bluuebunny/crossref_metadata_2025_split huggingface dataset:
Mass Homicide by Firearm in Canada: Effects of Legislation
Authors: Langmann Caillin 
Published: March 2022

AbstractCanada implemented a series of laws regulating firearms including background checks and licensing, references, psychological questionnaires, prohibition of paramilitary style rifles, and magazine capacity restrictions in order to decrease the incidences and deaths from mass shootings. The associated effects of these laws were examined over the years 1974 to 2020.A model was constructed using difference-in-differences analysis of firearms and non-firearms mass homicide incidences and death rates. Mass homicides were defined as a homicide due to one event involving three or more deaths.Incidence rates of mass homicide by firearm were found to be 0.11 (95%CI 0.08, 0.14) per million compared to a non-firearm mass homicide rate of 0.12 (95% CI 0.10, 0.15) per million. Mass homicide death rates by firearm were found to be 0.39 (95% CI 0.29, 0.49) per million compared to a non-firearm mass homicide rate of 0.47 (95% CI 0.34, 0.61) per million. Overall, there is a gradual declining trend in the incidence of mass homicide by firearm (IRR 0.97 (95% CI 0.96, 0.98)) and by non-firearm (IRR 0.97 (95% CI 0.97, 0.98)). The decline in mass homicide death rate by firearm and non-firearm is IRR 0.96 (95% CI 0.95, 0.97), and IRR 0.97 (95% CI 0.96, 0.98) respectively.No associated decrease in mass homicide incidence rates or death rates with firearms legislation was found after the implementation of background checks and prohibition of full auto firearms in 1980, by the implementation of references and psychological questionnaires in 1994, by the restriction of magazine capacity in 1994, the prohibition of paramilitary rifles in 1994, or licensing in 2001.
Lagrangian Formalism in Biology: I. Standard Lagrangians and their Role in Population Dynamics
Authors: Pham D.T. , Musielak Z.E. 
Published: March 2022

AbstractThe Lagrangian formalism is developed for the population dynamics of interacting species that are described by several well-known models. The formalism is based on standard Lagrangians, which represent differences between the physical kinetic and potential energy-like terms. A method to derive these Lagrangians is presented and applied to selected theoretical models of the population dynamics. The role of the derived Lagrangians and the energy-like terms in the population dynamics is investigated and discussed. It is suggested that the obtained standard Lagrangians can be used to identify physical similarities between different population models.
Cell type profiling in salamanders identifies innovations in vertebrate forebrain evolution
Authors: Woych Jamie , Gurrola Alonso Ortega , Deryckere Astrid , Jaeger Eliza C. B. , Gumnit Elias , Merello Gianluca , Gu Jiacheng , Araus Alberto Joven , Leigh Nicholas D. , Yun Maximina , Simon András , Tosches Maria Antonietta 
Published: March 2022

AbstractThe evolution of advanced cognition in vertebrates is associated with two independent innovations in the forebrain: the six-layered neocortex in mammals and the dorsal ventricular ridge (DVR) in sauropsids (reptiles and birds). How these novelties arose in vertebrate ancestors remains unclear. To reconstruct forebrain evolution in tetrapods, we built a cell type atlas of the telencephalon of the salamander Pleurodeles waltl. Our molecular, developmental, and connectivity data indicate that parts of the sauropsid DVR trace back to tetrapod ancestors. In contrast, the salamander dorsal pallium is devoid of cellular and molecular characteristics of the mammalian neocortex, yet shares similarities with entorhinal cortex and subiculum. Our findings chart the series of innovations that resulted in the emergence of the sauropsid DVR, and the mammalian six-layered neocortex.
Digitizing the coral reef: machine learning of underwater spectral images enables dense taxonomic mapping of benthic habitats
Authors: Schürholz Daniel , Chennu Arjun 
Published: March 2022

AbstractCoral reefs are the most biodiverse marine ecosystems, and host a wide range of taxonomic diversity in a complex spatial habitat structure. Existing coral reef survey methods struggle to accurately capture the taxonomic detail within the complex spatial structure of benthic communities.We propose a workflow to leverage underwater hyperspectral transects and two machine learning algorithms to produce dense habitat maps of 1150 m2 of reefs across the Curaçao coastline. Our multi-method workflow labelled all 500+ million pixels with one of 43 classes at taxonomic family, genus or species level for corals, algae, sponges, or to substrate labels such as sediment, turf algae and cyanobacterial mats.With low annotation effort (2% pixels) and no external data, our workflow enables accurate (Fbeta 87%) survey-scale mapping, with unprecedented thematic and spatial detail. Our assessments of the composition and configuration of the benthic communities of 23 transect showed high consistency.Digitizing the reef habitat structure enables validation and novel analysis of pattern and scale in coral reef ecology. Our dense habitat maps reveal the inadequacies of point sampling methods to accurately describe reef benthic communities.
The Modular µSiM: a Mass Produced, Rapidly Assembled, and Reconfigurable Platform for the Study of Barrier Tissue ModelsIn Vitro
Authors: McCloskey Molly C. , Kasap Pelin , Ahmad S. Danial , Su Shiuan-Haur , Chen Kaihua , Mansouri Mehran , Ramesh Natalie , Nishihara Hideaki , Belyaev Yury , Abhyankar Vinay V. , Begolo Stefano , Singer Benjamin H. , Webb Kevin F. , Kurabayashi Katsuo , Flax Jonathan , Waugh Richard E. , Engelhardt Britta , McGrath James L. 
Published: March 2022

AbstractAdvancedin vitrotissue chip models can reduce and replace animal experimentation and may eventually support ‘on-chip’ clinical trials. To realize this potential, however, tissue chip platforms must be both mass-produced and reconfigurable to allow for customized design. To address these unmet needs, we introduce an extension of our µSiM (microdevice featuring asilicon-nitridemembrane) platform. ThemodularµSiM (m-µSiM) uses mass-produced components to enable rapid assembly and reconfiguration by laboratories without knowledge of microfabrication. We demonstrate the utility of the m-µSiM by establishing an hiPSC-derived blood-brain barrier (BBB) in bioengineering and non-engineering, brain barriers focused laboratories. We develop and validatein situand sampling-based assays of small molecule diffusion as a measure of barrier function. BBB properties show excellent interlaboratory agreement and match expectations from literature, validating the m-µSiM as a platform for barrier models and demonstrating successful dissemination of components and protocols. We then demonstrate the ability to quickly reconfigure the m-µSiM for co-culture and immune cell transmigration studies through addition of accessories and/or quick exchange of components. Because the development of modified components and accessories is easily achieved, custom designs of the m-µSiM should be accessible to any laboratory desiring a barrier-style tissue chip platform.
The Modular μSiM Reconfigured: Integration of Microfluidic Capabilities to Study in vitro Barrier Tissue Models under Flow
Authors: Mansouri Mehran , Ahmed Adeel , Ahmad S. Danial , McCloskey Molly C. , Joshi Indranil M. , Gaborski Thomas R. , Waugh Richard E. , McGrath James L. , Day Steven W. , Abhyankar Vinay V. 
Published: March 2022

AbstractMicrofluidic approaches to study tissue barriers have emerged to address the lack of fluid flow in conventional “open-well” Transwell™-like devices. However, microfluidic techniques have not achieved widespread usage in bioscience laboratories because they are not fully compatible with traditional, tried-and-true experimental protocols. To advance barrier tissue research, there is a need for a platform that combines the advantages of both conventional open-well and microfluidic systems. Here, we develop a plug-and-play flow module to add on-demand microfluidic capabilities to amodularmicrofluidic system featuring asiliconmembrane “m-μSiM” as an open-well device with live-cell imaging capabilities. The magnetic latching assembly of our design enables bi-directional reconfiguration between open-well and fluidic modes. This design feature allows users to conduct an experiment in an open-well format with established protocols and then add or remove microfluidic capabilities as desired. Our work also provides an experimentally-validated flow model to help select desired flow conditions based on the experimental needs. As a proof-of-concept, we demonstrate flow-induced alignment of endothelial cells and visualize different phases of neutrophil transmigration across an endothelial monolayer under flow. We anticipate that our reconfigurable design will be adopted by both engineering and bioscience laboratories due to the compatibility with standard open-well protocols and the simple flow addition capabilities.
Canonical Wnt Signaling and the Regulation of Divergent Mesenchymal Fgf8 expression in Axolotl Limb Development and Regeneration
Authors: Glotzer Giacomo L. , Tardivo Pietro , Tanaka Elly M. 
Published: March 2022

AbstractThe expression of Fibroblast growth factors (Fgf) ligands in a specialized epithelial compartment, the Apical Ectodermal Ridge (AER), is a conserved feature of limb development across vertebrate species. In vertebrates, Fgf 4, 8, 9, and 17 are all expressed in the AER. An exception to this paradigm is the salamander (axolotl) developing and regenerating limb, where key Fgf ligands are expressed in the mesenchyme. The mesenchymal expression of Amex.Fgf8 in axolotl has been suggested to be critical for regeneration. To date, there is little knowledge regarding what controls Amex.Fgf8 expression in the axolotl limb mesenchyme. A large body of mouse and chick studies have defined a set of transcription factors and canonical Wnt signaling as the main regulators of epidermal Fgf8 expression in these organisms. In this study, we address the hypothesis that alterations to one or more of these components during evolution has resulted in mesenchymal Amex.Fgf8 expression in the axolotl. To sensitively quantify gene expression with spatial precision, we combined optical clearing of whole-mount axolotl limb tissue with single molecule fluorescent in situ hybridization and a semi-automated quantification pipeline. Several candidate upstream components were found expressed in the axolotl ectoderm, indicating that they are not direct regulators of Amex.Fgf8 expression. We found that Amex.Wnt3a is expressed in axolotl limb epidermis, similarly to chicken and mouse. However, unlike in amniotes, Wnt target genes are activated preferentially in limb mesenchyme rather than in epidermis. Inhibition and activation of Wnt signaling results in downregulation and upregulation of mesenchymal Amex.Fgf8 expression respectively. These results implicate a shift in tissue responsiveness to canonical Wnt signaling from epidermis to mesenchyme as one step contributing to the unique mesenchymal Amex.Fgf8 expression seen in the axolotl.
On whole-genome demography of world’s ethnic groups and individual genomic identity
Authors: Kim Byung-Ju , Choi JaeJin , Kim Sung-Hou 
Published: March 2022

AbstractAll current categorizations of human population, such as ethnicity, ancestry and race, are based on various selections and combinations ofsubjectively-and/orqualitatively-defined characteristics, such as ancestral lineage/location, cultural/societal norm, language, skin color and other phenotypes and traits perceived by the members within or from outside of the categorized group. Yet, such categorization has been broadly used also in the fields of human genetics, health sciences and medical practices (e.g.,1,2,3), where the observed health characteristics are objectively and quantitatively definable, but the population categorization is not yet available. Here we show the feasibility of deriving a whole-genome-based categorization that is objectively definable and quantitatively measurable. We observe that: (a) the world’s ethnic populations form about 14 genomic groups (GGs); (b) each GG consists of multiple ethnic groups (EGs); and (c) at an individual level, approximately 99.8%, on average, of the whole genome contents are identical between anytwo individualsregardless of their GGs or EGs.
The pre-Bötzinger complex is necessary for the expression of post-inspiration
Authors: Dhingra Rishi R. , Furuya Werner I. , Dutschmann Mathias 
Published: March 2022

AbstractThe mammalian three-phase respiratory motor pattern of inspiration, post-inspiration and expiration is expressed in spinal and cranial motor nerve activities. This pattern is generated by a hierarchical brainstem-wide pre-motor network. However, the local rhythmogenic circuit of the pre-Bötzinger complex (pre-BötC) was established as the ‘noeud vitale’ necessary and sufficient to initiate inspiration. In present study, we tested the effect of unilateral and bilateral inactivation of the pre-BötC (microinjection of the GABAA receptor agonist isoguvacine 10 mM, 50 nl) on respiratory motor activities in an in situ perfused brainstem preparation of rat. As expected, bilateral inactivation of the pre-BötC triggered cessation of phrenic (PNA), hypoglossal (HNA) and vagal (VNA) nerve activities for 15-20 min. Partial recovery from bilateral isoguvacine injection was characterized by erratic activity in all recorded motor nerves reminiscent to patterns observed after disturbed excitatory-inhibitory balance within the local pre-BötC circuit. Surprisingly, ipsilateral isoguvacine injections into the pre-BötC triggered transient (6-8 min) cessation of inspiratory and post-inspiratory VNA (p<0.001) and suppressed inspiratory HNA by -70 ± 15% (p<0.01), while inspiratory PNA burst frequency increased by 46 ± 30% (p<0.01). Taken together, these observations confirm the role of the pre-BötC as the ‘noeud vitale’ of the mammalian respiratory network in situ and highlight a significant role for the pre-BötC in the expression of vagal post-inspiratory and inspiratory activity.
Comprehensive profiling of antibody responses to the human anellome using programmable phage display
Authors: Venkataraman Thiagarajan , Swaminathan Harish , Arze Cesar A. , Jacobo Sarah M. , Bhattacharyya Agamoni , David Tyler , Nawandar Dhananjay M. , Delagrave Simon , Mani Vinidhra , Yozwiak Nathan L. , Larman H. Benjamin 
Published: March 2022

AbstractViruses belonging to the diverse Anelloviridae family represent a major constituent of the commensal human virome. Aside from their widespread prevalence and persistence in humans and their absence of detectable pathologic associations, little is known about the immunobiology of the human anellome. In this study, we employed the Phage ImmunoPrecipitation Sequencing (PhlP-Seq) assay for comprehensive analyses of antibody binding to 56 amino acid long anellovirus peptides. We designed and constructed a large and diverse “AnelloScan” T7 phage library comprising more than 32,000 non-redundant peptides representing the ORF1, ORF2, ORF3 and TTV-derived apoptosis-inducing protein (TAIP) sequences of more than 800 human anelloviruses (spanning three genera). We used this library to profile the antibody reactivities of serum samples from 156 subjects. The vast majority of anellovirus peptides were not reactive in any of the subjects tested (n=~28,000; ~85% of the library). Antibody reactive peptides were largely restricted to the C-terminal region of the putative capsid protein, ORF1. To characterize antibody responses to newly acquired anellovirus infections, we screened a longitudinal cohort of matched blood-transfusion donors and recipients. Most transmitted anelloviruses did not elicit detectable antibody reactivity in the recipient (29 out of a total of 40 transmitted anelloviruses) and the remainder demonstrated delayed reactivity (~100-150 days after transfusion). This study represents the first large-scale epitope-level serological survey of the antibody response to the human anellome.Graphical Abstract
Subcellular mapping of the protein landscape of SARS-CoV-2 infected cells for target-centric drug repurposing
Authors: Kaimal Jayasankar Mohanakrishnan , Tampere Marianna , Le Trang H. , Axelsson Ulrika , Xu Hao , Axelsson Hanna , Bäckström Anna , Marabita Francesco , Moussaud-Lamodière Elisabeth , Njenda Duncan , Sepulveda Carolina Oses , Oyuang Wei , Seashore-Ludlow Brinton , Vernersson Caroline , Mirazimi Ali , Lundberg Emma , Östling Päivi , Stadler Charlotte 
Published: March 2022

AbstractThe COVID-19 pandemic has resulted in millions of deaths and affected socioeconomic structure worldwide and the search for new antivirals and treatments are still ongoing. In the search for new drug target and to increase our understanding of the disease, we used large scale immunofluorescence to explore the host cell response to SARS-CoV-2 infection. Among the 602 host proteins studied in this host response screen, changes in abundance and subcellular localization were observed for 97 proteins, with 45 proteins showing increased abundance and 10 reduced abundances. 20 proteins displayed changed localization upon infection and an additional 22 proteins displayed altered abundance and localization, together contributing to diverse reshuffling of the host cell protein landscape. We then selected existing and approved small-molecule drugs (n =123) against our identified host response proteins and identified 3 compounds - elesclomol, crizotinib and rimcazole, that significantly reduced antiviral activity. Our study introduces a novel, targeted and systematic approach based on host protein profiling, to identify new targets for drug repurposing. The dataset of ∼75,000 immunofluorescence images from this study are published as a resource available for further studies.
Transcriptional dynamics of colorectal cancer risk associated variation at 11q23.1 are correlated with tuft cell abundance and marker expression in silico
Authors: Harris Bradley T. , Rajasekaran Vidya , Blackmur James P. , O’Callaghan Alan , Donnelly Kevin , Timofeeva Maria , Vaughan-Shaw Peter G. , Din Farhat V. N. , Dunlop Malcolm G. , Farrington Susan M. 
Published: March 2022

AbstractColorectal cancer (CRC) is characterised by heritable risk that is not well understood. Heritable, genetic variation at 11q23.1 is associated with increased colorectal cancer (CRC) risk, demonstrating eQTL effects on 3 cis- and 23 trans-eQTL targets. We sought to determine the relationship between 11q23.1 cis- and trans-eQTL target expression and test for potential cell-specificity. scRNAseq from 32,361 healthy colonic epithelial cells was aggregated and subject to weighted gene co-expression network analysis (WGCNA). One module (blue) included 19 trans-eQTL targets and was correlated with C11orf53 expression only. Following unsupervised clustering of single cells, the expression of 19 trans-eQTL targets was greatest and most variable in cluster number 11, which transcriptionally resembled tuft cells. 14 trans-eQTL targets were found to demarcate this cluster, 11 of which were corroborated in a second dataset. Intra-cluster WGCNA and module preservation analysis then identified twelve 11q23.1 trans-eQTL targets to comprise a network that was specific to cluster 11. Finally, linear modelling and differential abundance testing showed 11q23.1 trans-eQTL target expression was predictive of cluster 11 abundance. Our findings suggest 11q23.1 trans-eQTL targets comprise a C11orf53-related network that is likely tuft cell-specific and reduced expression of these genes correlates with reduced tuft cell abundance in silico.
Large scale in vivo acquisition, segmentation, and 3D reconstruction of cortical vasculature using open-source functional ultrasound imaging platform
Authors: Strumane Anoek , Lambert Théo , Aelterman Jan , Babin Danilo , Philips Wilfried , Montaldo Gabriel , Brunner Clément , Urban Alan 
Published: March 2022

AbstractThe brain is composed of a dense and ramified vascular network comprising various sizes of arteries, veins, and capillaries. One way to assess the risk of cerebrovascular pathologies is to use computational models to predict the physiological effects of a reduction of blood supply and correlate these responses with observations of brain damage. Therefore, it is crucial to establish a detailed 3D organization of the brain vasculature, which could be used to develop more accurate in silico models. For this purpose, we have adapted our open-access functional ultrasound imaging platform previously designed for recording brain-wide activity that is now capable of fast and reproducible acquisition, segmentation, and reconstruction of the cortical vasculature. For the first time, it allows us to digitize the cortical vasculature in awake rodents with a ∼100 µm3 spatial resolution. Contrary to most available strategies, our approach can be performed in vivo within minutes. Moreover, it is easy to implement since it neither requires exogenous contrast agents nor long post-processing time. Hence, we performed a cortex-wide reconstruction of the vasculature and its quantitative analysis, including i) classification of descending arteries versus ascending veins in more than 1500 vessels/animal, ii) quick estimation of their length. Importantly, we confirmed the relevance of our approach in a model of cortical stroke, which enables quick visualization of the ischemic lesion. This development contributes to extending the capabilities of ultrasound neuroimaging to understand better cerebrovascular pathologies such as stroke, vascular cognitive impairment, and brain tumors and is highly scalable for the clinic.
Development of a new 3D tracking system for multiple marmosets under free-moving conditions
Authors: Yurimoto Terumi , Kumita Wakako , Sato Kenya , Kikuchi Rika , Shibuki Yusuke , Hashimoto Rino , Kamioka Michiko , Hayasegawa Yumi , Yamazaki Eiko , Kurotaki Yoko , Goda Norio , Kitakami Junichi , Fujita Tatsuya , Inoue Takashi , Sasaki Erika 
Published: March 2022

AbstractAssessment of social interactions and behavioral changes in nonhuman primates is useful for understanding brain function changes during life events and pathogenesis of neurological diseases. The common marmoset (Callithrix jacchus), that lives in a nuclear family like humans, is a useful model, but long-term automated behavioral observation of multiple animals has not been achieved. Here, we developed aFullMonitoring andAnimal Identification (FulMAI) system for long-term detection of three-dimensional (3D) trajectories of each individual in multiple marmosets under free-moving conditions by combining video tracking, Light Detection And Ranging, and deep learning. Using this system, identification of each animal was more than 97% accurate. Location preferences and inter-individual distance could be calculated, and deep learning could detect grooming behavior. The FulMAI system allows us to analyze the natural behavior of individuals in a family over their lifetime and understand how behavior changes due to life events together with other data.
Validation of DeepLabCut as a tool for markerless 3D pose estimation
Authors: Kosourikhina Veronika , Kavanagh Diarmuid , Richardson Michael J. , Kaplan David M. 
Published: March 2022

AbstractDeep learning-based approaches to markerless 3D pose estimation have taken neuroscience by storm. Yet many of these tools remain unvalidated. Here, we report on the validation of one increasingly popular tool (DeepLabCut) against simultaneous measurements obtained from a reference measurement system (Fastrak) with well-known performance characteristics. Our results confirm close (mm range) agreement between the two, indicating that deep learning-based approaches can be used by the research community with confidence.