bluuebunny/crossref_metadata_2025_split huggingface dataset:
Relative Importance of Various Inflammatory Markers and Their Critical Thresholds for COVID-19 Mortality
Authors: Budhiraja Sandeep , Indrayan Abhaya , Das Poonam , Dewan Arun , Singh Omender , Nangia Vivek , Singh Y P , Pandey Rajesh , Gupta Ajay Kumar , Gupta Manish , Bhasin Deepak , Uniyal Bhupesh , Mathur Mohit , Pawar Mayur 
Published: December 2021

ABSTRACTBackgroundVarious inflammatory markers are commonly assessed in many patients to help in the management of COVID-19 patients. It is not clear, though, how much risk of mortality their different levels of elevations entail, and which marker signifies more risk than others and how much. This study was undertaken to describe their levels and to answer these questions regarding eight inflammatory markers, namely, CRP, D-dimer, ferritin, IL-6, LDH, CPK, troponin-I.MethodsThe data were retrieved from the electronic records of 19852 CoViD-19 patients admitted to a chain of hospitals in north India from March 2020 to July 2021. Levels for most markers were available for more than 10,000 patients. In view of widely different ranges of values of different markers, we divided their values into quintiles (Qs) and studied the pattern of mortality and for running the logistic regression. In addition, logarithm transformation was also tried. The statistical distribution of the values was compared by Mann-Whitney test. Relative importance was judged by the mortality rates, area under the ROC curves (AUROCs), and the odds ratios.ResultsAlthough the mortality increased with decreasing ALC and increasing level of all the other markers, more than 70% survived even with levels in the extreme quintile. The adjusted odds ratio was the highest (7.62) for the Q5 levels of IL-6, closely followed by D-dimer (OR = 6.04). The AUROC was the highest (0.817) for LDH and the least (0.612) for CPK. However, the optimal cut-off for any marker could correctly classify not more than 80% deaths and the multivariable logistic regression could correctly classify patients with mortality in less than 24% cases.ConclusionAlthough elevated levels of all the markers and low values of ALC were significant risk factor but no firm evidence was available for any of the eight markers to be a major indicator of the mortality in COVID-19 unless they reach to a critical threshold. Among those studied, D-Dimer (>192 ng/mL) followed by IL-6 (>4.5 pg/mL) had stronger association with mortality even with moderate and higher end of the normal levels and LDH (>433 U/L) and troponin-I (>0.002ng/mL) with only steeply increased levels. Ferritin had modest association, and CPK, CRP and ALC were a relatively poor risk of mortality.
Applying Benford’s law to COVID-19 data: The case of the European Union
Authors: Kolias Pavlos 
Published: December 2021

AbstractPrevious studies have used Benford’s distribution to assess whether there is misreporting of COVID-19 cases and deaths. Data inaccuracies provide false information to the media, undermine global response, and hinder the preventive measures taken by countries worldwide. In this study, daily new cases and deaths from all the countries of the European Union were analyzed and the conformance to Benford’s distribution was estimated. For each country, two statistical tests and two measures of deviation were calculated to determine whether the reported statistics comply with the expected distribution. Four country-level developmental indexes were also included, the GDP per capita, health expenditures, the Universal Health Coverage index, and the full vaccination rate. Regression analysis was implemented to show whether the deviation from Benford’s distribution is affected by the aforementioned indexes. The findings indicate that four countries were in line with the expected distribution, Bulgaria, Croatia, Lithuania, and Romania. For the daily cases, Denmark, Greece, and Ireland, showed the greatest deviation from Benford’s distribution and for deaths, Malta, Cyprus, Greece, Italy, and Luxemburg exhibited the highest deviation from Benford’s law. Furthermore, it was found that the vaccination rate is positively associated with deviation from Benford’s distribution. These results suggest that overall, official data provided by authorities are not confirming Benford’s law, yet this approach is not conclusive; it acts as a preliminary tool for data verification. More extensive studies should be made with a more thorough investigation of countries that showed the greatest deviation.
Selection on modifiers of genetic architecture under migration load
Authors: Proulx Stephen R. , Teotónio Henrique 
Published: December 2021

AbstractGene flow between populations adapting to differing local environmental conditions might be costly because individuals can disperse to habitats where their survival is low or because they can reproduce with locally maladapted individuals. The amount by which the mean relative population fitness is kept below one creates an opportunity for modifiers of the genetic architecture to spread due to selection. Prior work that separately considered modifiers changing dispersal, recombination rates, or altering dominance or epistasis, has typically focused on the direction of selection rather than its absolute magnitude. We here develop methods to determine the strength of selection on modifiers of the genetic architecture, including modifiers of the dispersal rate, in populations that have previously evolved local adaptation. We consider scenarios with up to five loci contributing to local adaptation and derive a new model for the deterministic spread of modifiers. We find that selection for modifiers of epistasis and dominance is stronger than selection for decreased recombination, and that selection for partial reductions in recombination are extremely weak, regardless of the number of loci contributing to local adaptation. The spread of modifiers that reduce dispersal depends on the number of loci, epistasis and extent of local adaptation in the ancestral population. We identify a novel effect, that modifiers of dominance are more strongly selected when they are unlinked to the locus that they modify. These findings help explain population differentiation and reproductive isolation and provide a benchmark to compare selection on modifiers under finite population sizes and demographic stochasticity.Author SummaryWhen populations of a species are spread over different habitats the populations can adapt to their local conditions, provided dispersal between habitats is low enough. Natural selection allows the populations to maintain local adaptation, but dispersal and gene flow create a cost called the migration load. The migration load measures how much fitness is lost because of dispersal between different habitats, and also creates an opportunity for selection to act on the arrangement and interaction between genes that are involved in local adaptation. Modifier genes can spread in these linked populations and cause functional, local adaptation genes, to become more closely linked on a chromosome, or change the way that these genes are expressed so that the locally adapted gene copy becomes dominant. We modeled this process and found that selection on modifiers that create tighter linkage between locally adapted genes is generally weak, and modifiers that cause gene interactions are more strongly selected. Even after these gene interactions have begun to evolve, further selection for increased gene interaction is still strong. Our results show that populations are more likely to adapt to local conditions by evolving new gene interactions than by evolving tightly linked gene clusters.
Cell-type specific neuromodulation of excitatory and inhibitory neurons via muscarinic acetylcholine receptors in layer 4 of rat barrel cortex
Authors: Qi Guanxiao , Feldmeyer Dirk 
Published: December 2021

AbstractThe neuromodulator acetylcholine (ACh) plays an important role in arousal, attention, vigilance, learning and memory. ACh is released during different behavioural states and affects the brain microcircuit by regulating neuronal and synaptic properties. Here, we investigated how a low concentration of ACh (30 µM) affects the intrinsic properties of electrophysiologically and morphologically identified excitatory and inhibitory neurons in layer 4 (L4) of rat barrel cortex. ACh altered the membrane potential of L4 neurons in a heterogeneous manner. Nearly all L4 regular spiking (RS) neurons responded to bath-application of ACh with a M4 muscarinic ACh receptor-mediated hyperpolarisation. In contrast, in the majority of L4 fast spiking (FS) and non-fast spiking (nFS) interneurons 30 µM ACh induced a depolarisation while the remainder showed a hyperpolarisation or no response. The ACh-induced depolarisation of L4 FS interneurons was much weaker than that in L4 nFS interneurons. There was no clear difference in the response to ACh for three morphological subtypes of L4 FS interneurons. However, in four morpho-electrophysiological subtypes of L4 nFS interneurons, VIP+-like interneurons showed the strongest ACh-induced depolarisation; occasionally, even action potential (AP) firing was elicited. The ACh-induced depolarisation in L4 FS interneurons was exclusively mediated by M1 muscarinic ACh receptors; in L4 nFS interneurons it was mainly mediated by M1 and/or M3/5 muscarinic ACh receptors. In a subset of L4 nFS interneurons, a co-operative activation of nicotinic ACh receptors was also observed. The present study demonstrates that low-concentrations of ACh affect the different L4 neurons types in a cell-type specific way. These effects result from a specific expression of different muscarinic and/or nicotinic ACh receptors on the somatodendritic compartments of L4 neurons. This suggests that even at low concentrations ACh may tune the excitability of L4 excitatory and inhibitory neurons and their synaptic microcircuits differentially depending on the behavioural state during which ACh is released.
Terpene volatiles mediates the chemical basis of blueberry aroma and consumer acceptability
Authors: Ferrão Luis Felipe V. , Sater Haley , Lyrene Paul , Amadeu Rodrigo R. , Sims Charlie , Tieman Denise , Munoz Patricio R. 
Published: December 2021

AbstractAmong the main features treasured by blueberry consumers, flavor is the most important. Human perception of food flavors can primarily be divided into two main sensory inputs, taste and aroma. Through retronasal olfaction, a group of metabolites called volatile organic compounds (VOCs) emitted from the fruit are able to produce the sensation of aroma, creating the myriad of flavors experienced during our life. In blueberry, breeders have noticed some genotypes with unique floral and sweet flavor notes that, ultimately, enhance human aroma perception. Despite the importance, both the understanding of which chemicals are mediating this variation across phenotypes and the potential impact on consumer preferences remains largely unknown. In this study we dissected the main components underlying blueberry aroma and associated it with consumer predilections by paring metabolomics with sensory analysis. Our contribution in this study is four-fold: (i) first, based on a representative blueberry germplasm cultivated at the University of Florida, we differentiated genotypes with floral and sweet aromatic notes and confirmed that such unique characteristics are preferred by consumers; (ii) at the chemical level, we showed that a group of eight terpene volatiles constitute the primary metabolic group associated with aroma sensation; (iii) we demonstrated that aromatic genotypes can be classified using information from a group of a few key volatiles; and finally, (iv) we combined pedigree and metabolomic information in a single predictive framework and showed the importance of metabolomic data for flavor-assisted selection. For the blueberry community, our findings open new venues to explore flavor. Broadly, we present an emerging view about flavor and provide a detailed blueprint of how this target could be addressed in fruits and vegetables.
OX40 agonism enhances efficacy of PD-L1 checkpoint blockade by shifting the cytotoxic T cell differentiation spectrum
Authors: Beyrend Guillaume , van der Sluis Tetje C. , van der Gracht Esmé T.I. , Abdelaal Tamim , Jochems Simon P. , Belderbos Robert A. , Wesselink Thomas H. , van Duikeren Suzanne , van Haften Floortje J. , Redeker Anke , Nejad Elham Beyranvand , Camps Marcel , Franken Kees LMC , Linssen Margot M. , Hohenstein Peter , de Miranda Noel F.C.C. , Mei Hailiang , Bins Adriaan D. , Haanen John B.A.G. , Aerts Joachim G. , Ossendorp Ferry , Arens Ramon 
Published: December 2021

AbstractImmune checkpoint therapy (ICT) has the potency to eradicate cancer but the mechanisms that determine effective versus non-effective therapy-induced immune responses are not fully understood. Here, using high-dimensional single-cell profiling we examined whether T cell states in the blood circulation could predict responsiveness to a combined ICT, sequentially targeting OX40 costimulatory and PD-1 inhibitory pathways, which effectively eradicated syngeneic mouse tumors. Unbiased assessment of transcriptomic alterations by single-cell RNA sequencing and profiling of cell-surface protein expression by mass cytometry revealed unique activation states for therapy-responsive CD4+ and CD8+ T cells. Effective ICT elicited T cells with dynamic expression of distinct NK cell and chemokine receptors, and these cells were systemically present in lymphoid tissues and in the tumor. Moreover, NK cell receptor-expressing CD8+ T cells were also present in the peripheral blood of immunotherapy-responsive cancer patients. Targeting of the NK cell and chemokine receptors in tumor-bearing mice showed their functional importance for therapy-induced anti-tumor immunity. These findings provide a better understanding of ICT and highlight the use of dynamic biomarkers on effector CD4+ and CD8+ T cells to improve cancer immunotherapy.
TaEXPB5 is responsible for male fertility in thermo-sensitive male-sterility wheat with Aegilops kotschyi cytoplasm
Authors: Geng Xingxia , Wang Xiaoxia , Wang Jingchen , Yang Xuetong , Zhang Lingli , Song Xiyue 
Published: December 2021

AbstractThermo-sensitive male sterility is of vital importance to heterosis, or hybrid vigor in crop production and hybrid breeding. Therefore, it is meaningful to study the function of the genes related to pollen development and male sterility, which is still not fully understand currently. Here, we conducted comparative analyses to screen fertility related genes using RNA-seq, iTRAQ, and PRM-based assay. A gene encoding expansin protein in wheat, TaEXPB5, was isolated in KTM3315A, which was in the cell wall and preferentially upregulated expression in the fertility anthers. The silencing of TaEXPB5 displayed pollen abortion, the declination or sterility of fertility. Further, cytological investigation indicated that the silencing of TaEXPB5 induced the early degradation of tapetum and abnormal development of pollen wall. These results revealed that the silencing of TaEXPB5 could eliminate the effects of temperature on male fertility, and resulting in functional loss of fertility conversion, which implied that TaEXPB5 may be essential for anther or pollen development and male fertility of KTM3315A. These findings provide a novel insight into molecular mechanism of fertility conversion for thermo-sensitive cytoplasmic male-sterility wheat, and contribute to the molecular breeding of hybrid wheat in the future.HighlightTaEXPB5 coffers to anther or pollen development and male fertility in KTM3315A, its silencing could eliminate the effects of temperature on male fertility, and resulting in functional loss of fertility conversion.
Valosin-containing protein regulates the stability of amyotrophic lateral sclerosis-causing fused in sarcoma granules in cells by changing ATP concentrations inside the granules
Authors: Yasuda Kyota , Watanabe Tomonobu M. , Kang Myeong-Gyun , Seo Jeong Kon , Rhee Hyun-Woo , Tate Shin-ichi 
Published: December 2021

AbstractFused in sarcoma (FUS) undergoes liquid-liquid phase separation (LLPS) to form granules in cells, leading to pathogenic aggregations that cause neurodegenerative diseases, including amyotrophic lateral sclerosis (ALS). Proteomics analysis revealed that FUS granules contain valosin-containing protein (VCP), a member of the AAA family ATPase. Confocal microscopy images showed that VCP co-localized in the FUS granules in cells. This study demonstrates that VCP in granules has a two-faced role in FUS granulation: VCP stabilizes de novo FUS granules, while VCP present in the granules for extended periods dissolves them. This VCP function relies on its ATPase activity to consume ATP in granules. VCP stabilizes de novo FUS by reducing intragranular ATP concentrations to a range below the cytosolic concentration. VCP continually consumes ATP during its stay in the granules, which eventually lowers ATP concentrations to a range that destabilizes the granules. VCP, therefore, acts as a timer to limit the residence of FUS granules in cells and thereby prohibits the FUS fibrillization that occurs in persistent granules. VCP ATPase activity plays a role in FUS granule turnover.Summary statementVCP recruited to FUS granules regulates the stability of the granules in a time-dependent manner by consuming intragranular ATP with its ATPase activity.
Serial interval and basic reproduction number of SARS-CoV-2 Omicron variant in South Korea
Authors: Kim Dasom , Jo Jisoo , Lim Jun-Sik , Ryu Sukhyun 
Published: December 2021

AbstractSouth Korea is experiencing the community transmission of the SARS-CoV-2 Omicron variant (B.1.1.529). We estimated that the mean (± standard deviation) serial interval was 2.22 (± 1.62) days, and the basic reproduction number was 1.90 (95% Credible Interval, 1.50–2.43) for the Omicron variant outbreak in South Korea.
Ultra-high-speed multi-parametric photoacoustic microscopy
Authors: Zhong Fenghe , Hu Song 
Published: December 2021

AbstractMulti-parametric photoacoustic microscopy (PAM) is uniquely capable of simultaneous, high-resolution mapping of blood hemoglobin concentration, oxygenation, and flow in vivo. However, its speed has been limited by the dense sampling required for blood flow quantification. To overcome this limitation, we have developed an ultra-high-speed multi-parametric PAM system, which enables simultaneous acquisition of ~500 densely sampled B-scans by superposing the rapid laser scanning across the line-shaped focus of a cylindrically focused ultrasonic transducer over the conventional mechanical scan of the optical-acoustic dual foci. A novel optical-acoustic combiner is designed and implemented to accommodate the short working distance of the transducer, enabling convenient confocal alignment of the dual foci in the reflection mode. This new system enables continuous monitoring of microvascular hemoglobin concentration, blood oxygenation, and flow over a 4.5 × 3 mm2 area in the awake mouse brain with high spatial and temporal resolution (6.9 μm and 0.3 Hz, respectively).
Joint dimension reduction and clustering analysis for single-cell RNA-seq and spatial transcriptomics data
Authors: Liu Wei , Liao Xu , Yang Yi , Lin Huazhen , Yeong Joe , Zhou Xiang , Shi Xingjie , Liu Jin 
Published: December 2021

AbstractDimension reduction and (spatial) clustering is usually performed sequentially; however, the low-dimensional embeddings estimated in the dimension-reduction step may not be relevant to the class labels inferred in the clustering step. We therefore developed a computation method, Dimension-Reduction Spatial-Clustering (DR-SC), that can simultaneously perform dimension reduction and (spatial) clustering within a unified framework. Joint analysis by DR-SC produces accurate (spatial) clustering results and ensures the effective extraction of biologically informative low-dimensional features. DR-SC is applicable to spatial clustering in spatial transcriptomics that characterizes the spatial organization of the tissue by segregating it into multiple tissue structures. Here, DR-SC relies on a latent hidden Markov random field model to encourage the spatial smoothness of the detected spatial cluster boundaries. Underlying DR-SC is an efficient expectation-maximization algorithm based on an iterative conditional mode. As such, DR-SC is scalable to large sample sizes and can optimize the spatial smoothness parameter in a data-driven manner. With comprehensive simulations and real data applications, we show that DR-SC outperforms existing clustering and spatial clustering methods: it extracts more biologically relevant features than conventional dimension reduction methods, improves clustering performance, and offers improved trajectory inference and visualization for downstream trajectory inference analyses.
Exploring careers through a qualitative lens: an investigation and invitation
Authors: Richardson Julia , O'Neil Deborah Anne , Thorn Kaye 
Published: December 2021

PurposeIn this paper, the authors investigate and celebrate the contributions that qualitative research has made to Career Development International (CDI) and careers scholarship over the past 25 years. The authors highlight the positive impact of understanding the “lived/emic experiences” of individual career actors using qualitative research designs and identify areas for future research.Design/methodology/approachThe authors employ multiple approaches in their investigation. The authors’ enquiry is part conceptual, part critical analysis and part bibliometric visualisation of qualitative papers published in CDI.FindingsThe authors identify the underlying ontological and epistemological assumptions of qualitative research, and the key tenets and contributions of qualitative research published in CDI. Their bibliometric analysis shows the interrelatedness and frequency of topics addressed by qualitative research and published in CDI, revealing areas for further research. While identifying some of the key criteria for rigor in qualitative research, the authors also engage with emerging calls to avoid rigid templates in how qualitative research is designed and implemented. In this regard, authors echo calls for “methodological bricolage” as an approach to qualitative research in the study of careers.Originality/valueThis is the first bibliographic and visual analysis of qualitative research published in a single journal. The authors offer this investigation as a way of looking back and as an invitation looking forward, encouraging further qualitative research in anticipation of future theoretical developments in career scholarship.
Meta-analysis of the impact of cross-cultural training on adjustment, cultural intelligence, and job performance
Authors: Chenyang Li 
Published: December 2021

PurposeThis research aims to provide an updated meta-analysis of cross-cultural training effectiveness through quantitatively reviewing the links between cross-cultural training and three outcomes: adjustment, cultural intelligence and job performance.Design/methodology/approachDrawing from 37 independent samples from 1991 through August 2021 involving a total of 7,040 trainees, the author adopt random-effects meta-analyses method to assess the relationships between cross-cultural training and three outcomes and examine potential moderators (i.e. training phase, training method and rating source) that influence these relationships.FindingsThe meta-analytical results mainly support our hypotheses. Cross-cultural training -adjustment exhibits a medium and significant positive effect, whereas cross-cultural training is positive significantly related to job performance and cultural intelligence of small effect sizes. Training method and data source significantly moderate the cross-cultural training's impact on cultural intelligence and performance correspondingly.Originality/valueThis study considers longitudinal statistics for measuring cross-cultural training effectiveness, breaking down the inadequacy of cross-sectional measurement and covers sub-dimensions of cross-cultural training outcomes to provide more comprehensive and advanced evidence of cross-cultural training effectiveness for the latest 30 years.