bluuebunny/crossref_metadata_2025_split huggingface dataset:
Emergency department return visits and hospital admissions in trauma team assessed patients initially discharged from the emergency department: A population-based cohort study
Authors: Evans Christopher C.D. , Li Wenbin , Balari Pardis , Ma Jennifer , Brogly Susan B. 
Published: March 2022

BACKGROUND
Many injured patients are transported directly to trauma centers, found to be minimally injured, and discharged directly home from the emergency department (ED). Our objectives were to characterize the short-term outcomes in this discharged patient population and to identify patient factors predictive of ED return visits.

METHODS
We conducted a retrospective population-based cohort study using linked administrative data sets involving patients assessed at trauma centers in Ontario, Canada between April 1, 2009, and March 31, 2020. Patients who were assessed by a trauma team and discharged directly home from ED were included. The primary outcome was the percentage of patients with an ED return visit within 14 days. We used multivariate logistic regression analyses to identify patient characteristics predictive of at least one ED return visit.

RESULTS
There were 5,550 patients included in the study. A total of 1,004 (18.1%) of patients had at least one ED return visit, but only 100 patients (1.8%) were admitted to hospital following initial discharge. Common reasons for ED return visits included wound care concerns (17.2%), head injury complaints (15.6%), and substance misuse (6.8%). Rural residence (odds ratio [OR], 1.83; 95% CI, 1.45–2.29), history of anxiety disorder (OR, 2.05; 95% CI, 1.54–2.73), high baseline ED usage (OR, 2.58; 95% CI, 2.03–3.28), penetrating injury (OR, 1.42; 95% CI, 1.20–1.68), and extremity fracture (OR, 1.52; 95% CI, 1.24–1.88) predicted return visits.

CONCLUSION
Patients discharged directly have high rates of ED return visits but low rates of hospital admission or delayed surgical intervention. Trauma services should expand quality assurance initiatives to capture return visits, understand any gaps in clinical service provision, and aim to minimize unnecessary ED return visits.

LEVEL OF EVIDENCE
Prognostic/Epidemiological; Level IV.
FFP maintains normal coagulation while Kcentra induces a hypercoagulable state in a porcine model of pulmonary contusion and hemorrhagic shock
Authors: Dixon Alexandra , Beiling Marissa , Smith Sawyer , Behrens Brandon , Appleman Luisa , Rick Elizabeth , Murphy James , Madtson Brianne , McCully Belinda , Goodman Andrew , Kanlerd Amonpon , Schaller Traci , Subramanian Sarayu , Trivedi Alpa , Pati Shibani , Schreiber Martin 
Published: March 2022

BACKGROUND
Moderate injury can lead to a coagulopathy. Fresh frozen plasma (FFP) corrects coagulopathy by means of a balanced array of clotting factors. We sought to compare the late effects of FFP and a prothrombin complex concentrate (PCC) on the coagulopathy of trauma using a porcine model of pulmonary contusion (PC) and hemorrhagic shock (HS) designed to evaluate the organ protective effects of these treatments.

METHODS
Female Yorkshire swine (40–50 kg) were randomized to receive PC + HS or control (instrumented and uninjured). A blunt PC was created using a captive bolt gun. To induce HS, a liver crush injury was performed. Eighty minutes after injury, swine were treated with 25 U·kg−1 PCC, 1 U FFP, or 50 mL lactated Ringer’s vehicle in a blinded manner. Arterial blood samples were drawn every 6 hours. Swine were euthanized 48 hours postinjury. Data were analyzed by Pearson χ2, analysis of variance and Kruskal-Wallis tests with Tukey’s or Mann-Whitney U tests for post hoc analysis.

RESULTS
Twenty-seven swine received PC + HS, 3 groups of 9 per group received PCC, FFP, or vehicle. Nine were noninjured controls. When compared with control, PC + HS swine had significantly shortened R time at 6 hours, 36 hours, and 42 hours, decreased LY30 at 12 hours, shortened K time at 30 hours and reduced α angle at 42 hours. PC + HS swine showed significant differences between treatment groups in K and α angle at 3 hours, LY30 at 12 hours and 18 hours, and MA at 12 hours, 18 hours, and 30 hours. Post hoc analysis was significant for higher α angle in PCC versus vehicle at 3 hours, higher MA in vehicle versus PCC at 12 hours and 18 hours, and higher LY30 in PCC versus vehicle at 18 hours (p < 0.012) with no significant differences between FFP and vehicle.

CONCLUSION
Severe injury with HS induced a coagulopathy in swine. While FFP maintained normal coagulation following injury, PCC induced more rapid initial clot propagation in injured animals.
Development of a COVID-19 risk-assessment model for participants at an outdoor music festival: Evaluation of the validity and control measure effectiveness
Authors: Murakami Michio , Fujita Tsukasa , Li Pinqi , Imoto Seiya , Yasutaka Tetsuo 
Published: March 2022

AbstractWe developed an environmental exposure model to estimate the Coronavirus Disease 2019 (COVID-19) risk among participants at an outdoor music festival and validated the model using a real cluster outbreak case. Furthermore, we evaluated the extent to which the risk could be reduced by additional infection control measures such as negative proofs of antigen tests on the day of the event, wearing masks, disinfection of environmental surfaces, and vaccination. The total number of already- and newly-infected individuals who participated in the event according to the new model was 47.0 (95% uncertainty interval: 12.5–185.5), which is in good agreement with the reported value (45). Among the additional control measures, vaccination, mask-wearing, and disinfection of surfaces were determined to be effective. Based on the combination of all measures, a 94% risk reduction could be achieved. In addition to setting a benchmark for an acceptable number of newly-infected individuals at the time of an event, the application of this model will enable us to determine whether it is necessary to implement additional measures, limit the number of participants, or refrain from holding an event.
Alzheimer’s Disease Classification Using Cluster-based Labelling for Graph Neural Network on Heterogeneous Data
Authors: McCombe Niamh , Bamrah Jake , Sanchez-Bornot Jose M. , Finn David P. , McClean Paula L. , Wong-Lin KongFatt ,   Alzheimer’s Disease Neuroimaging Initiative (ADNI)
Published: March 2022

AbstractBiomarkers for Alzheimer’s disease (AD) diagnosis do not always correlate reliably with cognitive symptoms, making clinical diagnosis inconsistent. In this study, the performance of a graphical neural network (GNN) classifier based on data-driven diagnostic classes from unsupervised clustering on heterogeneous data, is compared to the performance of a classifier using clinician diagnosis as outcome. Unsupervised clustering on tau-PET and cognitive and functional assessment data was performed. Five clusters embedded in a nonlinear UMAP space were identified. The individual clusters revealed specific feature characteristics with respect to clinical diagnosis of AD, gender, family history, age, and underlying neurological risk factors. In particular, one cluster comprised mainly diagnosed AD cases. All cases within this cluster were re-labelled AD cases. The re-labelled cases are characterised by high cerebrospinal fluid amyloid beta (CSF Aβ) levels at a younger age, even though Aβ data was not used for clustering. A GNN model was trained using the relabelled data with a multiclass area-under-the-curve (AUC) of 95.2%, higher than the AUC of a GNN trained on clinician diagnosis (91.7%; p=0.02). Overall, our work suggests that more objective cluster-based diagnostic labels combined with GNN classification may have value in clinical risk stratification and diagnosis of AD.
Attempt to replicate voxel-based morphometry analysis in fibromyalgia: Detection of below threshold differences framed by contributions of variable clinical presentation to low reproducibility
Authors: Baker Anne K. , Nanda Meghna , Park Su Hyoun , Martucci Katherine T. 
Published: March 2022

ABSTRACTBackgroundFibromyalgia is a prevalent chronic pain condition characterized by widespread pain and sensory hypersensitivity. While much remains unknown about fibromyalgia’s neurobiological underpinnings, central nervous system alterations appear to be heavily implicated in its pathophysiology. Previous research examining brain structural abnormalities associated with fibromyalgia has yielded inconsistent findings. Thus, we followed previous methods to examine brain gray matter differences in fibromyalgia. We hypothesized that, relative to healthy controls, participants with fibromyalgia would exhibit lower gray matter volume in regions consistently implicated in fibromyalgia: the anterior cingulate cortex and medial prefrontal cortex.MethodsThis study used magnetic resonance imaging to evaluate regional and whole brain differences in gray matter among females with and without fibromyalgia. Group differences were analyzed with two-sample t-tests, controlling for total intracranial volume.ResultsNo significant differences in regional or whole brain gray matter volumes were detected between fibromyalgia and healthy controls.ConclusionsResults add to an existing body of disparate findings regarding brain gray matter volume differences in fibromyalgia, and suggest structural differences previously detected in fibromyalgia should be examined for reproducibility. Absent significant differences may also suggest that functional, but not structural, brain adaptations are primarily associated with fibromyalgia.
Tract-based white matter hyperintensity patterns in patients with Systemic Lupus Erythematosus using an unsupervised machine learning approach
Authors: Rumetshofer Theodor , Inglese Francesca , de Bresser Jeroen , Mannfolk Peter , Strandberg Olof , Jönsen Andreas , Bengtsson Anders , Nilsson Markus , Knutsson Linda , Lätt Jimmy , Steup-Beekman Gerda M. , Huizinga Tom W.J. , van Buchem Mark A. , Ronen Itamar , Sundgren Pia C. 
Published: March 2022

ABSTRACTCurrently, little is known about the spatial distribution of white matter hyperintensities (WMH) in the brain of patients with Systemic Lupus erythematosus (SLE). Previous lesion markers, such as number and volume, ignore the strategic location of WMH. The goal of this work was to develop a fully-automated method to identify predominant patterns of WMH across WM tracts based on cluster analysis. A total of 221 SLE patients with and without neuropsychiatric symptoms from two different sites were included in this study. WMH segmentations and lesion locations were acquired automatically. Cluster analysis was performed on the WMH distribution in 20 WM tracts. Our pipeline identified five distinct clusters with predominant involvement of the forceps major, forceps minor, as well as right and left anterior thalamic radiations and the right inferior fronto-occipital fasciculus. The patterns of the affected WM tracts were consistent over the SLE subtypes and sites. Our approach revealed distinct and robust tract-based WMH patterns within SLE patients. This method could provide a basis, to link the location of WMH with clinical symptoms. Furthermore, it could be used for other diseases characterized by presence of WMH to investigate both the clinical relevance of WMH and underlying pathomechanism in the brain.
NKG2A and HLA-E define a novel alternative immune checkpoint axis in bladder cancer
Authors: Salomé Bérengère , Sfakianos John P. , Daza Jorge , Charap Andrew , Hammer Christian , Banchereau Romain , Farkas Adam M. , Geanon Daniel , Kelly Geoffrey , de Real Ronaldo M. , Lee Brian , Beaumont Kristin G. , Shroff Sanjana , Wang Yuan Shuo A. , Wang Ying-chih , Thin Tin Htwe , Garcia-Barros Monica , Hegewisch-Solloa Everardo , Mace Emily M. , Wang Li , O’Donnell Timothy , Chowell Diego , Fernandez-Rodriguez Ruben , Skobe Mihaela , Taylor Nicole , Kim-Schulze Seunghee , Sebra Robert P. , Palmer Doug , Clancy-Thompson Eleanor , Hammond Scott , Kamphorst Alice O. , Malmberg Karl-Johan , Marcenaro Emanuela , Romero Pedro , Brody Rachel , Viard Mathias , Yuki Yuko , Martin Maureen , Carrington Mary , Mehrazin Reza , Wiklund Peter , Mellman Ira , Mariathasan Sanjeev , Zhu Jun , Galsky Matthew D. , Bhardwaj Nina , Horowitz Amir 
Published: March 2022

SummaryPD-1/PD-L1-blockade immunotherapies have limited efficacy in the treatment of muscle-invasive bladder cancer (MIBC) and metastatic urothelial carcinoma. Here, we show thatKLRC1(NKG2A) expression associates with improved survival and responsiveness to PD-L1 blockade immunotherapy inCD8Ahighbladder tumors. The loss of antigen presentation is a common mechanism for tumor escape in bladder cancer. NKG2A+CD8 T cells are able to circumvent HLA-ABC loss through TCR-independent cytotoxicity, which is partly mediated by DNAM-1. In bladder tumors, NKG2A is acquired on a subset of PD-1+CD8 T cells, alongside stronger tissue-residency memory features, TCR-independent cytotoxicity and evidence of recent proliferation. HLA-E is low but variably expressed on bladder tumors. When expressed, NKG2A+CD8 T cell anti-tumor responses to HLA-ABC-deficient tumors are inhibited and partly restored upon NKG2A blockade. Overall, our study identifies an alternative path for CD8 T cell exhaustion, that is mediated by NKG2A upregulation and TCR-independent cytotoxicity.
Strategic stabilization of arousal boosts sustained attention
Authors: de Gee J.W. , Mridha Z. , Hudson M , Shi Y. , Ramsaywak H. , Smith S. , Karediya N. , Thompson M. , Jaspe K. , Jiang H. , Zhang W. , McGinley M. J. 
Published: March 2022

SummaryChanges in autonomic arousal, such as mounting sleep pressure, and changes in motivation, such as fluctuating environmental reward statistics, both profoundly influence behavior. Our experience tells us that we have some capacity to control our arousal when doing so is important, such as staying awake while driving a motor vehicle. However, little is known about how decision computations are jointly influenced by arousal and motivation, including whether animals, such as rodents, can adapt their arousal state to their needs. Here, we developed and show results from an auditory feature-based sustained-attention task with intermittently shifting task utility. We use pupil size to estimate arousal across a wide range of states and apply novel signal detection theoretic and accumulation-to-bound modeling approaches in a large behavioral cohort. We find that both pupil-linked arousal and task utility have major impacts on multiple aspects of performance. Although substantial arousal fluctuations persist across utility conditions, mice partially stabilize their arousal near an intermediate, and optimal, level when task utility is high. Behavioral analyses show that multiple elements of behavior improve during high task utility and that arousal influences some, but not all, of them. Specifically, arousal influences the likelihood and timescale of sensory evidence accumulation, but not the quantity of evidence accumulated per time step while attending. In sum, the results establish specific decision-computational signatures of arousal, motivation, and their interaction, in attention. So doing, we provide an experimental and analysis framework for studying arousal self-regulation in neurotypical brains and diseases such as attention-deficit/hyperactivity disorder.
A-type FHFs mediate resurgent currents through TTX-resistant voltage-gated sodium channels
Authors: Xiao Yucheng , Theile Jonathan W. , Zybura Agnes , Pan Yanling , Lin Zhixin , Cummins Theodore R. 
Published: March 2022

AbstractResurgent currents (INaR) produced by voltage-gated sodium channels are required for many neurons to maintain high-frequency firing, and contribute to neuronal hyperexcitability and disease pathophysiology. Here we show, for the first time, that INaR can be reconstituted in a heterologous system by co-expression of sodium channel α-subunits and A-type fibroblast growth factor homologous factors (FHFs). Specifically, A-type FHFs induces INaR from Nav1.8, Nav1.9 tetrodotoxin-resistant neuronal channels and, to a lesser extent, neuronal Nav1.7 and cardiac Nav1.5 channels. Moreover, we identified the N-terminus of FHF as the critical molecule responsible for A-type FHFs-mediated INaR. Among the FHFs, FHF4A is the most important isoform for mediating Nav1.8 and Nav1.9 INaR. In nociceptive sensory neurons, FHF4A knockdown significantly reduces INaR amplitude and the percentage of neurons that generate INaR, substantially suppressing excitability. Thus, our work reveals a novel molecular mechanism underlying TTX-resistant INaR generation and provides important potential targets for pain treatment.
Circulating mast cell progenitors migrate to atopic dermatitis-like skin then adapt locally
Authors: Keith Yuki Honda , Honda Tetsuya , Ono Sachiko , Lee Bernett , Hanakawa Sho , Ishida Yoshihiro , Nakamizo Satoshi , Kabashima Kenji 
Published: March 2022

AbstractBackgroundMast cells (MCs) are tissue-resident immune cells that are classified into two subsets in mice: connective tissue-type MCs (CTMCs) and mucosal type MCs (MMCs). Although both CTMCs and MMCs can be induced from bone marrow (BM)-derived hematopoietic stem cells (HSCs) in vitro, recent research on MC ontogeny has revealed that MMCs are maintained with a supply of BM-derived HSCs, while CTMCs are maintained locally by self-proliferation in steady state in vivo. However, how CTMCs, such as skin MCs, are maintained in an inflammatory state such as atopic dermatitis (AD) remains to be fully elucidated. Methods: MC903-induced AD model was used to identify BM-derived MCs in the skin. The infiltration and proliferation of MCs were evaluated by flow cytometry using CD45.1 BM-chimera mice and parabiosis. BM-derived MCs in AD-like skin were compared to resident MCs (rMCs) in gene expressions by RNA sequence analysis. The fate of BM-derived MCs in AD-like skin was investigated for expressions of CTMC markers and responses to compound 48/80. Results: In AD-like skin, significant increase of both rMCs and BM-derived MCs was observed. BM-derived MCs were derived from circulating MC progenitors (MCps) and were distinguished from rMCs by integrinβ7 expression, which was gradually downregulated in the skin. RNA sequence analysis showed that integrinβ7+ MCs in the skin shared characteristics of both MMC and CTMC. Integrinβ7+ MCs proliferated in situ and acquired the CTMC phenotypes in AD-like skin. Conclusions: Skin MCs are maintained in AD-like skin by both local proliferation of rMCs and infiltration/proliferation of BM-derived MCs, which differentiate toward CTMC in the skin.
Optimized Workflow for Enrichment and Identification of Biotinylated Peptides using Tamavidin 2-REV for BioID and Cell Surface Proteomics
Authors: Nishino Kohei , Yoshikawa Harunori , Motani Kou , Kosako Hidetaka 
Published: March 2022

ABSTRACTChemical or enzymatic biotinylation of proteins is widely used in various studies, and proximity-dependent biotinylation coupled to mass spectrometry is a powerful approach for analyzing protein–protein interactions in living cells. We recently developed a simple method to enrich biotinylated peptides using Tamavidin 2-REV, an engineered avidin-like protein with reversible biotin-binding capability. However, the low abundance of protein biotinylation in cells required large amounts of cellular proteins to detect enough biotinylated peptides. Here we optimized the workflow for efficient enrichment and identification of biotinylated peptides. The most efficient recovery was achieved by heat inactivation of trypsin, prewashing Tamavidin 2-REV beads, clean-up of biotin solution, mock elution, and the optimal temperature and salt concentration for elution. Using the optimized workflow, over 2-fold more biotinylated peptides were identified with higher purity from RAW264.7 macrophages expressing TurboID-fused STING. In addition, sequential digestion with Glu-C and trypsin led to the identification of biotinylation sites that were not identified by trypsin digestion alone. Furthermore, the combination of this workflow with TMT labeling enabled large-scale quantification of cell surface proteome changes upon EGF stimulation. This workflow would be useful not only for BioID and cell surface proteomics but also for various other applications based on protein biotinylation.
A scoping systematic review of implementation frameworks to effectively transition interventions into clinical practice in oncology, nuclear medicine and radiology
Authors: Delanerolle Gayathri , Cavalini Heitor , Phiri Peter , Gelling Leslie 
Published: March 2022

SummaryBackgroundClinical research studies have made significant strides globally requiring clear processes to transition research interventions into clinical practice. Theoretically, implementation of novel interventions require clear methods as part of a fit-for-purpose (FFP) framework comprising of effective adaptation processes in conjunction with practice policies. Implementation science (IS) based operational research (OR) is vital in global health as it addresses the ‘know-how-do’ gap using a real-world setting to achieve best practices to sustain healthcare. Despite this, limited OR is available to evaluate and validate implementation frameworks for complex clinical specialties such as oncology, diagnostic radiology (DR), nuclear medicine (NM) and interventional radiology (IR). This is the first study to systematically review implementation frameworks including its’ validity and applicability in healthcare.MethodWe searched 17 databases including PubMed, Medline/OvidSP, Science Direct, PROSPERO, PRISMA, PubMed Health, Embase, EBSCOhost, SciELO, TRIP, ProQuest, Academic search complete, Ageline, Cochrane, Web-of-Science and BIOSIS using a comprehensive search strategy and MeSH indexing to review publications from January 1st 1980 to 31st March 2019 in English. We selected 20 publications as per the inclusion/exclusion criteria developed under a review protocol registered with PROSPERO (CRDG42019124020).FindingsThere were no publications indicating a validated framework or a specific system used to implement evidence based interventions (EBIs) within oncology, IR, NM and DR although there were generalized implementation processes, adaptation models and policies. Furthermore, validation studies were not conducted against these frameworks to review their applicability and viability in healthcare especially in the UK.InterpretationIt is evident there is a research implementation gap in healthcare and further research is required to establish a fit for purpose framework to cover multiple ‘blind spots’ using a real-world (RW) setting. Current evidence also suggests, alignment of academic theories to healthcare including its applicability to various clinical specialties is needed.