bluuebunny/crossref_metadata_2025_split huggingface dataset:
Long-Read Sequencing Identifies the First Retrotransposon Insertion and Resolves Structural Variants Causing Antithrombin Deficiency
Authors: de la Morena-Barrio Belén , Stephens Jonathan , de la Morena-Barrio María Eugenia , Stefanucci Luca , Padilla José , Miñano Antonia , Gleadall Nicholas , García Juan Luis , López-Fernández María Fernanda , Morange Pierre-Emmanuel , Puurunen Marja , Undas Anetta , Vidal Francisco , Raymond Frances Lucy , Vicente Vicente , Ouwehand Willem H. , Corral Javier , Sanchis-Juan Alba ,   NIHR BioResource
Published: June 2022

AbstractThe identification of inherited antithrombin deficiency (ATD) is critical to prevent potentially life-threatening thrombotic events. Causal variants in SERPINC1 are identified for up to 70% of cases, the majority being single-nucleotide variants and indels. The detection and characterization of structural variants (SVs) in ATD remain challenging due to the high number of repetitive elements in SERPINC1. Here, we performed long-read whole-genome sequencing on 10 familial and 9 singleton cases with type I ATD proven by functional and antigen assays, who were selected from a cohort of 340 patients with this rare disorder because genetic analyses were either negative, ambiguous, or not fully characterized. We developed an analysis workflow to identify disease-associated SVs. This approach resolved, independently of its size or type, all eight SVs detected by multiple ligation-dependent probe amplification, and identified for the first time a complex rearrangement previously misclassified as a deletion. Remarkably, we identified the mechanism explaining ATD in 2 out of 11 cases with previous unknown defect: the insertion of a novel 2.4 kb SINE-VNTR-Alu retroelement, which was characterized by de novo assembly and verified by specific polymerase chain reaction amplification and sequencing in the probands and affected relatives. The nucleotide-level resolution achieved for all SVs allowed breakpoint analysis, which revealed repetitive elements and microhomologies supporting a common replication-based mechanism for all the SVs. Our study underscores the utility of long-read sequencing technology as a complementary method to identify, characterize, and unveil the molecular mechanism of disease-causing SVs involved in ATD, and enlarges the catalogue of genetic disorders caused by retrotransposon insertions.
Nothing for Me or About Me, Without Me: Codesign of Clinical Decision Support
Authors: van Leeuwen Danny , Mittelman Michael , Fabian Lacy , Lomotan Edwin A. 
Published: June 2022

Abstract
Background Partnerships among patients, families, caregivers, and clinicians are critical to helping patients lead their best lives given their specific genetics, conditions, circumstances, and the environments in which they live, work, and play. These partnerships extend to the development of health information technology, including clinical decision support (CDS). Design of these technologies, however, often occurs without a profound understanding of the true needs, wants, and concerns of patients and family members. Patient perspective is important not only for patient-facing applications but for provider-facing applications, especially those intended to support shared decision-making.
Objectives Our objective is to describe models for effectively engaging patients and caregivers during CDS development and implementation and to inspire CDS developers to partner with patients and caregivers to improve the potential impact of CDS.
Methods This article serves as a case study of how two patient activists successfully implemented models for engaging patients and caregivers in a federal program designed to increase the uptake of research evidence into clinical practice through CDS. Models included virtual focus groups, social media, agile software development, and attention to privacy and cybersecurity.
Results Impact on the federal program has been substantial and has resulted in improved CDS training materials, new prototype CDS applications, prioritization of new functionality and features, and increased engagement of patient and caregiver communities in ongoing projects. Among these opportunities is a group of developers and patient activists dedicated and committed to exploring strategic and operational opportunities to codesign CDS applications.
Conclusion Codesign and implementation of CDS can occur as a partnership among developers, implementers, patients, cybersecurity and privacy activists, and caregivers. Several approaches are viable, and an iterative process is most promising. Additional work is needed to investigate scalability of the approaches explored by this case study and to identify measures of meaningful inclusion of patients/caregivers in CDS projects.
Early expression of mature αβ TCR in CD4−CD8−T cell progenitors enables MHC to drive development of T-ALL bearing NOTCH mutations
Authors: Laffey Kimberly G. , Stiles Robert J. , Ludescher Melissa J. , Davis Tessa R. , Khwaja Shariq S. , Bram Richard J. , Wettstein Peter J. , Ramachandran Venkataraman , Parks Christopher A. , Reyes Edwin E. , Ferrer Alejandro , Canfield Jenna M. , Johnson Cory E. , Hammer Richard D. , Gil Diana , Schrum Adam G. 
Published: June 2022

During normal T cell development in mouse and human, a low-frequency population of immature CD4−CD8−double-negative (DN) thymocytes expresses early, mature αβ T cell antigen receptor (TCR). We report that these early αβ TCR+ DN (EADN) cells are DN3b-DN4 stage and require CD3δ but not major histocompatibility complex (MHC) for their generation/detection. When MHC - is present, however, EADN cells can respond to it, displaying a degree of coreceptor-independent MHC reactivity not typical of mature, conventional αβ T cells. We found these data to be connected with observations that EADN cells were susceptible to T cell acute lymphoblastic leukemia (T-ALL) transformation in both humans and mice. Using the OT-1 TCR transgenic system to model EADN-stage αβ TCR expression, we found that EADN leukemogenesis required MHC to induce development of T-ALL bearing NOTCH1 mutations. This leukemia-driving MHC requirement could be lost, however, upon passaging the tumors in vivo, even when matching MHC was continuously present in recipient animals and on the tumor cells themselves. These data demonstrate that MHC:TCR signaling can be required to initiate a cancer phenotype from an understudied developmental state that appears to be represented in the mouse and human disease spectrum.
L2 writing
Authors: Schoonen Rob 
Published: June 2022

Abstract
This chapter aims to identify sources of individual differences in writing proficiency, and ways to measure these differences. The construct of writing proficiency is delineated and embedded in cognitive approaches to writing research. It is considered to be a multi-faceted construct, which implies that various component skills contribute to the quality of the eventual writing performance. Writing in a second language often builds on L1 writing skills and procedures, but also raises its own questions, such as the role of transfer of (metacognitive) knowledge, and the writer’s strength and weaknesses in the target language. The best way to assess a language learner’s writing proficiency very much depends on the assessment purposes, and can range from a focused measurement of subskills with discrete-point tests, for diagnostic purposes, to a general performance assessment with holistic rating, for admission purposes. A number of characteristics of these measurements are discussed in the second part of this chapter.
L2 writing and its internal correlates
Authors: Kojima Masumi , Kaneta Taku 
Published: June 2022

Abstract
This study examined the overall average correlation between second/foreign language (L2) writing performance and frequently investigated features of writing (i.e., writing-internal correlates). The correlates of L2 writing performance included objective measures of text features (syntactic complexity, lexical complexity, accuracy, fluency, and cohesion) as well as subjective measures (content, argument, organization, cohesion, coherence, grammar, vocabulary, language use, mechanics, and accuracy). A series of moderator analyses were also carried out for each type of objective measure to examine the effects of participants’ age, L2 proficiency, learning context, first language (L1) and L2 distance, task type, writing scoring method, and some characteristics of objective measures. By doing so, the present study aimed to identify key correlates of L2 writing performance and compare their relative importance. To this end, a total of 103 retrieved studies contributed 1,045 effect sizes based on 15,537 independent participants. The results for objective measures demonstrated that fluency had the strongest mean correlation with L2 writing performance (r = .570), followed by accuracy (r = .477), lexical complexity (r = .295), syntactic complexity (r = .271), and cohesion (r = .198). All subjective measure components had strong mean correlations with L2 writing performance (r = .668 to .927), but content and language use features had the strongest effects and cohesion and coherence features showed the least effects. Participants’ age, learning context, L1–L2 distance, writing scoring method, and some measurement characteristics were found to be significant moderators for certain components. The findings of this study have implications for L2 instruction suggesting that fluency and language accuracy of L2 writing should be promoted across the various developmental stages of L2 learners in various conditions, whereas lexical and syntactic competence should be more focused upon when instructing child/adolescent or low/intermediate L2 writers.
L2 writing and its external correlates
Authors: Kojima Masumi , In'nami Yo , Kaneta Taku 
Published: June 2022

Abstract
The present meta-analysis examined the overall average correlation between second/foreign language (L2) writing performance and each of 11 key predictor variables frequently investigated in the research domain, and compared the relative importance of those variables. A series of moderator analyses were also carried out to examine the effects of age, L2 proficiency, first language (L1) and L2 distance, learning context, and measurement characteristics for six high-evidence correlates (L2 grammar, L2 vocabulary, L2 reading, L2 speaking, L1 writing, and motivational constructs). By doing so, we examined various L2 proficiency models, writing models, and hypotheses, particularly the core-periphery model proposed by Hulstijn (2015). To this end, a total of 103 retrieved studies contributed 377 effect sizes based on 112,475 independent participants. The results showed that L2 reading and speaking achievement had strong average correlations with L2 writing performance, whereas L1 writing performance had a medium correlation with it. L2 linguistic knowledge (grammar, vocabulary, transcription, decoding) had more medium to strong effects on L2 writing performance than language-general cognitive skills and motivational constructs, which had only weak effects. The effects of metacognitive knowledge were trivial and insignificant. L2 proficiency, age, and certain measurement characteristics were found to be significant moderators for certain components.
L2 listening comprehension
Authors: Wagner Elvis 
Published: June 2022

Abstract
This chapter examines how L2 listening ability has been modeled and operationalized in the research literature, and provides a critical overview of the dominant models. It also describes how researchers have used both taxonomies of listening skills as well as data-driven approaches to creating models of listening ability. The chapter then provides a critical discussion of how the constructs of L2 listening ability have been operationalized and measured by empirical researchers. The chapter concludes with an analysis of why models and operationalizations of L2 listening ability have often neglected to include or focus on those aspects of language that are unique to listening ability.
L2 speaking
Authors: Gao Jie , Ginther April 
Published: June 2022

Abstract
This chapter unpacks L2 speaking theories through a cognitive approach, where models such as the Blueprint (Levelt, 1989) and the bilingual speech model of Kormos (2006) are used to explain speech production. From the perspective of language testing and assessment, we further discuss fluency and vocabulary as measurable constructs, which reflects their contribution to the utterance-based strand of L2 speaking assessment research. In addition, we review the categorization framework of cognitive fluency, utterance fluency, and perceived fluency proposed by Segalowitz (2010). This framework emphasizes the operational mechanisms underlying speaking performance, meanwhile highlighting participation from both speakers and listeners. From the perspective of language teaching, we summarize different instructional approaches to L2 speaking, as well as the impact of segmental and suprasegmental features on pronunciation proficiency. We also synthesize the operationalization methods for intelligibility, comprehensibility, and accentedness, which are closely connected with both L2 speaking assessment and pronunciation instruction.
Mechanical testing of particle streaming and intact extracellular mucilage nanofibers reveal a role of elastic force in diatom motility
Authors: Gutiérrez-Medina Braulio , Peña Maldonado Ana Iris , García-Meza Jessica Viridiana 
Published: June 2022

Abstract
Diatoms are unicellular microalgae with a rigid cell wall, able to glide on surfaces by releasing nanopolymeric fibers through central slits known as raphes. Here we consider the model Nitszchia communis to perform quantitative studies on two complementary aspects involved in diatom gliding. Using video microscopy and automated image analysis, we measure the motion of test beads as they are pulled by extracellular polymeric substances (EPS) fibers at the diatom raphe (particle streaming). A multimodal distribution of particle speed is found, evidencing the appearance of short-time events of high speed and acceleration (known as jerky motion) and suggesting that different mechanisms contribute to set diatom velocity during gliding. Furthermore, we use optical tweezers to obtain force-extension records for extracellular diatom nanofibers; records are well described by the worm-like chain model of polymer elasticity. In contrast to previous studies based on application of denaturing force (in the nN regime), application of low force (up to 6 pN) and using enable us to obtain the persistence length of intact fibers. From these measurements, mechanical parameters of EPS fibers such as radius and elastic constant are estimated. Furthermore, by modeling particle streaming as a spring in parallel with a dashpot, we show that the time involved in the release of mechanical energy after fiber detachment from beads (elastic snapping) agrees with our observations of jerky motion. We conclude that the smooth and jerky motions displayed by gliding diatoms correspond to molecular motors and elastic snapping, respectively, thus providing quantitative elements that incorporate to current models of the mechanics behind diatom locomotion.
Directed network analysis reveals changes in cortical and muscular connectivity caused by different standing balance tasks
Authors: Liang Tie , Hong Lei , Xiao Jinzhuang , Wei Lixin , Liu Xiaoguang , Wang Hongrui , Dong Bin , Liu Xiuling 
Published: June 2022

Abstract

Objective. Standing balance forms the basis of daily activities that require the integration of multi-sensory information and coordination of multi-muscle activation. Previous studies have confirmed that the cortex is directly involved in balance control, but little is known about the neural mechanisms of cortical integration and muscle coordination in maintaining standing balance. Approach. We used a direct directed transfer function (dDTF) to analyze the changes in the cortex and muscle connections of healthy subjects (15 subjects: 13 male and 2 female) corresponding to different standing balance tasks. Main results. The results show that the topology of the EEG brain network and muscle network changes significantly as the difficulty of the balancing tasks increases. For muscle networks, the connection analysis shows that the connection of antagonistic muscle pairs plays a major role in the task. For EEG brain networks, graph theory-based analysis shows that the clustering coefficient increases significantly, and the characteristic path length decreases significantly with increasing task difficulty. We also found that cortex-to-muscle connections increased with the difficulty of the task and were significantly stronger than the muscle-to-cortex connections. Significance. These results show that changes in the difficulty of balancing tasks alter EEG brain networks and muscle networks, and an analysis based on the directed network can provide rich information for exploring the neural mechanisms of balance control.
Multi-view cross-subject seizure detection with information bottleneck attribution
Authors: Zhao Yanna , Zhang Gaobo , Zhang Yongfeng , Xiao Tiantian , Wang Ziwei , Xu Fangzhou , Zheng Yuanjie 
Published: June 2022

Abstract

Objective. Significant progress has been witnessed in within-subject seizure detection from electroencephalography (EEG) signals. Consequently, more and more works have been shifted from within-subject seizure detection to cross-subject scenarios. However, the progress is hindered by inter-patient variations caused by gender, seizure type, etc. Approach. To tackle this problem, we propose a multi-view cross-object seizure detection model with information bottleneck attribution (IBA). Significance. Feature representations specific to seizures are learned from raw EEG data by adversarial deep learning. Combined with the manually designed discriminative features, the model can detect seizures across different subjects. In addition, we introduce IBA to provide insights into the decision-making of the adversarial learning process, thus enhancing the interpretability of the model. Main results. Extensive experiments are conducted on two benchmark datasets. The experimental results verify the efficacy of the model.
Landscape structure of the territory of the State nature sanctuary of regional significance “Sursky Peaks” (Ulyanovsk region, Russia)
Authors: Astashin A E , Badin M M , Krivdina I Yu , Vatina O E , Pashkin O N 
Published: June 2022

Abstract
The article presents the results of landscape differentiation of the territory of the state nature sanctuary “Sursky Peaks” (Ulyanovsk region), performed at the hierarchical level of landscape types. The researched territory is located in the forest-steppe zone (northern forest-steppe subzone) within the Volga upland. The territory is characterized by high biological diversity. The high environmental significance determines the relevance of the landscape zoning scheme, which is necessary for the effective organization of environmental and recreational activities. During the research, 4 landscapes were identified, for each of which a list of characteristic stows was established, areas of violations of the environmental regime – clearings – were identified and mapped. The work was carried out on the basis of field researches, conducted in 2021, materials of remote sensing of the Earth, thematic maps, literary data processed using GIS.
Thermal conditions of storing seed grain in a hermetic container with a regulated air environment
Authors: Latyshenok M B , Shemyakin A V , Latyshenok N M , Slobodskova A A , Gasparyan S V 
Published: June 2022

Abstract
Grain production largely determines the level of development of the country, its food security and the standard of living of the population. Currently, about 70 000 enterprises and organizations in all agricultural regions of the country are engaged in grain production in the Russian Federation, of which more than half are peasant farms that do not have an adequate base for storing seed grain and scientifically based storage technologies, in particular. The choice of the storage method is determined by many conditions. It is necessary to consider climatic features of the area where grain will be stored, types and capacities of granaries, etc. The cheapest and easiest way to store grain is storage in metal silos, but it does not protect seeds from thermal processes occurring in the grain bulk under the influence of external climatic factors and therefore it is unsuitable for their storage.
The influence of highly dispersed humic acids on the growth and decorative qualities of Tagetes patula L.
Authors: Nazarova A A , Fadkin G N , Cherkasov O V , Borychev S N , Shemyakin A V 
Published: June 2022

Abstract
Ryazan Agrotechnological University. P.A. Kostychev, the biocatalytic properties of highly dispersed humic acids (HHA) on various crops are being studied, but the question of the influence of HHA on ornamental crops has not been studied at all. A laboratory experiment on seeds and seedlings of Tagetes patula L. (variety “Makkeny’s Gold”) showed that for the seeds of this crop, the most effective concentration of HHA is 5.0 g/t, which increases germination, the length of the sprout by 2.5 mm (+9.5 %) and root by 3.8 mm (+20.9%), as well as the weight of the sprout by 36.7% and root by 55.9% relative to the control. An experiment on vegetative plants Tagetes patula L. showed that a dose of HHA of 5.0 g/t increases the decorative qualities of this crop, so there was an increase in plant height by 5.1 cm (+21%) and root system weight by 1.3 g ( + 25.5%), the number of leaves per 1 plant increased by 5 pcs (+14.7%), the number of flowers per 1 plant increased by 1.9 pcs (+25%), as well as the flower diameter by 0.9 cm ( +15.3%) relative to control. HHA at a dose of 6.0 g/t most effectively influenced the speed of the vegetation phases, reducing the period from germination to the beginning of flowering by 6 days. Also, when using HHA 6.0 g/t, the maximum seed productivity of Tagetes patula L. was determined, the weight of seeds from 1 plant was 5.3 g, which is higher than the control by 0.8 g (+17.8%).
Neural network modeling as a means of providing free access to the results of agronomic research in the scientific community
Authors: Nikiforov A G , Rekovets A V , Konova A M , Takhumova O V , Morkovkin D E , Zubovov Ya O , Chernikina E V 
Published: June 2022

Abstract
The results of field studies of the yield of spring barley are considered in order to use them to build a neural network model. The main stages of obtaining the model are described. An accuracy of about 2% was obtained, which makes it possible to use the model for research and practical activities. The model was verified, which showed new ways of conducting scientific research on the yield of grain crops.