bluuebunny/crossref_metadata_2025_split huggingface dataset:
A Cascaded Droplet Microfluidic Platform Enables High‐Throughput Single Cell Antibiotic Susceptibility Testing at Scale
Authors: Zhang Pengfei , Kaushik Aniruddha M. , Hsieh Kuangwen , Li Sixuan , Lewis Shawna , Mach Kathleen E. , Liao Joseph C. , Carroll Karen C. , Wang Tza‐Huei 
Published: December 2021

AbstractThe global threat of antibiotic resistance underscores critical but unmet needs for rapid antibiotic susceptibility testing (AST) technologies. To this end, droplet microfluidic‐based single‐cell AST offers promise by achieving unprecedented rapidity, but its potential for clinical use is marred by the capacity of testing one to few antibiotic conditions per device, which falls short from the required scale in clinically relevant scenarios. To lift the scalability constraint in rapid single‐cell AST technologies, a new cascaded droplet microfluidic platform that can streamline bacteria/antibiotic mixing, single‐cell encapsulation within picoliter droplets, incubation, and detection in a continuous, assembly‐line‐like workflow is developed. The scalability of the platform is demonstrated by generating 32 groups of ≈10 000 droplets with custom antibiotic conditions within a single device, from which a new statistics‐based method is used to analyze the single cell data and produce clinically useful antibiograms with minimum inhibitory concentrations in ≈90 min for the first antibiotic, plus 2 min for each subsequent antibiotic condition. Potential clinical utility of this platform is demonstrated by testing three clinical isolates and eight urine specimens against four frequently used antibiotics, and 100% and 93.8% categorical agreements are achieved compared to laboratory‐based results that became available after 48 h.
Association of Ovar‐DRB1 alleles with innate immune responses in sheep
Authors: Esmailnejad Atefeh , Ganjiani Vahid , Hosseini‐Nasab Elhamsadat , Nazifi Saeed 
Published: December 2021

AbstractBackgroundMajor histocompatibility complex (MHC) is the best characterised genetic region associated with adaptive immune responses, including humoral and cell‐mediated immunities.ObjectivesIn this study, the association of MHC class II alleles with inflammatory cytokines and acute‐phase proteins was evaluated in sheep population.MethodsAllelic diversity of second exon of ovine DRB1 locus (Ovar‐DRB1.2) was determined in 100 indigenous Iranian Lori‐Bakhtiari fat‐tailed sheep using restriction fragment length polymorphism and direct sequencing methods. The association of DRB1.2 alleles with inflammatory cytokines (interleukin‐1β, IL‐1β; IL‐6 and tumour necrosis factor‐α) and acute‐phase proteins (serum amyloid A, alpha‐1‐acid glycoprotein and haptoglobin) was examined using generalised linear model and multivariate regression analysis.ResultsSeven distinct RsaI restriction patterns and fourteen alleles were identified in this population. Allele DRB1*2101 showed a negative influence on the IL‐6 response and was associated with lower serum level of IL‐6. DRB1.2 heterozygous individuals also showed higher haptoglobin concentration than homozygotes.ConclusionsThese results provide additional support for the association between Ovar‐DRB1 alleles and regulation of immune responses in sheep population. Description of MHC polymorphism and its role in the controlling of immune responses will increase our understanding of host–pathogen interactions, and ultimately facilitate the selection of disease‐resistant flocks in genetic breeding programs.
Narrativity in Complex Systems
Authors: Fuchs Hans U. , Corni Federico , Dumont Elisabeth 
Published: December 2021

AbstractHumans use narrative for making sense of their environment. In this chapter we ask if, and if so how and to what extent, our narrative mind can help us deal scientifically with complexity. In order to answer this question, and to show what this means for education, we discuss fundamental aspects of narrative understanding of dynamical systems by working on a concrete story. These aspects involve perception of complex systems, experientiality of narrative, decomposition of systems into mechanisms, perception of forces of nature in mechanisms, and the relation of story-worlds to modelling-worlds, particularly in so-called ephemeral mechanisms. In parallel to describing fundamental issues, we develop a practical heuristic strategy for dealing with complex systems in five steps. (1) Systems thinking: Identify phenomena and foreground a system associated with these phenomena. (2) Mechanisms: Find and describe mechanisms responsible for these phenomena. (3) Forces of nature: Learn to perceive forces of nature as agents acting in these mechanisms. (4) Story-worlds and models: Learn how to use stories of forces (of nature) to construct story-worlds; translate the story-worlds into dynamical-model-worlds. (5) Ephemeral mechanisms for one-time, short-lived, unpredictable, and historical (natural) events: Learn how to create and accept ephemeral story-worlds and models. Ephemeral mechanisms and ephemeral story-worlds are a means for dealing with unpredictability inherent in complex dynamical systems. We argue that unpredictability does not fundamentally deny storytelling, modelling, explanation, and understanding of natural complex systems.
Open Science, Replicability, and Transparency in Modelling
Authors: Prike Toby 
Published: December 2021

AbstractRecent years have seen large changes to research practices within psychology and a variety of other empirical fields in response to the discovery (or rediscovery) of the pervasiveness and potential impact of questionable research practices, coupled with well-publicised failures to replicate published findings. In response to this, and as part of a broader open science movement, a variety of changes to research practice have started to be implemented, such as publicly sharing data, analysis code, and study materials, as well as the preregistration of research questions, study designs, and analysis plans. This chapter outlines the relevance and applicability of these issues to computational modelling, highlighting the importance of good research practices for modelling endeavours, as well as the potential of provenance modelling standards, such as PROV, to help discover and minimise the extent to which modelling is impacted by unreliable research findings from other disciplines.
Bayesian Model-Based Approach: Impact on Science and Policy
Authors: Bijak Jakub , Hinsch Martin , Nurse Sarah , Prike Toby , Reinhardt Oliver 
Published: December 2021

AbstractIn this chapter, we summarise the scientific and policy implications of the Bayesian model-based approach, starting from an evaluation of its possible advantages, limitations, and potential to influence further scientific developments, policy and practice. We focus here specifically on the role of limits of knowledge and reducible (epistemic), as well as irreducible (aleatory) uncertainty. To that end, we also reflect on the scientific risk-benefit trade-offs of applying the proposed approaches. We discuss the usefulness of proposed methods for policy, exploring a variety of uses, from scenario analysis, to foresight studies, stress testing and early warnings, as well as contingency planning, illustrated with examples generated by the Risk and Rumours models presented earlier in this book. We conclude the chapter by providing several practical recommendations for the potential users of our approach, including a blueprint for producing and assessing the impact of policy interventions in various parts of the social system being modelled.
Konzepte für eine sprachbewusste Hochschullehre
Authors: Schacht Florian , Guckelsberger Susanne 
Published: December 2021

ZusammenfassungIn Kapitel 2 werden die Leitideen und hochschuldidaktischen Design-Prinzipien aus Kap. 1 aufgegriffen und anhand von Beispielen für eine sprachbewusste und forschungsbezogene Lehre in der Lehramtsausbildung Mathematik konkretisiert. In Abschn. 2.1 wird zunächst eine Spielsituation vorgestellt, in der die Studierendenden Kontext „Sprache im Fach Mathematik“ bewusst erleben können. Ein für den Mathematikunterricht – und damit für die Lehramtsausbildung Mathematik – zentraler Aspekt ist die Arbeit mit und die Variation von Aufgaben. In Abschn. 2.2 steht daher die Frage im Mittelpunkt, wie Studierende bei der sprachbewussten Aufgabenplanung bzw. -variation systematisch unterstützt werden können. Abschn. 2.3 vertieft das Thema mit einem Schwerpunkt auf Darstellungsvernetzung. Empirische Daten aus dem Unterricht bieten für eine sprachbewusste Lehramtsausbildung einen interessanten Lerngegenstand: Sie lassen Einblicke in unterschiedliche Formen der fachlichen Kommunikation zu, ermöglichen eine Rekonstruktion von Lernprozessen und können wertvolle fach- und sprachdiagnostischeAuskünfte geben. In Abschn. 2.4 wird daher der Fokus auf Lernerdaten als Analyse- und Lerngegenstand gelegt. Abschn. 2.5 widmet sich dem aus hochschuldidaktischer Sicht zentralen Paradigma des forschenden Lernens. Abschn. 2.6 knüpft daran an und vertieft das für viele Studierende besonders herausfordernde Thema der Entwicklung von Forschungsfragen.
Targeted Hsp70 fluorescence molecular endoscopy detects dysplasia in Barrett’s esophagus
Authors: Fang Hsin-Yu , Stangl Stefan , Marcazzan Sabrina , Carvalho Marcos J. Braz , Baumeister Theresa , Anand Akanksha , Strangmann Julia , Huspenina Julia Slotta , Wang Timothy C. , Schmid Roland M. , Feith Marcus , Friess Helmut , Ntziachristos Vasilis , Multhoff Gabriele , Gorpas Dimitris , Quante Michael 
Published: December 2021

Abstract

Purpose
The incidence of esophageal adenocarcinoma (EAC) has been increasing for decades without significant improvements in treatment. Barrett’s esophagus (BE) is best established risk factor for EAC, but current surveillance with random biopsies cannot predict progression to cancer in most BE patients due to the low sensitivity and specificity of high-definition white light endoscopy.

Methods
Here, we evaluated the membrane-bound highly specific Hsp70-specific contrast agent Tumor-Penetrating Peptide (Hsp70-TPP) in guided fluorescence molecular endoscopy biopsy.

Results
Hsp70 was significantly overexpressed as determined by IHC in dysplasia and EAC compared with non-dysplastic BE in patient samples (n = 12) and in high-grade dysplastic lesions in a transgenic (L2-IL1b) mouse model of BE. In time-lapse microscopy, Hsp70-TPP was rapidly taken up and internalized by human BE dysplastic patient–derived organoids. Flexible fluorescence endoscopy of the BE mouse model allowed a specific detection of Hsp70-TPP-Cy5.5 that corresponded closely with the degree of dysplasia but not BE. Ex vivo application of Hsp70-TPP-Cy5.5 to freshly resected whole human EAC specimens revealed a high (> 4) tumor-to-background ratio and a specific detection of previously undetected tumor infiltrations.

Conclusion
In summary, these findings suggest that Hsp70-targeted imaging using fluorescently labeled TPP peptide may improve tumor surveillance in BE patients.
EANM procedure guidelines for brain PET imaging using [18F]FDG, version 3
Authors: Guedj Eric , Varrone Andrea , Boellaard Ronald , Albert Nathalie L. , Barthel Henryk , van Berckel Bart , Brendel Matthias , Cecchin Diego , Ekmekcioglu Ozgul , Garibotto Valentina , Lammertsma Adriaan A. , Law Ian , Peñuelas Iván , Semah Franck , Traub-Weidinger Tatjana , van de Giessen Elsmarieke , Van Weehaeghe Donatienne , Morbelli Silvia 
Published: December 2021

AbstractThe present procedural guidelines summarize the current views of the EANM Neuro-Imaging Committee (NIC). The purpose of these guidelines is to assist nuclear medicine practitioners in making recommendations, performing, interpreting, and reporting results of [18F]FDG-PET imaging of the brain. The aim is to help achieve a high-quality standard of [18F]FDG brain imaging and to further increase the diagnostic impact of this technique in neurological, neurosurgical, and psychiatric practice. The present document replaces a former version of the guidelines that have been published in 2009. These new guidelines include an update in the light of advances in PET technology such as the introduction of digital PET and hybrid PET/MR systems, advances in individual PET semiquantitative analysis, and current broadening clinical indications (e.g., for encephalitis and brain lymphoma). Further insight has also become available about hyperglycemia effects in patients who undergo brain [18F]FDG-PET. Accordingly, the patient preparation procedure has been updated. Finally, most typical brain patterns of metabolic changes are summarized for neurodegenerative diseases. The present guidelines are specifically intended to present information related to the European practice. The information provided should be taken in the context of local conditions and regulations.
NF-кB c-Rel modulates pre-fibrotic changes in human fibroblasts
Authors: Micus Lara Carolina , Trautschold-Krause Franziska Susanne , Jelit Anna Lena , Schön Michael Peter , Lorenz Verena Natalie 
Published: December 2021

AbstractSkin fibrosis is one central hallmark of the heterogeneous autoimmune disease systemic sclerosis. So far, there are hardly any standardized and effective treatment options. Pathogenic mechanisms underlying fibrosis comprise excessive and uncontrolled myofibroblast differentiation, increased extracellular matrix protein (ECM) synthesis and an intensification of the forces exerted by the cytoskeleton. A deeper understanding of fibroblast transformation could help to prevent or reverse fibrosis by specifically interfering with abnormally regulated signaling pathways. The transcription factor NF-κB has been implicated in the progression of fibrotic processes. However, the cellular processes regulated by NF-κB in fibrosis as well as the NF-κB isoforms preferentially involved are still completely unknown. In an in vitro model of fibrosis, we consistently observed the induction of the c-Rel subunit of NF-κB. Functional abrogation of c-Rel by siRNA resulted in diminished cell contractility of dermal fibroblasts in relaxed, but not in stressed 3D collagen matrices. Furthermore, directed migration was reduced after c-Rel silencing and total N-cadherin expression level was diminished, possibly mediating the observed cellular defects. Therefore, NF-кB c-Rel impacts central cellular adhesion markers and processes which negatively regulate fibrotic progression in SSc pathophysiology.
Recent changes in the climate-growth response of European larch (Larix decidua Mill.) in the Polish Sudetes
Authors: Danek Małgorzata , Danek Tomasz 
Published: December 2021

Abstract
Key message
Recently observed temporal changes in the climate-growth relationship of larch in the Polish Sudetes suggest growth limitations in the future.

Abstract
Larches in the Sudetes are very sensitive to the currently changing climatic factors, and an extreme negative response to drought is observed. In this study, temporal changes in the climate-growth relationship of European larch were analyzed using moving-window correlation. Change-point detection analysis was performed to determine whether there is a temporal connection between tree-ring growth responses and changes in climatic factors trends. The Random Forest predictor importance determination method was used to establish the set of climatic factors that influence larch tree-ring growth the most and to show how this set changes over time. Additionally, cluster analysis was applied to find spatial growth patterns and to generalize the growth response of larch. The results indicate that the main clustering factor is altitude. Nevertheless, an increasing unification of the larch’s response to dominant climatic factors is observable throughout the whole study area. This unification is expressed in the increasingly positive and recently dominant effect of May temperature. A progressively negative influence of the temperature in the summer and late autumn of the year preceding growth was observed, as was an increasing influence of water availability in the summer months. The study indicates that there is a connection between the observed changes and the recent rapid rise in temperature, which has consequently had a negative influence on water availability. The growth of this tree species in the Sudetes is expected to be very limited in the future due to its sensitivity to drought, the predicted increase in temperatures and thermal extremes, and the decrease of the share of summer precipitation in the annual total.
Receiver operating characteristic (ROC) movies, universal ROC (UROC) curves, and coefficient of predictive ability (CPA)
Authors: Gneiting Tilmann , Walz Eva-Maria 
Published: December 2021

AbstractThroughout science and technology, receiver operating characteristic (ROC) curves and associated area under the curve ($$\mathrm{AUC}$$AUC) measures constitute powerful tools for assessing the predictive abilities of features, markers and tests in binary classification problems. Despite its immense popularity, ROC analysis has been subject to a fundamental restriction, in that it applies to dichotomous (yes or no) outcomes only. Here we introduce ROC movies and universal ROC (UROC) curves that apply to just any linearly ordered outcome, along with an associated coefficient of predictive ability ($${\mathrm{CPA}}$$CPA) measure.$${\mathrm{CPA}}$$CPAequals the area under the UROC curve, and admits appealing interpretations in terms of probabilities and rank based covariances. For binary outcomes$${\mathrm{CPA}}$$CPAequals$$\mathrm{AUC}$$AUC, and for pairwise distinct outcomes$${\mathrm{CPA}}$$CPArelates linearly to Spearman’s coefficient, in the same way that the C index relates linearly to Kendall’s coefficient. ROC movies, UROC curves, and$${\mathrm{CPA}}$$CPAnest and generalize the tools of classical ROC analysis, and are bound to supersede them in a wealth of applications. Their usage is illustrated in data examples from biomedicine and meteorology, where rank based measures yield new insights in the WeatherBench comparison of the predictive performance of convolutional neural networks and physical-numerical models for weather prediction.
Initial carbonate weathering is linked with vegetation development along a 127-year glacial retreat chronosequence in the subtropical high mountainous Hailuogou region (SW China)
Authors: Basdediós Nuria , Zhong Zhilin , Wu Yanhong , Wilcke Wolfgang 
Published: December 2021

Abstract
Aims
The retreat of glaciers is exposing new terrains to primary plant succession around the globe. To improve the understanding of vegetation development along a glacier retreat chronosequence, we (i) evaluated a possible link between base metal (Ca, Mg, K, Na) supply and vegetation establishment, (ii) determined the rates of the establishment of soil and plant base metal stocks, and (iii) estimated the size of the main base metal fluxes.

Methods
We determined base metal stocks in the soil organic layer, the mineral topsoil (0–10 cm), and in leaves/needles, trunk, bark, branches and roots of the dominating shrub and tree species and estimated fluxes of atmospheric deposition, plant uptake and leaching losses along the 127-yr Hailuogou chronosequence.

Results
Total ecosystem Ca and Mg stocks decreased along the chronosequence, while those of K and Na were unrelated with ecosystem age. Fortyfour and 30% of the initial stocks of Ca and Mg, respectively, were leached during the first 47 years, at rates of 130 ± 10.6 g m−2 year−1 Ca and 35 ± 3.1 g m−2 year−1 Mg. The organic layer accumulated at a mean rate of 288 g m−2 year−1 providing a bioavailable base metal stock, which was especially important for K cycling.

Conclusions
We suggest that the initial high Ca bioavailability because of a moderately alkaline soil pH and carbonate depletion in 47 years, together with the dissolution of easily-weatherable silicates providing enough Mg and K to the pioneer vegetation, contributed to the establishment of the mature forest in ca. 80 years.
East Slavic indefinite pronouns: a corpus-based approach
Authors: Penkova Yana , Rabus Achim 
Published: December 2021

AbstractThe paper focuses on the development and functional distribution of indefinite pronouns in Old East Slavic, taking into account different sources, genres and registers. All the examples in the collected dataset were taken from the historical modules of the Russian National Corpus. They were tagged for type of indefinite marker, source (including originality and date), type of reference of the indefinite marker, semantics, type of discourse, and the degree of formality (formal or informal) present in the context. We then applied both descriptive and inferential statistical methods such as Random Forest analysis as well as multinomial logistic regression. Our analysis enabled us to identify the primary and secondary predictors of the choice of a particular indefinite marker and to trace the functional distribution of indefinite markers according to these factors.
Mapping cortical disease-burden at individual-level in frontotemporal dementia: implications for clinical care and pharmacological trials
Authors: McKenna Mary Clare , Tahedl Marlene , Lope Jasmin , Chipika Rangariroyashe H. , Li Hi Shing Stacey , Doherty Mark A. , Hengeveld Jennifer C. , Vajda Alice , McLaughlin Russell L. , Hardiman Orla , Hutchinson Siobhan , Bede Peter 
Published: December 2021

AbstractImaging studies of FTD typically present group-level statistics between large cohorts of genetically, molecularly or clinically stratified patients. Group-level statistics are indispensable to appraise unifying radiological traits and describe genotype-associated signatures in academic studies. However, in a clinical setting, the primary objective is the meaningful interpretation of imaging data from individual patients to assist diagnostic classification, inform prognosis, and enable the assessment of progressive changes compared to baseline scans. In an attempt to address the pragmatic demands of clinical imaging, a prospective computational neuroimaging study was undertaken in a cohort of patients across the spectrum of FTD phenotypes. Cortical changes were evaluated in a dual pipeline, using standard cortical thickness analyses and an individualised, z-score based approach to characterise subject-level disease burden. Phenotype-specific patterns of cortical atrophy were readily detected with both methodological approaches. Consistent with their clinical profiles, patients with bvFTD exhibited orbitofrontal, cingulate and dorsolateral prefrontal atrophy. Patients with ALS-FTD displayed precentral gyrus involvement, nfvPPA patients showed widespread cortical degeneration including insular and opercular regions and patients with svPPA exhibited relatively focal anterior temporal lobe atrophy. Cortical atrophy patterns were reliably detected in single individuals, and these maps were consistent with the clinical categorisation. Our preliminary data indicate that standard T1-weighted structural data from single patients may be utilised to generate maps of cortical atrophy. While the computational interpretation of single scans is challenging, it offers unrivalled insights compared to visual inspection. The quantitative evaluation of individual MRI data may aid diagnostic classification, clinical decision making, and assessing longitudinal changes.