bluuebunny/crossref_metadata_2025_split huggingface dataset:
Myocardial deformation imaging by 2D speckle tracking echocardiography for assessment of diastolic dysfunction in murine cardiopathology
Authors: Daniels Lorna J. , Macindoe Calum , Koutsifeli Parisa , Annandale Marco , Raaijmakers Antonia J. A. , Weeks Kate L , Bell James R. , Janssens Johannes V. , Curl Claire L. , Delbridge Lea M.D. , Mellor Kimberley M. 
Published: August 2022

ABSTRACTDiastolic dysfunction is increasingly identified as a key, early onset subclinical condition characterizing cardiopathologies of rising prevalence, including diabetic heart disease and heart failure with preserved ejection fraction (HFpEF). Diastolic dysfunction characterization has important prognostic value in management of disease outcomes. Validated tools for in vivo monitoring of diastolic function in rodent models of diabetes are required for progress in pre-clinical cardiology studies. 2D speckle tracking echocardiography has emerged as a powerful tool for evaluating cardiac wall deformation throughout the cardiac cycle. The aim of this study was to examine the applicability of 2D speckle tracking echocardiography for comprehensive global and regional assessment of diastolic function in a pre-clinical murine model of cardio-metabolic disease. Type 2 diabetes (T2D) was induced in C57Bl/6 male mice using a high fat high sugar dietary intervention for 20 weeks. Significant impairment in left ventricle peak diastolic strain rate was evident in longitudinal, radial and circumferential planes in T2D mice. Peak diastolic velocity was similarly impaired in the longitudinal and radial planes. Regional analysis of longitudinal peak diastolic strain rate revealed that the anterior free left ventricular wall is particularly susceptible to T2D-induced diastolic dysfunction. These findings provide a significant advance on characterization of diastolic dysfunction in a pre-clinical mouse model of cardiopathology and offer a comprehensive suite of benchmark values for future pre-clinical cardiology studies.
Sensitive multimodal profiling of native DNA by transposase-mediated single-molecule sequencing
Authors: Nanda Arjun S , Wu Ke , Kasinathan Sivakanthan , Ostrowski Megan S , Clugston Andrew S , Satpathy Ansuman T , Sweet-Cordero E Alejandro , Goodarzi Hani , Ramani Vijay 
Published: August 2022

ABSTRACTWe present SMRT-Tag: a multiplexable, PCR-free approach for constructing low-input, single-molecule Pacific Biosciences (PacBio) sequencing libraries through Tn5 transposition. As proof-of-concept, we apply SMRT-Tag to resolve human genetic and epigenetic variation in gold-standard human reference samples. SMRT-Tag requires 1-5% as much input material as existing protocols (15,000 – 50,000 human cell equivalents) and enables highly- sensitive and simultaneous detection of single nucleotide variants, small insertions / deletions, and CpG methylation comparable to the current state-of-the-art. We further combine SMRT-Tag with in situ adenine methyltransferase footprinting of nuclei (SAMOSA-Tag) to facilitate joint analysis of nucleosome repeat length, CTCF occupancy, and CpG methylation on individual chromatin fibers in osteosarcoma cells. SMRT-Tag promises to enable basic and clinical research by offering scalable, sensitive, and multimodal single-molecule genomic and epigenomic analyses in rare cell populations.
Nuclear m6A Reader YTHDC1 Promotes Muscle Stem Cell Activation/Proliferation by Regulating mRNA Splicing and Nuclear Export
Authors: Qiao Yulong , Sun Qiang , Chen Xiaona , Wang Di , Su Ruibao , Xue Yuanchao , Sun Hao , Wang Huating 
Published: August 2022

AbstractSkeletal muscle stem cells (also known as satellite cells, SCs) are essential for muscle regeneration and the regenerative activities of SCs are intrinsically governed by gene regulatory mechanisms but the post-transcriptional regulation in SCs remains largely unknown. N(6)-methyladenosine (m6A) modification of RNAs is the most pervasive and highly conserved RNA modification in eukaryotic cells and exerts powerful impact on almost all aspects of mRNA processing which is mainly endowed by its binding with m6A reader proteins. Here in this study, we investigate the previously uncharacterized regulatory roles of YTHDC1, a m6A reader in SCs. Our results demonstrate YTHDC1 is an essential regulator of SC activation and proliferation upon acute injury induced muscle regeneration. The induction of YTHDC1 is indispensable for SC activation and proliferation thus inducible YTHDC1 depletion almost abolishes SC regenerative capacity. Mechanistically, transcriptome-wide profiling using LACE-seq in both SCs and C2C12 myoblasts identifies m6A mediated binding targets of YTHDC1. Next, splicing analysis defines splicing mRNA targets of m6A-YTHDC1. Furthermore, nuclear export analysis also leads to identification of potential mRNA export targets of m6A-YTHDC1 in SCs and C2C12 myoblasts and interestingly some mRNAs can be regulated at both splicing and export levels. Lastly, we map YTHDC1 interacting protein partners in myoblasts and unveil a myriad of factors governing mRNA splicing, nuclear export and transcription, among which hnRNPG appears to be a bona fide interacting partner of YTHDC1. Altogether, our findings uncover YTHDC1 as an essential factor controlling SC regenerative ability through multi-faceted gene regulatory mechanisms in myoblast cells.
Pink1-mediated mitophagy in the endothelium releases proteins encoded by mitochondrial DNA and activates neutrophil responses
Authors: Gajwani Priyanka , Wang Li , Srivastava Shubhi , Ye Zijing , Kim Young-Mee , Krantz Sarah , Wang Dong-Mei , Tiruppathi Chinnaswamy , Toth Peter T. , Rehman Jalees 
Published: August 2022

AbstractGiven their ancient evolutionary origins, eukaryotic mitochondria possess multiple vestiges of their prokaryotic ancestors. One such factor is the N-terminal formylation of proteins encoded by mitochondrial DNA. N-formylated proteins are also released by bacteria and trigger activation of immune cells such as neutrophils. Growing evidence indicate that circulating levels of mitochondrial formyl proteins are elevated in the serum of patients with excessive inflammatory responses and trigger neutrophil activation like their bacterial counterparts. However, the cellular source of these proteins, and the mechanism by which they are released into the circulation is not known. In this study, we have identified vascular endothelial cells as a source of mitophagy induced release of formyl proteins in response to inflammatory mediators in vitro. Mechanistically, endothelial mitophagy required activation of the Pink1 pathway. Using liposomal delivery of sgRNA targeting Pink1 in mice expressing endothelial-specific Cas9, we developed a mouse model in which Pink1 is specifically depleted in the endothelium. Deletion of endothelial Pink1 was remarkably protective in endotoxin-induced lung inflammation, resulting in reduced neutrophil infiltration and significantly reduced death in mice. We thus propose that endothelial cells upregulate pro-inflammatory mitophagy in response to inflammation, leading to release of mitochondrial formyl peptides and detrimental neutrophil recruitment into the lung.
Isoform-specific Disruption of the TP73 Gene Reveals a Critical Role for TAp73gamma in Tumorigenesis via Leptin
Authors: Kong Xiangmudong , Yan Wensheng , Sun Wenqiang , Zhang Yanhong , Yang Hee Jung , Chen Mingyi , Chen Hongwu , de Vere White Ralph W. , Zhang Jin , Chen Xinbin 
Published: August 2022

AbstractTP73, a member of the p53 family, is expressed as TAp73 and ΔNp73 along with multiple C-terminal isoforms (α−η). ΔNp73 is primarily expressed in neuronal cells and necessary for neuronal development. Interestingly, while TAp73α is a tumor suppressor and predominantly expressed in normal cells, TAp73 is found to be frequently altered in human cancers, suggesting a role of TAp73 C-terminal isoforms in tumorigenesis. To test this, the TCGA SpliceSeq database was searched and showed that exon 11 (E11) exclusion occurs frequently in several human cancers. We also found that p73α to p73γ isoform switch resulting from E11 skipping occurs frequently in human prostate cancers and dog lymphomas. To determine whether p73α to p73γ isoform switch plays a role in tumorigenesis, CRISPR technology was used to generate multiple cancer cell lines and a mouse model in that Trp73 E11 is deleted. Surprisingly, we found that in E11-deificient cells, p73γ becomes the predominant isoform and exerts oncogenic activities by promoting cell proliferation and migration. In line with this, E11-deficient mice were more prone to obesity and B-cell lymphomas, indicating a unique role of p73γ in lipid metabolism and tumorigenesis. Additionally, we found that E11-deficient mice phenocopies Trp73-deficient mice with short lifespan, infertility, and chronic inflammation. Mechanistically, Mechanistically, we showed that Leptin, a pleiotropic adipocytokine involved in energy metabolism and oncogenesis, was highly induced by p73γ, necessary for p73γ-mediated oncogenic activity, and associated with p73α to γ isoform switch in human prostate cancer and dog lymphoma. Finally, we showed that E11-knockout promoted, whereas knockdown of p73γ or Leptin suppressed, xenograft growth in mice. Our study indicates that the p73γ-Leptin pathway promotes tumorigenesis and alters lipid metabolism, which may be targeted for cancer management.
Robin’s Viewer: Using Deep-Learning Predictions to Assist EEG Annotation
Authors: Weiler Robin , Diachenko Marina , Juarez-Martinez Erika , Avramiea Arthur-Ervin , Bloem Peter , Linkenkaer-Hansen Klaus 
Published: August 2022

AbstractMachine learning techniques such as deep learning have been increasingly used to assist EEG annotation, by automating artifact recognition, sleep staging, and seizure detection. In lack of automation, the annotation process is prone to bias, even for trained annotators. On the other hand, completely automated processes do not offer the users the opportunity to inspect the models’ output and re-evaluate potential false predictions. As a first step towards addressing these challenges, we developed Robin’s Viewer (RV), a Python-based EEG viewer for annotating time-series EEG data. The key feature distinguishing RV from existing EEG viewers is the visualization of output predictions of deep-learning models trained to recognize patterns in EEG data. RV was developed on top of the plotting library Plotly, the app-building framework Dash, and the popular M/EEG analysis toolbox MNE. It is an open-source, platform-independent, interactive web application, which supports common EEG-file formats to facilitate easy integration with other EEG toolboxes. RV includes common features of other EEG viewers, e.g., a view-slider, tools for marking bad channels and transient artifacts, and customizable preprocessing. Altogether, RV is an EEG viewer that combines the predictive power of deep-learning models and the knowledge of scientists and clinicians to optimize EEG annotation. With the training of new deep-learning models, RV could be developed to detect clinical patterns other than artifacts, for example sleep stages and EEG abnormalities.
Transmissible SARS-CoV-2 variants with resistance to clinical protease inhibitors
Authors: Moghadasi Seyed Arad , Heilmann Emmanuel , Khalil Ahmed Magdy , Nnabuife Christina , Kearns Fiona L. , Ye Chengjin , Moraes Sofia N. , Costacurta Francesco , Esler Morgan A. , Aihara Hideki , Laer Dorothee von , Martinez-Sobrido Luis , Palzkill Timothy , Amaro Rommie E. , Harris Reuben S. 
Published: August 2022

AbstractVaccines and drugs have helped reduce disease severity and blunt the spread of SARS-CoV-2. However, ongoing virus transmission, continuous evolution, and increasing selective pressures have the potential to yield viral variants capable of resisting these interventions. Here, we investigate the susceptibility of natural variants of the main protease (Mpro/3CLpro) of SARS-CoV-2 to protease inhibitors. Multiple single amino acid changes in Mproconfer resistance to nirmatrelvir (the active component of Paxlovid). An additional clinical-stage inhibitor, ensitrelvir (Xocova), shows a different resistance mutation profile. Importantly, phylogenetic analyses indicate that several of these resistant variants have pre-existed the introduction of these drugs into the human population and are capable of spreading. These results encourage the monitoring of resistance variants and the development of additional protease inhibitors and other antiviral drugs with different mechanisms of action and resistance profiles for combinatorial therapy.One Sentence SummaryResistance to protease inhibitor drugs, nirmatrelvir (Paxlovid) and ensitrelvir (Xocova), exists in SARS-CoV-2 variants in the human population.
No Free Lunch from Deep Learning in Neuroscience: A Case Study through Models of the Entorhinal-Hippocampal Circuit
Authors: Schaeffer Rylan , Khona Mikail , Fiete Ila Rani 
Published: August 2022

AbstractResearch in Neuroscience, as in many scientific disciplines, is undergoing a renaissance based on deep learning. Unique to Neuroscience, deep learning models can be used not only as a tool but interpreted as models of the brain. The central claims of recent deep learning-based models of brain circuits are that they make novel predictions about neural phenomena or shed light on the fundamental functions being optimized. We show, through the case-study of grid cells in the entorhinal-hippocampal circuit, that one may get neither. We begin by reviewing the principles of grid cell mechanism and function obtained from first-principles modeling efforts, then rigorously examine the claims of deep learning models of grid cells. Using large-scale architectural and hyperparameter sweeps and theory-driven experimentation, we demonstrate that the results of such models may be more strongly driven by particular, non-fundamental, and post-hoc implementation choices than fundamental truths about neural circuits or the loss function(s) they might optimize. We discuss why these models cannot be expected to produce accurate models of the brain without the addition of substantial amounts of inductive bias, an informal No Free Lunch result for Neuroscience. Based on first principles work, we provide hypotheses for what additional loss functions will produce grid cells more robustly. In conclusion, circumspection and transparency, together with biological knowledge, are warranted in building and interpreting deep learning models in Neuroscience.
Can Artificial Intelligence Detect Monkeypox from Digital Skin Images?
Authors: Islam Towhidul , Hussain M.A. , Chowdhury Forhad Uddin Hasan , Islam B.M. Riazul 
Published: August 2022

AbstractAn outbreak of Monkeypox has been reported in 75 countries so far, and it is spreading at a fast pace around the world. The clinical attributes of Monkeypox resemble those of Smallpox, while skin lesions and rashes of Monkeypox often resemble those of other poxes, for example, Chickenpox and Cowpox. These similarities make Monkeypox detection challenging for healthcare professionals by examining the visual appearance of lesions and rashes. Additionally, there is a knowledge gap among healthcare professionals due to the rarity of Monkeypox before the current outbreak. Motivated by the success of artificial intelligence (AI) in COVID-19 detection, the scientific community has shown an increasing interest in using AI in Monkeypox detection from digital skin images. However, the lack of Monkeypox skin image data has been the bottleneck of using AI in Monkeypox detection. Therefore, in this paper, we used a web-scrapping-based Monkeypox, Chickenpox, Smallpox, Cowpox, Measles, and healthy skin image dataset to study the feasibility of using state-of-the-art AI deep models on skin images for Monkeypox detection. Our study found that deep AI models have great potential in the detection of Monkeypox from digital skin images (precision of 85%). However, achieving a more robust detection power requires larger training samples to train those deep models.
Innovation beyond the pandemic: the powerful potential of digital principal leadership
Authors: Sterrett William L. , Richardson Jayson W. 
Published: August 2022

Purpose
This article presents findings from a recent study that examined award-winning digital principals. Findings are summarized with regard to the preparation and practice of school administrators.

Design/methodology/approach
The participants in the research study were 12 U.S. principals recognized for their digital principal leadership. The researchers interviewed the leaders to better understand the challenges and opportunities of being an innovative principal.

Findings
Digital principals engage their teachers in professional development in a differentiated manner rather than a ‘one size fits all’ approach. They are resourceful advocates for infrastructure upgrades and curriculum change. They are actively involved in professional networks that extend beyond their school walls. These principals empower teachers as leaders within and outside of their school. Finally, they helped tell the story of their school culture in unique ways.

Originality/value
With the onset of the pandemic, principal leadership has changed. Organizations can learn from innovative principals in this work and incorporate it into their preparation, professional development, and evaluation practices. School building leaders must emerge from the pandemic equipped to proactively lead the new normal of technology-savvy leadership opportunities.
The integration of logistics and marketing practice into baseline supply chain practices in the emerging markets
Authors: Dadzie Kofi , Dadzie Charlene , Johnston Wesley J. , Winston Evelyn , Wang Haizhong 
Published: August 2022

Purpose
This study aims to draw on the strategy–structure–performance framework to investigate baseline supply chain (BSC) practices as a function of how firms structure logistics and marketing mix activities to achieve market share in the emerging market (EM) supply chain ecosystems.

Design/methodology/approach
The authors validate the study’s conceptual framework with survey data collected in two contrasting EM supply chain ecosystems. They include supply chains in EM economies with an advanced logistics/distribution infrastructure such as China and those in economies with poor logistics/distribution infrastructure such as Ghana. The authors use ordinary least squares regression and structural equation modeling analysis to examine the relative market share outcomes of different configurations of logistics-marketing practices (logistics-affordability marketing, logistics-accessibility marketing, logistics-acceptability marketing, logistics-and awareness and full integration into BSC).

Findings
Key findings confirm that the integration of logistics with marketing activities into BSC practice is more pervasive in EMs with high logistics performance index, such as China than in firms in EMs with low logistics performance index, such as Ghana. Moreover, the authors confirm that integrating logistics and marketing into BSC generates higher market share performance than logistics- or marketing-only practices in China and Ghana. These differences are driven more by the firm’s strategic orientation than the demands of competitive market conditions.

Research limitations/implications
The study focuses on BSC integration activities in the logistics and marketing functions because researchers have not updated this issue for the past two decades.

Practical implications
The study results provide managers with much-needed empirical evidence of the strategic benefit of BSC integration under different supply chain ecosystems in the EMs.

Originality/value
Linking BSC activities in logistics management and marketing management mix activities within the 4As marketing mix framework provides evidence to support the argument that the 4As marketing mix is an appropriate planning framework for EMs’ unique ecosystems.
Sustainability management and the success of international development projects: the role of political and social skills
Authors: Sawadogo Dieudonné , Sané Seydou , Kaboré Somnoma Edouard 
Published: August 2022

PurposeThe objectives of this study are twofold: first, to identify the effect of sustainability management on the success of international development projects, and second, to investigate the moderating role of political and social skills on this relationship.Design/methodology/approachThis study adopted a quantitative research methodology based on questionnaire data collected from 43 international development project managers from various fields in Burkina Faso (West Africa). Descriptive statistics and exploratory and confirmatory analyses using principal component analysis were used to assess the quality of the measurement model. A multiple regression analysis based on the partial least squares approach was used to test the hypotheses.FindingsThe results show that sustainability management positively contributes to the success of international development projects. However, given the specificities of these projects and their perception of success, the project coordinator's political and social skills do not predict a greater impact of sustainability management on the success of international development projects. The study also found that project coordinators prioritize their technical skills over behavioral ones.Originality/valueThis study fills a gap in the literature, given that little is known about the moderating role of political and social skills in the effect of sustainability management on the success of specific projects such as international development projects.
Impacts of game attractiveness and color of message on sport viewers' attention to prosocial message: an eye-tracking study
Authors: (Abdolreza) Oboudi Behnam , Elahi Alireza , Akbari Yazdi Hossein , Pyun Do Young 
Published: August 2022

PurposeIn recent years, neurophysiological tools have been vastly applied in sport marketing research. Eye tracking, a pervasive sensor technology, has received a growing interest to examine the effects of advertising through sport on viewer attention. While there is a plethora of evidence in advertising that supports the positive effects of various advertising types and locations on viewer attention in various sport contexts, little is known about the role of a prosocial overlay ad on viewer attention when watching televised football matches. Therefore, this research aims to examine the differences in viewers' attention (i.e. fixation and duration) with regard to game attractiveness and colors of the prosocial message during televised football matches.Design/methodology/approachTo identify the research gap, the authors first reviewed the relevant sport marketing and neuroscience research on advertising effectiveness. The authors selected a prosocial message displayed. Adopting an experimental research design and using eye tracking, this study examined the impacts of game attractiveness and colors of message on viewer attention to the prosocial message displayed on an overlay advertisement during a football match.FindingsThe authors found that the colors of prosocial messages and game attractiveness had significant effects on viewer attention to the prosocial message.Originality/valueIn this study, the authors sought to add advertisement color, as well as game attractiveness, to the extant knowledge in marketing literature as effective advertising factors in capturing viewers' attention. These variables can offer marketers new insights in designing effective advertisements for the context of televised sports events in a specialized field.