bluuebunny/crossref_metadata_2025_split huggingface dataset:
Systematic discovery of gene fusions in pediatric cancer by integrating RNA-seq and WGS
Authors: van Belzen Ianthe A.E.M. , Cai Casey , van Tuil Marc , Badloe Shashi , Strengman Eric , Janse Alex , Verwiel Eugène T. , van der Leest Douwe F.M. , Kester Lennart , Molenaar Jan J. , Meijerink Jules , Drost Jarno , Peng Weng Chuan , Kerstens Hinri H.D. , Tops Bastiaan B.J. , Holstege Frank C.P. , Kemmeren Patrick , Hehir-Kwa Jayne Y. 
Published: September 2021

AbstractBackgroundGene fusions are important cancer drivers in pediatric cancer and their accurate detection is essential for diagnosis and treatment. Clinical decision-making requires high confidence and precision of detection. Recent developments show RNA sequencing (RNA-seq) is promising for genome-wide detection of fusion products, but hindered by many false positives that require extensive manual curation and impede discovery of pathogenic fusions.ResultsWe developed Fusion-sq to detect tumor-specific gene fusions by integrating and “fusing” evidence from RNA-seq and whole genome sequencing (WGS) using intron-exon gene structure. In a pediatric pan-cancer cohort of 130 patients, we identified 165 high confidence tumor-specific gene fusions and their underlying structural variants (SVs). This includes all clinically relevant fusions known to be present in this cohort (30 patients). Fusion-sq distinguishes healthy-occurring from tumor-specific fusions, and resolves fusions in amplified regions and copy number unstable genomes. A high gene fusion burden is associated with copy number instability. We identified 27 potentially pathogenic fusions involving oncogenes or tumor-suppressor genes characterised by underlying SVs or expression changes indicative of activating or disruptive effects.ConclusionsOur results indicate how clinically relevant and potentially pathogenic gene fusions can be identified and their functional effects investigated by combining WGS and RNA-seq. Integrating RNA fusion predictions with underlying SVs advances fusion detection beyond extensive manual filtering. Taken together, we developed a method for identifying candidate fusions that is suitable for precision oncology applications. Our method provides multi-omics evidence for assessing the pathogenicity of tumor-specific fusions for future clinical decision making.
The cause of on-target point mutations generated by CRISPR-Cas9 treatment in the yeast Xanthophyllomyces dendrorhous
Authors: Hong Jixuan , Meng Ziyue , Zhang Zixi , Su Hang , Fan Yuxuan , Huang Ruilin , Ding Ruirui , Zhang Ning , Li Fuli , Wang Shi’an 
Published: September 2021

ABSTRACTRecognizing outcomes of DNA repair induced by CRISPR-Cas9 cutting is vital for precise genome editing. Reported DNA repair outcomes after Cas9 cutting include deletions/insertions and low frequency of genomic rearrangements and nucleotide substitutions. Thus far, substitution mutations caused by CRISPR-Cas9 has not attracted much attention. Here, we identified on-target point mutations induced by CRISPR-Cas9 treatment in the yeast Xanthophyllomyces dendrorhous by Sanger and Illumina sequencing. Different from previous studies, our findings suggested that the on-target mutations are not random and they cannot render the gRNA effective. Moreover, these point mutations showed strong sequence dependence that is not consistent with the observations in Hela cells, in which CRISPR-mediated substitutions were considered lacking sequence dependence and conversion preferences. Furthermore, this study demonstrated that the NHEJ components Ku70, Ku80, Mre11, or RAD50, and the overlapping roles of non-essential DNA polymerases were necessary for the emergence of point mutations, increasing the knowledge on CRISPR-Cas9 mediated DNA repair.
Stability of spectral estimates in resting-state magnetoencephalography: recommendations for minimal data duration with neuroanatomical specificity
Authors: Wiesman Alex I. , Castanheira Jason Da Silva , Baillet Sylvain 
Published: September 2021

AbstractThe principle of resting-state paradigms is appealing and practical for collecting data from impaired patients and special populations, especially if data collection times can be minimized. To achieve this goal, researchers need to ensure estimated signal features of interest are robust. In electro- and magnetoencephalography (EEG, MEG) we are not aware of studies of the minimal length of recording required to yield a robust one-session snapshot of the frequency-spectrum derivatives that are typically used to characterize the complex dynamics of the brain’s resting-state. We aimed to fill this knowledge gap by studying the stability of common spectral measures of resting-state MEG source time series obtained from large samples of single-session recordings from shared data repositories featuring different recording conditions and instrument technologies (OMEGA: N = 107; Cam-CAN: N = 50). We discovered that the rhythmic and arrhythmic spectral properties of intrinsic brain activity can be robustly estimated in most cortical regions when derived from relatively short recordings of 30-s to 120-s of resting-state data, regardless of instrument technology and resting-state paradigm. Using an adapted leave-one-out approach and Bayesian analysis, we also provide evidence that the stability of spectral features over time is unaffected by age, sex, handedness, and general cognitive function. In summary, short MEG sessions are sufficient to yield robust estimates of frequency-defined brain activity during resting-state. This study may help guide future empirical designs in the field, particularly when recording times need to be minimized, such as with patient or special populations.
“IL1B loss is associated with increased AR activity in castration-resistant prostate cancer”
Authors: Awadallah Wisam N. , Nanda Jagpreet S. , Kohrt Sarah E. , Grabowska Magdalena M. 
Published: September 2021

AbstractCastration-resistant prostate cancer represents a continuum of phenotypes, including tumors with high levels of androgen receptor (AR) expression and activity and those which do not express AR and rely on alternative pathways for survival. The process by which AR-positive prostate cancer cells and tumors lose AR expression and acquire neuroendocrine features is referred to as neuroendocrine differentiation. Numerous therapies and exposures have been demonstrated to induce neuroendocrine differentiation in vitro, including the pro-inflammatory cytokine, interleukin 1 beta (IL-1β), encoded by the gene IL1B. The purpose of our studies was to determine the relationship between the expression and activity of AR in relationship to IL-1β and IL1B in prostate cancer. We performed analysis of de-identified human clinical data and generated prostate cancer cell lines with overexpression or knockout of IL1B. In primary prostate cancer, higher expression of IL1B predicts longer time to biochemical recurrence. In metastatic castration-resistant prostate cancer, IL1B expression is decreased and inversely correlates with AR and AR-target gene expression and AR activity, while positively correlating with the neuroendocrine prostate cancer (NEPC) score and neuroendocrine marker gene expression. In vitro, we report that AR-positive castration-resistant prostate cancer cells (C4-2B, 22Rv1) secrete IL-1β, and knockout of IL1B in these cells results in increased AR activity, in the presence and absence of dihydrotestosterone (DHT). Importantly, knockout of IL1B prevented AR attrition during androgen-deprivation. Taken together, our studies demonstrate that loss of IL1B in AR-positive castration-resistant prostate cancer cells can increase and maintain AR activity in the absence of androgens, suggesting another potential mechanism of high AR activity in castration-resistant prostate cancer.
Quantifying charge state heterogeneity for proteins with multiple ionizable residues
Authors: Fossat Martin J. , Posey Ammon E. , Pappu Rohit V. 
Published: September 2021

ABSTRACTIonizable residues can release and take up protons and this has an influence on protein structure and function. The extent of protonation is linked to the overall pH of the solution and the local environments of ionizable residues. Binding or unbinding of a single proton generates a distinct charge microstate defined by a specific pattern of charges. Accordingly, the overall partition function is a sum over all charge microstates and Boltzmann weights of all conformations associated with each of the charge microstates. This ensemble-of-ensembles description recast as aq-canonical ensemble allows us to analyze and interpret potentiometric titrations that provide information regarding net charge as a function of pH. In theq-canonical ensemble, charge microstates are grouped into mesostates where each mesostate is a collection of microstates of the same net charge. Here, we show that leveraging the structure of theq-canonical ensemble allows us to decouple contributions of net proton binding and release from proton arrangement and conformational considerations. Through application of theq-canonical formalism to analyze potentiometric measurements of net charge in proteins with repetitive patterns of Lys and Glu residues, we are able to determine the underlying mesostate pKavalues and, more importantly, we estimate relative mesostate populations as a function of pH. This is a strength of using theq-canonical approach and cannot be obtained using purely site-specific analyses. Overall, our work shows how measurements of charge equilibria, decoupled from measurements of conformational equilibria, and analyzed using the framework of theq-canonical ensemble, provide protein-specific quantitative descriptions of pH-dependent populations of mesostates. This method is of direct relevance for measuring and understanding how different charge states contribute to conformational, binding, and phase equilibria of proteins.STATEMENT OF SIGNIFICANCEThe net charge of a protein in solution is governed by the overall pH as well as context and conformational contexts. Measurements of net charge are accessible via techniques such as potentiometry that quantify the buffering capacity of a protein solution. Here, we use the formal structure of theq-canonical ensemble to identify charge states that are compatible with a measured net charge profile as a function of pH. Our approach highlights how measurements of charge, decoupled from measurements of conformation, can be used to identify the ensembles of charge states that contribute to the overall population for given solution conditions. The methods introduced will be useful for measuring charge states and interpreting these measurements in different contexts.
Molecular determinants of the modulation of the VSD-PD coupling mechanism of the KV7.1 channel by the KCNE1 ancillary subunits
Authors: Kongmeneck Audrey Deyawe , Kasimova Marina A. , Tarek Mounir 
Published: September 2021

AbstractThe IKS current is diffused through the plasma membranes of cardiomyocytes during the last phase of the cardiac action potential. This repolarization current is conducted by a tetrameric protein complex derived from the co-expression of four voltage-gated potassium channel KV7.1 α-subunits and KCNE1 ancillary subunits from KCNQ1 and KCNE1 genes, respectively. We studied here the conformational space of KV7.1 in presence and absence of KCNE1, by building transmembrane models of their known Resting, Intermediate, and Activated states. We conducted Molecular Dynamics simulations of these models in lipid bilayers including the phosphatidyl-inositol-4,5-bisphosphate (PIP2) lipids. The comparative analysis of MD trajectories obtained for the KV7.1 and IKS models reveals how KCNE1 shifts the coupling mechanism between the activation state of the Voltage Sensor Domain of the channel and the conformation (open or closed) of its Pore Domain.
The Correlation Between Cell and Nucleus Size is Explained by an Eukaryotic Cell Growth Model
Authors: Wu Yufei , Janmey Paul , Sun Sean X. 
Published: September 2021

AbstractIn eukaryotes, the cell volume is observed to be strongly correlated with the nuclear volume. The slope of this correlation depends on the cell type, growth condition, and the physical environment of the cell. We develop a computational model of cell growth and proteome increase, incorporating the kinetics of amino acid import, protein/ribosome synthesis and degradation, and active transport of proteins between the cytoplasm and the nucleoplasm. We also include a simple model of ribosome biogenesis and assembly. Results show that the cell volume is tightly correlated with the nuclear volume, and the cytoplasm-nucleoplasm transport rates strongly influences the cell growth rate as well as the cytoplasm/nucleoplasm ratio. Ribosome assembly and the ratio of ribosomal proteins to mature ribosomes also influence the cell volume and the cell growth rate. We find that in order to regulate the cell growth rate and the cytoplasm/nucleoplasm ratio, the cell must optimally control groups of kinetic parameters together, which could explain the quantitative roles of canonical growth pathways. Finally, using an extension of our model and single cell RNAseq data, it is possible to construct a detailed proteome distribution, provided that a quantitative cell division mechanism is known.Author summaryWe develop computational model of cell proteome increase and cell growth to compute the cell volume to nuclear volume ratio. The model incorporates essential kinetics of protein and ribosome synthesis/degradation, and their transport across the nuclear envelope. The model also incorporates ribosome biogenesis and assembly. The model identifies the most important parameters in determining the cell growth rate and the nucleoplasm/cytoplasm ratio, and provides a computational starting point to construct the cell proteome based on the RNAseq data.
Corrosion mechanism and fatigue behavior of 2A70-T6 aluminum alloy under alternating corrosion and fatigue
Authors: Fu Lei , Li Hui , Lin Li , Wang Qingyuan , Fan Qi , Huang Xinjie , Li XiuLan , Lai Sheng , Chen Lifei 
Published: September 2021

Purpose
Most supersonic aircraft were manufactured using 2A70 aluminum alloy. The purpose of this paper is to study the corrosion mechanism and fatigue behavior of an aircraft in a semi-industrial atmospheric corrosive environment, alternating effects of corrosion and fatigue were used to simulate the aircraft’s ground parking corrosion and air flight fatigue.

Design/methodology/approach
For this purpose, the aluminum alloy samples were subjected to pre-corrosion and alternating corrosion-fatigue experiments. The failure mechanisms of corrosion and corrosion fatigue were analyzed using microscopic characterization methods of electrochemical testing, X-ray diffraction and scanning electron microscopy. Miner’s linear cumulative damage rule was used to predict the fatigue life of aluminum alloy and to obtain its safe fatigue life.

Findings
The results showed that the corrosion damage caused by the corrosive environment was gradually connected by pitting pits to form denudation pits along grain boundaries. The deep excavation of chloride ions and the presence of intergranular copper-rich phases result in severe intergranular corrosion morphology. During cyclic loading, alternating hardening and softening occurred. The stress concentration caused by surface pitting pits and denudation pits initiated fatigue cracks at intergranular corrosion products. At the same time, the initiation of multiple fatigue crack sources was caused by the corrosion environment and the morphology of the transient fracture zone was also changed, but the crack propagation rate was not basically affected. The polarization curve and impedance analysis results showed that the corrosion rate increases first, decreases and then increases. Fatigue failure behavior was directly related to micro characteristics such as corrosion pits and microcracks.

Originality/value
In this research, alternating effects of corrosion and fatigue were used to simulate the aircraft’s ground parking corrosion and air flight fatigue. To study the corrosion mechanism and fatigue behavior of an aircraft in a semi-industrial atmospheric corrosive environment, the Miner’s linear cumulative damage rule was used to predict the fatigue life of aluminum alloy and to obtain its safe fatigue life.
Information seeking for coping with cancer: a systematic review
Authors: Petersen Emil , Jensen Jesper Gabs , Frandsen Tove Faber 
Published: September 2021

PurposeInformation seeking can be used to make sense of a situation or solve a problem. Information seeking can be considered a coping strategy when facing illness, crisis or other life-changing events. Cancer is a globally occurring, life-threatening disease, and this review aims to provide an overview of the existing literature on the active information seeking behaviour of cancer patients specifically focussing on how active information seeking serves as a coping strategy.Design/methodology/approachThis study adheres to current guidelines for conducting systematic reviews and consequently, thorough literature searches were conducted in four databases: Medline, Embase, CINAHL and Scopus which resulted in 7,179 publications. Following a careful screening process, this systematic review identifies 14 studies on the use of information seeking to cope with cancer.FindingsThe included studies consist of both qualitative and quantitative approaches to analysing the use of information seeking to cope with cancer. The included studies have focussed primarily on demographic factors, the impact of affect, information needs, sources and coping strategies.Research limitations/implicationsA number of research gaps within library and information science are identified. Bringing research in this field into information science could allow for a greater understanding of information literacy, the use of existing information and the process of information searching when using information seeking to cope with serious illness.Originality/valueThis systematic review focusses on how information seeking serves as a coping strategy for cancer patients and provides an overview of the recent literature.
Automation in Colombia: assessing skills needed for the future of work
Authors: Jones Michael , Idrovo-Carlier Sandra , Rodriguez Alfredo J. 
Published: September 2021

PurposeThe purpose of this paper is to identify workforce skills that protect an occupation from elimination due to automation technology.Design/methodology/approachThe authors apply a Gaussian process (GP) classifier, based on the level of non-automatable work activities in an occupation, to USA and Colombian occupational datasets.FindingsThe authors find that communication, interpersonal relationship management and decision-making skills are most important in occupations that are resistant to automation.Research limitations/implicationsThe results are based on work activities data from the Occupational Information Network (O*NET) database developed for the USA labor market. This dataset does not capture significant differences in work activities, where they exist, for the same occupation between the two countries. The findings are also limited to Colombia. Readers should be careful to extrapolate the findings outside of this geography.Originality/valueThe authors discover that automation is likely to be a global phenomenon that can only be slightly mitigated by cultural and political factors.
Moderated mediation between work–life conflict and employee turnover intentions: the role of job dissatisfaction and workplace social support
Authors: Shakoor Arsalan , Haider Sajid , Akhtar Muhammad Hanif , Asadullah Muhammad Ali 
Published: September 2021

PurposeThe purpose of this study was to examine a moderated mediation model of job dissatisfaction and workplace social support in the relationship between work–life conflict and turnover intentions.Design/methodology/approachData were collected in a cross-sectional survey of 220 police investigation officers. Partial least squares structural equation modeling was applied for data analysis.FindingsEmpirical findings of study indicate that work–life conflict enhances employee turnover intentions by creating job dissatisfaction. However, workplace social support buffers this effect and reduces turnover intentions by weakening the effect of work–life conflict on job dissatisfaction.Research limitations/implicationsThis study contributes to personnel management and organizational psychology literature by explaining how workplace social support can affect the mediating process of job dissatisfaction through which the relationship between work–life conflict and turnover intentions is determined. The limitations are related to external validity, single source data and cross-sectional nature of data.Practical implicationsOrganizational leaders and practitioners can take insights from the findings of this study that if workplace social support prevails at a level greater than work–life conflict, it will nullify or suppress the effect of work–life conflict on turnover intentions by reducing job dissatisfaction.Originality/valueThe originality value of this study is that it has addressed the scarcity of testing boundary conditions of the indirect effect of work–life conflict on turnover intentions through job dissatisfaction.
Pro softball fan segments: a two-step cluster analysis
Authors: Mumcu Ceyda , Lough Nancy 
Published: September 2021

PurposeNiche sports such as women's professional sport leagues face many challenges to developing and expanding their fan base. Understanding sport fans, segmenting consumer bases and targeting them effectively can assist in both developing the fan base and competing for investments like sponsorships and media rights. The purpose of this study was to explore consumer segments of the National Pro Fastpitch (NPF), a niche softball league, by identifying demographic and psychographic characteristics of the segments and developing a persona for each segment.Design/methodology/approachData were collected from 3,463 NPF consumers with the assistance of NPF league officials using their social media outlets. A two-step cluster analysis was performed employing both categorical and continuous variables to inform the segmentation, which was followed with chi-squared statistics and two MANOVAs to compare the segments' demographic characteristics, points of attachment (POAs) levels and attendance and viewership of NPF games.FindingsThree distinct consumer segments with unique demographic, POA and softball participation characteristics were identified. Differences among these segments' consumption of NPF games validated the existence of three distinct consumer segments.Originality/valueThis research is the first to examine consumer behavior in women's softball, and it expands the sport marketing literature through the identification of consumer segments of a niche sport league with a novel cluster analysis. Blending theory and practice by incorporating both demographic and psychographic variables into market segmentation, the research uniquely serves this niche sport and thereby informs improved marketing practice.