bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Role of Artificial Intelligence in Modern Medical Education and Practice: A Systematic Literature Review
Authors: Rasouli Shiva , Alkurdi Duha , Jia Bochen 
Published: July 2024

AbstractThe integration of Artificial Intelligence (AI) into medical education has emerged as a transformative element in the modern healthcare educational system. With the exponential growth of medical knowledge and the increasing complexity of healthcare systems, AI offers innovative solutions to enhance learning outcomes, facilitate personalized education pathways, and improve clinical decision-making skills among medical professionals. This literature review explores the transformative role of AI in the training of healthcare providers, focusing on advancements in medical education, medical diagnostics, and emergency care training. Additionally, it addresses the readiness of healthcare professionals to employ AI technologies, analyzing their current knowledge, attitudes, and the training provided. By synthesizing findings from multiple studies, we aim to highlight AI’s potential to enhance medical education, address challenges, and propose future directions for integrating AI into healthcare training.
Spindle morphology changes between meiosis and mitosis driven by CK2 regulation of the Ran pathway
Authors: Cantwell Helena , Nguyen Hieu , Kettenbach Arminja , Heald Rebecca 
Published: July 2024

AbstractThe transition from meiotic divisions in the oocyte to embryonic mitoses is a critical step in animal development. Despite negligible changes to cell size and shape, following fertilization the small, barrel-shaped meiotic spindle is replaced by a large zygotic spindle that nucleates abundant astral microtubules at spindle poles. To probe underlying mechanisms, we applied a drug screening approach usingCionaeggs and found that inhibition of Casein Kinase 2 (CK2) caused a shift from meiotic to mitotic-like spindle morphology with nucleation of robust astral microtubules, an effect reproduced in cytoplasmic extracts prepared fromXenopuseggs. In both species, CK2 activity decreased at fertilization. Phosphoproteomic differences betweenXenopusmeiotic and mitotic extracts that also accompanied CK2 inhibition pointed to RanGTP-regulated factors as potential targets. Interfering with RanGTP-driven microtubule formation suppressed astral microtubule growth caused by CK2 inhibition. These data support a model in which CK2 activity attenuation at fertilization leads to activation of RanGTP-regulated microtubule effectors that induce mitotic spindle morphology.
Phonological representations of auditory and visual speech in the occipito-temporal cortex and beyond
Authors: Van Audenhaege Alice , Mattioni Stefania , Cerpelloni Filippo , Gau Remi , Szmalec Arnaud , Collignon Olivier 
Published: July 2024

AbstractSpeech is a multisensory signal that can be extracted from the voice and the lips. Previous studies suggested that occipital and temporal regions encode both auditory and visual speech features but their precise location and nature remain unclear. We characterized brain activity using fMRI (in male and female) to functionally and individually define bilateral Fusiform Face Areas (FFA), the left Visual Word Form Area (VWFA), an audio-visual speech region in the left Superior Temporal Sulcus (lSTS) and control regions in bilateral Para-hippocampal Place Areas (PPA). In these regions, we performed multivariate patterns classification of corresponding phonemes (speech sounds) and visemes (lip movements). We observed that the VWFA and lSTS represent phonological information from both vision and sounds. The multisensory nature of phonological representations appeared selective to the anterior portion of VWFA, as we found viseme but not phoneme representation in adjacent FFA or even posterior VWFA, while PPA did not encode phonology in any modality. Interestingly, cross-modal decoding revealed aligned phonological representations across the senses in lSTS, but not in VWFA. A whole-brain cross-modal searchlight analysis additionally revealed aligned audio-visual phonological representations in bilateral pSTS and left somato-motor cortex overlapping with oro-facial articulators. Altogether, our results demonstrate that auditory and visual phonology are represented in the anterior VWFA, extending its functional coding beyond orthography. The geometries of auditory and visual representations do not align in the VWFA as they do in the STS and left somato-motor cortex, suggesting distinct multisensory representations across a distributed phonological network.Significance statementSpeech is a multisensory signal that can be extracted from the voice and the lips. Which brain regions encode both visual and auditory speech representations? We show that the Visual Word Form Area (VWFA) and the left Superior Temporal Sulcus (lSTS) both process phonological information from speech sounds and lip movements. However, while the lSTS aligns these representations across the senses, the VWFA does not, indicating different encoding mechanisms. These findings extend the functional role of the VWFA beyond reading. An additional whole-brain approach reveals shared representations in bilateral superior temporal cortex and left somato-motor cortex, indicating a distributed network for multisensory phonology.
The metaplastic precursor state to oesophageal adenocarcinoma represents reversion to a transient epithelial cell state in the developing oesophagus
Authors: Baker Syed Murtuza , Mullan Aoibheann , Jennings Rachel E , Hanley Karen Piper , Ang Yeng , Palles Claire , Hanley Neil A. , Sharrocks Andrew D. 
Published: July 2024

ABSTRACTIn Barrett’s oesophagus (BO), the precursor of oesophageal adenocarcinoma, the adult stratified squamous epithelium is replaced by a simple columnar phenotype. This has been considered metaplasia; the inappropriate conversion from one adult cell-type to another. In fact, BO could be a reversal of mammalian embryogenesis when the early foregut is first lined by simple columnar epithelium. Exploring this hypothesis has been hampered by inadequate molecular details of human oesophageal development. Here, we adopted single cell transcriptomic and epigenomic approaches to discover and decode the cell types that constitute the initial primitive columnar, transitory and subsequently stratified lower oesophageal epithelium. Each stage is comprised of several previously undefined epithelial sub-populations. HNF4A, a major driver of the BO phenotype, is a prominent transcriptional regulator in the early foregut columnar cells, but not in the later ciliated or stratified cells, and is central to gene regulatory programmes known to be reactivated in BO. Moreover, GWAS susceptibility SNPs for BO mapped to putative regulatory regions in fetal epithelial cells, which are inaccessible in the corresponding adult epithelial cells. Collectively, these data argue that the path to BO involves reactivation of pathways that define primitive fetal epithelial cell states.
An orexin-sensitive subpopulation of layer 6 neurons regulates cortical excitability and anxiety behaviour
Authors: Messore Fernando , Therpurakal Rajeevan Narayanan , Dufour Jean-Philippe , Hoerder-Suabedissen Anna , Guidi Luiz , Korrell Kim , Mueller Marissa , Lak Armin , Bannerman David , Mann Edward O , Molnár Zoltán 
Published: July 2024

ABSTRACTCortical layer 6 (L6) neurons uniquely respond to orexin – a neuropeptide influencing arousal and emotion. We show that Drd1a-Cre+ neurons in the prefrontal cortex are selectively sensitive to orexin and regulate prefrontal network activation in vitro and in vivo. Chronically silencing these neurons impairs orexin-induced prefrontal activation and reduces anxiety-like behaviour, indicating that orexin-responsive L6 neurons modulate emotional states and may be a substrate for anxiety regulation.
Interpretable representation learning for 3D multi-piece intracellular structures using point clouds
Authors: Vasan Ritvik , Ferrante Alexandra J. , Borensztejn Antoine , Frick Christopher L. , Gaudreault Nathalie , Mogre Saurabh S. , Morris Benjamin , Pires Guilherme G. , Rafelski Susanne M. , Theriot Julie A. , Viana Matheus P. 
Published: July 2024

AbstractA key challenge in understanding subcellular organization is quantifying interpretable measurements of intracellular structures with complex multi-piece morphologies in an objective, robust and generalizable manner. Here we introduce a morphology-appropriate representation learning framework that uses 3D rotation invariant autoencoders and point clouds. This framework is used to learn representations of complex multi-piece morphologies that are independent of orientation, compact, and easy to interpret. We apply our framework to intracellular structures with punctate morphologies (e.g. DNA replication foci) and polymorphic morphologies (e.g. nucleoli). We systematically compare our framework to image-based autoencoders across several intracellular structure datasets, including a synthetic dataset with pre-defined rules of organization. We explore the trade-offs in the performance of different models by performing multi-metric benchmarking across efficiency, generative capability, and representation expressivity metrics. We find that our framework, which embraces the underlying morphology of multi-piece structures, facilitates the unsupervised discovery of sub-clusters for each structure. We show how our approach can also be applied to phenotypic profiling using a dataset of nucleolar images following drug perturbations. We implement and provide all representation learning models using CytoDL, a python package for flexible and configurable deep learning experiments.
Early life microbial succession in the gut follows common patterns in humans across the globe
Authors: Bottino Guilherme Fahur , Bonham Kevin S. , Patel Fadheela , McCann Shelley , Zieff Michal , Naspolini Nathalia , Ho Daniel , Portlock Theo , Joos Raphaela , Midani Firas S. , Schüroff Paulo , Das Anubhav , Shennon Inoli , Wilson Brooke C. , O’Sullivan Justin M. , Britton Robert A. , Murray Deirdre M. , Kiely Mairead E. , Taddei Carla R. , Beltrão-Braga Patrícia C. B. , Campos Alline C. , Polanczyk Guilherme V. , Huttenhower Curtis , Donald Kirsten A. , Klepac-Ceraj Vanja 
Published: July 2024

AbstractCharacterizing the dynamics of microbial community succession in the infant gut microbiome is crucial for understanding child health and development, but no normative model currently exists. Here, we estimate child age using gut microbial taxonomic relative abundances from metagenomes, with high temporal resolution (±3 months) for the first 1.5 years of life. Using 3,154 samples from 1,827 infants across 12 countries, we trained a random forest model, achieving a root mean square error of 2.61 months. We identified key taxonomic predictors of age, including declines inBifidobacteriumspp. and increases inFaecalibacterium prausnitziiand Lachnospiraceae. Microbial succession patterns are conserved across infants from diverse human populations, suggesting universal developmental trajectories. Functional analysis confirmed trends in key microbial genes involved in feeding transitions and dietary exposures. This model provides a normative benchmark of “microbiome age” for assessing early gut maturation that can be used alongside other measures of child development.
CD11b suppresses TLR7-driven inflammatory signaling to protect against lupus nephritis
Authors: Li Xiaobo , Villanueva Veronica , Jimenez Viviana , Nguyen Billy , Chauhan Nishant Ranjan , Khan Samia Q. , Dorschner Jessica M. , Jensen Mark A. , Alzahrani Khulood , Wei Huiting , Cimbaluk David J. , Wei David C. , Jolly Meenakshi , Lopez-Rodriguez Darlah , Pineda Santiago Balza , Barbosa Antonio , Vazquez-Padron Roberto I. , Faridi Hafeez M. , Reiser Jochen , Niewold Timothy B. , Gupta Vineet 
Published: July 2024

AbstractLupus Nephritis (LN) is a severe complication of systemic lupus erythematosus (SLE) that affects kidney function. Here, we investigated the role of CD11b, a protein encoded by theITGAMgene, in the development of LN and its functional activation as a therapeutic strategy. Genetic coding variants ofITGAMsignificantly increase the risk for SLE and LN by producing a less active CD11b and leading to elevated levels of type I interferon (IFN I). However, a molecular mechanism for how these variants increase LN risk has been unclear. Here, we determined that these variants also significantly associate with elevations in soluble urokinase plasminogen activator receptor (suPAR), a known biomarker linked to kidney disease, suggesting a novel molecular connection. Pharmacologic activation of CD11b with a novel, clinical-stage agonist ONT01 significantly suppressed suPAR production in myeloid cells and reduced systemic inflammation and kidney damage in multiple experimental models of LN. Importantly, delaying treatment with ONT01 until after disease onset also significantly reduced serum suPAR and inflammatory cytokines, and decreased immune complex deposition in the glomerulus, glomerulonephritis and albuminuria, suggesting that CD11b activation is therapeutic for LN. Genetic activation of CD11b via a gain-of-function CD11b mutation also showed complete protection from LN, whereas genetic deletion of CD11b worsened the disease in mice, providing further evidence of the role of CD11b activation in regulating LN. Finally, transfer of human LN PBMCs generated human LN like disease in mice that was significantly reduced by ONT01. Together, these data provide strong evidence that ONT01 mediated CD11b activation can therapeutically modulate TLR7-driven inflammation and protect against LN. These findings support clinical development of CD11b agonists as novel therapeutics for treating lupus nephritis in human patients.
A single microRNA miR-195 rescues the arrested B cell development induced by EBF1 deficiency
Authors: Miyatake Y. , Ikawa T. , Yanagiya R. , Kotaki R. , Kameda K. , Koyama-Nasu R. , Okuyama K. , Hirano K. , Hosokawa H. , Hozumi K. , Ohtsuka M. , Kishikawa T. , Shibata C. , Otsuka M. , Maruyama R. , Ando K. , Kurosaki T. , Kawamoto H. , Kotani A. 
Published: July 2024

AbstractAccumulated studies have reported that hematopoietic differentiation was primarily regulated by transcription factors. Early B cell factor 1 (EBF1) is an essential transcription factor for B lymphopoiesis. Contrary to the canonical notion, we found that a single miRNA, miRNA-195 (miR-195) transduction let EBF1 deficient hematopoietic progenitor cells (HPCs) express CD19, carry out V(D)J recombination and class switch recombination, which implied that B cell matured without EBF1. A part of the mechanism was caused by FOXO1 accumulation via inhibition of FOXO1 phosphorylation pathways in which targets of miR-195 are enriched. These results suggested that some miRNA transductions could function as alternatives to transcription factors.
Development of a new flippase-dependent mouse model for red fluorescence-based isolation of KrasG12Doncogene-expressing tumor cells
Authors: Hrckulak Dusan , Krausova Michaela , Onhajzer Jakub , Stastna Monika , Kriz Vitezslav , Janeckova Lucie , Korinek Vladimir 
Published: July 2024

AbstractProto-oncogene KRAS, GTPase (KRAS) is one of the most intensively studied oncogenes in cancer research. Although several mouse models allow for regulated expression of mutant Kras, selective isolation and analysis of transforming or tumor cells that produce the Kras oncogene remains a challenge. In our study, we present a knock-in model of oncogenic variant KrasG12Dthat enables the “activation” of KrasG12Dexpression together with production of red fluorescent protein tdTomato. Both proteins are expressed from the endogenousKraslocus after recombination of a transcriptional stop box in the genomic DNA by the enzyme flippase (Flp). We have demonstrated the functionality of the allele termedRedRas(abbreviatedKrasRR) underin vitroconditions with mouse embryonic fibroblasts and organoids andin vivoin the lung and colon epithelium. After recombination with adenoviral vectors carrying theFlpgene, theKrasRRallele itself triggers formation of lung adenomas. In the colon epithelium, it causes the progression of adenomas that are triggered by the loss of tumor suppressor adenomatous polyposis coli (Apc). Importantly, cells in which recombination has successfully occurred can be visualized and isolated using the fluorescence emitted by tdTomato. Furthermore, we show that KrasG12Dproduction enables intestinal organoid growth independent of epidermal growth factor (EGF) signaling and that the KrasG12Dfunction is effectively suppressed by specific inhibitor MRTX1133.
Conformational dynamics and asymmetry in multimodal inhibition of membrane-bound pyrophosphatases
Authors: Liu Jianing , Shah Anokhi , Ma Yue , Hardman Katie , Johansson Niklas G. , Ribeiro Orquidea , Brookfield Adam , Bowen Alice , Yli-Kauhaluoma Jari , Xhaard Henri , Jeuken Lars J.C. , Goldman Adrian , Pliotas Christos , Vidilaseris Keni 
Published: July 2024

AbstractMembrane-bound pyrophosphatases (mPPases) are homodimeric proteins that hydrolyse pyrophosphate and pump H+/Na+across membranes. They are crucial for the virulence of protist pathogens, making them attractive drug targets. In this study, we investigate the inhibitory effects of seven distinct bisphosphonates againstThermotoga maritimamPPase to explore their mode of action and assist in future small molecule inhibitor development. We solved two structures of mPPase bound to the inhibitors in the enzyme active sites and probed the conformational dynamics of mPPase under multiple inhibitors and functionally relevant conditions by double electron-electron resonance (DEER) spectroscopy. We found that mPPase adopts five distinct conformations within the ensemble in the presence of different inhibitors. Combined with solid-supported membrane-based electrophysiology recordings, this revealed that during catalysis, one monomer of the dimer remains open, and Na+can only be pumped in a closed state. These results further support the existence of catalytic asymmetry in our pumping-before-hydrolysis model.
A non-autonomous protein quality control mechanism targeting tau aggregate propagation
Authors: Bluemke Anika , Hagemeier Birte , Ripkens Kamilla , Schulze Nina , Strzala Michal , Koci Michelle , Kaschani Farnusch , Kaiser Markus , Erkelenz Michael , Schluecker Sebastian , Merdanovic Melisa , Poepsel Simon , Hellerschmied Doris , Burston Steve , Ehrmann Michael 
Published: July 2024

SUMMARYTauopathies such as Alzheimer’s disease, frontotemporal dementia with Parkinsonism, and other neurodegenerative disorders are characterized by the spread of tau pathology from an initial brain region to neuroanatomically connected areas. At the molecular level, spreading involves aggregation of tau in a donor cell, externalization of transmissible fragments of amyloid fibrils, internalization by an acceptor cell, followed by seeded aggregation of endogenous tau. However, the protein quality control mechanisms that counteract tau aggregation, and in particular its spreading process, are not well understood. In this context, a co-migrating factor performing location-independent interference of fibril formation and transmission would be an appropriate conceptual solution. Here, we show that the cell-to-cell transfer of the widely conserved serine protease HTRA1 impedes tau pathology by targeting multiple steps within the spreading process. Our results suggest a defense mechanism against the intercellular spread of pathogenic protein conformations.
A limit to how much you can plan – planned and improvised strategic communication during COVID-19
Authors: Offerdal Truls Strand 
Published: July 2024

PurposeThis paper investigates the relationship between prior planning and the practical adaptation and improvisation conducted by organizations during the COVID-19 pandemic through a qualitative case study of Norwegian Public Health Institutions.Design/methodology/approachThis paper draws on a unique set of qualitative data, interviews and field observations, gathered from organizations during an ongoing crisis. Through this access it becomes possible to examine how organizations practically navigated the complex relationship between structured plans and the situational, short term forms of crisis communication.FindingsThe paper finds that prior plans played a key role as points of reference, and as a prior set of principles that could be drawn on during a crisis. Organizations did however have to adapt and respond to the crisis in ways that could not have been designed in advance. In order to do so employees would deliberate and discuss in search of a fitting response that could help them in reaching their goals.Originality/valueThe paper builds on prior work that has discussed limitations and challenges to planning and linear approaches in crisis communication and strategic communication, but provides empirical insight into how members of organizations navigate this work in practice. By employing theories from rhetoric it provides a framework for the further study of crisis communication as a practical ongoing activity, and provides some suggested implications for how organizations can prepare increase crisis preparedness.
Riding the crypto wave: How does country R&D spending respond?
Authors: Sami Mina , Abdallah Wael 
Published: July 2024

Purpose
This paper aims to explore how the expansion in cryptocurrency users affects the country's research and development (R&D) investments.

Design/methodology/approach
The analysis covers 53 countries over the period 2019–2022. The empirical methodology implements an instrumental variable approach to overcome endogeneity and omitted variable bias issues. In particular, this study introduces novel instruments developed from Google data, specifically related to trends observed in the cryptocurrency markets.

Findings
The results show that macroeconomic and institutional factors, as well as technology infrastructure affect the country's R&D expenditure, as previously noted in the literature. The country's R&D spending significantly responds to cryptocurrency expansions. Conspicuously, each 10% increase in cryptocurrency market users boosts the ratio of R&D to GDP by 1.35%. The countries that have imposed an adequate taxation policy on cryptocurrency gains experienced more improvement in their R&D budget, in contrast to those that forced aggressive tax brackets or did not apply adequate policies. Cryptocurrency dynamics affect both religiously regulated and nonreligious countries.

Originality/value
This study has three main contributions. First, it introduces the role of the cryptocurrency market as one of the leading global trends to affect the countries’ R&D budget. Second, this paper documents the importance of forcing an adequate tax policy on cryptocurrency capital gains. Third, the results of this paper serve as guidelines for governments to face the challenges raised by the cryptocurrency market.