bluuebunny/crossref_metadata_2025_split huggingface dataset:
Development of a 3D Bioprinted Airway Smooth Muscle Model for Manipulating Structure and Measuring Contraction
Authors: Osagie Jeffery O , Syeda Sanjana S , Turner-Brannen Emily , Guimond Michelle , Parrenas Lumiere , Haroon Ahsen , Imasuen Philip , West Adrian R 
Published: December 2022

ABSTRACTThe contractile function of airway smooth muscle (ASM) is inextricably linked to its mechanical properties and interaction with the surrounding mechanical environment. As tissue engineering approaches become more commonplace for studying lung biology, the inability to replicate realistic mechanical contexts for ASM will increasingly become a barrier to a fulsome understanding of lung health and disease. To address this knowledge gap, we describe the use of 3D bioprinting technology to generate a novel experimental model of ASM with a wide scope for modulating tissue mechanics.Using a stiffness modifiable alginate-collagen-fibrinogen bioink, we demonstrate that modulating the stiffness of free-floating ASM ‘bare rings’ is unfeasible; bioink conditions favorable for muscle formation produce structures that rapidly collapse. However, the creation of novel ‘sandwich’ and ‘spiderweb’ designs that encapsulate the ASM bundle within stiff acellular load bearing frames successfully created variable elastic loads opposing tissue collapse and contraction. Sandwich and spiderweb constructs demonstrated realistic actin filament organisation, generated significant baseline tone, and responded appropriately to acetylcholine, potassium chloride and cytochalasin D. Importantly, the two designs feasibly simulate different mechanical contexts within the lung. Specifically, the sandwich was relatively compliant and subject to plastic deformation under high contractile loads, whereas the stiffer spiderweb was more robust and only deformed minimally after repeated maximal contractions.Thus, our model represents a new paradigm for studying ASM contractile function in a realistic mechanical context. Moreover, it holds significant capacity to study the effects of ECM composition, multiple cell types and fibrosis on lung health and disease.GRANTSNatural Sciences and Engineering Research Council, Discovery Grant (Adrian West)Research Manitoba, New Investigator Operating Grant (Adrian West)Children’s Hospital Research Institute of Manitoba, Operating Grant (Adrian West)Canadian Foundation for Innovation, John R. Evans Leaders Fund (Adrian West)University of Manitoba, Manitoba Graduate Scholarship (Jeffery Osagie)Research Manitoba, Master’s Studentship Award (Jeffery Osagie)Research Manitoba, Master’s Studentship Award (Sanjana Syeda)Children’s Hospital Research Institute of Manitoba, Summer Studentship (Michelle Guimond)University of Manitoba, Jack Prior Memorial Undergraduate Student Research Award (Lumiere Parrenas)University of Manitoba, Undergraduate Research Award (Ahsen Haroon)University of Manitoba, UMSU Undergraduate Research Award (Philip Imasuen)The grant bodies had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
Assessing multiple evidence streams to decide on confidence for identification of post-translational modifications, within and across data sets
Authors: Camacho Oscar M , Ramsbottom Kerry A , Collins Andrew , Jones Andrew R 
Published: December 2022

AbstractPhosphorylation is a post-translational modification of great interest to researchers due to its relevance in many biological processes. LC-MS/MS techniques have enabled high-throughput data acquisition with studies claiming identification and localisation of thousands of phosphosites. The identification and localisation of phosphosites emerge from different analytical pipelines and scoring algorithms, with uncertainty embedded throughout the pipeline. For many pipelines and algorithms, arbitrary thresholding is used, but little is known about the actual global false localisation rate in these studies. Recently, it has been suggested using decoy amino acids to estimate global false localisation rates of phosphosites, amongst the peptide-spectrum matches reported. We here describe a simple pipeline aiming to maximize the information extracted from these studies by objectively collapsing from peptide-spectrum match to peptidoform-site level, as well as combining findings from multiple studies while maintaining track of false localisation rates. We show that the approach is more effective than current processes that use a simpler mechanism for handling phosphosite identification redundancy within and across studies. In our case study using 8 rice phophoproteomics data sets, 6,368 unique sites were identified confidently identified using our decoy approach compared to 4,687 using traditional thresholding in which false localisation rates are unknown.
Okapi-EM – a napari plugin for processing and analysing cryogenic serial FIB/SEM images
Authors: Perdigão Luís M. A. , Ho Elaine M. L. , Cheng Zhiyuan C. , Yee Neville B.-y. , Glen Thomas , Wu Liang , Grange Michael , Dumoux Maud , Basham Mark , Darrow Michele C. 
Published: December 2022

AbstractAn emergent volume electron microscopy (vEM) technique called cryogenic serial plasma focused ion beam milling scanning electron microscopy (pFIB/SEM) can decipher complex biological structures by building a three-dimensional picture of biological samples at mesoscale resolution. This is achieved by collecting consecutive SEM images after successive rounds of FIB milling that expose a new surface after each milling step. Due to instrumental limitations, some image processing is necessary before 3D visualisation and analysis of the data is possible. SEM images are affected by noise, drift, and charging effects, that can make precise 3D reconstruction of biological features difficult. This paper presents Okapi-EM, an open-source Napari plugin(1)developed to process and analyse cryogenic serial FIB/SEM images. Okapi-EM enables automated image registration of slices, evaluation of image quality metrics specific to FIB-SEM imaging, and mitigation of charging artefacts. Implementation of Okapi-EM within the Napari framework ensures that the tools are both user- and developer-friendly, through provision of a graphical user interface and access to Python programming. Napari also hosts a variety of other image processing plugins so Okapi-EM tools can be integrated into and combined with other workflows. Okapi-EM can be downloaded freely athttps://github.com/rosalindfranklininstitute/okapi-em, or installed from Python package index (PyPI).Impact statementCryogenic serial pFIB/SEM is an emerging microscopy technique that is used to visualise 3D structures of biological features at mesoscale resolutions(2). This technique requires common post processing of data such as alignment and charge mitigation to enable robust segmentation and analysis. In addition, approaches are needed to quantify data quality to enable an assessment of features and tune data acquisition parameters to enable optimal image acquisition. This article presents Okapi-EM, a combination of software tools designed to facilitate these important initial steps in assessing and processing images from these experiments. These tools have been assembled as a plugin for a popular 3D biological image visualiser called Napari, making their usage user-friendly and readily accessible.
Surface tension drives neuronal sorting in magnetically engineered brain-like tissue
Authors: Perez Jose E. , Jan Audric , Villard Catherine , Wilhelm Claire 
Published: December 2022

AbstractEngineered 3D brain-like models have advanced the understanding of neurological mechanisms and disease, yet their mechanical signature, while fundamental for brain function, remains understudied. The surface tension for instance controls brain development and is a marker of cell-cell interactions. Here, we engineered 3D magnetic brain-like tissue spheroids composed of intermixed primary glial and neuronal cells at different ratios. Remarkably, the two cell types self-assemble into a functional tissue, with the sorting of the neuronal cells towards the periphery of the spheroids, whereas the glial cells constitute the core. The magnetic fingerprint of the spheroids then allows their deformation when placed under a magnetic field gradient, at a force equivalent to a 70 g increased gravity at the spheroid level. The tissue surface tension and elasticity can be directly inferred from the resulting deformation, revealing a transitional dependence on the glia/neuron ratio, with the surface tension of neuronal tissue being much lower. This provides the underlying mechanical explanation for the exclusion of the neurons towards the outer spheroid region, and depicts the glia/neuron organization as a surface tension-driven sophisticated mechanism that should in turn influence brain development and homeostasis.
Drinkable, liquidin situ-forming and tough hydrogels for gastrointestinal therapeutics
Authors: Liu Gary W. , Pickett Matthew J. , Kuosmanen Johannes L. P. , Ishida Keiko , Madani Wiam A. M. , White Georgia N. , Jenkins Joshua , Feig Vivian R. , Jimenez Miguel , Lopes Aaron , Morimoto Joshua , Fitzgerald Nina , Cheah Jaime H. , Soule Christian K. , Fabian Niora , Hayward Alison , Langer Robert S. , Traverso Giovanni 
Published: December 2022

ABSTRACTTablets and capsules are a cornerstone of medicine, but these solid dosage forms can be challenging to swallow for geriatric and pediatric patients. While liquid formulations are easier to ingest, these formulations lack the capacity to localize therapeutics and excipients nor act as controlled release devices. To bridge the advantages of solid and liquid dosage forms, here we describe drug formulations based on liquidin situ-forming and tough (LIFT) hydrogels. Drug-loaded LIFT hydrogels are formed directly in the stomach through the sequential ingestion of a crosslinker solution of calcium and dithiol crosslinkers, followed by the ingestion of a drug-containing polymer solution of alginate and 4-arm poly(ethylene glycol)-maleimide. We show that LIFT hydrogels are mechanically tough and able to robustly form in the presence of complex gastric fluid andin vivoin rat and porcine stomachs. LIFT hydrogels are retained within the porcine stomach for up to 24 h, biocompatible, and safely cleared. These hydrogels deliver a total dose comparable to unencapsulated drug but with delayed and lower maximum drug plasma concentrations, providing a method for controlled release that may mitigate drug toxicity. Co-encapsulation of lactase as a model biologic drug and calcium carbonate mitigated gastric-mediated deactivation of encapsulated enzyme in rat and porcine models. We also demonstrate the potential of these hydrogels to encapsulate and protect a model therapeutic bacterium,E. coliNissle 1917, against acid. LIFT hydrogels present a biocompatible means of tough, double-network hydrogel formationin situin the gastric cavity, and may expand medication access for patients with difficulty swallowing.
A new simulation framework to evaluate the suitability of eDNA for marine and aquatic Environmental Impact Assessments
Authors: Coston-Guarini J. , Hinz S. , Mirimin L. , Guarini J.-M. 
Published: December 2022

AbstractThis study evaluates how eDNA information could be used within Environmental Impact Assessment (EIA). We developed an original model to simulate the conditions for which an eDNA signal detects, or does not detect, an impact on a targeted (receptor) species in a given project area. The simulation has four consecutive steps. First, a deterministic model simulated the dynamics of the receptor population and their eDNA fragment concentrations in the environment. Second, random distributions of receptor organisms and eDNA fragment quantities at steady-state were simulated within the project area. Then Simple Random Samplings were performed for both the receptor and eDNA. Third, post-sampling processes (eDNA extraction, amplification, analysis) were simulated to estimate the detection probability of the species from sample plan characteristics (size of sampling unit, number of samples collected). Fourth, we simulated an impact by modifying the growth, mortality and mobility (null, passive and active) parameters of the receptor species, then determined if an impact was detected. Detection probability curves were estimated for a range of sample volumes fitted with a Weibull cumulative distribution function. An F-like statistic compared detection curves before and after impact. Twelve scenarios were simulated. A statistically significant impact was detected with eDNA when receptor species growth rate was halved, but only in cases of null or passive mobility. When the receptor experienced both reduced growth and increased mortality rates, an impact was detected in all three mobility cases (null, passive and active). Our results suggest that an impact could be detected using eDNA if both the population dynamics of the receptor and the dynamics of DNA shed into the environment are known. These results indicate that caution should be exercised with eDNA data for EIA, but the proposed framework provides a valuable starting point to improve interpretation of indirect observation methods such as eDNA.
Mapping current and future thermal limits to suitability for malaria transmission by the invasive mosquitoAnopheles stephensi
Authors: Ryan Sadie J. , Lippi Catherine A. , Villena Oswaldo C. , Singh Aspen , Murdock Courtney C. , Johnson Leah R. 
Published: December 2022

AbstractBackgroundAnopheles stephensiis a malaria-transmitting mosquito that has recently expanded from its primary range in Asia and the Middle East, to locations in Africa. This species is a competent vector of bothP. falciparum(PF) andP. vivax(PV) malaria. Perhaps most alarming, the characteristics ofAn. stephensi, such as container breeding and anthropophily, make it particularly adept at exploiting built environments in areas with no prior history of malaria risk.MethodsIn this paper we created global maps of thermal transmission suitability and people at risk (PAR) for malaria transmission byAn. stephensi, under current and future climate. Temperature-dependent transmission suitability thresholds derived from recently published species-specific thermal curves were used to threshold gridded, monthly mean temperatures under current and future climatic conditions. These temperature driven transmission models were coupled with gridded population data for 2020 and 2050, under climate-matched scenarios for future outcomes, to compare with baseline predictions for 2020 populations.ResultsUsing the Global Burden of Disease regions approach, we found that heterogenous regional increases and decreases in risk did not mask the overall pattern of massive increases of PAR for malaria transmission suitability withAn. stephensipresence. General patterns of poleward expansion for thermal suitability were seen for both PF and PV transmission potential.ConclusionsUnderstanding the potential suitability forAn. stephensitransmission in a changing climate provides a key tool for planning, given an ongoing invasion and expansion of the vector. Anticipating the potential impact of onward expansion to transmission suitable areas, and the size of population at risk under future climate scenarios, andwherethey occur, can serve as a large-scale call for attention, planning, and monitoring.
Accurate cell type deconvolution in spatial transcriptomics using a batch effect-free strategy
Authors: Wang Linhua , Wu Ling , Liu Chaozhong , Wang Wanli , Zhang Xiang H.-F. , Liu Zhandong 
Published: December 2022

ABSTRACTSequencing-based spatial transcriptomics (ST) techniques have been groundbreaking in dissecting cell-cell communications within tissues by profiling positional gene expression. However, the most widely used ST technique, Visium Spatial Gene Expression by 10x Genomics (Visium), does not provide single-cell resolution, making it difficult to profile cell type-level information. Many reference-based deconvolution methods have been developed to increase its resolution, but the platform and batch effects between the reference and ST data compromise their accuracy. Here, we propose a new approach,Region-based cellSorting (ReSort), that generates a pseudo-internal-reference to reduce these platform effects. By simulating ST datasets under various scenarios, we demonstrate that ReSort significantly improves the accuracy of six state-of-the-art reference-based deconvolution methods. Moreover, applying ReSort to a mouse breast cancer tumor bearing both epithelial and mesenchymal clones identifies the spatial differences of immune cells between the clones, providing important insights for understanding the relationship between epithelial-mesenchymal transition and immune infiltration in breast cancer.
Highly contiguous genome assembly and population sequencing reveal three distinct populations and signatures of insecticide resistance ofTuta absolutain Latin America
Authors: Lewald Kyle M. , Tabuloc Christine A. , Godfrey Kristine E. , Arnó Judit , Perini Clérison R. , Guedes Jerson C. , Chiu Joanna C. 
Published: December 2022

AbstractTuta absolutais one of the largest threats to tomato agriculture worldwide. Native to South America, it has rapidly spread throughout Europe, Africa, and Asia over the past two decades. To understand howT. absolutahas been so successful and to improve containment strategies, high quality genomic resources and an understanding of population history is critical. Here, we describe a highly contiguous annotated genome assembly, as well as a genome-wide population analysis of samples collected across Latin America. The new genome assembly has an L50 of 17 with only 132 contigs. Based on hundreds of thousands of SNPs, we detect three major population clusters in Latin America with some evidence of admixture along the Andes Mountain range. Based on coalescent simulations, we find these clusters diverged from each other tens of thousands of generations ago prior to domestication of tomatoes. We further identify several genomic loci under selection related to insecticide resistance, immunity, and metabolism. This data will further future research toward genetic control strategies and inform future containment policies.
Effect of pregnancy and hypertension on kidney function in female rats: Modeling and functional implications
Authors: Stadt Melissa M. , West Crystal A. , Layton Anita T. 
Published: December 2022

AbstractThroughout pregnancy, the kidneys undergo significant adaptations in morphology, hemodynamics, and transport to achieve the volume and electrolyte retention required to support a healthy pregnancy. Additionally, during pregnancies complicated by chronic hypertension, altered renal function from normal pregnancy occurs. The goal of this study is to analyze how inhibition of critical transporters affects gestational kidney function as well as how renal function is affected during chronic hypertension in pregnancy. To do this, we developed epithelial cell-based multi-nephron computational models of solute and water transport in the kidneys of a female rat in mid- and late pregnancy. We simulated the effects of key individual pregnancy-induced changes on renal Na+and K+transport: proximal tubule length, Na+/H+exchanger isoform 3 (NHE3) activity, epithelial Na+channel activity (ENaC), K+secretory channel expression, and H+-K+-ATPase activity. Additionally, we conducted simulations to predict the effects of inhibition and knockout of the ENaC and H+-K+-ATPase transporters on virgin and pregnant rat kidneys. Our simulation results predicted that the ENaC and H+-K+-ATPase transporters are essential for sufficient Na+and K+reabsorption during pregnancy. Last, we developed models to capture changes made during hypertension in female rats and considered what may occur when a rat with chronic hypertension becomes pregnant. Model simulations predicted that in hypertension for a pregnant rat there is a similar shift in Na+transport from the proximal tubules to the distal tubules as in a virgin rat.
Identification of EPHB4 variants in dilated cardiomyopathy patients
Authors: Luxán Guillermo , Muhly-Reinholz Marion , Glaser Simone F. , Trebing Johannes , Reich Christoph , Haas Jan , Sedaghat-Hamedani Farbod , Meder Benjamin , Dimmeler Stefanie 
Published: December 2022

AbstractCardiac homeostasis relies on the appropriate provision of nutrients to the working myocardium. EPHB4 is required for the maintenance of vascular integrity and correct fatty acid transport uptake in the heart via regulating the caveolar trafficking of the fatty acid receptor CD36. In the mouse, endothelial specific loss-of-function of the receptor EphB4, or its ligand ephrin-B2, induces Dilated Cardiomyopathy (DCM) like defects. Now, we have identified six newEPHB4variants with deleterious potential in a cohort of 573 DCM patients. Similar to the EphB4 mutant mice,EPHB4variants carrying patients show an altered expression pattern of CD36 and CAV1 in the heart. For the first time, our data identifies EPHB4 mutations in DCM patients. This observation supports the notion that the Eph-ephrin signalling pathway, and in particular the receptor EPHB4, plays a role in the development of DCM in human patients.
Patient Flow in Congested Intensive Care Unit /Step-down Unit system: Premature Step-down or not?
Authors: Kobara Yawo M. , Rodrigues Felipe F. , de Souza Camila P. E. , Stanford David A. 
Published: December 2022

AbstractA Step-Down Unit (SDU) provides an intermediate Level of Care for patients from an Intensive Care Unit (ICU) as their condition becomes less acute. SDU congestion, as well as upstream patient arrivals, forces ICU administrators to incur costs, either in the form of overstays or premature step-downs. Basing on a proxy for patient acuity level called the ‘Nine Equivalents of Nursing Manpower Score (NEMS)’, patients were classified into two groups: high-acuity and low-acuity. Two patient flow policies were developed that select actions to optimize the system’s net health service benefit: one allowing for premature step-down actions, and the other allowing for patient rejection actions when the system is congested. The results show that the policy with patient rejection has a net health service benefit that significantly exceeds that of the policy with the premature step-down option. Based on these results, it can be concluded that premature step-down contributes to congestion downstream. Counter-intuitively, premature step-down should therefore be discouraged and patient rejection actions should be further explored as viable options for congested ICUs.