August 2020

ABSTRACTClimate variability is the most important force affecting distributional range dynamics of common and widespread species with important impacts on biogeographic patterns. This study integrates phylogeography with distributional analyses to understand the demographic history and range dynamics of a widespread bird species, the Ruffed Grouse (Bonasa umbellus), under several climate change scenarios. For this, I used an ecological niche modelling approach, together with Bayesian based phylogeographic analysis and landscape genetics, to develop robust inferences regarding this species’ demographic history and range dynamics. The model’s predictions were mostly congruent with the present distribution of the Ruffed Grouse. However, under the Last Glacial Maximum bioclimatic conditions, the model predicted a substantially narrower distribution than the present. The predictions for the Last Glacial Maximum also showed three allopatric refugia in south-eastern and west-coast North America, and a cryptic refugium in Alaska. The prediction for the Last Interglacial showed two separate distributions to the west and east of the Rocky Mountains. In addition, the predictions for 2050 and 2070 indicated that the Ruffed Grouse will most likely show slight range shifts to the north and will become more widely distributed than in the past or present. At present, effective population connectivity throughout North America was weakly positively correlated with Fstvalues. That is, the species’ distribution range showed a weak isolation-by-resistance pattern. The extended Bayesian Skyline Plot analysis, which provided good resolution of the effective population size changes over the Ruffed Grouse’s history, was mostly congruent with ecological niche modelling predictions for this species. This study offers the first investigation of the late-Quaternary history of the Ruffed Grouse based on ecological niche modelling and Bayesian based demographic analysis. The species’ present genetic structure is significantly affected by past climate changes, particularly during the last 130 kybp. That is, this study offers valuable evidence of the ‘expansion–contraction’ model of North America’s Pleistocene biogeography.
Temporally-Divergent Regulatory Mechanisms Govern Neuronal Development and Diversification in the Neocortex
Authors: Yuan Wen , Ma Sai , Brown Juliana R. , Kim Kwanho , Murek Vanessa , Trastulla Lucia , Meissner Alexander , Lodato Simona , Shetty Ashwin , Levin Joshua Z. , Buenrostro Jason D. , Ziller Michael J. , Arlotta Paola 
Published: August 2020

AbstractMammalian neocortical neurons span one of the most diverse cell type spectra of any tissue. The regulatory strategies that neurons use during progressive development and maturation remain unclear. We present an integrated single-cell epigenomic and transcriptional analysis of individual classes of neurons from both mouse and marmoset neocortex, sampled during both early postmitotic stages of identity acquisition and later stages of neuronal plasticity and circuit integration. We find that in both species, the regulatory strategies controlling these early and late stages diverge: early postmitotic neurons use molecular regulatory programs with broader tissue distribution and greater evolutionary conservation, while programs active during later neuronal maturation implement more brain- and neuron-specific mechanisms showing greater evolutionary divergence. The data uncovers a temporally-regulated shift in regulatory choices, likely reflecting unique evolutionary constraints on distinct events of neuronal development in the neocortex.
Cell intercalation driven by SMAD3 underlies secondary neural tube formation
Authors: Gonzalez-Gobartt Elena , Blanco-Ameijeiras José , Usieto Susana , Allio Guillaume , Benazeraf Bertrand , Martí Elisa 
Published: August 2020

SUMMARYBody axis elongation is a hallmark of the vertebrate embryo, involving the architectural remodelling of the tailbud. Although it is clear how bi-potential neuro-mesodermal progenitors (NMPs) contribute to embryo elongation, the dynamic events that lead tode novolumen formation and that culminate in the formation of a 3-Dimensional, secondary neural tube from NMPs, are poorly understood. Here, we used in vivo imaging of the chicken embryo to show that cell intercalation downstream of TGF-beta/SMAD3 signalling is required for secondary neural tube formation. Our analysis describes the initial events in embryo elongation including lineage restriction, the epithelial-to-mesenchymal transition of NMPs, and the initiation of lumen formation. Importantly, we show that the resolution of a single, centrally positioned continuous lumen, which occurs through the intercalation of central cells, requires SMAD3 activity. We anticipate that these findings will be relevant to understand caudal, skin-covered neural tube defects, amongst the most frequent birth defects detected in humans.HIGHLIGHTS.- Initiation of the lumen formation follows the acquisition of neural identity and epithelial polarization..- Programmed cell death is not required for lumen resolution..- Resolution of a single central lumen requires cell intercalation, driven by Smad3 activity.- The outcome of central cell division preceding cell intercalation, varies along the cranio-caudal axis.
Macrophages provide a transient muscle stem cell niche via NAMPT secretion
Authors: Ratnayake Dhanushika , Nguyen Phong D. , Rossello Fernando J. , Wimmer Verena C. , Isiaku Abdulsalam I. , Galvis Laura A. , Wood Alasdair J. , Julier Ziad , Boudier Thomas , Oorschot Viola , Rogers Kelly L. , Martino Mikaël M. , Marcelle Christophe , Lieschke Graham J. , Bakkers Jeroen , Currie Peter D. 
Published: August 2020

AbstractSkeletal muscle is paradigmatic of a regenerative tissue that repairs itself via the activation of a resident stem cell1. Termed the satellite cell, these normally quiescent cells are induced to proliferate by ill-defined wound-derived signals2. Identifying the source and nature of these pro-regenerative cues has been hampered by an inability to visualise the complex cellular interactions that occur within the wound environment. We therefore developed a zebrafish muscle injury model to systematically capture satellite cell interactions within the injury site, in real time, throughout the repair process. This analysis identified that a specific subset of macrophages ‘dwells’ within the injury, establishing a transient but obligate stem cell niche required for stem cell proliferation. Single cell profiling identified specific signals secreted from dwelling macrophages that include the cytokine, Nicotinamide phosphoribosyltransferase (NAMPT/Visfatin/PBEF). Here we show that NAMPT secretion from the macrophage niche is required for muscle regeneration, acting through the C-C motif chemokine receptor type 5 (CCR5) expressed on muscle stem cells. This analysis reveals that along with their well-described ability to modulate the pro-inflammatory and anti-inflammatory phases of wound repair, specific macrophage populations also provide a transient stem cell-activating niche, directly supplying pro-proliferative cues that govern the timing and rate of muscle stem cell-mediated repair processes.
Meta-transcriptomic discovery of a divergent circovirus and a chaphamaparvovirus in captive reptiles with proliferative respiratory syndrome
Authors: Chang Wei-Shan , Li Ci-Xiu , Hall Jane , Eden John-Sebastian , Hyndman Timothy H. , Holmes Edward C. , Rose Karrie 
Published: August 2020

AbstractViral pathogens are being increasingly described in association with mass morbidity and mortality events in reptiles. However, our knowledge of reptile viruses and their role in population health remains limited. Herein, we describe a meta-transcriptomic investigation of a mass morbidity and mortality event in a colony of central bearded dragons (Pogona vitticeps) in 2014. Severe, extensive proliferation of the respiratory epithelium was consistently found in affected dragons. Similar proliferative lung lesions were identified in bearded dragons from the same colony in 2020 in association with increased intermittent mortality. Total RNA sequencing of bearded dragon tissue identified two divergent DNA viruses: a reptile-infecting circovirus, denoted bearded dragon circovirus (BDCV), and the first exogeneous reptilian chaphamaparvovirus - bearded dragon chaphamaparvovirus (BDchPV). Phylogenetic analysis revealed that BDCV was most closely related to bat-associated circoviruses, exhibiting 70% amino acid sequence identity. In contrast, the newly discovered BDchPV showed approximately 35-40% identity in the non-structural (NS) protein to parvoviruses obtained from tilapia fish and crocodiles in China. Subsequent specific PCR assays detected BDCV exclusively and comprehensively within animals with proliferative pulmonary lesions and respiratory disease. This study expands our understanding of viral diversity in the context of diseased reptiles in captivity.
N-terminus of the third PDZ Domain of PSD-95 Orchestrates Allosteric Communication for Selective Ligand Binding
Authors: Guclu Tandac F. , Kocatug Nazli , Atilgan Ali Rana , Atilgan Canan 
Published: August 2020

AbstractPDZ domains constitute common models to study single domain allostery without significant structural changes. The third PDZ domain of PSD-95 (PDZ3) is known to have selective structural features that confer unique modulatory roles to this unit. In this model system two residues, H372 directly connected to the binding site and G330 holding an off-binding-site position, were designated to assess the effect of mutations on binding selectivity. It has been observed that the H372A and G330T/H372A mutations change ligand preferences from class I (T/S amino acid at position −2 of the ligand) to class II (hydrophobic amino acid at the same position). Alternatively, the G330T single mutation leads to the recognition of both ligand classes. We have performed a series of molecular dynamics (MD) simulations for wild-type, H372A, G330T single mutants and a double mutant of PDZ3 in the absence and presence of both types of ligands. With the combination of free energy difference calculations and a detailed analysis of MD trajectories, ‘class switching’ and ‘class bridging’ behavior of PDZ3 mutants, as well as their effects on ligand selection and binding affinities are explained. We show that the dynamics of the charged N-terminus plays a fundamental role in determining the binding preferences in PDZ3 by altering the electrostatic energy. These findings are corroborated by simulations on N-termini truncated versions of these systems. The dynamical allostery orchestrated by the N-terminus offers a fresh perspective to the study of communication pathways in proteins.
Artificial bee colony–based Kalman filter hybridization for three–dimensional position estimation of a quadrotor
Authors: Kaba Aziz , Kiyak Emre 
Published: August 2020

Purpose
The purpose of this paper is to introduce an artificial bee colony-based Kalman filter algorithm along with an extended objective function to ensure the optimality of the estimator of the quadrotor in the presence of unknown measurement noise statistics.

Design/methodology/approach
Six degree-of-freedom mathematical model of the quadrotor is derived. Position controller for the quadrotor is designed. Kalman filter-based estimation algorithm is implemented in the sensor feedback loop. Artificial bee colony-based hybrid algorithm is used as an optimization method to handle the unknown noise statistics. Existing objective function is extended with a penalty term. Mathematical proof of the extended objective function is derived. Results of the proposed algorithm is compared with de facto genetic algorithm-based Kalman filter.

Findings
Artificial bee colony algorithm-based Kalman filter and extended objective function duo are able to optimize the measurement noise covariance matrix with an absolute error as low as 0.001 [m2]. Proposed method and function is capable of reducing the noise from 2 to 0.09 [m] for x-axis, 3.4 to 0.14 [m] for y-axis and 3.7 to 0.2 [m] for z-axis, respectively.

Originality/value
The motivation behind this paper is to bring a novel optimization-based solution for the estimation problem of the quadrotor when the measurement noise statistics are unknown along with an extended objective function to prevent the infeasible solutions with mathematical convergence analysis.
Does entrepreneurial experience always promote novelty-centered business model design in new venture?
Authors: Wang Lingling , Zhao Wenhong , Wei Zelong , Zhou Changbao 
Published: August 2020

PurposeThis paper aims to explore how intra-industry entrepreneurial experience and failure entrepreneurial experience affect novelty-centered business model design in a new venture. Moreover, the authors also consider whether the contingent value of entrepreneurial experience may differ according to competitive intensity.Design/methodology/approachA survey via questionnaire was conducted with 290 entrepreneurs and top managers from Chinese new ventures that provided the research data. Hierarchical regression analysis was used to test the proposed theoretical hypotheses.FindingsThe empirical results indicate that intra-industry entrepreneurial experience has an inverted U-shaped effect on novelty-centered business model design, whereas failure entrepreneurial experience has a negative effect on novelty-centered business model design. Furthermore, the authors also find that competitive intensity weakens the inverted U-shaped effect of intra-industry entrepreneurial experience on novelty-centered business model design.Originality/valueThis study offers new insights into the effects of intra-industry entrepreneurial experience and failure entrepreneurial experience on novelty-centered business model design and provides useful suggestions for new ventures to promote business model design.
A constraint-based optimization technique for estimating physical parameters of Jiles – Atherton hysteresis model
Authors: Upadhaya Brijesh , Rasilo Paavo , Perkkiö Lauri , Handgruber Paul , Belahcen Anouar , Arkkio Antero 
Published: August 2020

Purpose
Improperly fitted parameters for the Jiles–Atherton (JA) hysteresis model can lead to non-physical hysteresis loops when ferromagnetic materials are simulated. This can be remedied by including a proper physical constraint in the parameter-fitting optimization algorithm. This paper aims to implement the constraint in the meta-heuristic simulated annealing (SA) optimization and Nelder–Mead simplex (NMS) algorithms to find JA model parameters that yield a physical hysteresis loop. The quasi-static B(H)-characteristics of a non-oriented (NO) silicon steel sheet are simulated, using existing measurements from a single sheet tester. Hysteresis loops received from the JA model under modified logistic function and piecewise cubic spline fitted to the average M(H) curve are compared against the measured minor and major hysteresis loops.

Design/methodology/approach
A physical constraint takes into account the anhysteretic susceptibility at the origin. This helps in the optimization decision-making, whether to accept or reject randomly generated parameters at a given iteration step. A combination of global and local heuristic optimization methods is used to determine the parameters of the JA hysteresis model. First, the SA method is applied and after that the NMS method is used in the process.

Findings
The implementation of a physical constraint improves the robustness of the parameter fitting and leads to more physical hysteresis loops. Modeling the anhysteretic magnetization by a spline fitted to the average of a measured major hysteresis loop provides a significantly better fit with the data than using analytical functions for the purpose. The results show that a modified logistic function can be considered a suitable anhysteretic (analytical) function for the NO silicon steel used in this paper. At high magnitude excitations, the average M(H) curve yields the proper fitting with the measured hysteresis loop. However, the parameters valid for the major hysteresis loop do not produce proper fitting for minor hysteresis loops.

Originality/value
The physical constraint is added in the SA and NMS optimization algorithms. The optimization algorithms are taken from the GNU Scientific Library, which is available from the GNU project. The methods described in this paper can be applied to estimate the physical parameters of the JA hysteresis model, particularly for the unidirectional alternating B(H) characteristics of NO silicon steel.