bluuebunny/crossref_metadata_2025_split huggingface dataset:
Differences in functional connectivity distribution after transcranial direct-current stimulation: a connectivity density point of view
Authors: Tang Bohao , Zhao Yi , Venkataraman Archana , Tsapkini Kyrana , Lindquist Martin A , Pekar James , Caffo Brian 
Published: November 2020

AbstractIn this manuscript we consider the problem of relating functional connectivity measurements viewed as statistical distributions to outcomes. We demonstrate the utility of using the distribution of connectivity on a study of resting state functional magnetic resonance imaging association with an intervention. Specifically, we consider 47 primary progressive aphasia (PPA) patients with various levels of language abilities. These patients were randomly assigned to two treatment arms, tDCS (transcranial direct-current stimulation and language therapy) vs sham (language therapy only), in a clinical trial. We propose a novel approach to analyze the effect of direct stimulation on functional connectivity. We estimate the density of correlations among the regions of interest (ROIs) and study the difference in the density post-intervention between treatment arms. We discover that it is the tail of the density, rather than the mean or lower order moments of the distribution, that demonstrates a significant impact in the classification. This approach has several benefits. Among them, it drastically reduces the number of multiple comparisons compared to edge-wise analysis. In addition, it allows for the investigation of the impact of functional connectivity on the outcomes where the connectivity is not geometrically localized.
A comparison of machine learning models versus clinical evaluation for mortality prediction in patients with sepsis
Authors: van Doorn William P.T.M. , Stassen Patricia M. , Borggreve Hella F. , Schalkwijk Maaike J. , Stoffers Judith , Bekers Otto , Meex Steven J.R. 
Published: November 2020

AbstractIntroductionPatients with sepsis who present to an emergency department (ED) have highly variable underlying disease severity, and can be categorized from low to high risk. Development of a risk stratification tool for these patients is important for appropriate triage and early treatment. The aim of this study was to develop machine learning models predicting 31-day mortality in patients presenting to the ED with sepsis and to compare these to internal medicine physicians and clinical risk scores.MethodsA single-center, retrospective cohort study was conducted amongst 1,344 emergency department patients fulfilling sepsis criteria. Laboratory and clinical data that was available in the first two hours of presentation from these patients were randomly partitioned into a development (n=1,244) and validation dataset (n=100). Machine learning models were trained and evaluated on the development dataset and compared to internal medicine physicians and risk scores in the independent validation dataset. The primary outcome was 31-day mortality.ResultsA number of 1,344 patients were included of whom 174 (13.0%) died. Machine learning models trained with laboratory or a combination of laboratory + clinical data achieved an area-under-the ROC curve of 0.82 (95% CI: 0.80-0.84) and 0.84 (95% CI: 0.81-0.87) for predicting 31-day mortality, respectively. In the validation set, models outperformed internal medicine physicians and clinical risk scores in sensitivity (92% vs. 72% vs. 78%;p<0.001,all comparisons) while retaining comparable specificity (78% vs. 74% vs. 72%;p>0.02). The model had higher diagnostic accuracy with an area-under-the-ROC curve of 0.85 (95%CI: 0.78-0.92) compared to abbMEDS (0.63,0.54-0.73), mREMS (0.63,0.54-0.72) and internal medicine physicians (0.74,0.65-0.82).ConclusionMachine learning models outperformed internal medicine physicians and clinical risk scores in predicting 31-day mortality. These models are a promising tool to aid in risk stratification of patients presenting to the ED with sepsis.
COVI-Prim survey: Challenges for Austrian and German general practitioners during initial phase of COVID-19
Authors: Siebenhofer Andrea , Huter Sebastian , Avian Alexander , Mergenthal Karola , Schaffler-Schaden Dagmar , Spary-Kainz Ulrike , Bachler Herbert , Flamm Maria 
Published: November 2020

AbstractBackgroundCoronavirus disease 2019 (COVID-19) represents a significant challenge to health care systems around the world. A well-functioning primary care system is crucial in epidemic situations as it plays an important role in the development of a system-wide response.Methods2,187 Austrian and German GPs answered an internet suvey on preparedness, testing, staff protection, perception of risk, self-confidence, a decrease in the number of patient contacts, and efforts to control the spread of the virus in the practice during the early phase of the COVID-pandemic (3rd to 30th April).ResultsThe completion rate of the questionnaire was high (90.9%). GPs gave low ratings to their preparedness for a pandemic, testing of suspected cases and efforts to protect staff. The provision of information to GPs and the perception of risk were rated as moderate. On the other hand, the participants rated their self-confidence, a decrease in patient contacts and their efforts to control the spread of the disease highly.ConclusionPrimary care is an important resource for dealing with a pandemic like COVID-19. The workforce is confident and willing to take an active role, but needs to be provided with the appropriate surrounding conditions. This will require that certain conditions are met.RegistrationTrial registration at the German Clinical Trials Register: DRKS00021231Primary Funding SourceThe study was financed by the cooperating University Institutes without any external financial support.
Lithium inhibits tryptophan catabolism via the inflammation-induced kynurenine pathway in human microglia
Authors: Göttert Ria , Fidzinski Pawel , Kraus Larissa , Schneider Ulf Christoph , Holtkamp Martin , Endres Matthias , Gertz Karen , Kronenberg Golo 
Published: November 2020

SummaryActivation of the kynurenine pathway may lead to depletion of the serotonin precursor tryptophan, which has been implicated in the neurobiology of depression. This study describes a mechanism whereby lithium inhibits inflammatory tryptophan breakdown. Upon activation, immortalized human microglia showed a robust increase in indoleamine-2,3-dioxygenase (IDO1) mRNA transcription, IDO1 protein expression, and activity. Further, chromatin immunoprecipitation verified enriched binding of both STAT1 and STAT3 to theIDO1promoter. Lithium counteracted these effects, increasing inhibitory GSK3βS9phosphorylation and reducing STAT1S727and STAT3Y705phosphorylation levels in activated cells. Experiments in primary human microglia and human induced pluripotent stem cell (hiPSC)-derived microglia corroborated lithium’s effects. Moreover, IDO activity was reduced by GSK3 inhibitor SB-216763 and STAT inhibitor nifuroxazide via downregulation of P-STAT1S727and P-STAT3Y705. Our study demonstrates that lithium inhibits the inflammatory kynurenine pathway in the microglia compartment of the human brain.
Emerging Concern of Scientific Fraud: Deep Learning and Image Manipulation
Authors: Qi Chang , Zhang Jian , Luo Peng 
Published: November 2020

AbstractScientific fraud by image duplications and manipulations within western blot images is a rising problem. Currently, problematic western blot images are mainly detected by checking repeated bands or through visual observation. However, the completeness of the above methods in detecting problematic images has not been demonstrated. Here we show that Generative Adversarial Nets (GANs) can generate realistic western blot images that indistinguishable from real western blots. The overall accuracy of researchers for identifying synthetic western blot images is 0.52, which almost equal to blind guess (0.5). We found that GANs can generate western blot images with bands of the expected lengths, widths, and angles in desired positions that can fool researchers. For the case study, we find that the accuracy of detecting the synthetic western blot images is related to years of researchers performed studies relevant to western blots, but there was no apparent difference in accuracy among researchers with different academic degrees. Our results demonstrate that GANs can generate fake western blot images to fool existing problematic image detection methods. Therefore, more information is needed to ensure that the western blots appearing in scientific articles are real. We argue to require every western blot image to be uploaded along with a unique identifier generated by the laboratory machine and to peer review these images along with the corresponding submitted articles, which may reduce the incidence of scientific fraud.
CloneSeq: A Highly Sensitive Single-cell Analysis Platform for Comprehensive Characterization of Cells from 3D Culture
Authors: Bavli Danny , Sun Xue , Kozulin Chen , Ennis Dena , Motzik Alex , Biran Alva , Brielle Shlomi , Alajem Adi , Meshorer Eran , Buxboim Amnon , Ram Oren 
Published: November 2020

AbstractSingle-cell assays have revealed the scope and importance of heterogeneity in many biological systems. However, in many cases, single cell limited sensitivity is a major hurdle for uncovering the full range of cellular variation. To overcome this limitation, we developed a complementary single cell technology, CloneSeq that combines clonal expansion under controlled culture conditions inside three-dimensional (3D) hydrogel spheres and droplet-based RNA sequencing (RNA-seq). We show that unlike single cell transcriptomes, clonal cells maintain cell states and share similar transcriptional profiles. CloneSeq analysis of Non-small-cell lung carcinoma (NSCLC) cells revealed the presence of novel cancer-specific subpopulations, including cancer stem-like cells (CSLCs). Standard single cell RNA-seq assays as well as cell-to-clone tracing by genetic barcoding failed to identify these rare CSLCs. In addition to CSLCs, clonal expansion within 3D soft microenvironments supported cellular stemness of embryonic stem cells (ESCs) that retained their pluripotent state in the absence of pluripotent media and improved epigenetic reprogramming efficiency of mouse embryonic fibroblasts. Our results demonstrate the capacity of CloneSeq, which can be effectively adapted to different biological systems, to discover rare and previously hidden subpopulations of cells, including CSLCs, by leveraging the broader expression space within clones.
Mechanism of autonomous synchronization of the circadian KaiABC rhythm
Authors: Sasai Masaki 
Published: November 2020

ABSTRACTThe cyanobacterial circadian clock can be reconstituted by mixing three proteins, KaiA, KaiB, and KaiC, in vitro. In this protein mixture, oscillations of the phosphorylation level of KaiC molecules are synchronized to show the coherent oscillations of the ensemble of many molecules. However, the mechanism of this synchronization remains elusive. In this paper, we explain a theoretical model that considers the multifold feedback relations among the structure and reactions of KaiC. The simulated KaiC hexamers show stochastic switch-like transitions at the level of single molecules, which are synchronized in the ensemble through the sequestration of KaiA into the KaiC-KaiB-KaiA complexes. The proposed mechanism quantitatively reproduces the synchronization that was observed by mixing two oscillating solutions in different phases. The model results suggest that biochemical assays with varying concentrations of KaiA or KaiB can be used to test this hypothesis.
Heterotrimeric kinesin-2 motor subunit, KLP68D, localisesDrosophilaodour receptor coreceptor in the distal domain of the olfactory cilia
Authors: Jana Swadhin C. , Jain Akanksha , Dutta Priya , Singh Anjusha , Adusumilli Lavanya , Girotra Mukul , Shirolikar Seema , Ray Krishanu 
Published: November 2020

AbstractCiliary localisation of the odour receptor coreceptor (Orco) is essential for insect olfaction. Here, we show that in theDrosophilaantenna Orco enters the bipartite cilia expressed on the olfactory sensory neurons in two discrete, one-hour intervals after the adult eclosion. Genetic analyses suggest that the heterotrimeric kinesin-2 is essential for Orco transfer from the base into the cilium. Using in vitro pulldown assay, we show that Orco binds to the C-terminal tail domain of KLP68D, the β-subunit of kinesin-2. Reduced Orco enrichment decreases electrophysiological response to odours and loss of olfactory behaviour. Finally, we show that kinesin-2 function is necessary to compact Orco to an approximately four-micron stretch at the distal portion of the ciliary outer-segment bearing singlet microtubule filaments. Altogether, these results highlight an independent, tissue-specific regulation of Orco entry at specific developmental stages and its localisation to a ciliary subdomain by kinesin-2.Graphical AbstractAuthor SummaryJana, Jain, Dutta et al., show that the odour receptor coreceptor only enters the cilia expressed on olfactory sensory neurons at specified developmental stages requiring heterotrimeric kinesin-2. The motor also helps to localise the coreceptor in a compact, environment-exposed domain at the ciliary outer-segment.Highlights:Odorant receptor coreceptor (Orco) selectively enters the olfactory cilia.Orco localises in a specific domain at the distal segment of the olfactory cilium.Orco/ORx binds to the C-terminal tail domain of the kinesin-2β motor subunit.Orco entry across the transition zone and its positioning require Kinesin-2.
Debates about vaccines and climate change on social media networks: a study in contrasts
Authors: Schonfeld Justin , Qian Edward , Sinn Jason , Cheng Jeffery , Anand Madhur , Bauch Chris T. 
Published: November 2020

ABSTRACTVaccines and climate change have much in common. In both cases, a scientific consensus contrasts with a divided public opinion. They also exemplify coupled human-environment systems involving common pool resources. Here we used machine learning algorithms to analyze the sentiment of 87 million tweets on climate change and vaccines in order to characterize Twitter user sentiment and the structure of user and community networks. We found that the vaccine conversation was characterized by much less interaction between individuals with differing sentiment toward vaccines. Community-level interactions followed this pattern, showing less interaction between communities of opposite sentiment toward vaccines. Additionally, vaccine community networks were more fragmented and exhibited numerous isolated communities of neutral sentiment. Finally, pro-vaccine individuals overwhelmingly believed in anthropogenic climate change, but the converse was not true. We propose mechanisms that might explain these results, pertaining to how the spatial scale of an environment system can structure human populations.
Npas4aexpression in the teleost forebrain is associated with stress coping style differences in fear learning
Authors: Baker Matthew R , Wong Ryan Y 
Published: November 2020

AbstractLearning to anticipate potentially dangerous contexts is an adaptive behavioral response to coping with stressors. An animal’s stress coping style (e.g. proactive-reactive axis) is known to influence how it encodes salient events. However, the neural and molecular mechanisms underlying these stress coping style differences in learning are unknown. Further, while a number of neuroplasticity-related genes have been associated with alternative stress coping styles, it is unclear if these genes may bias the development of conditioned behavioral responses to stressful stimuli, and if so, which brain regions are involved. Here, we trained adult zebrafish to associate a naturally aversive olfactory cue with a given context. Next, we investigated if expression of two neural plasticity and neurotransmission-related genes (npas4aandgabbr1a) were associated with the contextual fear conditioning differences between proactive and reactive stress coping styles. Reactive zebrafish developed a stronger conditioned fear response and showed significantly highernpas4aexpression in the medial and lateral zones of the dorsal telencephalon (Dm, Dl), and the supracommissural nucleus of the ventral telencephalon (Vs). Our findings suggest that the magnitude of expression of activity-dependent genes likenpas4amay be differentially expressed across several interconnected forebrain regions in response to fearful stimuli and promote biases in fear learning among different stress coping styles.
DNA Methylation Patterns Expose Variations in Enhancer-Chromatin Modifications during Embryonic Stem Cell Differentiation
Authors: Alajem Adi , Roth Hava , Ratgauzer Sofia , Bavli Danny , Motzik Alex , Lahav Shlomtzion , Peled Itay , Ram Oren 
Published: November 2020

AbstractIn mammals, cellular identity is defined through strict regulation of chromatin modifications and DNA methylation that control gene expression. Methylation of cytosines at CpG sites in the genome is mainly associated with suppression; however, the reason for enhancer-specific methylation is not fully understood. We used sequential ChIP-bisulfite-sequencing for H3K4me1 and H3K27ac histone marks. By collecting data from the same genomic region, we identified enhancers differentially methylated between these two marks. We observed a global gain of CpG methylation primarily in H3K4me1-marked nucleosomes during mouse embryonic stem cell differentiation. This gain occurred largely in enhancer regions that regulate genes critical for differentiation. The higher levels of DNA methylation in H3K4me1-versus H3K27ac-marked enhancers, despite it being the same genomic region, indicates cellular heterogeneity of enhancer states. Analysis of single-cell RNA-seq profiles demonstrated that this heterogeneity correlates with gene expression during differentiation. Furthermore, heterogeneity of enhancer methylation correlates with transcription start site methylation. Our results provide insights into enhancer-based functional variation in complex biological systems.Author summaryCellular dynamics are underlined by numerous regulatory layers. The regulatory mechanism of interest in this work are enhancers. Enhancers are regulatory regions responsible, mainly, for increasing the possibility of transcription of a certain gene. Enhancers are marked by two distinct chemical groups-H3K4me1 and H3K27ac on the tail of histones. Histones are the proteins responsible for DNA packaging into condensed chromatin structure. In contrast, DNA methylation is a chemical modification often found on enhancers, and is traditionally associated with repression. A long debated question revolves around the functional relevance of DNA methylation in the context of enhancers. Here, we combined the two regulatory layers, histone marks and DNA methylation, to a single measurement that can highlight DNA methylation separately on each histone mark but at the same genomic region. When isolated with H3K4me1, enhancers showed higher levels of methylation compared to H3K27ac. As we measured the same genomic locations, we show that differences of DNA methylation between these marks can only be explained by cellular heterogeneity. We also demonstrated that these enhancers tend to play roles in stem cell differentiation and expression levels of the genes they control correlate with cell-to-cell variation.
Human capital, income diversification and bank performance–an empirical study of East African banks
Authors: Githaiga Peter Nderitu 
Published: November 2020

PurposeThe purpose of this paper is to examine whether income diversification moderates the relationship between human capital and bank performance.Design/methodology/approachThe study uses a sample of 53 banks and panel data for the years 2010–2018. The hypotheses are tested through hierarchical multiple regression and the choice between fixed effect and random effect estimation is based on the results of the Hausman test.FindingsThe study finds that human capital and income diversification significantly influence bank performance; however, the direction of the causality varies. While human capital has a positive effect, income diversification has a negative effect. Additionally, the interaction term has a negative and significant effect on bank performance, inferring that income diversification has an antagonistic effect on the human capital and bank performance relationship. For the control variable, liquidity and asset quality negatively affects bank performance while capitalization has a positive effect.Research limitations/implicationsHuman capital was measured as human capital efficiency (HCE), which is a quantitative measure of human capital, hence future studies can use qualitative measures. Also, the study focused on commercial banks in East Africa, future researcher may possibly consider other regions and industries, which would shed more insights.Practical implicationsThe results of this paper provide valuable insights. Bank managers can get a better understanding of the impact of human capital on bank performance, and the need to invest more in human capital development. Further, the study cautions bank managers that engaging in non-lending activities might destroy the economic value of human capital and ultimately lower performance. The study also recommends that policymakers should address the obstacles to banks' income diversification, for instance relaxing regulations restricting diversification; this might enable banks to leverage related financial service activities for optimal utilization of human capital and improve banks' profitability.Originality/valueWhile a good number of previous studies investigated the direct effect of human capital and income diversification on the performance of banks, this study examines the moderating role of income diversification on the relationship between human capital and performance of banks in East Africa.
Uncovering the effects of prior founding experience of entrepreneurs on early board selection
Authors: Gasiorowski Laura , Lee Ahreum 
Published: November 2020

PurposeThis study aims to show what type of directors founders (or entrepreneurs) first appoint to the board and how these appointments differ across experienced and novice entrepreneurs.Design/methodology/approachThe sample consists of the human capital of board members in 443 new ventures in the computer software and information technology industries between 2000 and 2014. The hypotheses were tested using tobit regression.FindingsThe findings in this study reveal that compared to novice entrepreneurs, experienced entrepreneurs tend to appoint early boards with greater human capital (entrepreneurial, technical/scientific and industry-specific) and with greater functional diversity. In contrast, novice entrepreneurs tend to appoint early boards with greater finance and director experience.Originality/valueThe value of this research lies in filling the gap in the current literature by comparing the board appointment/selection behavior of novice and experienced entrepreneurs, which is relatively underexplored.