bluuebunny/crossref_metadata_2025_split huggingface dataset:
Single-cell Transcriptional Analysis of the Cellular Immune Response in the Oral Mucosa of Mice
Authors: Cantalupo P , Diacou A , Park S , Soman V , Chen J , Glenn D , Chandran U , Clark D 
Published: October 2023

AbstractPeriodontal health is dependent on a symbiotic relationship of the host immune response with the oral microbiota. Pathologic shifts of the microbial plaque elicit an immune response that eventually leads to the recruitment and activation of osteoclasts and matrix metalloproteinases and the eventual tissue destruction that is evident in periodontal disease. Once the microbial stimulus is removed, an active process of inflammatory resolution begins. The goal of this work was to use scRNAseq to demonstrate the unique cellular immune response across three distinct conditions of periodontal health, disease, and resolution using mouse models. Periodontal disease was induced using a ligature model. Resolution was modeled by removing the ligature and allowing the mouse to recover. Immune cells (Cd45+) were isolated from the periodontium and analyzed via scRNAseq. Gene signature shifts across the three conditions were characterized and shown to be largely driven by macrophage and neutrophils during the periodontal disease and resolution conditions. Resolution of periodontal disease was characterized by the differential regulation of unique gene subsets. Clustering analysis characterized multiple cellular subpopulations within B Cells, macrophages, and neutrophils that demonstrated differential expansion and contraction across conditions of periodontal health, disease, and resolution. Interestingly, we identified a transcriptionally distinct macrophage subpopulation that expanded during the resolution condition and demonstrated an immunoregulatory gene signature. We identified a cell surface marker for this resolution-associated macrophage subgroup (Cd74) and validated the expansion of this subgroup during resolution via flow cytometry. This work presents a robust immune cell atlas for study of the immunological changes in the oral mucosa during three distinct conditions of periodontal health, disease, and resolution and it improves our understanding of the cellular and molecular markers that characterize health from disease for the development of future diagnostics and therapies.
Cerebral hypoperfusion exacerbates traumatic brain injury in male but not female mice
Authors: Whitehead Bailey J. , Corbin Deborah , Alexander Megan L. , Bumgarner Jacob , Zhang Ning , Karelina A. Kate , Weil Zachary M. 
Published: October 2023

AbstractMild-moderate traumatic brain injuries are common and while many individuals recover fully there is mounting clinical and epidemiological evidence that for a substantial subset, even when the acute TBI symptoms resolve, long term health can still be impacted. Individuals with a history of TBI are disproportionately vulnerable to many disease conditions including age-related neurodegeneration. These relationships are difficult to predict but these outcomes very likely interact with other disease risk factors such as cardiovascular disease. Here we tested the hypothesis that a mild pre-injury reduction in cerebral blood flow (bilateral carotid artery stenosis; BCAS) would impair recovery from TBI. Male and female mice underwent BCAS using steel microcoils around the carotid arteries, a mild-moderate closed-head TBI, or a combination of BCAS followed by TBI 30 days post-implantation. Cerebral blood flow, spatial learning and memory, axonal damage, and gene expression profiles were assessed. BCAS led to a ∼10% reduction in CBF, while TBI caused a similar decrease. However, mice exposed to both BCAS and TBI exhibited more pronounced reductions in CBF, associated with marked spatial learning and memory deficits, particularly in males. Axonal damage in male mice was also exacerbated by the combination of BCAS and TBI compared to either injury alone. Females exhibited spatial memory deficits associated with BCAS, but this was not exacerbated by TBI. We performed single nuclei RNA sequencing on male brain tissue to investigate the mechanisms underlying poorer long term functional outcomes in in TBI-BCAS animals. TBI and BCAS independently altered gene expression profiles in neurons and glia but in most cases BCAS and TBI together produced markedly different transcriptional patterns than either challenge alone. Overall, our findings reveal that the presence of mild reductions in cerebrovascular blood flow as a proxy for preexisting cardiovascular disease significantly exacerbated TBI outcomes in male but not female mice, indicating that even relatively mild comorbidities could significantly alter TBI outcomes and increase the probability of secondary disease processes.
Hybrid Cellular Automata Modelling Reveals the Effects of Glucose Gradients on Tumour Spheroid Growth
Authors: Messina Luca , Ferraro Rosalia , Peláez Maria J. , Wang Zhihui , Cristini Vittorio , Dogra Prashant , Caserta Sergio 
Published: October 2023

AbstractPurposeIn recent years, mathematical models have become instrumental in cancer research, offering insights into tumor growth dynamics, and guiding the development of pharmacological strategies. These models, encompassing diverse biological and physical processes, are increasingly used in clinical settings, showing remarkable predictive precision for individual patient outcomes and therapeutic responses.MethodsMotivated by these advancements, our study introduces an innovativein silicomodel for simulating tumor growth and invasiveness. The Automated Hybrid Cell emulates critical tumor cell characteristics, including rapid proliferation, heightened motility, reduced cell adhesion, and increased responsiveness to chemotactic signals. This model explores the potential evolution of 3D tumor spheroids by manipulating biological parameters and microenvironment factors, focusing on nutrient availability.ResultsOur comprehensive Global and Local Sensitivity Analyses reveal that tumor growth primarily depends on cell duplication speed and cell-to-cell adhesion, rather than external chemical gradients. Conversely, tumor invasiveness is predominantly driven by chemotaxis. These insights illuminate tumor development mechanisms, providing vital guidance for effective strategies against tumor progression. Our proposed model is a valuable tool for advancing cancer biology research and exploring potential therapeutic interventions.Simple SummaryIn recent years, mathematical models have revolutionized cancer research, illuminating the complex dynamics of tumor growth and aiding drug development. These models, reflecting biological and physical processes, are increasingly used in clinical practice, offering precise patient-specific predictions. Our work introduces an innovative in silico model to simulate tumor growth and invasiveness. The Automated Hybrid Cell, replicating key tumor cell features, enables exploration of 3D tumor spheroid evolution. Sensitivity analyses reveal that tumor growth is primarily influenced by cell replication speed and adhesion, while invasiveness relies on chemotaxis. These insights shed light on tumor development mechanisms, guiding effective strategies against tumor progression. Our model serves as a valuable tool for advancing cancer biology research and potential therapeutic interventions.
LKB1 suppresses growth and promotes the internalization of EGFR through the PIKFYVE lipid kinase
Authors: Ferrarone John R. , Thomas Jerin , Unni Arun M. , Zheng Yuxiang , Nagiec Michal J. , Gardner Eric E. , Mashadova Oksana , Li Kate , Koundouros Nikos , Montalbano Antonino , Mustafa Meer , Cantley Lewis C. , Blenis John , Sanjana Neville E. , Varmus Harold 
Published: October 2023

SUMMARYThe tumor suppressor LKB1 is a serine/threonine protein kinase that is frequently mutated in human lung adenocarcinoma (LUAD). LKB1 regulates a complex signaling network that is known to control cell polarity and metabolism; however, the pathways that mediate the tumor suppressive activity of LKB1 are incompletely defined. To identify mechanisms of LKB1- mediated growth suppression we developed a spheroid-based cell culture assay to study LKB1- dependent growth. Using this assay, along with genome-wide CRISPR screens and validation with orthogonal methods, we discovered that LKB1 suppresses growth, in part, by activating the PIKFYVE lipid kinase, which promotes the internalization of wild-type EGFR. Our findings reveal a new mechanism of regulation of EGFR, which may have implications for the treatment ofLKB1-mutant LUAD.
Study of Motor Unit Action Potential Conduction Velocity and Firing Rate in Low Force Contractions using Empirical Mode Decomposition
Authors: Dogadov Anton , Hogrel Jean-Yves 
Published: October 2023

AbstractArrays of surface electrodes may be used to record individual motor unit action potential (MUAP) trains from the skin surface. Processing of the later gives access to direct estimation of instantaneous conduction velocity and firing rate of individual MUAPs, which are informative physiological features. However, the estimation of conduction velocity and firing rate may be sensitive to additive noise, which is always present in surface EMG recordings. In this paper, we propose to use the Ensemble Empirical Mode Decomposition (EEMD) to represent individual MU instantaneous conduction velocity and firing rate time-series as a sum of components (intrinsic mode functions) and to omit the components with energy lower than the expected noise level. This approach enables to denoise the conduction velocity and firing rate time-sequencies, extracted from the surface EMG recordings, and to unmask a physiological relationship between them.
Metabolic changes that allowPlasmodium falciparumartemisinin-resistant parasites to tolerate the oxidative stress
Authors: Bonive-Boscan Alejandro David , Acosta Héctor , Rojas Ascanio 
Published: October 2023

1.Abstract1.1BackgroundArtemisinin-based treatments (ACTs) are the first therapy currently used to treat malaria produced byPlasmodium falciparum. However, in recent years increasing evidence shows that some strains ofP. falciparumare less susceptible to ACT in the Southeast Asian region.1.2Materials & MethodsA data reanalysis of several omics approaches currently available about parasites ofP. falciparumthat have some degree of resistance to ACT was carried out. The data used was from transcriptomics and metabolomics studies. One mitochondrial carrier of the parasite possibly involved in the mechanisms of tolerance to oxidative stress was modelled and subjected to molecular dockings with citrate and oxoglutarate.1.3ResultsAn increase in glutathione production was detected, changing the direction of the flux of metabolites in the tricarboxylic acid cycle, and boosting glucose consumed. The models of the mitochondrial carrier, called PfCOCP, show that it may be important in transporting citrate and oxoglutarate from the mitochondrial matrix to cytosol. If so, it may allow the parasite to tolerate the oxidative stress produced by artemisinin.1.4ConclusionsThisin-silicoanalysis shows thatP. falciparummay tolerate the artemisinin’s oxidative stress through metabolic changes not reported before, showing the need for further research on the many metabolic aspects linked to this phenotype.
Dense Sampling of Taxa and Genomes Untangles the Phylogenetic Backbone of a Non-model Plant Lineage Rife with Deep Hybridization and Allopolyploidy
Authors: Xu Chao , Jin Zetao , Wang Hui , Xie Siyu , Lin Xiaohua , Hodel Richard G.J. , Zhang Yu , Ma Daikun , Liu Bing , Liu Guangning , Jin Shuihu , Zhao Liang , Wu Jun , Ren Chen , Hong Deyuan , Liu Binbin 
Published: October 2023

AbstractPhylogenetic networks, rather than purely bifurcating trees, more accurately depict the intricate evolutionary dynamics of most lineages, especially those characterized by extensive hybridization and allopolyploidization events. However, the challenges of achieving complete taxon sampling, and limited financial resources for studying non-model plant lineages, have hindered comprehensive and robust estimation of phylogenetic backbones with guidance from networks. The bellflower tribe, Campanuleae, characterized by a reticulate evolutionary history, serves as an ideal model to investigate how to diagnose nested ancient reticulation events. Here, by integrating multiple genomic data sources and a range of phylogenetic inference methods, we produced a robust phylogenetic backbone for the tribe Campanuleae. Our investigation of reticulate evolution indicates that hybridization and allopolyploidization were instrumental in shaping the diversity of the bellflower tribe, particularly during the initial diversification of the subtribe Phytematinae. Additionally, we ascertained that conflicting topologies resulting from distinct genomic datasets and inference methodologies significantly impact downstream estimates of divergence dating, ancestral area construction, and diversification rates. This study offers a universally relevant framework for deciphering how to use network-based phylogenetic structures using various genomic sources and inference methods. [Campanulaceae, Campanuleae, Cytonuclear discordance, paralog, phylogenomics, reticulate evolution]
Fragrance and color production by corona and perianth tissues of Iranian narcissus genotypes (Narcissus tazettaL.)
Authors: Haghshenas Azra , Jowkar Abolfazl , Chehrazi Mehrangiz , Moghadam Ali , Karami Akbar 
Published: October 2023

AbstractFlower color, shape and scent are the most attracting factors for consumers in the floriculture industry. The most fragrant Iranian narcissi (Narcissus tazettaL.) grown in natural habitats are Shahla, Meskinak, and Porpar genotypes. The present study was conducted to evaluate the color, scent, and also their interaction separately in corona and perianth of eleven Iranian narcissus accessions, for a better understanding of the bio-physiological differences in these tissues. For this purpose, the volatile organic compounds (VOCs) were analyzed using Headspace GCMS (gas chromatography/mass spectrometry); and total carotenoid, color values, and tissue thickness were measured in both perianth and corona tissues. Sensory analysis for corona and perianth was also conducted to evaluate scent perception. Besides, the expression of genes related to scent and color in corona and perianth was evaluated. Moreover, epidermal cells of perianth and corona were assessed by polarized light and SEM microscopy. The two most abundant compounds in both tissues were E-β-ocimene and benzyl acetate, respectively; among which the first compound was higher in perianth, while the second one was higher in corona. Among identified VOCs, α-terpineol, acetic acid, 2-phenylethyl ester, α-pinene, β-myrcene, and limonene were detected in corona of all genotypes ofN. tazetta; however, these compounds were not identified in perianth of every genotypes. In corona, the negative correlations between the measured values of E-β-ocimene and carotenoid and also, between the expression level of ocimene synthase and PSY (Phytoene synthase) with DXR (1-Deoxy-D-xylulose 5-phosphate reductoisomerase) suggested that there might be a competition between carotenoids and monoterpenes precursors in the MEP (methyl-D-erythritol phosphate) pathway. Volatile organic compound, color, scent emission, fresh weight and thickness of tissue were different in perianth and corona; while the surface coverage (with epidermal conical cells) were similar in these tissues. The findings of this research illustrated clearly for the first time that while both perianth and corona play important roles in scent production, corona has a more distinguished role in greater production of scent and color in Iranian narcissus flowers.
Comprehensive reanalysis for CNVs in ES data from unsolved rare disease cases results in new diagnoses
Authors: Demidov German , Yaldiz Burcu , Garcia-Pelaez José , de Boer Elke , Schuermans Nika , Van de Vondel Liedewei , Paramonov Ida , Johansson Lennart F. , Musacchia Francesco , Benetti Elisa , Bullich Gemma , Sablauskas Karolis , Beltran Sergi , Gilissen Christian , Hoischen Alexander , Ossowski Stephan , de Voer Richarda , Lohmann Katja , Oliveira Carla , Topf Ana , Vissers Lisenka E.L.M. ,   the Solve-RD Consortia, Laurie Steven 
Published: October 2023

AbstractWe report the diagnostic results of a comprehensive copy number variant (CNV) reanalysis of 9,171 exome sequencing (ES) datasets from 5,757 families, including 6,143 individuals affected by a rare disease (RD). The data analysed was extremely heterogeneous, having been generated using 28 different exome enrichment kits, and sequenced on multiple short-read sequencing platforms, by 42 different research groups across Europe partnering in the Solve-RD project. Each of these research groups had previously undertaken their own analysis of the ES data but had failed to identify disease-causing variants.We applied three CNV calling algorithms to maximise sensitivity: ClinCNV, Conifer, and ExomeDepth. Rare CNVs overlapping genes of interest in custom lists provided by one of four partner European Reference Networks (ERN) were identified and taken forward for interpretation by clinical experts in RD. To facilitate interpretation, Integrative Genomics Viewer (IGV) screenshots incorporating a variety of custom-made tracks were generated for all prioritised CNVs.These analyses have resulted in a molecular diagnosis being provided for 51 families in this sample, with ClinCNV performing the best of the three algorithms in identifying disease-causing CNVs. We also identified pathogenic CNVs that are partially explanatory of the proband’s phenotype in a further 34 individuals. This work illustrates the value of reanalysing EScold casesfor CNVs even where analyses had been undertaken previously. Crucially, identification of these previously undetected CNVs has resulted in the conclusion of the diagnostic odyssey for these RD families, some of which had endured decades.
Chronic post-COVID neuropsychiatric symptoms persisting beyond one year from infection: a case-control study and network analysis
Authors: Chau Steven Wai Ho , Chue Timothy Mitchell , Chan Rachel Ngan Yin , Lai Yee Lok , Wong Paul WC , Li Shirley Xin , Liu Yaping , Chan Joey Wing Yan , Chan Paul Kay-sheung , Lai Christopher KC , Leung Thomas WH , Wing Yun Kwok 
Published: October 2023

AbstractBackgroundLimited data about chronic post-COVID neuropsychiatric complaints exist in the literature.AimOur study aims to delineate the phenotypes of chronic neuropsychiatric symptoms among adult subjects recovering from their first COVID that occurred more than one year ago. We also aim to explore the clinical and socioeconomic risk factors of having a high loading of chronic neuropsychiatric symptoms.MethodsWe recruited a post-COVID group who suffered from their first pre-Omicron COVID more than a year ago, and a control group who had never had COVID. The subjects completed app-based questionnaires on demographic, socioeconomic and health status, a COVID symptoms checklist, mental and sleep health measures, and neurocognitive tests.ResultsThe post-COVID group has a statistically significantly higher level of fatigue compared to the control group (p<0.001). Among the post-COVID group, the lack of any COVID vaccination before the first COVID and a higher level of material deprivation before the COVID pandemic predicts a higher load of chronic post-COVID neuropsychiatric symptoms. Partial correlation network analysis suggests that the chronic post-COVID neuropsychiatric symptoms can be clustered into two major (cognitive complaints -fatigue and anxiety-depression) and one minor (headache-dizziness) cluster. A higher level of material deprivation predicts a higher number of symptoms in both major clusters, but the lack of any COVID vaccination before the first COVID only predicts a higher number of symptoms in the cognitive complaints-fatigue cluster.ConclusionsOur result suggests heterogeneity among chronic post-COVID neuropsychiatric symptoms, which are associated with the complex interplay of biological and socioeconomic factors.
Improving the assessment of embryo developmental potential via morphokinetic forecasting of future events using language modeling
Authors: Zabari Nir , Kan-Tor Yoav , Srebnik Naama , Buxboim Amnon 
Published: October 2023

ABSTRACTIn IVF treatments, accurate assessment of the developmental potential of embryos to implant is essential for reaching reasonable pregnancy rates while shortening time-to-pregnancy. Hence, clinical guidelines recommend extended incubation to blastocyst transfers, which provide better evaluation of embryo developmental potential. However, cleavage stage transfer is often favored owing to various clinical considerations. To improve embryo assessment of cleavage stage embryos without extended incubation, we present a computational strategy for forecasting future morphokinetic events. Motivated by the advances in language modeling, we adapt generative pre-training to forecast future morphokinetic events based on the sequence of present events. We demonstrate < 12% forecasting error in forecasting up to three consecutive events. A new policy is proposed that combines morphokinetic forecasting and assessment of the risk of embryo developmental arrest. Using this policy, we demonstrate an improvement in the prediction of known implantation outcome of day-3 embryos from AUC 0.667 to 0.707. We expect morphokinetic forecasting to address the inherent hurdles in the selection of cleavage-stage embryos for transfer. In addition, we hope that demonstrating for the first time the utilization of language modeling on non-textual data in healthcare will stimulate future applications in reproductive medicine and other disciplines.