bluuebunny/crossref_metadata_2025_split huggingface dataset:
Navigability of Residential Care Homes From Residents’, Family Members’, and Staff’s Points of View: The Residential Care Home Navigability Scale
Authors: Miola Laura , Carbone Elena , Toffalini Enrico , Pazzaglia Francesca 
Published: March 2023

Abstract

Background and Objectives
Navigational skills display clear signs of decline with increasing age, especially in pathological aging. Therefore, navigability—the extent to which destinations can be reached with reasonable effort and time—should be considered in residential care home design. We aimed to develop a scale assessing environmental features (i.e., indoor visual differentiation, signage, and layout) for navigability in residential care homes: the Residential Care Home Navigability (RCHN) scale. To this end, we examined whether navigability and its factors were associated with a sense of direction within the residential care homes to different degrees for older adult residents, caregivers, and staff. The relationship between navigability and residential satisfaction was also considered.

Research Design and Methods
A sample of 523 participants (230 residents, 126 family caregivers, and 167 staff members) responded to the RCHN, assessed their sense of orientation and general satisfaction, and performed a pointing task.

Results
Results confirmed the RCHN scale’s 3-level factor structure, good reliability, and validity. A subjective sense of direction, but not pointing task performance, was associated with navigability and its factors. In particular, visual differentiation is positively associated with a sense of direction regardless of group, whereas signage and layout contributed to a better experience of a sense of direction, especially among older residents. Navigability was not related to residents’ satisfaction.

Discussion and Implications
Navigability supports perceived orientation in residential care homes, especially for older residents. Moreover, the RCHN is a reliable tool for the assessment of RCHN, with important implications for minimizing spatial disorientation through environmental interventions.
Characterization and expression of highly active recombinant human glucuronyl C5-epimerase in mammalian cells
Authors: Cui Hao , Li Qingwen , Wang Peipei , Fang Jianping 
Published: March 2023

Abstract
Heparin, a highly sulfated and epimerized form of heparan sulfate, is a linear polysaccharide with anticoagulant activity widely used in the clinic to prevent and treat thrombotic diseases. However, there are several noteworthy drawbacks associated with animal-sourced heparin during the preparation process. The in vitro enzymatic synthesis of heparin has become a promising substitute for animal-derived heparin. The synthesis of bioengineered heparin involves recombinant expression and preparation of polymerases, sulfotransferases, and an epimerase. D-glucuronyl C5-epimerase (HSepi) catalyzes D-glucuronic acids immediately adjacent to N-sulfo-glucosamine units to L-iduronic acid. Preparation of recombinant HSepi with high activity and production yield for in vitro heparin synthesis has not been resolved as of now. The findings of this study indicate that the catalytic activity of HSepi is regulated using post-translational modifications, including N-linked glycosylation and disulfide bond formation. Further mutation studies suggest that tyrosine residues, such as Tyr168, Tyr222, Tyr500, Tyr560, and Tyr578, are crucial in maintaining HSepi activity. A high-yield expression strategy was established using the lentiviral-based transduction system to produce recombinant HSepi (HSepi589) with a specific activity of up to 1.6 IU/mg. Together, this study contributes to the preparation of highly active HSepi for the enzymatic synthesis of heparins by providing additional insights into the catalytic activity of HSepi.
Variant spectrum of von Hippel–Lindau disease and its genomic heterogeneity in Japan
Authors: Tamura Kenji , Kanazashi Yuki , Kawada Chiaki , Sekine Yuya , Maejima Kazuhiro , Ashida Shingo , Karashima Takashi , Kojima Shohei , Parrish Nickolas F , Kosugi Shunichi , Terao Chikashi , Sasagawa Shota , Fujita Masashi , Johnson Todd A , Momozawa Yukihide , Inoue Keiji , Shuin Taro , Nakagawa Hidewaki 
Published: March 2023

Abstract
Von Hippel–Lindau (VHL) disease is an autosomal dominant, inherited syndrome with variants in the VHL gene, causing predisposition to multi-organ neoplasms with vessel abnormality. Germline variants in VHL can be detected in 80–90% of patients clinically diagnosed with VHL disease. Here, we summarize the results of genetic tests for 206 Japanese VHL families, and elucidate the molecular mechanisms of VHL disease, especially in variant-negative unsolved cases. Of the 206 families, genetic diagnosis was positive in 175 families (85%), including 134 families (65%) diagnosed by exon sequencing (15 novel variants) and 41 (20%) diagnosed by multiplex ligation-dependent probe amplification (MLPA) (one novel variant). The deleterious variants were significantly enriched in VHL disease Type 1. Interestingly, five synonymous or non-synonymous variants within exon 2 caused exon 2 skipping, which is the first report of exon 2 skipping caused by several missense variants. Whole genome and target deep sequencing analysis were performed for 22 unsolved cases with no variant identified and found three cases with VHL mosaicism (variant allele frequency: 2.5–22%), one with mobile element insertion in the VHL promoter region, and two with a pathogenic variant of BAP1 or SDHB. The variants associated with VHL disease are heterogeneous, and for more accuracy of the genetic diagnosis of VHL disease, comprehensive genome and DNA/RNA analyses are required to detect VHL mosaicism, complicated structure variants and other related gene variants.
Geographic–genomic and geographic–phenotypic differentiation of the Aquilegia viridiflora complex
Authors: Zhang Wei , Wang Huaying , Zhang Tengjiao , Fang Xiaoxue , Liu Meiying , Xiao Hongxing 
Published: March 2023

Abstract
How species diverge into different lineages is a central issue in evolutionary biology. Despite the increasing evidence indicating that such divergences do not need geographic isolation, the correlation between lineage divergence and the adaptive ecological divergence of phenotype corresponding to distribution is still unknown. In addition, gene flow has been widely detected during and through such diverging processes. We used one widely distributed Aquilegia viridiflora complex as a model system to examine genomic differentiation and corresponding phenotypic variations along geographic gradients. Our phenotypic analyses of 20 populations from northwest to northeast China identified two phenotypic groups along the geographic cline. All examined traits are distinct from each other, although a few intermediate individuals occur in their contacting regions. We further sequenced the genomes of representative individuals of each population. However, four distinct genetic lineages were detected based on nuclear genomes. In particular, we recovered numerous genetic hybrids in the contact regions of four lineages. Gene flow is widespread and continuous between four lineages but much higher between contacting lineages than geographically isolated lineages. Gene flow and natural selection might result in inconsistency between heredity and phenotype. Moreover, many genes with fast lineage-specific mutations were identified to be involved in local adaptation. Our results suggest that both geographic isolation and local selection exerted by the environment and pollinators may together create geographic distributions of phenotypic variations as well as the underlying genomic divergences in numerous lineages.
Integrated model simulates bigger, sweeter tomatoes under changing climate under reduced nitrogen and water input
Authors: Zhou Huiping , Kang Shaozhong , Génard Michel , Vercambre Gilles , Chen Jinliang 
Published: March 2023

Abstract
When simulating the response of fruit growth and quality to environmental factors and cultivation practices, the interactions between the mother plant and fruit need to be considered as a whole system. Here, we developed the integrative Tomato plant and fruit Growth and Fruit Sugar metabolism (TGFS) model by coupling equations describing the biophysical processes of leaf gas exchange, water transport, carbon allocation, organ growth and fruit sugar metabolism. The model also accounts for effects of soil nitrogen and atmospheric CO2 concentration on gaseous exchange of water and carbon by the leaf. With different nitrogen and water input values, TGFS performed well at simulating the dry mass of the tomato leaf, stem, root, and fruit, and the concentrations of soluble sugar and starch in fruit. TGFS simulations showed that increasing air temperature and CO2 concentration has positive effects on fruit growth, but not on sugar concentrations. Further model-based analyses of cultivation scenarios suggest that, in the context of climate change, decreasing N by 15%–25% and decreasing irrigation by 10%–20% relative to current levels would increase tomato fresh weight by 27.8%–36.4% while increasing soluble sugar concentration by up to 10%. TGFS provides a promising tool to optimise N and water inputs for sustainable high-quality tomatoes.
Developing and Evaluating a Virtual Reality Videogame Using Biofeedback for Stress Management in Sports
Authors: Téllez Arturo Morales , Castro Luis A , Tentori Monica 
Published: March 2023

AbstractStress is a reaction of the body to external challenges, whether physical or psychological. In sports, there are stress factors that affect the athlete's performance, especially in team sports that involve short, high-intensity exercise cycles followed by short recovery periods, such as American football. The lack of stress regulation mechanisms can be detrimental to the individual and collective performance of athletes. Biofeedback systems have shown promising clinical results in regulating stress for sports competitions. However, there is a lack of scientific evidence to support their efficacy, and technologies, such as virtual reality videogames, have not been extensively explored. In this article, we present the development and pilot testing of Virtual Autonomic Nervous System (VANS), a virtual reality videogame using biofeedback that supports stress management training in athletes. VANS uses an optical heart rate sensor and aims at keeping the heart rate below a given threshold to control features within the game. We evaluated the usability and user experience of VANS through a 1-week deployment study with 10 American footballers. Our results show that VANS outperformed a commercial videogame used for biofeedback training and considerably reduced stress in our participants. Therefore, VANS could provide stress management training for future matches and competitions. Finally, we reflect on aspects of our design and discuss future directions of our work.
Understanding the perceived role of electronic health records and workflow fragmentation on clinician documentation burden in emergency departments
Authors: Moy Amanda J , Hobensack Mollie , Marshall Kyle , Vawdrey David K , Kim Eugene Y , Cato Kenrick D , Rossetti Sarah C 
Published: March 2023

Abstract

Objective
Understand the perceived role of electronic health records (EHR) and workflow fragmentation on clinician documentation burden in the emergency department (ED).

Methods
From February to June 2022, we conducted semistructured interviews among a national sample of US prescribing providers and registered nurses who actively practice in the adult ED setting and use Epic Systems’ EHR. We recruited participants through professional listservs, social media, and email invitations sent to healthcare professionals. We analyzed interview transcripts using inductive thematic analysis and interviewed participants until we achieved thematic saturation. We finalized themes through a consensus-building process.

Results
We conducted interviews with 12 prescribing providers and 12 registered nurses. Six themes were identified related to EHR factors perceived to contribute to documentation burden including lack of advanced EHR capabilities, absence of EHR optimization for clinicians, poor user interface design, hindered communication, increased manual work, and added workflow blockages, and five themes associated with cognitive load. Two themes emerged in the relationship between workflow fragmentation and EHR documentation burden: underlying sources and adverse consequences.

Discussion
Obtaining further stakeholder input and consensus is essential to determine whether these perceived burdensome EHR factors could be extended to broader contexts and addressed through optimizing existing EHR systems alone or through a broad overhaul of the EHR’s architecture and primary purpose.

Conclusion
While most clinicians perceived that the EHR added value to patient care and care quality, our findings underscore the importance of designing EHRs that are in harmony with ED clinical workflows to alleviate the clinician documentation burden.
Lysine Acetyltransferases (KATs) in Disguise: Diseases Implications
Authors: Srivastava Swati , Kumar Sanjay , Bhatt Rohini , Ramachandran Ravishankar , Trivedi Arun K , Kundu Tapas K 
Published: March 2023

Abstract
Acetylation is one of the key post-translational protein modifications catalysed by the protein lysine acetyltransferases (KATs). KATs catalyse the transfer of acetyl groups to the epsilon-amino groups of lysine residues in histones and non-histone proteins. Because of its wide range of target proteins, KATs regulate many biological processes, and their aberrant activities may underlie several human diseases, including cancer, asthma, Chronic Obstructive Pulmonary Disease (COPD), and neurological disorders. Unlike most of the histone modifying enzymes, such as lysine methyltransferases, KATs do not possess any conserved domain like SET domain of lysine methyltransferases. However, almost all the major families of KATs are found to be transcriptional coactivators or adaptor proteins, with defined catalytic domains, called canonical KATs. Over the past two decades, a few proteins have been discovered to possess intrinsic KAT activity but are not classical coactivators. We would like to categorize them as non-canonical KATs (NC-KATs). These NC-KATs include general transcription factors TAFII250, mammalian TFIIIC complex, and mitochondrial protein GCN5L1, etc. This review focuses on our understanding, as well as controversies regarding non-canonical KATs, where we compare the structural and functional similarities and dissimilarities of non-canonical KATs with the canonical KATs. This review also highlights the potential role of NC-KATs in health and diseases.
Notoginsenoside R1 Facilitates Cell Angiogenesis by Inactivating the Notch Signaling During Wound Healing
Authors: Li Dongjin , Wang Deping , Cai Jun , Guo Qinghao , Jiang Lintao 
Published: March 2023

Abstract
The development of chronic, nonhealing wounds is a persistent medical problem that drives patient morbidity and increases healthcare costs. Angiogenesis is a critical accompanying activity in the proliferation stage during the wound healing process. Notoginsenoside R1 (NGR1) isolated from Radix notoginseng has been reported to alleviate diabetic ulcers by promoting angiogenesis and decreasing inflammatory responses and apoptosis. In the present study, we investigated the effect of NGR1 on angiogenesis and its therapeutic functions in cutaneous wound healing. For in vitro evaluation, cell counting kit-8 assays, migration assays, Matrigel-based angiogenic assays, and western blotting were conducted. The experimental results showed that NGR1 (10–50 μM) had no cytotoxicity to human skin fibroblasts (HSFs) and human microvascular endothelial cells (HMEC), and NGR1 treatment facilitated the migration of HSFs and enhanced angiogenesis in HMECs. Mechanistically, NGR1 treatment inhibited the activation of Notch signaling in HMECs. For in vivo analysis, hematoxylin-eosin staining, immunostaining, and Masson’s trichrome staining were performed, and we found that NGR1 treatment promoted angiogenesis, reduced wound widths, and facilitated wound healing. Furthermore, HMECs were treated with N-[N-(3,5-difluorophenacetyl)-L-alanyl]-S-phenylglycine t-butyl ester (DAPT; a Notch inhibitor), and DAPT treatment was found to exert pro-angiogenic effects. Simultaneously, DAPT was administrated into experimental cutaneous wound healing model, and we found that DAPT administration prevented the development of cutaneous wounds. Collectively, NGR1 promotes angiogenesis and wound repair via activation of the Notch pathway and exhibits therapeutic effects on cutaneous wound healing.
A novel embedding composition for the evaluation of the internal structure of carbon materials using electron microscopy
Authors: Yahagi Tsukaho 
Published: March 2023

Abstract
The image contrast obtained in electron microscopy depends on the atomic number of the sample. Therefore, obtaining a clear contrast is challenging when samples composed of light elements (carbon materials and polymers) are embedded in the resin. Herein, a newly developed embedding composition exhibiting low viscosity and high electron density is reported, which can be solidified using physical or chemical methods. When used for carbon materials, this embedding composition allows clear microscopic observation with higher contrast compared to conventional resin embedding. Furthermore, details of the observation of samples such as graphite and carbon black using this embedding composition are reported.
The ‘Arbitralization’ of Courts: The Role of International Commercial Arbitration in the Establishment and the Procedural Design of International Commercial Courts
Authors: Antonopoulou Georgia 
Published: March 2023

Abstract
International commercial arbitration is the most preferred dispute resolution method in cross-border commercial disputes. It has been, however, claimed that arbitration has lost its flexibility by becoming increasingly formal and by incorporating litigation practices. In academic literature, this trend has been termed the ‘judicialization’ of international commercial arbitration. This article argues that while arbitration is becoming progressively judicialized, international commercial courts evidence an opposite, less studied trend; namely, the ‘arbitralization’ of courts. Through a comparative analysis of different international commercial courts, the article explores how the competition with arbitration has prompted the establishment of these courts, and how arbitration has served as the inspiration for some of their most innovative features. The article concludes that while the incorporation of arbitration features could improve court proceedings, some of international commercial courts’ arbitration features undermine procedural justice and the role of courts as public institutions and therefore hit the limits of arbitralization.
Accretion of substellar companions as the origin of chemical abundance inhomogeneities in globular clusters
Authors: Winter Andrew J , Clarke Cathie J 
Published: March 2023

ABSTRACTGlobular clusters exhibit abundance variations, defining ‘multiple populations’, which have prompted a protracted search for their origin. Properties requiring explanation include the high fraction of polluted stars (∼40−90 per cent, correlated with cluster mass), the absence of pollution in young clusters, and the lower pollution rate with binarity and distance from the cluster centre. We present a novel mechanism for late delivery of pollutants into stars via accretion of substellar companions. In this scenario, stars move through a medium polluted with asymptotic giant branch (AGB) and massive star ejecta, accreting material to produce companions with typical mass ratio q ∼ 0.1. These companions undergo eccentricity excitation due to dynamical perturbations by passing stars, culminating in a merger with their host star. The accretion of the companion alters surface abundances via injected pollutant. Alongside other self-enrichment models, the companion accretion model can explain the dilution of pollutant and correlation with intracluster location. The model also explains the ubiquity and discreteness of the populations and correlations of enrichment rates with cluster mass, cluster age, and stellar binarity. Abundance variations in some clusters can be broadly reproduced using AGB and massive binary ejecta abundances from the literature. In other clusters, some high companion mass ratios (q ≳ 1) are required. In these cases, the available mass budget necessitates a variable degree of mixing of the polluted material with the primary star, deviations from model ejecta abundances, or mixing of internal burning products. We highlight the avenues of further investigation that are required to explore some of the key processes invoked in this model.
Hidden deep in the halo: selection of a reduced proper motion halo catalogue and mining retrograde streams in the velocity space
Authors: Viswanathan Akshara , Starkenburg Else , Koppelman Helmer H , Helmi Amina , Balbinot Eduardo , Esselink Anna F 
Published: March 2023

ABSTRACTThe Milky Way halo is one of the few galactic haloes that provides a unique insight into galaxy formation by resolved stellar populations. Here, we present a catalogue of ∼47 million halo stars selected independent of parallax and line-of-sight velocities, using a combination of Gaia DR3 proper motion and photometry by means of their reduced proper motion. We select high tangential velocity (halo) main sequence stars and fit distances to them using their simple colour-absolute-magnitude relation. This sample reaches out to ∼21 kpc with a median distance of 6.6 kpc thereby probing much further out than would be possible using reliable Gaia parallaxes. The typical uncertainty in their distances is $0.57_{-0.26}^{+0.56}$ kpc. Using the colour range 0.45 &lt; (G0 − GRP, 0) &lt; 0.715, where the main sequence is narrower, gives an even better accuracy down to $0.39_{-0.12}^{+0.18}$ kpc in distance. The median velocity uncertainty for stars within this colour range is 15.5 km s−1. The distribution of these sources in the sky, together with their tangential component velocities, are very well-suited to study retrograde substructures. We explore the selection of two complex retrograde streams: GD-1 and Jhelum. For these streams, we resolve the gaps, wiggles and density breaks reported in the literature more clearly. We also illustrate the effect of the kinematic selection bias towards high proper motion stars and incompleteness at larger distances due to Gaia’s scanning law. These examples showcase how the full RPM catalogue made available here can help us paint a more detailed picture of the build-up of the Milky Way halo.