bluuebunny/crossref_metadata_2025_split huggingface dataset:
Validation of AI-based software for objectification of conjunctival provocation test results in routine examinations and clinical studies
Authors: Yarin Yury , Kalaitzidi Alexandra , Bodrova Kira , Mösges Ralf , Kalaidzidis Yannis 
Published: March 2022

Abstracts1.BackgroundProvocation tests are widely used in allergology to objectively reveal patients’ sensitivity to specific allergens. The objective quantification of an allergic reaction is a crucial characteristic of these tests. Due to the absence of objective quantitative measurements the conjunctival provocation test (CPT) is a less frequently used method despite its sensitivity and simplicity. We developed a new method AllergoEye based on AI for quantitative evaluation of conjunctival allergic reactions and validated it in a clinical study.2.MethodsAllergoEye was implemented as a two component system. The first component is based on an Android smartphone camera for screening and imaging the patient’s eye and the second one is PC based for image analysis and quantification. For the validation of AllergoEye an open-label, prospective, monocentric study was carried out on 41 patients. Standardized CPT was performed with sequential titration of grass allergens in 4 dilutions with the reaction evaluated by subjective/qualitative symptom scores and by quantitative AllergoEye scores.3.ResultsAllergoEye demonstrated high sensitivity (98%) and specificity (90%) as compared with human-estimated allergic reaction. Tuning cut-off thresholds allowed to increase the specificity of AllergoEye to 97%, where the correlation between detected sensitivity to allergen and sIgE CAP-class becomes obvious. Strikingly, such correlation was not found with sensitivity to allergen detected by subjective and qualitative symptom scores.4.ConclusionThe clinical validation demonstrated that AllergoEye is a sensitive and efficient instrument for objective measurement of allergic reactions in CPT for clinical studies as well as for routine therapy control.
Study Protocol for a Phase III Randomised Controlled Trial of Sailuotong (SLT) for Vascular Dementia and Alzheimer’s Disease with Cerebrovascular Disease
Authors: Karamacoska Diana , Chan Daniel K.Y. , Leung Isabella , Liu Jian-xun , Brodaty Henry , Fahey Paul P , Bensoussan Alan , Chang Dennis H. 
Published: March 2022

ABSTRACTBackgroundVascular dementia (VaD) accounts for 15-20% of all dementia cases. It is a syndrome of acquired cognitive impairment with a complex pathophysiological basis. A novel herbal formulation (Sailuotong; SLT) consisting of Panax ginseng, Ginkgo biloba and Crocus sativus extracts was developed to treat VaD. Preclinical animal studies found significant improvements in memory and in pathogenic biochemical parameters. Appropriate safety of SLT was shown in acute and chronic toxicity studies, and early clinical trials of SLT demonstrated enhancements in cognition in VaD patients. A fully powered study with a long intervention period is needed to confirm the efficacy and safety of this novel intervention.MethodsA rigorous phase III clinical trial was developed with the aim of recruiting 238 patients diagnosed with mild to moderate probable VaD, or VaD mixed with Alzheimer’s disease (where cerebrovascular disease is the clinical dominant contributor to dementia, abbreviated as CVD+AD). Using a permuted block strategy, participants will be randomly allocated to receive SLT (120 mg bd) or placebo capsules for an intervention period of 52 weeks and will be followed-up for an additional 13 weeks. The primary outcome measures are the Vascular Dementia Assessment Scale-cognitive subscale and Alzheimer’s Disease Cooperative Study-Activities of Daily Living scale. Secondary outcome measures include the Clinician’s Interview Based Impression of Change-Plus, CLOX, EXIT-25, Neuropsychiatric Inventory-Clinician rating scale, and Dementia Quality of Life questionnaire. Safety is assessed through adverse event reports and liver, renal, and coagulation studies.DiscussionPrimary and secondary outcome measures will be compared between treatment and placebo groups, using intention to treat and per protocol analyses. We hypothesise that a 52-week treatment of SLT will be clinically effective and well tolerated in participants with VaD or AD+CVD. This project will provide vital efficacy and safety data for this novel treatment approach to VaD.Trial registrationAustralian New Zealand Clinical Trials Registry (ANZCTR), ACTRN 12616000057482. Registered on 20 January 2016. https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=369471&isReview=true
Antiviral roles of interferon regulatory factor (IRF)-1, 3 and 7 against human coronavirus infection
Authors: Xu Danyang , Sampson Duncan Joseph K. , Licursi Maria , Gohda Jin , Kawaguchi Yasushi , Hirasawa Kensuke 
Published: March 2022

AbstractInterferon regulatory factors (IRFs) are key elements of antiviral innate responses that regulate transcription of interferons (IFNs) and IFN-stimulated genes (ISGs). As many human coronaviruses are known to be sensitive to IFN, antiviral roles of IRFs are yet to be fully understood. TypeI or II IFN treatment protected MRC5 cells from infection of human coronavirus 229E, but not human coronavirus OC43. Infection of 229E or OC43 efficiently upregulated ISGs, indicating that antiviral transcription is not suppressed during their infection. Antiviral IRFs, IRF1, IRF3 and IRF7, were activated in cells infected with 229E, OC43 or severe acute respiratory syndrome-associated coronavirus 2 (SARS-CoV-2). RNAi knockdown and overexpression of the IRFs demonstrated that IRF1 and IRF3 have antiviral property against OC43 while only IRF3 and IRF7 are effective to restrict 229E infection. Our study demonstrates that IRF3 plays critical roles against infection of human coronavirus 229E and OC43, which may be an anti-human coronavirus therapeutic target.
Transcriptional and translational profiling in yeast reveals the use of diverse genome decoding mechanisms to generate functionally distinct proteoforms
Authors: Fenton Darren A , Świrski Michał , O’Connor Patrick B F , Kiniry Stephen J , Michel Audrey M , Kufel Joanna , Baranov Pavel V , Morrissey John P 
Published: March 2022

ABSTRACTThe coding potential of the eukaryotic genome can be greatly expanded by the regulated use of mechanisms that generate more than one protein product from a gene. We combined techniques for mapping 5’ and 3’ ends of RNA transcripts with ribosome profiling to study the organisation of protein coding gene expression in the yeast Kluyveromyces marxianus. We uncovered over 1000 cases of novel proteoforms due to use of alternative transcription or translation start sites, identified 800 translated upstream open reading frames, observed surprising translation of antisense RNAs, and discovered a novel case of programmed ribosomal frameshifting. In some cases, features are conserved across yeast species, whereas others are species-specific. This offers new possibilities to explore the evolution of genomes and gene regulation in budding yeasts. Our analysis also enabled us to improve the genome annotation of K. marxianus by adding or correcting annotations of over 300 protein coding genes. The processed data has been made available on the GWIPS-viz and Trips-Viz browsers, thus providing an accurate data-driven annotation of transcripts and their protein coding regions along with quantitative information on their transcription and translation.
Multicellular Reservoir Computing
Authors: Nikolić Vladimir , Echlin Moriah , Aguilar Boris , Shmulevich Ilya 
Published: March 2022

AbstractThe capacity of cells to process information is currently used to design cell-based tools for ecological, industrial, and biomedical applications such as detecting dangerous chemicals or for bioremediation. In most applications, individual cells are used as the information processing unit. However, single cell engineering is limited by the necessary molecular complexity and the accompanying metabolic burden of synthetic circuits. To overcome these limitations, synthetic biologists have begun engineering multicellular systems that combine cells with designed subfunctions. To further advance information processing in synthetic multicellular systems, we introduce the application of reservoir computing. Reservoir computers (RCs) approximate a temporal signal processing task via a fixed-rule dynamic network (the reservoir) with a regression-based readout. Importantly, RCs eliminate the need of network rewiring, as different tasks can be approximated with the same reservoir. Previous work has already demonstrated the capacity of single cells, as well as populations of neurons, to act as reservoirs. In this work, we extend reservoir computing in multicellular populations with the widespread mechanism of diffusion-based cell-cell signaling. As a proof-of-concept, we simulated a reservoir made of a 3D community of cells communicating via diffusible molecules and used it to approximate two benchmark signal processing tasks, computing median and parity functions from binary input signals. We demonstrate that a diffusion-based multicellular reservoir is a feasible synthetic framework for performing complex temporal computing tasks that provides a computational advantage over single cell reservoirs. We also identified a number of biological properties that can affect the computational performance of these processing systems.
Leveraging the local genetic structure for trans-ancestry association mapping
Authors: Xiao Jiashun , Cai Mingxuan , Yu Xinyi , Hu Xianghong , Wan Xiang , Chen Gang , Yang Can 
Published: March 2022

AbstractOver the past two decades, genome-wide association studies (GWASs) have successfully advanced our understanding of genetic basis of complex traits. Despite the fruitful discovery of GWASs, most GWAS samples are collected from European populations, and these GWASs are often criticized for their lack of ancestry diversity. Trans-ancestry association mapping (TRAM) offers an exciting opportunity to fill the gap of disparities in genetic studies between non-Europeans and Europeans. Here we propose a statistical method, LOG-TRAM, to leverage the local genetic architecture for TRAM. By using biobank-scale datasets, we showed that LOG-TRAM can greatly improve the statistical power of identifying risk variants in under-represented populations while producing well-calibrated p-values. We applied LOG-TRAM to the GWAS summary statistics of 29 complex traits/diseases from Biobank Japan (BBJ) and UK Biobank (UKBB), and achieved substantial gains in power (the effective sample sizes increased by 49% in average compared to the BBJ GWASs) and effective correction of confounding biases compared to existing methods. Finally, we demonstrated that LOG-TRAM can be successfully applied to identify ancestry-specific loci and the LOG-TRAM output can be further used for construction of more accurate polygenic risk scores (PRSs) in under-represented populations.
T cells induce interferon-responsive oligodendrocytes during white matter aging
Authors: Kaya Tuğberk , Mattugini Nicola , Liu Lu , Ji Hao , Besson-Girard Simon , Kaiji Seiji , Liesz Arthur , Gokce Ozgun , Simons Mikael 
Published: March 2022

SUMMARYA hallmark of nervous system aging is a decline of white matter volume and function, but the underlying mechanisms leading to white matter pathology are unknown. Here, we found age-related alterations of oligodendrocytes with a reduction of total oligodendrocyte density in the aging murine white matter. Using single-cell RNA sequencing, we identify interferon-responsive oligodendrocytes, which localize in proximity of CD8+ T cells in the aging white matter. Absence of functional lymphocytes decreased oligodendrocyte reactivity and rescued oligodendrocyte loss, while T-cell checkpoint inhibition worsened the aging affect. In summary, we provide evidence that T cells induced interferon-responsive oligodendrocytes are important modifiers of white matter aging.
Telomere to telomere sequence of modelAspergillus fumigatusgenomes
Authors: Bowyer Paul , Currin Andrew , Delneri Daniela , Fraczek Marcin G. 
Published: March 2022

ABSTRACTThe pathogenic fungusAspergillus fumigatusis a major etiological agent of fungal invasive and chronic diseases affecting tens of millions of individuals worldwide. A high-quality reference genome is a fundamental resource to study its biology, pathogenicity and virulence as well as to discover better and more effective treatments against diseases caused by this fungus. Here, we used PacBio Single Molecule Real-Time (SMRT) and Oxford Nanopore sequencing forde novogenome assembly of two laboratory reference strains ofA. fumigatus,CEA10 and A1160. We generated full length chromosome assemblies and a comprehensive telomere to telomere coverage for these two strains including ribosomal repeats and the sequences of centromeres, which we discovered to be composed of long transposon elements.
A Bayesian approach to incorporate structural data into the mapping of genotype to antigenic phenotype of influenza A(H3N2) viruses
Authors: Harvey William T. , Davies Vinny , Daniels Rodney S. , Whittaker Lynne , Gregory Victoria , Hay Alan J. , Husmeier Dirk , McCauley John W. , Reeve Richard 
Published: March 2022

AbstractSurface antigens of pathogens are commonly targeted by vaccine-elicited antibodies but antigenic variability, notably in RNA viruses such as influenza, HIV and SARS-CoV-2, pose challenges for control by vaccination. For example, influenza A(H3N2) entered the human population in 1968 causing a pandemic and has since been monitored, along with other seasonal influenza viruses, for the emergence of antigenic drift variants through intensive global surveillance and laboratory characterisation. Statistical models of the relationship between genetic differences among viruses and their antigenic similarity provide useful information to inform vaccine development though accurate identification of causative mutations is complicated by highly correlated genetic signals that arise due to the evolutionary process. Here, using a sparse hierarchical Bayesian analogue of an experimentally validated model for integrating genetic and antigenic data, we identify the genetic changes in influenza A(H3N2) virus that underpin antigenic drift. We show that incorporating protein structural data into variable selection helps resolve ambiguities arising due to correlated signals, with the proportion of variables representing haemagglutinin positions decisively included, or excluded, increased from 59.8% to 72.4%. The accuracy of variable selection judged by proximity to experimentally determined antigenic sites was improved simultaneously. Structure-guided variable selection thus improves confidence in the identification of genetic explanations of antigenic variation and we also show that prioritising the identification of causative mutations is not detrimental to the predictive capability of the analysis. Indeed, incorporating structural information into variable selection resulted in a model that could more accurately predict antigenic assay titres for phenotypically-uncharactrised virus from genetic sequence. Combined, these analyses have the potential to inform choices of reference viruses, the targeting of laboratory assays, and predictions of the evolutionary success of different genotypes, and can therefore be used to inform vaccine selection processes.
Organizational silofication: implications in grouping experts for organizational performance
Authors: Silberman Dave , Carpenter Rob E. , Cabrera Elena , Kernaleguen Jasmine 
Published: March 2022

Purpose
This paper presents a viewpoint that considers the construction of ‘expertise’ as an impediment to successfully using cross-functional expertise in the organization. The construction of expertise forms a bounded perspective that creates hidden impediments to success that culminate in organizational underachievement.

Design/methodology/approach
Experiential knowledge of the authors that incorporated 20 years of organizational management experience and extensive practice of hiring experts to progress organizational learning, knowledge, and development is the primary basis of this work.

Findings
A common misperception of ‘expertise’ relates to a limiting perspective on what expertise is? Organizations segregate expertise (silo) as a way of increasing functionality and division of labor in an organizational structure. However, organizational underachievement is not due to functional arrangement in the organization’s structure (which is a commonly held belief) rather a byproduct of a bounded perspective necessary to construct expertise.

Practical implications
Organizations who understand that the bounded perspective of expertise is the source constraining use of their acquired expertise gain insight to an actionable opportunity to rectify cross-functional restraints. Core elements are offered to minimize the impact of organizational silofication.

Originality/value
This paper is unique in that it introduces a bounded perspective as the source impeding the use of workplace expertise rather than functional placement.
A perspective on collaborative partnerships to expand campus buy-in for digital collections
Authors: Latham Bethany 
Published: March 2022

Purpose
The purpose of this paper is to explore, from the perspective of a medium-sized academic library, how libraries can pursue and use collaboration with other units on campus to increase support and buy-in for digital collections.

Design/methodology/approach
This paper is approached from the perspective of a medium-sized academic library located in Alabama, USA. This study examines ways to foster collaboration with diverse campus units, the challenges that can be encountered and ways to overcome these barriers to collaboration. Examples of the potential and realized benefits are also enumerated.

Findings
This paper demonstrates that, while there are challenges that must be overcome, regular and sustained collaboration with nonlibrary campus units can result in the creation of unique digital collections that such units are not capable of pursuing without library partnership. These partnerships increase visibility for the library and its services, as well as buy-in and support for digital collections from other campus units and, importantly, university administration.

Practical implications
Academic libraries, especially those at small- to medium-sized institutions, face continual budget restrictions and calls to justify the resources expended. This impacts all aspects of library services, but especially the creation of digital collections, which are cost- and labor-intensive. By offering examples of collaboration, libraries can explore ways to partner that will foster buy-in and support at their own institutions.

Originality/value
This paper provides examples and details considerations that can make the process of collaboration simpler and more effective for other academic libraries to pursue.
Mobility and sustainable transportation in higher education: evidence from Monterrey Metropolitan Area in Mexico
Authors: Moreno Jorge O. , Caamal-Olvera Cinthya G. , Luna Edgar M. 
Published: March 2022

Purpose
This paper aims to analyze the demand for mobility in higher education to understand the critical elements of students' mobility and the potential impact of accessing sustainable alternatives. The demand for different means of transportation accounts for socioeconomic variables such as household income and size, gender, age, among other travel factors such as distance, time, speed and direct cost.

Design/methodology/approach
This research uses a unique data set encompassing a representative sample of households across gender and municipalities in the Monterrey Metropolitan Area in Mexico. This paper uses the value of transportation time savings approach to estimate the derived demand for mobility in higher education across different means. The empirical strategy uses a linear utility framework in a multinomial non-ordered logit model to analyze the conditional selection of transportation as a function of sociodemographics, direct monetary costs and travel determinants such as travel time, distance and speed.

Findings
Men students are more likely to use an unsustained transportation mode such as a car or cab than women. Income is a crucial determinant for transportation demand. There is a negative relationship between household income and walking or riding the bus but positive with driving a car. An increase in the time of the trip decreases the probability of walking while increasing the likelihood of using a car or riding the bus to school. Students who feel safe while riding a bus are more likely to use the bus or walk as transportation than using a car. Finally, having access to better quality sidewalks significantly incentive walking over other transportation options.

Practical implications
Results show that individuals would almost always choose private vehicles because of the personal comforts and time savings.

Social implications
Understanding the demand for higher education and access to sustainable transportation might provide new insights into campus planning and development. Access to public transportation options can reduce the travel costs for students with lower incomes and enlarge options for students who have to commute longer distances by car. Sustainable transportation access plays a role in promoting equality and economic development.

Originality/value
This study’s results bring new light on how transportation becomes an essential component of the opportunity cost of college education and could define its role in promoting equality or increasing inequality. This study’s finding is of particular interest for cities where housing location seems to be independent of access to school, work or other amenities.
Credit-to-GDP ratios – non-linear trends and persistence: evidence from 44 OECD economies
Authors: Cuestas Juan Carlos , Gil-Alana Luis A. , Malmierca María 
Published: March 2022

PurposeIn particular, in this article, the authors investigate the degree of persistence in the credit-to-gross domestic product (GDP) ratio in 44 Organisation for Economic Co-operation and Development (OECD) economies in the context of nonlinear deterministic trends.Design/methodology/approachThe authors use Chebyshev's polynomials in time, which allow us to model changes in the data in a smoother way than by structural breaks.FindingsThis study’s results indicate that approximately one-quarter of the series display non-linear structures, and only Argentina displays a mean reverting pattern.Research limitations/implicationsPolicy implications of the results obtained are discussed at the end of the manuscript.Originality/valueThe authors use an approach developed that allows for non-linear trends based on Chebyshev polynomials in time, with the residuals being fractionally integrated or integrated of order d, where d can be any real value.