bluuebunny/crossref_metadata_2025_split huggingface dataset:
Regenotyping structural variants through an accurate force-calling method
Authors: Jiang Tao , Cao Shuqi , Liu Yadong , Liu Shiqi , Liu Bo , Wang GuoHua , Wang Yadong 
Published: August 2022

AbstractLong-read sequencing technologies have great potential for the comprehensive discovery of structural variation (SV). However, accurate genotype assignment for SV is still a challenge due to unavoidable factors, such as specific sequencing errors or limited coverage. Herein, we propose cuteSV2, a fast and accurate long-read-based regenotyping approach that is used to force calling genotypes for given records. In cuteSV2, which is an upgraded version of cuteSV, an improved refinement strategy is applied on the signatures, and the heuristic extracted signatures are purified through spatial and allele similarity estimation. The benchmarking results on several baseline evaluations demonstrate that cuteSV2 outperforms the state-of-the-art methods and is a scalable and robust approach for population studies and clinical practice. cuteSV2 is available athttps://github.com/tjiangHIT/cuteSV.
Synaptic Expression of TAR-DNA-Binding Protein 43 in the Mouse Spinal Cord Determined Using Super-Resolution Microscopy
Authors: Broadhead Matthew J. , Doucet Katherine , Kantelberg Owen , Zhu Fei , Grant Seth GN , Horrocks Mathew H , Miles Gareth B. 
Published: August 2022

AbstractCellular inclusions of hyperphosphorylated TAR-DNA-Binding Protein 43 (TDP-43) are a key hallmark of neurodegenerative diseases such as Amyotrophic Lateral Sclerosis (ALS). ALS is characterised by a loss of motor neurons in the brain and spinal cord that is preceded by early-stage changes in synaptic function that may be associated with TDP-43 pathology. However, there has been little characterisation of the synaptic expression of TDP-43 in spinal cord synapses. This study utilises a range of high-resolution and super-resolution microscopy techniques with immunolabelling, as well as an aptamer-based TDP-43 labelling strategy visualised with single-molecule localisation microscopy, to characterise and quantify the presence of phosphorylated TDP-43 (pTDP-43) in spinal cord synapses. We observe that TDP-43 is expressed in the majority of spinal cord synapses as nanoscale clusters as small as 60 nm in diameter. Synaptic TDP-43 expression is more frequently associated with presynaptic terminals than postsynaptic densities, and is more enriched in VGLUT1-associated synapses, compared to VGLUT2-associated synapses. Our nanoscopy techniques showed no difference in the subsynaptic expression of pTDP-43 in the ALS mouse model, SOD1G93a compared to healthy controls. This research characterizes the basic synaptic expression of TDP-43 with nanoscale precision and provides a framework with which to investigate the potential relationship between TDP-43 pathology and synaptic pathology in neurodegenerative diseases.
Small Training Dataset Convolutional Neural Networks for Application Specific Super-Resolution Microscopy
Authors: Mannam Varun , Howard Scott 
Published: August 2022

ABSTRACTSignificanceMachine learning (ML) models based on deep convolutional neural networks have been used to significantly increase microscopy resolution, speed (signal-to-noise ratio), and data interpretation. The bottleneck in developing effective ML systems is often the need to acquire large datasets to train the neural network. This paper demonstrates how adding a “dense encoder-decoder” block can be used to effectively train a neural network that produces super-resolution images from conventional microscopy diffraction-limited images trained using a small dataset (15 field-of-views).AimML helps to retrieve super-resolution information from a diffraction-limited image when trained with a massive training dataset. The aim of this work is to demonstrate a neural network that estimates super-resolution images from diffraction-limited images using modifications that enable training with a small dataset.ApproachWe employ “Dense Encoder-Decoder” (called DenseED) blocks in existing super-resolution ML network architectures. DenseED blocks use a dense layer that concatenates features from the previous convolutional layer to the next convolutional layer. DenseED blocks in fully convolutional networks (FCNs) estimate the super-resolution images when trained with a small training dataset (15 field-of-views) of human cells from the Widefield2SIM dataset and in fluorescent-labeled fixed bovine pulmonary artery endothelial cells (BPAE samples).ResultsConventional ML models without DenseED blocks trained on small datasets fail to accurately estimate super-resolution images while models including the DenseED blocks can. The average peak signal-to-noise ratio (PSNR) and resolution improvements achieved by networks containing DenseED blocks are ≈3.2 dB and 2×, respectively. We evaluated various configurations of target image generation methods (e.g, experimentally captured target and computationally generated target) that are used to train FCNs with and without DenseED blocks and showed including DenseED blocks in simple FCNs outperforms compared to simple FCNs without DenseED blocks.ConclusionsDenseED blocks in neural networks show accurate extraction of super-resolution images even if the ML model is trained with a small training dataset of 15 field-of-views. This approach shows that microscopy applications can use DenseED blocks to train on smaller datasets that are application-specific imaging platforms and there is a promise for applying this to other imaging modalities such as MRI/X-ray, etc.
Dlg1 regulates subcellular distribution of non-muscle myosin II during Drosophila germband extension
Authors: Fuentes Melisa A. , Piper Hayley N. , He Bing 
Published: August 2022

AbstractElongation of the body axis through convergent extension is a conserved developmental process that is mediated by cell intercalation. During convergent extension of the germband epithelium in Drosophila embryos, planar polarized activation of non-muscle myosin II (“myosin”) promotes cell intercalation by facilitating patterned remodeling of adherens junctions. Here, we report that loss of the basolateral determinant Dlg1 leads to defects in the subcellular distribution of myosin during germband extension, and consequently, impairs proper junctional remodeling and apical area maintenance during cell intercalation. In dlg1 mutant embryos, ectopic accumulation of myosin is observed at the medioapical domain and along the lateral membrane, whereas junctional myosin is greatly reduced. Analogous myosin mis-localization patterns are observed upon knockdown of other basolateral determinants, Scrib and Lgl, but not the apical determinants. The function of Dlg1 in regulating the spatial distribution of myosin requires its intact SH3 and GUK domains and involves the Rho1 GEF Cyst, active Rho1 and Rok. We propose that Dlg1 facilitates correct junctional remodeling and prevents undesired apical area variation during cell intercalation by regulating the subcellular location of myosin activation.
Geldanamycin treatment does not result in anti-cancer activity in a preclinical model of orthotopic mesothelioma
Authors: Orozco Morales M. Lizeth , Rinaldi Catherine A. , de Jong Emma , Lansley Sally M. , Gary Lee Y. C. , Zemek Rachael M. , Bosco Anthony , Lake Richard A. , Lesterhuis W. Joost 
Published: August 2022

ABSTRACTMesothelioma is characterised by its aggressive invasive behaviour, affecting the surrounding tissues of the pleura or peritoneum. We compared an invasive pleural model with a non-invasive subcutaneous model of mesothelioma and performed transcriptomic analyses on the tumour samples. Invasive pleural tumours were characterised by a transcriptomic signature enriched for genes associated with MEF2C and MYOCD signaling, muscle differentiation and myogenesis. Further analysis using the CMap and LINCS databases identified geldanamycin as a potential antagonist of this signature, so we evaluated its potential in vitro and in vivo. Nanomolar concentrations of geldanamycin significantly reduced cell growth, invasion, and migration in vitro. However, administration of geldanamycin in vivo did not result in significant anti-cancer activity. Our findings show that myogenesis and muscle differentiation pathways are upregulated in pleural mesothelioma which may be related to the invasive behaviour. However, geldanamycin as a single agent does not appear to be a viable treatment for mesothelioma.
Diversity and functional analysis of rumen and fecal microbial communities associated with dietary changes in crossbreed dairy cattle
Authors: Kibegwa Felix M. , Bett Rawlynce C. , Gachuiri Charles K. , Machuka Eunice , Stomeo Francesca , Mujibi Fidalis D. 
Published: August 2022

AbstractThe objective of this study was to investigate the effect of varying roughage and concentrate proportions, in diet of crossbreed dairy cattle, on the composition and associated functional genes of rumen and fecal microbiota. We also explored fecal samples as a proxy for rumen liquor samples. Six crossbred dairy cattle were reared on three diets with an increasing concentrate and reducing roughage amount in three consecutive 10-day periods. After each period, individual rumen liquor and fecal samples were collected and analyzed through shotgun metagenomic sequencing. Average relative abundance of identified Operational Taxonomic Units (OTU) and microbial functional roles from all animals were compared between diets and sample types (fecal and rumen liquor). Results indicated that dietary modifications significantly affected several rumen and fecal microbial OTUs. In the rumen, an increase in dietary concentrate resulted in an upsurge in the abundance of Proteobacteria, while reducing the proportions of Bacteroidetes and Firmicutes. Conversely, changes in microbial composition in fecal samples were not consistent with dietary modification patterns. Microbial functional pathway classification identified that carbohydrate metabolism and protein metabolism pathways dominated microbial roles. Assessment of dietary effects on the predicted functional roles of these microbiota revealed that a high amount of dietary concentrate resulted in an increase in central carbohydrate metabolism and a corresponding reduction in protein synthesis. Moreover, we identified several microbial stress-related responses linked to dietary changes.BacteroidesandClostridiumgenera were the principal hosts of these microbial functions. Therefore, the roughage to concentrate proportion has more influence on the microbial composition and microbial functional genes in rumen samples than fecal samples. As such, we did not establish a significant relationship between the rumen and fecal metagenome profiles, and the rumen and fecal microbiota from one animal did not correlate more than those from different animals.
Cardiomyocyte alpha-1A adrenergic receptors mitigate post-infarct remodeling and mortality by constraining necroptosis
Authors: Zhang Jiandong , Sandroni Peyton B. , Huang Wei , Oswalt Leah , Smith Alan J. , Ash Tyler , Lee Sung-Hoo , Shih Yen-Yu I. , Rossi Joseph S. , Huang Hsiao-Ying S. , Myagmar Bat E. , Simpson Paul C. , Schisler Jonathan C. , Jensen Brian C. 
Published: August 2022

AbstractActivation of alpha-1-adrenergic receptors (α1-ARs), particularly the α1A subtype, protects the murine heart against injury, whereas human studies show that α1-AR antagonists (α-blockers) may increase the risk of heart failure. We created a cardiomyocyte-specific α1A-AR knockout mouse (cmAKO) to define the mechanisms underlying these effects and to elucidate whether they arise from cardiomyocyte α1A-ARs or systemic factors. Myocardial infarction (MI) resulted in 70% 7-day mortality in cmAKO compared to 10% in wild type (WT) mice. cmAKO mice exhibited exaggerated ventricular remodeling and increased cell death compared to WT mice 3 days post-MI, coupled to upregulation of canonical mediators of necroptosis: receptor-interacting protein (RIP) kinases RIP1 and RIP3 and mixed lineage kinase domain-like protein. An α1A-AR agonist mitigated ischemia-induced cardiomyocyte death and necroptotic signaling in vitro. A RIP1 antagonist abrogated the protective effects of α1A activation in vivo and in vitro. We found that patients at our center who were taking α-blockers at the time of MI experienced a higher risk of mortality (hazard ratio 1.53, p=0.029) during 5-year follow-up, providing clinical correlation for our experimental data. Collectively our findings indicate that cardiomyocyte α1A-ARs constrain ischemia-induced necroptosis and suggest caution in the use of α-blockers in patients at risk for MI.
Deep Neural Networks Predict MHC-I Epitope Presentation and Transfer Learn Neoepitope Immunogenicity
Authors: Albert Benjamin Alexander , Yang Yunxiao , Shao Xiaoshan M. , Singh Dipika , Smith Kellie N. , Anagnostou Valsamo , Karchin Rachel 
Published: August 2022

AbstractIdentifying neoepitopes that elicit an adaptive immune response is a major bottleneck to developing personalized cancer vaccines. Experimental validation of candidate neoepitopes is extremely resource intensive, and the vast majority of candidates are non-immunogenic, making their identification a needle-in-a-haystack problem. To address this challenge, we present computational methods for predicting MHC-I epitopes and identifying immunogenic neoepitopes with improved precision. The BigMHC method comprises an ensemble of seven pan-allelic deep neural networks trained on peptide-MHC eluted ligand data from mass spectrometry assays and transfer learned on data from assays of antigen-specific immune response. Compared with four state-of-the-art classifiers, BigMHC significantly improves the prediction of epitope presentation on a test set of 45,409 MHC ligands among 900,592 random negatives (AUROC=0.9733, AUPRC=0.8779). After transfer learning on immunogenicity data, BigMHC yields significantly higher precision than seven state-of-the-art models in identifying immunogenic neoepitopes, making BigMHC effective in clinical settings. All data and code are freely available athttps://github.com/KarchinLab/bigmhc.
Polycomb response elements reduce leaky expression of Cas9 under temperature-inducibleHsp70Bbpromoter inDrosophila melanogaster
Authors: Warsinger-Pepe Natalie , Chang Carly , Desroberts Connor R. , Akbari Omar S. 
Published: August 2022

AbstractHeat shock inducible expression of genes through the use of heat inducible promoters is commonly used in research despite leaky expression of downstream genes of interest without targeted induction (i.e. heat shock). The development of non-leaky inducible expression systems are of broad interest for both basic and applied studies, to precisely control gene expression. Here we characterize the use of Polycomb response elements and the inducibleHeat shock protein 70Bbpromoter, previously described as a non-leaky inducible system, to regulate Cas9 endonuclease levels and function inDrosophila melanogasterafter varying both heat shock durations and rearing temperatures. We show that Polycomb response elements can significantly reduce expression ofCas9underHeat shock protein 70Bbpromoter control using a range of conditions, corroborating previously published results. We further demonstrate that this low transcript level of heat-inducedCas9is sufficient to induce mutant mosaic phenotypes. Incomplete suppression of an inducibleCas9system by Polycomb response elements with no heat shock suggests that further regulatory elements are required to precisely controlCas9expression and abundance.
Whether the audit expectation-performance gap is expanding amid changes in audit landscape? New evidence from an emerging economy
Authors: Kumari J.S. , Ajward Roshan 
Published: August 2022

PurposeThe purpose of this study is to provide fresh insights into whether there is an expectation gap between external auditors' and other stakeholders' perceptions of external auditors' responsibilities in an emerging economy, in light of recent changes to the global audit landscape.Design/methodology/approachA quantitative approach in the positivistic paradigm was adopted, and a structured questionnaire was used to gather data.FindingsThe findings suggested that there was a statistically significant discrepancy between external auditors' and social groups' perceptions of the responsibilities of external auditors. More than half of the gap was due to deficiency in standards, 19% due to unreasonable expectations by society, while 25% of the gap was found to be due to deficient performance.Research limitations/implicationsThe study focused on the duties of external auditors and not on the duties of other types of auditors while examining the audit expectation-performance gap (AEG), and this was due to the drastic differences in the scope of their duties.Practical implicationsThe findings of this study are likely to have direct policy implications for regulators, authorities, educators and auditing professionals, who should take immediate actions and measures to reduce the AEG in light of the current global audit landscape advancements and changes.Originality/valueThe present study used a substantially updated model to measure the AEG to suit the contemporary changes in the auditing landscape, and could be considered as a pioneering study that measures the AEG in an emerging economy amid recent changes.
Examining the role of team climate, transactive memory system, and team leader humility in teams: an empirical study of Indian generational cohorts
Authors: Maan Pratibha , Srivastava Dinesh Kumar 
Published: August 2022

PurposeThe study aims to define the term “generation” by proposing an integrated design based on age-period-cohort effects and by proposing an Indian generational cohort framework categorizing Indian generational cohorts into four categories, namely, Baby Boomers, GenX, GenY, and GenZ. The study further aimed to capture the existing generational differences between GenY and GenZ cohorts in the Indian teams on team climate, transactive memory system, and team leader humility.Design/methodology/approachFor the first two objectives a literature review methodology along with the author's proposition was adopted. An integrated design was proposed by reviewing the relevant sociological literature to define generations. Thereafter, an Indian cohort framework was proposed categorizing them into four groups Baby Boomers, GenX, GenY, and GenZ. Following that, for the last objective, i.e. to identify the differences between cohorts, empirical data were collected by a structured questionnaire that was disseminated to GenY and GenZ Indian working professionals. A total of 229 responses were used for observing the differences or similarities between GenY and GenZ cohorts on the study variables by employing an independent samples t-test.FindingsThe study proposed an integrated design (age, period, and cohort effect). Following that, an Indian generational cohort's framework has been outlined categorizing Indian cohorts based on their birth years, age groups, developmental stages, formative years, major Indian historical events, and various characteristics possessed by them. Moreover, the empirical findings support the existing generational disparities and depict that GenZ holds a higher inclination towards transactive memory systems and team climate whereas GenY holds more inclination toward leader humility.Practical implicationsThe study put forth its contribution to research scholars by categorizing Indian generational cohorts in a rationalized manner based on an integrated design (age-period-cohort) effect. The study would further assist concerned authorities and managers in formulating HR policies to deal with the underlying generational differences highlighted by the study.Originality/valueAs there lies a paucity of generational frameworks in the Indian context, this study is the first attempt in this direction which categorizes Indian generational cohorts based on a unique integrated design including age-period-cohort effects. In addition, the study also investigated these cohorts in Indian organizations to observe the existing variations.
Sociotechnical dimensions of BIM-induced changes in stakeholder management of public and private building projects
Authors: Mani Saba , Ahmadi Eftekhari Navid , Hosseini M. Reza , Bakhshi Javad 
Published: August 2022

Purpose
This paper aims to explore the various sociotechnical dimensions of building information modelling (BIM)-induced changes associated with stakeholder management of projects.

Design/methodology/approach
This paper relies on grounded theory and data collection from two case studies – one in the public sector and one in the private sector – and is underpinned by Leavitt’s (1964) sociotechnical model.

Findings
Findings reveal four new dimensions of stakeholder management as being affected through BIM-induced changes: commitment; transparency; learning and experience; and stakeholder satisfaction, with these extending beyond the dimensions recognised in the existing literature. Another novelty lies in bringing to light the highly context-specific nature of BIM-induced changes pertinent to stakeholder management, with the two case studies demonstrating differences in these changes. Furthermore, a theoretical model of the causal impacts of various identified dimensions is presented, in which the sequence of changes and the causal associations between the identified dimensions are conceptualised.

Originality/value
Through Leavitt’s (1964) Diamond lens, the procedure of change and its evolutionary procedure for various components of the sociotechnical system of stakeholder management are theorised. The tentative conceptualisations presented offer a springboard from which to further investigate the episode of change pertinent to various dimensions of stakeholder management in BIM-enabled projects.
Understanding the effects of educational decentralization through the perspectives of education managers and teachers
Authors: Khilji Gulab , Jogezai Nazir Ahmed , Bibi Nadra , Baloch Fozia Ahmed 
Published: August 2022

PurposeThe study was designed to investigate the effects of the decentralization of education through the perceptions of education managers.Design/methodology/approachThis was a qualitative case study research. The decentralization notification of 2014, issued by the secondary education department, Government of Balochistan, Pakistan was taken as a case. Some administrative and financial powers were devolved at cluster and district levels through this notification. In pursuance of data collection, focus group discussions were conducted with 20 education managers, 20 teachers, and 5 high-ranked education policy actors. The gathered data were analyzed using thematic analysis.FindingsThe study found that the intent of the decentralization move was positive, where some of the issues of teachers are now resolved at district and school levels. However, academic decentralization was utterly neglected. Furthermore, with the inclusion of district administration in the education decision-making, powers seem to be recentralized. The study concluded that decentralization should occur through a proper legislative process based on sound planning. There should be a balance between central authorities and local/district-level education management in education management and decision-making.Research limitations/implicationsThe study adds to the existing literature relating to education management and informs education managers, teachers, school principals, and policy actors for research-based and informed decision-making.Originality/valueThis study was conducted in a developing country to understand the effects of decentralized education management. The authors declare the organicity of the data. The authors also declare that the paper has not been submitted to any other journal or in review elsewhere.