bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cerebellar degeneration impairs strategy discovery but not strategy recall
Authors: Tsay Jonathan S. , Schuck Lauren , Ivry Richard B. 
Published: October 2022

AbstractThe cerebellum is recognized to play a critical role in the automatic and implicit process by which movement errors are used to keep the sensorimotor system precisely calibrated. However, its role in other learning processes frequently engaged during sensorimotor adaptation tasks remains unclear. In the present study, we tested the performance of individuals with cerebellar degeneration on a variant of a visuomotor adaptation task in which learning requires the use of strategic re-aiming, a process that can nullify movement errors in a rapid and volitional manner. Our design allowed us to assess two components of this learning process, the discovery of an appropriate strategy and the recall of a learned strategy. Participants were exposed to a 60° visuomotor rotation twice, with the initial exposure block assessing strategy discovery and the re-exposure block assessing strategy recall. Compared to age-matched controls, individuals with cerebellar degeneration were slower to derive an appropriate aiming strategy in the initial Discovery block but exhibited similar recall of the aiming strategy during the Recall block. This dissociation underscores the multi-faceted contributions of the cerebellum to sensorimotor learning, highlighting one way in which this subcortical structure facilitates volitional action selection.
The methyltransferases METTL7A and METTL7B confer resistance to thiol-based histone deacetylase inhibitors
Authors: Robey Robert W. , Fitzsimmons Christina M. , Guiblet Wilfried M. , Frye William J.E. , González Dalmasy José M. , Wang Li , Russell Drake A. , Huff Lyn M. , Perciaccante Andrew J. , Ali-Rahmani Fatima , Lipsey Crystal C. , Wade Heidi M. , Mitchell Allison V. , Maligireddy Siddhardha S. , Terrero David , Butcher Donna , Edmondson Elijah F. , Jenkins Lisa M. , Nikitina Tatiana , Zhurkin Victor B. , Tiwari Amit K. , Piscopio Anthony D. , Totah Rheem A. , Bates Susan E. , Efsun Arda H. , Gottesman Michael M. , Batista Pedro J. 
Published: October 2022

ABSTRACTHistone deacetylase inhibitors (HDACis) are part of a growing class of epigenetic therapies used for the treatment of cancer. While elevated levels of the efflux pump P-gp are associated within vitroresistance to romidepsin, this mechanism does not translate to the clinic. We developed a romidepsin-resistant cell line with a resistance mechanism independent of P-gp function that acts upstream of the deacetylation process. We found that expression of the methyltransferase METTL7A is necessary for resistance, and that expression of METTL7A in naïve cells can drive resistance to thiol-containing HDACis. We demonstrate that METTL7A can methylate romidesinin vitroand that the ability of METTL7A to drive resistance to thiol-containing HDACis can be blocked by the methyltransferase inhibitor DCMB. Our data supports a model whereby exposure of cells to romidepsin selects for upregulation of the methyltransferase METTL7A, which in turn modifies the zinc-binding thiol, inactivating the drug.
Quantifying common and distinct information in single-cell multimodal data with Tilted-CCA
Authors: Lin Kevin Z. , Zhang Nancy R. 
Published: October 2022

ABSTRACTMultimodal single-cell technologies profile multiple modalities for each cell simultaneously and enable a more thorough characterization of cell populations alongside investigations into cross-modality relationships. Existing dimension-reduction methods for multimodal data focus on capturing the “union of information,” producing a lower-dimensional embedding that combines the information across modalities. While these tools are useful, we develop Tilted-CCA to quantify the “intersection and difference of information”, that is, a decomposition of a paired multimodal dataset into common axes of variation that is shared between both modalities and distinct axes of variation that is found only in one modality. Through examples, we show that Tilted-CCA enables meaningful visualization and quantification of the cross-modal information overlap. We also demonstrate the application of Tilted-CCA to two specific types of analyses. First, for single-cell experiments that jointly profile the transcriptome and surface antibody markers, we show how to use Tilted-CCA to design the target antibody panel to best complement the transcriptome. Second, for single-cell multiome data that jointly profiles transcriptome and chromatin accessibility, we show how to use the common embedding given by Tilted-CCA to identify development-informative genes and distinguish between transient versus terminal cell types.
The proto-oncogene c-Src phosphorylates cGAS to reduce DNA binding and activation
Authors: Dunker William , Zaver Shivam A , Howard Cameron J , Woodward Joshua J 
Published: October 2022

SummarycGMP-AMP synthase (cGAS) is a DNA sensor and responsible for inducing an anti-tumor immune response. Recent studies reveal cGAS is frequently inhibited in cancer, and therapeutic targets to promote anti-tumor cGAS function remain elusive. c-Src is a proto-oncogene tyrosine kinase and is expressed at elevated levels in numerous cancers. Here, we demonstrate that c-Src expression in tumors from various cancers negatively correlates with innate immune gene expression and patient survival. We determine that c-Src restricts cGAS signaling in human cell lines through c-Src small molecule inhibitors, depletion, and overexpression. cGAS and c-Src interact in cells and in vitro, while c-Src directly inhibits cGAS enzymatic activity and DNA binding in a kinase-dependent manner. c-Src phosphorylates cGAS, and inhibition of cGAS Y248 phosphorylation partially reduces c-Src inhibition. Collectively, our study demonstrates that cGAS anti-tumor signaling is hindered by the proto-oncogene c-Src and describes how cancer-associated proteins can regulate the innate immune system.
Inter-individual variation in human cortical cell type abundance and expression
Authors: Johansen Nelson , Somasundaram Saroja , Travaglini Kyle J. , Yanny Anna Marie , Shumyatcher Maya , Casper Tamara , Cobbs Charles , Dee Nick , Ellenbogen Richard , Ferreira Manuel , Goldy Jeff , Guzman Junitta , Gwinn Ryder , Hirschstein Daniel , Jorstad Nikolas L. , Keene C. Dirk , Ko Andrew , Levi Boaz P. , Ojemann Jeffrey G. , Pham Thanh , Shapovalova Nadiya , Silbergeld Daniel , Sulc Josef , Torkelson Amy , Tung Herman , Smith Kimberly , Lein Ed S. , Bakken Trygve E. , Hodge Rebecca D. , Miller Jeremy A. 
Published: October 2022

AbstractSingle cell transcriptomic studies have identified a conserved set of neocortical cell types from small post-mortem cohorts. We extend these efforts by assessing cell type variation across 75 adult individuals undergoing epilepsy and tumor surgeries. Nearly all nuclei map to one of 125 robust cell types identified in middle temporal gyrus, but with varied abundances and gene expression signatures across donors, particularly in deep layer glutamatergic neurons. A minority of variance is explainable by known factors including donor identity and small contributions from age, sex, ancestry, and disease state. Genomic variation was significantly associated with variable expression of 150-250 genes for most cell types. Thus, human individuals display a highly consistent cellular makeup, but with significant variation reflecting donor characteristics, disease condition, and genetic regulation.One-Sentence SummaryInter-individual variation in human cortex is greatest for deep layer excitatory neurons and largely unexplainable by known factors.
vamos: VNTR annotation using efficient motif sets
Authors: Ren Jingwen , Gu Bida , Chaisson Mark JP 
Published: October 2022

AbstractMotivationRoughly 3% of the human genome is composed of variable-number tandem repeats (VNTRs): tandemly repeated arrays of motifs at least six bases. These loci are highly polymorphic: over 61% of insertion and deletion variants at least 50 bases found from long-read assemblies are inside VNTRs. Furthermore, long-read assemblies reveal that VNTR loci are multiallelic, and can vary by both motif composition and copy number. Current approaches that define and merge variants based on alignment breakpoints do not capture this complexity of variation. A natural alternative approach is to instead define the motif composition of VNTR sequences from samples, and to detect differences based on comparisons of repeat composition. However, due to the complexity of VNTR sequences, it is difficult to establish a common reference set of motif sequences that may be used to describe variation in large sequencing studies.ResultsHere we present a method vamos: VNTR Annotation using efficient Motif Sets that for any VNTR locus selects a set of representative motifs from all motifs observed at that locus that may be used to encode VNTR sequences within a bounded edit distance of the original sequence. We use our method to characterize VNTR variation in 32 haplotype-resolved human genomes. In contrast to current studies that merge multi-allelic calls, we estimate an average of 3.1-4.0 alleles per locus.Availabilitygithub.com/chaissonlab/vamos, zenodo.org/record/7158427Contactmchaisso@usc.edu
CHK2 Regulates MUS81-EME2 Function in Response to Replication Stress and BRCA2 Deficiency
Authors: Malacaria Eva , Palma Anita , Rinalducci Sara , Franchitto Annapaola , Pichierri Pietro 
Published: October 2022

ABSTRACTMUS81 is a structure-specific endonuclease that processes DNA intermediates in mitosis and in S-phase following replication stress. MUS81 is crucial to cleave deprotected reversed forks in BRCA2-deficient cells. However, how MUS81 is regulated during replication stress in human cells remains unknown.Our study reveals that CHK2 binds the MUS81-EME2 complex and positively regulates formation of DSBs upon replication stress or in the absence of BRCA2. The association with MUS81 occurs through the FHA domain of CHK2 and is disabled by the Li-Fraumeni-associated mutation I157T. The CHK2-MUS81-EME2 complex forms downstream fork reversal and degradation, and phosphorylation of MUS81 at CHK2-targeted sites is crucial to introduce DSBs at deprotected replication forks ensuring the replication fork recovery in BRCA2-deficient cells.Collectively, our work sheds light into the regulation of the MUS81-EME2 complex and identifies a novel function of the ATM-CHK2 axis in the response to deprotected replication forks in the absence of BRCA2.
Hyperactive mTOR in Lung Mesenchyme Induces Endothelial Dysfunction and Pulmonary Vascular Remodeling
Authors: Lin Susan M. , Rue Ryan , Goel Akansha , Obraztsova Kseniya , Mukhitov Alexander R. , Vanka Kanth Swaroop , Smith Carly J. , Basil Maria C. , Ferguson Laura T. , Planer Joseph D. , Cantu Edward , Kwapiszewska Grazyna , Morrisey Edward E. , Evans Jillian F. , Krymskaya Vera P. 
Published: October 2022

AbstractPulmonary vascular remodeling is the key structural abnormality in pulmonary hypertension (PH). Mechanistic target of rapamycin (mTOR) has long been suspected to play a role in the development of pulmonary vascular remodeling. However, underlying cellular and molecular mechanisms leading to this pathophysiological condition remain incompletely understood. To elucidate the crosstalk between lung mesenchyme with activated mTOR and endothelial cells (ECs), we focused on a monogenic lung disease, pulmonary lymphangioleiomyomatosis (LAM). LAM is a progressive cystic lung disease caused by a mutational inactivation of tuberous sclerosis complex (TSC1/TSC2), which results in constitutive mTOR activation in mesenchymal LAM cells. ECs derived from LAM lung explants showed increased proliferation, migration, and defective angiogenesis compared to age- and sex-matched ECs from control human lung. In LAM cells, we found increased WNT2 ligand expression. We also identified corresponding Frizzled 4 (FZD) receptors on ECs isolated from distal LAM lung, suggesting cellular crosstalk between LAM cells and ECs. In endothelial-fibroblast cocultures, treatment of normal ECs with WNT2 ligands recapitulated LAM EC phenotype and morphology. We observed transcriptomic upregulation in metabolic, angiogenic and growth pathways in ECs of young mice, while 1-year-old Tsc2KO mice spontaneously developed pulmonary vascular remodeling with concurrent elevation in right ventricular systolic pressure. Our study demonstrates that LAM cells are not just a pathological mesenchymal cell state but a signaling hub that contributes to dysregulated cellular response in the surrounding vasculature, eventual pulmonary vascular remodeling and PH.
Coaxiality and perpendicularity prediction of saddle surface rotor based on deep belief networks
Authors: Sun Chuanzhi , Wang Yin Chu , Lu Qing , Liu Yongmeng , Tan Jiubin 
Published: October 2022

Purpose
Aiming at the problem that the transmission mechanism of the assembly error of the multi-stage rotor with saddle surface type is not clear, the purpose of this paper is to propose a deep belief network to realize the prediction of the coaxiality and perpendicularity of the multi-stage rotor.

Design/methodology/approach
First, the surface type of the aero-engine rotor is classified. The rotor surface profile sampling data is converted into image structure data, and a rotor surface type classifier based on convolutional neural network is established. Then, for the saddle surface rotor, a prediction model of coaxiality and perpendicularity based on deep belief network is established. To verify the effectiveness of the coaxiality and perpendicularity prediction method proposed in this paper, a multi-stage rotor coaxiality and perpendicularity assembly measurement experiment is carried out.

Findings
The results of this paper show that the accuracy rate of face type classification using convolutional neural network is 99%, which meets the requirements of subsequent assembly process. For the 80 sets of test samples, the average errors of the coaxiality and perpendicularity of the deep belief network prediction method are 0.1 and 1.6 µm, respectively.

Originality/value
Therefore, the method proposed in this paper can be used not only for rotor surface classification but also to guide the assembly of aero-engine multi-stage rotors.
Rethinking digital construction: a study of BIM uptake capability in BIM infant construction industries
Authors: Adeniyi Onaopepo , Thurairajah Niraj , Leo-Olagbaye Feyisetan 
Published: October 2022

Purpose
Practitioners have reported a minimal and non-use of building information modelling (BIM), especially in small and medium-sized organisations and BIM infant construction industries. This development calls for a reappraisal of organisations’ strength in capabilities required for BIM uptake towards the target of global construction digitalisation. This study aims to assess the BIM Level 2 uptake capability of organisations in a BIM infant construction industry and identify the underlying interactions between the capability criteria.

Design/methodology/approach
The study used a multivariable analysis of fifteen descriptors identified from the people, process, policy, finance and technology domain. Data collection was done in the BIM infant construction industry in Nigeria. Verification of the descriptors and an evaluation of BIM uptake capability in organisations was done. Seventy-three responses were received within the selected context, and data analysis was done with mean weighting and exploratory factor analysis. Maximum Likelihood extraction and Direct Oblimin rotation were used.

Findings
Factor analysis revealed three factors that explained 53.28% of the total variance in the BIM Level 2 uptake capability of construction organisations. The factors are workforce capacity and continuous development, an affinity for innovation and strength in physical and operational facilities.

Research limitations/implications
This study provides an overarching and insightful discussion on BIM uptake capability and construction digitalisation with evidence from a BIM-infant construction industry.

Practical implications
The findings of this study are a piece of valuable empirical evidence on Level 2 BIM uptake capability. This empirical situation analysis will inform the advocacy for the advancement of BIM and enhanced utilisation of building information. Evidence on the capability performance of the BIM infant industry has been revealed.

Originality/value
The outcome is expected to stir debate on the preparedness of organisations to further exploit the benefits of BIM in the BIM infant construction industry. Examination of the capability for a particular phase of BIM is scanty in the literature.
Converting commercial and industrial property into rented residential accommodation: development of a decision support tool
Authors: Taylor Kieran , Edwards David J. , Lai Joseph H.K. , Rillie Iain , Thwala Wellington Didibhuku , Shelbourn Mark 
Published: October 2022

Purpose
This study aims to develop a decision-making tool that assesses the economic feasibility of converting commercial and industrial buildings into rented residential accommodation. This tool also enables developers to provide high-quality rented residential accommodation that contribute to the gentrification of formerly industrialised inner city or developed areas.

Design/methodology/approach
The overarching epistemological approach adopted used inductive reasoning and a postpositivist philosophical design to structure the research problem and devise new theories about the phenomena under investigation. From an operational perspective, a two-phase “waterfall” research approach was adopted. Phase one used extant literature to identify development factors and variables for consideration, risks posed and conversion appraisal criteria. Two case studies formed the basis of a cross comparative analysis, namely, a new build and conversion of a former industrial building into rented residential accommodation. Phase two identified development appraisal criteria, conducted a cost analysis and premised upon the findings, developed a decision support appraisal tool as a “proof of concept”.

Findings
The research combined key decision factors and variables that assist property developers when evaluating whether to convert commercial and industrial property into rented residential accommodation. The appraisal tool’s functionality was validated via a focus group discussion with senior property developers to ensure that assessment criteria and development weightings were appropriate. Feedback revealed that the tool was suitable for purpose and should now be adopted in practice and refined as appropriate and with usage.

Research limitations/implications
The appraisal tool presented could yield a far more accurate means of decision-making which, in turn, could ensure that predicted investment returns are received (thus reducing errors and lowering risk for investors). Future work is required to robustly test and validate the tool’s accuracy in practice. It is envisaged that future projects will provide a rich stream of data for such testing.

Originality/value
To the best of the authors’ knowledge, this work constitutes the first attempt to conceptualise a decision support tool for rented residential property development.
Priority setting for 2050 future images and policy agendas of the Republic of Korea: engaging the national assembly
Authors: Heo Jongho , Lee Chaejeong , Min Bogyeong 
Published: October 2022

PurposeThis study aims to identify and prioritize preferable 2050 future images and the policy agendas of the Republic of Korea using a bottom-up approach, involving legislative staff of the National Assembly as well as experts from various fields.Design/methodology/approachThe authors derived three future images from the future policy agendas selected by experts: society for growth of smart generations (GS), society for sustainability and safety (SS) and society for coexistence and diversity (CD). The survey conducted among legislative staff (n= 189) shows that the most preferred future image was SS. Then, the authors prioritized the policy agendas that aligned with future images using priority calculating methods.FindingsThe most prioritized policy agenda was “Social system for coexistence to resolve social conflict,” followed by “Social sustainability through tackling low birth rate.” The next was “Social integration policies to embrace diverse family composition” and “Responding to social change and knowledge transformation caused by artificial intelligence.” Among the top five rankings, two agendas from each SS and CD were selected.Practical implicationsTo achieve the preferred future images, implementing policies related to sustainability, human rights and coexistence are necessary for continuous collaboration among stakeholders, especially those from the legislature.Originality/valueThis study presents a method of involving the National Assembly, which is a representative institution of the people and composed of various political parties, to set the national’s future vision and agenda from a long-term perspective.
Delivering remote therapy during the COVID-19 pandemic: a qualitative study with service users accessing a community personality disorder service
Authors: White Jasmin , Nillo Anne-Marie , Rowsell Kathryn , Roberts Victoria , Dudley-Hicks Duncan , Urbasch Michael , Cordwell John 
Published: October 2022

PurposeThe purpose of this study is to qualitatively explore the views and opinions of service users accessing remote therapy through a community forensic personality disorder service during the COVID-19 pandemic.Design/methodology/approachA qualitative exploratory approach was adopted. Nine community forensic service users accessing virtual/telephone therapy through a community forensic mental health service were interviewed using semi-structed interviews. Data was analysed using Braun and Clarke (2006) thematic analysis techniques.FindingsAnalysis resulted in three overall themes: experience of communication in the therapeutic relationship; impacts of the change to remote working and making the best of what we have. A further seven subthemes were developed. A range of advantages and disadvantages to remote therapy were highlighted.Research limitations/implicationsThis study was based on a small sample of service users accessing one community forensic service in England, and therefore caution should be taken when generalising the findings. All interviews were conducted remotely and thus may have only supported those who are able to engage in this way.Practical implicationsThis paper has the potential to inform future remote therapy guidelines. Health services should consider keeping some elements of remote working and offering this as a choice to all service users.Originality/valueThis study is, to the best of the authors’ knowledge, the first study that attempts to explore the experiences of individuals accessing remote therapy within a forensic population who have personality disorders or traits.