bluuebunny/crossref_metadata_2025_split huggingface dataset:
Clustering of predicted loss-of-function variants in genes linked with monogenic disease can explain incomplete penetrance
Authors: Beaumont Robin N. , Hawkes Gareth , Gunning Adam C. , Wright Caroline F. 
Published: October 2023

AbstractPredicted loss-of-function variants (pLoFs) are often associated with disease. For genes linked with monogenic diseases, we hypothesised that pLoFs present in apparently unaffected individuals may cluster in LoF-tolerant regions. We compared the distribution of pLoFs in ClinVar versus 454,773 individuals in UK Biobank and clustered the variants using Gaussian mixture models. We found that genes in which haploinsufficiency causes developmental disorders with incomplete penetrance were less likely to have a uniform pLoF distribution than other genes (P<2.2x10-6). In some cases (e.g.,ARID1BandGATA6), pLoF variants in the first quarter of the gene could be rescued by an alternative translation start site and should not be reported as pathogenic. In other cases (e.g.,ODC1), pathogenic pLoFs were clustered only at the end of the gene, consistent with a gain-of-function disease mechanism. Our results support the use of localised constraint metrics when interpreting variants.
The effect of protein levels of ABO on pregnancy related outcomes: a Mendelian randomization study
Authors: Sun Yuqi , Zheng Haonan , Wang Manqing , Gu Rongrong , Wu Xueyan , Yang Qian , Zhao Huiling , Bi Yufang , Zheng Jie 
Published: October 2023

AbstractProtein level of Histo-Blood Group ABO System Transferase (ABO) has been reported to be associated with cardiometabolic diseases. But its effect on pregnancy related outcomes was still unclear. Here we conducted a two-sample Mendelian randomization study to ascertain the putative causal roles of protein levels of ABO in pregnancy related outcomes. Cis-acting protein quantitative trait loci (pQTLs) robustly associated with protein level of ABO (P < 5x10-8) were used as instruments to proxy the ABO level (N = 35,559, data from deCODE), with two additional pQTL datasets from Fenland (N = 10,708) and INTERVAL (N = 3,301) used as validation exposures. Ten pregnancy related diseases and complications were selected as outcomes. We observed that a higher protein level of ABO showed a putative causal effect on venous complications and haemorrhoids in pregnancy (OR = 1.207, 95%CI = 1.107-1.316, colocalization probability = 91.3%), which was validated by using pQTLs from Fenland and INTERVAL. The Mendelian randomization results further showed effects of the ABO protein on gestational hypertension (OR = 0.974, 95%CI = 0.953-0.995), despite insignificance after multiple testing correction and little colocalization evidence. Sensitivity analyses, including proteome-wide Mendelian randomization of the cis-acting ABO pQTLs, showed little evidence of horizontal pleiotropy. Correctively, our study prioritised ABO as a putative causal protein for venous complications and haemorrhoids in pregnancy. Future epidemiology and clinical studies are needed to investigate whether ABO can be considered as a drug target to prevent adverse pregnancy outcomes.
Safety of SARS-CoV-2 test-to-stay in daycare: a regression discontinuity in time analysis
Authors: Dewald Felix , Steger Gertrud , Fish Irina , Torre-Lage Ivonne , Hellriegel Christina , Milz Esther , Kolb-Bastigkeit Anja , Heger Eva , Fries Mira , Buess Michael , Marizy Niklas , Michaelis Barbara , Suárez Isabelle , Rubio Quintanares Gibran Horemheb , Pirkl Martin , Aigner Annette , Oberste Max , Hellmich Martin , Wong Anabelle , Orduz Juan Camilo , Fätkenheuer Gerd , Dötsch Jörg , Kossow Annelene , Moench Eva-Maria , Quade Gustav , Neumann Udo , Kaiser Rolf , Schranz Madlen , Klein Florian 
Published: October 2023

AbstractBackground and ObjectivesTest-to-stay concepts apply serial testing of children in daycare after exposure to SARS-CoV-2 without use of quarantine. This study aims to assess safety of a test-to-stay screening in daycare facilities.Methods714 daycare facilities and approximately 50,000 children ≤6 years in Cologne, Germany participated in a SARS-CoV-2 Pool-PCR screening from March 2021 to April 2022. The screening initially comprised post-exposure quarantine and was adapted to a test-to-stay approach during its course. To assess safety of the test-to-stay approach, we explored potential changes in frequencies of infections among children following the adaptation to the test-to-stay approach by applying regression discontinuity in time (RDiT) analyses. To this end, PCR-test data were linked with routinely collected data on reported infections in children and analyzed using ordinary least squares regressions.Results219,885 Pool-PCRs and 352,305 Single-PCRs were performed. 6,440 (2.93%) Pool-PCRs tested positive, and 17,208 infections in children were reported. We estimated that during a period of 30 weeks, the test-to-stay concept avoided between 7 and 20 days of quarantine per eligible daycare child. RDiT revealed a 26% reduction (Exp. Coef: 0.74, CI:0.52;1.06) in infection frequency among children and indicated no significant increase attributable to the test-to-stay approach. This result was not sensitive to adjustments for 7-day incidence, season, SARS-CoV-2 variant, and socioeconomic status.ConclusionOur analyses provide evidence that suggest safety of the test-to-stay approach compared to traditional quarantine measures. This approach offers a promising option to avoid use of quarantine after exposure to respiratory pathogens in daycare settings.
Mapping the multidimensional geometric landscape of graded phenotypic variation and progression in neurodegenerative syndromes
Authors: Ramanan Siddharth , Akarca Danyal , Henderson Shalom K. , Rouse Matthew A. , Allinson Kieren , Patterson Karalyn , Rowe James B. , Lambon Ralph Matthew A. 
Published: October 2023

AbstractClinical variants of Alzheimer’s disease and frontotemporal lobar degeneration display a spectrum of cognitive-behavioural changes varying between individuals and over time. Understanding the landscape of these graded individual-/group-level longitudinal variations is critical for precise phenotyping; however, this remains challenging to model. Addressing this challenge, we leverage the National Alzheimer’s Coordinating Center database to derive a unified geometric framework of graded longitudinal phenotypic variation in Alzheimer’s disease and frontotemporal lobar degeneration. We included three time-point, cognitive-behavioural and clinical data from 390 typical, atypical and intermediate Alzheimer’s disease and frontotemporal lobar degeneration variants (114 typical Alzheimer’s disease; 107 behavioural variant frontotemporal dementia; 42 motor variants of frontotemporal lobar degeneration; and 103 primary progressive aphasia patients). On this data, we applied advanced data-science approaches to derive low-dimensional geometric spaces capturing core features underpinning clinical progression of Alzheimer’s disease and frontotemporal lobar degeneration syndromes. To do so, we first used principal component analysis to derive six axes of graded longitudinal phenotypic variation capturing patient-specific movement along and across these axes. Then, we distilled these axes into a visualisable 2D manifold of longitudinal phenotypic variation using Uniform Manifold Approximation and Projection. Both geometries together enabled the assimilation and inter-relation of paradigmatic and mixed cases, capturing dynamic individual trajectories, and linking syndromic variability to neuropathology and key clinical end-points such as survival. Through these low-dimensional geometries, we show that (i) specific syndromes (Alzheimer’s disease and primary progressive aphasia) converge over time into a de-differentiated pooled phenotype, while others (frontotemporal dementia variants) diverge to look different from this generic phenotype; (ii) phenotypic diversification is predicted by simultaneous progression along multiple axes, varying in a graded manner between individuals and syndromes; and (iii) movement along specific principal axes predicts survival at 36 months in a syndrome-specific manner and in individual pathological groupings. The resultant mapping of dynamics underlying cognitive-behavioural evolution potentially holds paradigm-changing implications to predicting phenotypic diversification and phenotype-neurobiological mapping in Alzheimer’s disease and frontotemporal lobar degeneration.
Diastolic function and its relationship with the ATP-III criteria for metabolic syndrome in a Latin American cohort
Authors: Estévez Gómez María Juliana , Acevedo Peña Diego Andrey , Castillo Goyeneche Silvia Fernanda , Arias Anderson Felipe , Dulcey Sarmiento Luis Andres , Gomez Jaime , Hernandez Carlos , Theran Leon Juan Sebastián , Caltagirone Raimondo , Blanco Edgar , Ciliberti María , Calderon Amaya Silvia Yulieth , Gutierrez Emily , Lizcano Angie , Amaya Maria Camila , Lobo Diego 
Published: October 2023

AbstractINTRODUCTIONIn South America, heart failure poses a substantial concern due to its widespread occurrence and insufficient data accuracy. Metabolic syndrome, a risk factor for heart disease and diabetes, is the focal point of the study, which seeks to examine its correlation with left ventricular diastolic function (LVDF) and indications of heart failure in adults within a South American hospital.MATERIALS AND METHODSA cross-sectional study with 2380 adults aged 65-79 in a South American hospital reveals connections between metabolic syndrome (MetS) and heart health. Using ATP-III criteria, MetS was identified, and cardiac function was assessed by echocardiography. Significant associations between MetS and various cardiac indicators were found.RESULTSMetabolic Syndrome (MetS) affected 33.1% of the sample, showing health differences and cardiac alterations, including ejection fraction changes. Associations with diastolic dysfunction criteria and complex relationships between natriuretic peptides and ventricular filling pressure were observed.CONCLUSIONSMetabolic syndrome links to significant changes in diastolic function and left ventricular structure, but not with alterations in the left atrium. Nevertheless, individuals with Metabolic Syndrome are more prone to receiving a diagnosis of chronic heart failure. Further extensive studies in diverse populations are advised.
Genomic Insights into the 2023 Outbreak of Acute Hemorrhagic Conjunctivitis in Pakistan: Identification of Coxsackievirus A24 Variant through Next Generation Sequencing
Authors: Haider Syed Adnan , Jamal Zunera , Ammar Muhammad , Hakim Rabia , Salman Muhammad , Umair Massab 
Published: October 2023

AbstractAcute Hemorrhagic Conjunctivitis (AHC) has caused a significant outbreak in Pakistan in 2023, leading to a surge in cases across various cities. To gain insights into the genetic makeup of the virus responsible for the outbreak, the National Institute of Health, Islamabad conducted a study involving twenty individuals with suspected conjunctivitis in Islamabad. Five of these samples underwent whole-genome sequencing for the first-time in Pakistan, revealing Coxsackievirus A24 variant (CVA24v), genotype IV. Phylogenetic analysis revealed a higher homology (99.38-99.43%) with isolates from Zhongshan, China, in June 2023, with notable mutations concentrated in the 3D and VP1 regions. The sample also exhibited a 94% homology with 2015 France isolates. Comparing the 2023 study sequence with partial 2005 Pakistan sequences revealed divergence in the VP1 region, marked by three non-synonymous mutations (“H25P,” “I89V,” and “I90L”), while no mutation was found in the VP3 region. Notably, no intertypic recombination events were detected. This study underscores the significance of genomic surveillance for effective understanding and management of infectious disease outbreaks, offering crucial insights for public health interventions.
Machine learning based on event-related oscillations of working memory differentiates between preclinical Alzheimer’s disease and neurotypical aging
Authors: Liao Ke , Martin Laura E. , Fakorede Sodiq , Brooks William M. , Burns Jeffrey M. , Devos Hannes 
Published: October 2023

AbstractThere is increasing evidence of the usefulness of electroencephalography (EEG) as an early neurophysiological marker of preclinical AD. Our objective was to apply machine learning approaches on event-related oscillations to discriminate preclinical AD from neurotypical controls. Twenty-two preclinical AD participants who were cognitively normal with elevated amyloid and 21 cognitively normal with no elevated amyloid controls completed n-back working memory tasks (n= 0, 1, 2). EEG signals were recorded through a high-density sensor net. The event-related spectral changes were extracted using the discrete wavelet transform in the delta, theta, alpha, and beta bands. The support vector machine (SVM) machine learning method was employed to classify participants, and classification performance was assessed using the Area Under the Curve (AUC) metric. The relative power of the beta and delta bands outperformed other frequency bands with higher AUC values. The 2-back task obtained higher AUC values than the 0 and 1-back tasks. The highest AUC values were from the 2-back task beta band (AUC = 0.86) and delta bands (AUC = 0.85) nontarget data. This study demonstrates the promise of using machine learning on EEG event-related oscillations from working memory tasks to detect preclinical AD.
The library's influence and impact on learning: a case study from The Open University (UK)
Authors: Killick Selena 
Published: October 2023

PurposeThe Open University (OU) in the UK has been providing distance learning since 1969. The purpose of this case study is to outline the impact that The OU Library in the UK has had on student learning outcomes by embedding academic literature and digital and information literacy (DIL) skills materials in the curriculum.Design/methodology/approachThe case study presents an overview of the university context, including how the curriculum is developed. It discusses the role of the library in this process, outlining how librarians work with academic staff to embed skills and literature in the curriculum. Unique in-house technical solutions are presented to aid future approaches to providing distance library services.FindingsThe impact of the library on university education is discussed. Findings from qualitative research are presented, outlining the value the university places on the role of the library as an educational partner. Quantitative research studies are also presented, outlining the positive relationships between library content access and training attendance with student success.Practical implicationsAs universities are considering their distance-learning offerings post-COVID-19, it is hoped that this case study will help both library and university administrators examine the role of their libraries in this strategy.Originality/valueA case study on the approach The OU Library takes to support education in its broadest sense has not been published before.
The influences of eccentricity on the fastener load and bearing strength of eccentric connection in aircraft structure
Authors: Li Chenghu 
Published: October 2023

Purpose
This paper aims to study the influences of eccentricity on the fastener load and bearing strength of the eccentric connection in the aircraft structure.

Design/methodology/approach
The special experiment is designed for the researches. The fastener loads of the eccentric connection are gained by using the derived formulas and numerical analysis, and the fastener load rules is verified by the experiment. The bearing strength of the eccentric connection is investigated by the experiments under different eccentricities compared with that gained from the experiment.

Findings
The study results are summarized as follows. Magnitude of the fastener load in the eccentric connection is greatly affected by distance from the fastener to the centroid of the fastener cluster and that from the fastener to the concentrated load. With the increase of eccentricity of the homolateral concentrated load, the fastener load increases, and difference of the fastener loads becomes larger, forming the short plate effect of the bucket. It means that fastener with the maximum load (the shortest plate of the bucket) leads to decrease of the bearing strength of the eccentric connection (the capacity of the bucket).

Originality/value
The investigation on the influence of eccentricity on the bearing strength of eccentric connection is firstly presented. The vector expression of the fastener load in eccentric connection is firstly derived. And the influencing mechanism of the fastener load on the bearing strengths of the different eccentric connections is demonstrated. The study results can provide guidance for the structure design of the eccentric connection.
Platform-based support for AI uptake by SMEs: guidelines to design service bundles
Authors: Gladysz Bartlomiej , Matteri Davide , Ejsmont Krzysztof , Corti Donatella , Bettoni Andrea , Haber Guerra Rodolfo 
Published: October 2023

PurposeManufacturing small and medium-sized enterprises (SMEs) have already noticed the tangible benefits offered by artificial intelligence (AI). Several approaches have been proposed with a view to support them in the processes entailed in this innovation path. These include multisided platforms created to enable the connection between SMEs and AI developers, making it easier for them to network each other. While such platforms are complex, they facilitate simultaneous interaction with several stakeholders and reaching out to new potential users (both SMEs and AI developers), through a collaboration with supporting ecosystems such as digital innovation hubs (DIHs).Design/methodology/approachMixed methods were used. The literature review was performed to identify the existing approaches within and outside the manufacturing domain. Computer-assisted telephonic (in-depth) interviewing , was conducted to include perspectives of AI platform stakeholders and collect primary data from various European countries.FindingsSeveral challenges and barriers for AI platform stakeholders were identified alongside the corresponding best practices and guidelines on how to address them.Originality/valueAn effective approach was proposed to provide support to the industrial platform managers in this field, by developing guidelines and best practices on how a platform should build its services to support the ecosystem.
Stiffness analysis of nutation face gear considering roughness
Authors: Zhu Lili , Bai Jinxu , Liang Xu , Jia Maojin 
Published: October 2023

PurposeThe purpose of this paper is to calculate the meshing stiffness of nutation face gear considering the roughness, establish the calculation method of time-varying meshing stiffness of rough tooth surface and analyze the influence of roughness, load and other factors on the meshing stiffness of tooth surface.Design/methodology/approachThe Weierstrass–Mandelbrot (W-M) function in the Majumdar–Bhushan model is used to characterize the rough contact line of the tooth surface, the normal height and radius of the micro convex body are calculated and the contact flexibility of the contact point of the tooth surface is obtained. The contact flexibility and the bending shear deformation flexibility obtained previously are substituted into the improved deformation compatibility equation for iterative calculation, and the time-varying meshing stiffness of the nutation face gear considering the roughness is obtained.FindingsCompared with ABAQUS finite element simulation results, it is found that the meshing stiffness curve of rough tooth surface is more gentle than that of smooth tooth surface, the meshing stiffness value is smaller and the meshing stiffness change is smaller at the position where the number of gear teeth coincide changes.Originality/valueIn the process of calculating contact deformation, the fractal theory W-M function is used to characterize the contact line of the rough nutation face gear, and the deformation coordination condition considering roughness is improved. Therefore, the method of time-varying meshing stiffness considering roughness can obtain more accurate results, which provides theory and data for the subsequent dynamics analysis of the nutation face gear transmission.
The impact of economic policy uncertainty on stock types while considering the economic cycle. A quantile regression approach
Authors: Paule-Vianez Jessica , Orden-Cruz Carmen , Prado-Román Camilo , Gómez-Martínez Raúl 
Published: October 2023

PurposeThis study aims to analyse the effects of Economic Policy Uncertainty (EPU) on the return of growth/value and small/large-cap stocks during expansionary and recessionary periods across a conditional distribution.Design/methodology/approachThe authors selected a sample covering the period between 01/1995–05/2021. Quantile regressions were applied to the EPU and Russell indices. Business cycles were established following the NBER.FindingsThe results show that EPU has a negative effect on stocks with the intensity of the effect depending on the stock's profile. Small-cap and growth stocks were found to be most sensitive to EPU, especially during recessions. The negative effect is moderated by the economic cycle but is progressively diluted at the lower tail of the stock return distribution.Practical implicationsThe findings shed more light on investment strategies for growth/value investors that pursue opportunities arising from a changing economic cycle.Originality/valueThis study makes the following contributions: (1) explores the impact of EPU on the return of different stocks across a conditional distribution, and (2) provides evidence on how the economic cycle influences EPU impact on growth/value stocks and small/large stocks.
Gamification design: toward developing image perception scales for generation Z consumers
Authors: Stylos Nikolaos , Vassiliadis Chris A. 
Published: October 2023

Purpose
Drawing from the Personal Construct Theory, this study aims to analyze the impact of using gamified apps on user behavior by investigating the service-related images and individual preferences of Generation Z (GenZ) consumers, as these emerge from gamified applications in a tourism context.

Design/methodology/approach
The repertory grid analysis (RGA) elicited the top elements that reflect GenZer perceptions in tourism from empirical studies in the UK and Greece. Generalized procrustes analysis was used to investigate the structure of the data for the creation of representative consensus biplots of the most important conceptual constructs to advance consumer decision-making modeling via gamification.

Findings
As per different gamified app best-practices considered, the authors extract not only common perceptual elements (e.g. place informative aspects, exploration, lodgings, food/catering) but also different image components (e.g. virtual/interactive, business vs commercial traveling, entertainment, heritage/cultural informative aspects) from comparing UK with Greek GenZers’ responses. These extracted attributes are then presented in two dimensional charts, respectively, toward creating tourist perception scales.

Research limitations/implications
Notwithstanding the wide availability of gamified apps, research on gamification design in tourism and hospitality is still in the early phase. This study demonstrates the need to identify and optimize the formation of different images among GenZers. It also highlights the advantageous nature of the proposed combination of procrustes analysis with the RGA.

Originality/value
To the best of the authors’ knowledge, this research is among the first empirical ones toward creating scales for measuring tourist perceptions of GenZers coming from different consumer markets. It responds to scholars’ recent calls for better informing gamification design and improving contemporary consumer experience.