bluuebunny/crossref_metadata_2025_split huggingface dataset:
Time is Tissue: Barriers to Timely Transfusion after Pediatric Injury
Authors: Sullivan Travis M. , Gestrich-Thompson Waverly V. , Milestone Zachary P. , Burd Randall S. 
Published: August 2022

ABSTRACT
Strategies to improve outcomes among children and adolescents in hemorrhagic shock have primarily focused on component resuscitation, pharmaceutical coagulation adjuncts, and hemorrhage control techniques. Many of these strategies have been associated with better outcomes in children, but the barriers to their use and the impact of timely use on morbidity and mortality has received little attention. Because transfusion is uncommon in injured children, few studies have identified and described barriers to the processes of using these interventions in bleeding patients, processes that move from the decision to transfuse, to obtaining the necessary blood products and adjuncts, and to delivering them to the patient. In this review, we identify and describe the steps needed to ensure timely blood transfusion and propose practices to minimize barriers in this process. Given the potential impact of time on hemorrhage associated outcomes, ensuring timely intervention may have a similar or greater impact than the interventions themselves.

Level of Evidence:
Regular Review: Level III and IV
PEMT: A patent enrichment tool for drug discovery
Authors: Gadiya Yojana , Zaliani Andrea , Gribbon Philip , Hofmann-Apitius Martin 
Published: August 2022

AbstractMotivationDrug discovery practitioners in industry and academia use semantic tools to extract information from online scientific literature to generate new insights into targets, therapeutics and diseases. However, due to complexities in access and analysis, patent-based literature is often overlooked as a source of information. As drug discovery is a highly competitive field, naturally, tools that tap into patent literature can provide any actor in the field an advantage in terms of better informed decision making. Hence, we aim to facilitate access to patent literature through the creation of an automatic tool for extracting information from patents described in existing public resources.ResultsHere, we present PEMT, a novel patent enrichment tool, that takes advantage of public databases like ChEMBL and SureChEMBL to extract relevant patent information linked to chemical structures and/or gene names described through FAIR principles and metadata annotations. PEMT aims at supporting drug discovery and research by establishing a patent landscape around genes of interest. The pharmaceutical focus of the tool is mainly due to the subselection of International Patent Classification (IPC) codes, but in principle, it can be used for other patent fields, provided that a link between a concept and chemical structure is investigated. Finally, we demonstrate a use-case in rare diseases by generating a gene-patent list based on the epidemiological prevalence of these diseases and exploring their underlying patent landscapes.Availability and implementationPEMT is an open-source Python tool and its source code and PyPi package are available athttps://github.com/Fraunhofer-ITMP/PEMTandhttps://pvpi.org/project/PEMT/respectively.Contactyojana.gadiya@itmp.fraunhofer.deSupplementary informationSupplementary data are available atBioinformaticsonline.
A measure of the somatosensory blink reflex to parametric variation of mechanical stimulation
Authors: Kaiser Eric A , Haggery Edda B , Garner Dena P , Bunya Vatinee Y , Aguirre Geoffrey K 
Published: August 2022

AbstractThe primary goal of this study was to develop a parametric model that relates variation in stimulation of the trigeminal nerve to properties of the blink response. We measured blink responses in 17 healthy, adult participants to air puffs directed at the lateral canthus of the eye at five different, log-spaced intensities (3.5 - 60 PSI). Lid position over time was decomposed into amplitude and velocity components. We found that blink amplitude was systematically related to log stimulus intensity, with the relationship well described by a sigmoidal function. The parameters of the model fit correspond to the slope of the function and the stimulus intensity required to produce half of a maximal blink response (the half-response threshold). There was a reliable decrease in the half-response threshold for the contralateral as compared to the ipsilateral blink response. This decrease was consistent across participants despite substantial individual differences in the half-response threshold and slope parameters of the overall sensitivity function, suggesting that the laterality effect arises in the neural circuit subsequent to individual differences in sensitivity. Overall, we find that graded mechanical stimulation of the somatosensory trigeminal afferents elicits a graded response that is well described by a simple parametric model. We discuss the application of parametric measurements of the blink response to the detection of group differences in trigeminal sensitivity.Impact statementThere has been limited study of how variation in stimulus intensity influences the cutaneous blink response. We describe how variation in the intensity of an air-puff stimulus relates to the amplitude of the blink response using a two-parameter model. The parameters of the model capture individual differences in response, which may be used in future studies to identify population differences in trigeminal sensitivity.
SVR-based Multimodal Active Subspace Analysis for the Brain using Neuroimaging Data
Authors: Batta Ishaan , Abrol Anees , Calhoun Vince D. ,   the Alzheimer’s Disease Neuroimaging Initiative
Published: August 2022

ABSTRACTUnderstanding the patterns of changes in brain function and structure due to various disorders and diseases is of utmost importance. There have been numerous efforts toward successful biomarker discovery for complex brain disorders by evaluating neuroimaging datasets with novel analytical frameworks. However, due to the multi-faceted nature of the disorders involving a wide and overlapping range of symptoms as well as complex changes in structural and functional brain networks, it is increasingly important to devise computational frameworks that can consider the underlying patterns of heterogeneous changes with specific target assessments, at the same time producing a summarizing output from the high-dimensional neuroimaging data. While various machine learning approaches focus on diagnostic prediction, many learning frameworks analyze important features at the level of brain regions involved in prediction using supervised methods. Unsupervised learning methods have also been utilized to break down the neuroimaging features into lower dimensional components. However, most learning frameworks either do not consider the target assessment information while extracting brain subspaces, or can extract only higher dimensional importance associations as an ordered list of involved features, making manual interpretation at the level of subspaces difficult. We present a novel multimodal active subspace learning framework to understand various subspaces within the brain that are associated with changes in particular biological and cognitive traits. For a given cognitive or biological trait, our framework performs a decomposition of the feature importances to extract robust multimodal subspaces that define the most significant change in the given trait. Through a rigorous cross-validation procedure on an Alzheimer’s disease (AD) dataset, we show that our framework can extract subspaces covering both functional and structural modalities, which are specific to a given clinical assessment (like memory and other cognitive skills) and also retain predictive performance in standard machine learning algorithms. We show that our framework not only uncovers AD-related brain regions (e.g., hippocampus, entorhinal cortex) in the associated brain subspaces, but also enables an automated identification of multiple underlying structural and functional sub-systems of the brain that collectively characterize changes in memory and cognitive skill proficiency related to brain disorders like AD.
Spatial Scale of Non-Target Effects of Cotton Insecticides
Authors: Bordini Isadora , Naranjo Steven E. , Fournier Alfred , Ellsworth Peter C. 
Published: August 2022

AbstractPlot size is of practical importance in any integrated pest management (IPM) study that has a field component. Such studies need to be conducted at a scale relevant to species dynamics because their abundance and distribution in plots might vary according to plot size. An adequate plot size is especially important for researchers, technology providers and regulatory agencies in understanding effects of various insect control technologies on non-target arthropods. Plots that are too small might fail to detect potential harmful effects of these technologies due to arthropod movement and redistribution among plots, or from untreated areas and outside sources. The Arizona cotton system is heavily dependent on technologies for arthropod control, thus we conducted a 2-year replicated field experiment to estimate the optimal plot size for non-target arthropod studies in our system. Experimental treatments consisted of plot sizes and insecticides in a full factorial. We established three plot sizes that measured 144 m2, 324 m2 and 576 m2. For insecticides, we established an untreated check, a positive control insecticide with known negative effects on the arthropod community and a selective insecticide. We investigated how plot size impacts the estimation of treatment effects relative to community structure (27 taxa), community diversity, individual abundance, effect sizes, biological control function and success of arthropod taxa with a wide range of mobility, including Collops spp., Orius tristicolor, Geocoris spp., Misumenops celer, Drapetis nr. divergens and Chrysoperla carnea. The 144 m2 plots supported similar results for all parameters compared to larger plots, thus being sufficiently large to measure insecticidal effects on non-target arthropods in Arizona cotton. Though results might be system-specific, they point to a scale of testing that should be considered when developing any IPM guidelines, especially for systems that share a similar fauna of predators and pests.
Multidimensional topography of memory revealed from thousands of daily documented memories
Authors: Bainbridge Wilma A. , Baker Chris I. 
Published: August 2022

AbstractOur memories form a rich, colorful tapestry of emotions, events, people, and places, woven across the decades of our lives. However, research has typically been limited in its ability to assess the multidimensional nature of episodic memory, given the short time scales and artificial stimulus sets often required in experiments. In an era when people are constantly recording their lives through social media, we can now examine key questions about the behavioral and neural underpinnings of diverse and extensive real-world memories. Here, we tested the neural representations of episodic memory in a naturalistic setting, specifically focusing on the age, location, subjective memory strength, and emotional content of memories. We recruited 23 users of a video diary app (“1 Second Everyday”), who had recorded a total of 9,266 daily memory videos spanning up to 7 years prior to our study. During a 3T fMRI scan, participants viewed a set of 300 of their own memory videos intermixed with 300 videos from another individual. We identified key areas specifically engaged for one’s own memories versus another’s. Delving into the multidimensional nature of these memories, we find that their features are tightly interrelated, highlighting the need to consider these features in conjunction when conducting memory research. Importantly, when looking at the distinct contributions of these features, we find a topography of memory content extending across the medial parietal lobe with separate representations of a memory’s age, it’s strength, and the familiarity of the people and places involved.
A chromosome-level genome resource for studying virulence mechanisms and evolution of the coffee rust pathogen Hemileia vastatrix
Authors: Tobias Peri A , Edwards Richard J. , Surana Priyanka , Mangelson Hayley , Inácio Vera , do Céu Silva Maria , Várzea Vitor , Park Robert F. , Batista Dora 
Published: August 2022

AbstractRecurrent epidemics of coffee leaf rust, caused by the fungal pathogen Hemileia vastatrix, have constrained the sustainable production of Arabica coffee for over 150 years. The ability of H. vastatrix to overcome resistance in coffee cultivars and evolve new races is inexplicable for a -pathogen that supposedly only utilizes clonal reproduction. Understanding the evolutionary complexity between H. vastatrix and its only known host, including determining how the pathogen evolves virulence so rapidly is crucial for disease management. Achieving such goals relies on the availability of a comprehensive and high-quality genome reference assembly. To date, two reference genomes have been assembled and published for H. vastatrix that, while useful, remain fragmented and do not represent chromosomal scaffolds. Here, we present a complete scaffolded pseudochromosome-level genome resource for H. vastatrix strain 178a (Hv178a). Our initial assembly revealed an unusually high degree of gene duplication (over 50% BUSCO basidiomycota_odb10 genes). Upon inspection, this was predominantly due to a single scaffold that itself showed 91.9% BUSCO Completeness. Taxonomic analysis of predicted BUSCO genes placed this scaffold in Exobasidiomycetes and suggests it is a distinct genome, which we have named Hv178a associated fungal genome (Hv178a AFG). The high depth of coverage and close association with Hv178a raises the prospect of symbiosis, although we cannot completely rule out contamination at this time. The main Ca. 546 Mbp Hv178a genome was primarily (97.7%) localised to 11 pseudochromosomes (51.5 Mb N50), building the foundation for future advanced studies of genome structure and organization.
Spatial attention in perceptual decision making as revealed by response-locked classification image analysis
Authors: Sano Hironobu , Ueno Natsuki , Maruyama Hironori , Motoyoshi Isamu 
Published: August 2022

AbstractIn many situations, humans serially sample information from many locations in an image to make an appropriate decision about a visual target. Spatial attention plays a crucial role in this serial vision process. To investigate the effect of spatial attention in such dynamic decision making, we applied a classification image (CI) analysis locked to the observer’s reaction time (RT). We asked human observers to detect as rapidly as possible a target whose contrast gradually increased on the left or right side of dynamic noise, with the presentation of a spatial cue. The analysis revealed a spatiotemporally biphasic profile of the CI which peaked at ∼350 ms before the observer’s response. We found that a valid cue presented at the target location shortened the RT and increased the overall amplitude of the CI, especially when the cue appeared 500-1250 ms before the observer’s response. The results were quantitatively accounted for by a simple perceptual decision mechanism that accumulates the outputs of the spatiotemporal contrast detector, whose gain is increased by sustained attention to the cued location.
Absorbable Conductive Electrotherapeutic Scaffolds (ACES) for Enhanced Peripheral Nerve Regeneration and Stimulation
Authors: Srinivasan Shriya , Gfrerer Lisa , Karandikar Paramesh , Som Avik , Alshareef Amro , Liu Sabrina , Higginbotham Haley , Ishida Keiko , Hayward Alison , Kalva Sanjeeva P. , Langer Robert , Traverso Giovanni 
Published: August 2022

AbstractWhile peripheral nerve stimulation (PNS) has shown promise in applications ranging from peripheral nerve regeneration after injury to therapeutic organ stimulation, clinical implementation has been impeded by various technological limitations, including surgical placement, lead migration, and atraumatic removal. Here, we describe the design and validation of a new platform for nerve regeneration and interfacing: Absorbable, Conductive, Electrotherapeutic Scaffolds (ACES). ACES are comprised of an alginate/poly-acrylamide interpenetrating network hydrogel optimized for both open and minimally invasive percutaneous approaches. In a rodent model of sciatic nerve repair, ACES significantly improved motor and sensory recovery (p< 0.05), increased muscle mass (p< 0.05), and increased axonogenesis (p< 0.05). Triggered dissolution of ACES enabled atraumatic, percutaneous removal of leads at forces significantly lower than controls (p< 0.05). In a porcine model, ultrasound-guided percutaneous placement of leads with an injectable ACES near the femoral and cervical vagus nerves facilitated stimulus conduction at significantly greater lengths than saline controls (p< 0.05). Overall, ACES facilitated lead placement, stabilization, stimulation and atraumatic removal enabling therapeutic PNS as demonstrated in small and large animal models.
Magnetique: An interactive web application to explore transcriptome signatures of heart failure
Authors: Britto-Borges Thiago , Ludt Annekathrin , Boileau Etienne , Gjerga Enio , Marini Federico , Dieterich Christoph 
Published: August 2022

AbstractDespite a recent increase in the number of RNA-seq datasets investigating heart failure (HF), accessibility and usability remain critical issues for medical researchers. We present Magnetique (https://shiny.dieterichlab.org/app/magnetique), an interactive web application to explore the transcriptional signatures of heart failure. We reanalyzed the Myocardial Applied Genomics Network RNA-seq dataset, one of the largest publicly available datasets of left ventricular RNA-seq samples from patients with dilated (DCM) or hypertrophic (HCM) cardiomyopathy, as well as unmatched non-failing hearts from organ donors and patient characteristics that allowed us to model confounding factors. Focusing on the DCM versus HCM contrast, we identified 201 differentially expressed genes and associated pathway signatures. Moreover, we predict underlying signaling networks based on inferred transcription factor activities. To the best of our knowledge, Magnetique is the first online application to provide an interactive view of the HF transcriptome by analyzing differential transcript isoform usage. Finally, another graphical view on statistically predicted RNA-binding protein to target transcript interactions complements the Magnetique web application.The source code for both the analyses (https://github.com/dieterich-lab/magnetiqueCode2022) and the web application (https://github.com/AnnekathrinSilvia/magnetique) is available to the public. We hope that our application will help users to uncover the molecular basis of heart failure.
Notch Signaling and Fluid Shear Stress in Regulating Osteogenic Differentiation
Authors: Zhao Yuwen , Richardson Kiarra , Yang Rui , Bousraou Zoe , Lee Yoo Kyoung , Fasciano Samantha , Wang Shue 
Published: August 2022

AbstractOsteoporosis is a common bone and metabolic disease that is characterized by bone density loss and microstructural degeneration. Human bone marrow-derived mesenchymal stem cells (hMSCs) are multipotent progenitor cells with the potential to differentiate into various cell types, including osteoblasts, chondrocytes, and adipocytes, which have been utilized extensively in the field of bone tissue engineering and cell-based therapy. Although fluid shear stress plays an important role in bone osteogenic differentiation, the cellular and molecular mechanisms underlying this effect remain poorly understood. Here, an LNA/DNA nanobiosensor was exploited to monitor mRNA gene expression of hMSCs that were exposed to physiologically relevant fluid shear stress to examine the regulatory role of Notch signaling during osteogenic differentiation. First, the effects of fluid shear stress on cell viability, proliferation, morphology, and osteogenic differentiation were investigated and compared. Our results showed shear stress modulates hMSCs morphology and osteogenic differentiation depending on the applied shear and duration. By incorporating this LNA/DNA nanobiosensor and alkaline phosphatase (ALP) staining, we further investigated the role of Notch signaling in regulating osteogenic differentiation. Pharmacological treatment is applied to disrupt Notch signaling to investigate the mechanisms that govern shear stress induced osteogenic differentiation. Our experimental results provide convincing evidence supporting that physiologically relevant shear stress regulates osteogenic differentiation through Notch signaling. Inhibition of Notch signaling mediates the effects of shear stress on osteogenic differentiation, with reduced ALP enzyme activity and decreased Dll4 mRNA expression. In conclusion, our results will add new information concerning osteogenic differentiation of hMSCs under shear stress and the regulatory role of Notch signaling. Further studies may elucidate the mechanisms underlying the mechanosensitive role of Notch signaling in stem cell differentiation.
Surgical techniques and tips for a reliable murine model of primary and metastatic pancreatic cancer
Authors: Hue Jonathan J. , Zarei Mehrdad , Graor Hallie J. , Hajihassani Omid , Katayama Erryk S. , Loftus Alexander W. , Vaziri-Gohar Ali , Winter Jordan M. 
Published: August 2022

ABSTRACTFor patients with pancreatic cancer, survival rates lag behind other common cancers. This is in part due to the relative resistance to conventional chemotherapeutics and novel immune- or targeted-therapies. Ongoing research efforts are needed to identify and validate effective therapies. It is the unfortunate reality that a significant proportion of pre-clinical success does not translate into improved patient outcomes, likely due to a multitude of factors. In the current research landscape, flank xenograft models are commonly utilized to study pancreatic cancer, as this technique is fast, fairly non-invasive, and reliable. However, this model is not anatomically or physiologically accurate, does not impact other intra-abdominal organs, and experiments are often ended based on tumor size rather than systemic illness. Orthotopic injections of cancer cells directly into the pancreas for study of localized disease or into the spleen for study of hepatic metastases can be performed via a quick, reliable, minimally invasive surgical procedure with minimal morbidity and mortality. Existing methodologic reports are often sparse. Thus, there are significant knowledge and technical gaps for researchers attempting these techniques for the first time. In the current report, details of orthotopic pancreatic injections and splenic injections for metastatic disease are provided. Details of commonly encountered operative issues and mistakes are presented with suggestions to improve performance are described. A summary of expected outcomes is also provided herein.