bluuebunny/crossref_metadata_2025_split huggingface dataset:
Trauma patients in the pediatric ICU: rational use of a limited resource
Authors: Arshad Ahmed , Polcari Ann M. , Pinto Neethi P. , Slidell Mark B. 
Published: October 2020

Purpose of review
Traumatic injuries are a leading cause of pediatric mortality; pediatric ICUs (PICUs) are an important but potentially limited resource associated with high costs. In an era of rising healthcare costs, appropriate resource utilization is important. Here, we examine evidence-based guidelines supporting the management of pediatric traumatic injury outside of the PICU.

Recent findings
Historical management of solid organ injury and traumatic brain injury was focused on operative management. However, over the past four decades, management of solid organ injury has shifted from invasive management to nonsurgical management with a growing body of evidence supporting the safety and efficacy of this trend. The management of traumatic brain injury (TBI) has had a similar evolution to that of solid organ injury with regard to nonoperative management and management outside the critical care setting.

Summary
The use of evidence-based guidelines to support expectant management in the setting of pediatric trauma has the potential to reduce unnecessary resource utilization of the PICU. In this review, we present findings that support nonoperative management and management of pediatric trauma outside of the PICU setting. In resource-poor areas, this approach may facilitate care for pediatric trauma patients. The implications are also important in resource-rich settings because of the unintended risks associated with PICU.
Improving the Safety of an Emergency Department-Based Direct Admission Process at a Children's Hospital
Authors: Huy Tess , Lowrie Lia , Flood Robert , Chambers Rebecca , Weiss Nancy , Nordike Keith , Wathen David 
Published: October 2020

Objectives
Direct admission refers to admitting a patient to a unit avoiding usual entry points such as the emergency department. Inappropriate placement of direct admissions can result in rapid response activations, codes and unanticipated pediatric intensive care unit (PICU) transfers, which correlate with higher mortality and longer lengths of stay. The objective of the project was to improve the safety of the direct admission process as evidenced by decreasing the transfer of direct admission patients to the PICU within 6 hours.

Methods
Utilizing the model for improvement, a multidisciplinary team was assembled to improve our screening process and reduce unanticipated direct admission-to-PICU transfers within 6 hours of arrival. Our emergency department–based direct admission process includes screening vital signs (temperature, heart rate, respiratory rate, blood pressure, and pulse oximetry) and a Pediatric Early Warning Score. Five Plan-Do-Study-Act cycles focused on role definition, improved documentation, referring facility and family awareness, improved visual management within the ED, and education of partner EMS and transport providers. The primary outcome was PICU transfer within 6 hours of direct admission arrival. Compliance with full screening was a process measure and number of direct admissions a balancing measure. Statistical process control charts and run charts were used to follow the measures.

Results
The total number of direct admissions from January 2014 to the end of data collection, June 2018, was 3070 patients. Screening protocol compliance improved from 56% to over 80% for the entire hospital. Unanticipated direct admission-to-PICU transfers decreased from a baseline of 1 every 98 patients to a special cause of 1 in 1126 patients.

Conclusions
By utilizing QI methodology our team was able to implement and sustain a direct admission process that was more consistent, easier to document and improved the safety of our patients. Our study demonstrates that screening direct admissions reliably and consistently can decrease the rate of unanticipated transfer to a higher level of care.
Antiplatelet and anticoagulant agents have minimal impact on traumatic brain injury incidence, surgery, and mortality in geriatric ground level falls: A multi-institutional analysis of 33,710 patients
Authors: Fakhry Samir M. , Morse Jennifer L. , Garland Jeneva M. , Wilson Nina Y. , Shen Yan , Wyse Ransom J. , Watts Dorraine D. 
Published: October 2020

BACKGROUND
Falls are the leading cause of traumatic brain injury (TBI) and TBI-related deaths for older persons (age, ≥65 years). Antiplatelet and/or anticoagulant therapy (antithrombotics [ATs]) is generally felt to increase this risk, but the literature is inconsistent. The purpose of this study was to determine the impact of AT use on the rate, severity, and outcomes of TBI in older patients following ground level falls.

METHODS
Ground level fall patients from 90 hospitals’ trauma registries were selected. Patients were excluded if younger than 65 years or had an Abbreviated Injury Scale score of >2 in a region other than head. Electronic medical record data for preinjury AT therapy were obtained. Patients were grouped by regimen for no AT, single, or multiple agents. Groups were compared on rates of diagnosed TBI, TBI surgery, and mortality.

RESULTS
There were 33,710 patients (35% male; mean age, 80.5 years; mean Glasgow Coma Scale, 14.6), with 47.6% on single or combination AT therapy. The proportion of patients with TBI diagnoses did not differ between those on no AT (21.25%) versus AT (21.61%; p = 0.418). Apixaban (15.7%; p < 0.001) and rivaroxaban (13.19%; p = 0.011) were associated with lower rates of TBI, and acetylsalicylic acid-clopidogrel was associated with a higher TBI rate (24.34%; p = 0.002) versus no AT. acetylsalicylic acid-clopidogrel was associated with a higher cranial surgery rate (2.9%; p = 0.006) versus no AT (1.96%), but surgery rates were similar for all other regimens. No regimen was associated with higher mortality.

CONCLUSION
In this large multicenter study, the intake of ATs in older patients with ground level falls was associated with inconsistent effects on risk of TBI and no significant increases in mortality, indicating that AT use may have negligible impact on patient clinical management. A large, confirmatory, prospective study is needed because the commonly held belief that ATs uniformly increase the risk of traumatic intracranial bleeding and mortality is not supported.

LEVEL OF EVIDENCE
Therapeutic/care management, level II.
Structural stability of SARS-CoV-2 degrades with temperature
Authors: Sharma A. , Preece B. , Swann H , Fan X. , McKenney R.J. , Ori-McKenney K.M. , Saffarian S. , Vershinin M.D. 
Published: October 2020

AbstractSARS-CoV-2 is a novel coronavirus which has caused the COVID-19 pandemic. Other known coronaviruses show a strong pattern of seasonality, with the infection cases in humans being more prominent in winter. Although several plausible origins of such seasonal variability have been proposed, its mechanism is unclear. SARS-CoV-2 is transmitted via airborne droplets ejected from the upper respiratory tract of the infected individuals. It has been reported that SARS-CoV-2 can remain infectious for hours on surfaces. As such, the stability of viral particles both in liquid droplets as well as dried on surfaces is essential for infectivity. Here we have used atomic force microscopy to examine the structural stability of individual SARS-CoV-2 virus like particles at different temperatures. We demonstrate that even a mild temperature increase, commensurate with what is common for summer warming, leads to dramatic disruption of viral structural stability, especially when the heat is applied in the dry state. This is consistent with other existing non-mechanistic studies of viral infectivity, provides a single particle perspective on viral seasonality, and strengthens the case for a resurgence of COVID-19 in winter.Statement of Scientific SignificanceThe economic and public health impact of the COVID-19 pandemic are very significant. However scientific information needed to underpin policy decisions are limited partly due to novelty of the SARS-CoV-2 pathogen. There is therefore an urgent need for mechanistic studies of both COVID-19 disease and the SARS-CoV-2 virus. We show that individual virus particles suffer structural destabilization at relatively mild but elevated temperatures. Our nanoscale results are consistent with recent observations at larger scales. Our work strengthens the case for COVID-19 resurgence in winter.
Circulating tumour cell and cell-free DNA kinetics during radiotherapy in patients with intact head and neck squamous cell carcinoma
Authors: Ng Sweet Ping , Hall Carolyn S , Meas Salyna , Sarli Vanessa N , Bahig Houda , Cardenas Carlos E , Elgohari Baher , Wang JiHong , Johnson Jason M , Moreno Amy C , Skinner Heath , Garden Adam S , Na Lumine , Yuan Ying , Urbauer Diana , Phan Jack , Gunn G Brandon , Frank Steven J , Shah Shalin , Rosenthal David I , Morrison William H , MacManus Michael P , Fuller Clifton D , Lucci Anthony 
Published: October 2020

AbstractHead and neck squamous cell carcinoma (HNSCC) treatment response relies heavily on macroscopic clinical findings. Blood monitoring of circulating markers during treatment may improve earlier detection of responders versus non-responders during radiotherapy. In this study, patients with intact tumour of HNSCC were enrolled in the prospective PREDICT-HN study. Pre-, after first treatment, weekly, and post-treatment blood samples were collected. CTC was enumerated using the CellSearch system. cfDNA was quantified from cfNA isolated at pre-, mid- and post-treatment timepoints. Blood samples were collected from 45 patients. Of the 339 samples analysed for CTC, 31% had detectable CTCs. Nine patients had detectable CTCs (1-3/7.5ml blood) in pre-treatment samples. After 1 fraction, 16 patients had CTCs detected, with 12 who had no pre-treatment CTC. Sixteen (36%) patients had detectable CTC in final week of treatment. There was no correlation between cancer stage, nodal status and tumour burden with CTC. cfDNA levels increased during treatment, with its highest level in the final week and lowest at post-treatment. Our results showed in HNSCC that CTCs can be detected during radiotherapy, suggesting mobilization into circulation during treatment, with as-yet-unknown viability. cfDNA kinetics during treatment correlated with CTC release, and may indicate apoptotic change.Simple SummaryHead and neck squamous cell carcinoma (HNSCC) treatment response relies heavily on macroscopic clinical findings. Blood monitoring of circulating markers such as circulating tumour cell (CTC) and cell-free DNA (cfDNA) during treatment may improve earlier detection of responders versus non-responders during definitive radiotherapy. Although the detection of CTCs and cfDNA in patients with HNSCC has been described, there is minimal data on the kinetics of CTC counts and cfDNA levels during radiotherapy in patients with HNSCC. Here, our study prospectively describes the changes in CTC and cfDNA enumeration during radiotherapy in patients with HNSCC. Our results showed, for the first time to our knowledge, in HNSCC, that CTCs can be detected during radiotherapy, suggesting mobilization into peripheral circulation during treatment, with as-yet-unknown viability. cfDNA kinetics during treatment correlated with CTC release, may indicate apoptotic change during radiotherapy. Combined cfDNA-CTC as an early marker of treatment response should be investigated further.
Development of a deep learning classifier to accurately distinguish COVID-19 from look-a-like pathology on lung ultrasound
Authors: Arntfield Robert , VanBerlo Blake , Alaifan Thamer , Phelps Nathan , White Matt , Chaudhary Rushil , Ho Jordan , Wu Derek 
Published: October 2020

AbstractObjectivesLung ultrasound (LUS) is a portable, low cost respiratory imaging tool but is challenged by user dependence and lack of diagnostic specificity. It is unknown whether the advantages of LUS implementation could be paired with deep learning techniques to match or exceed human-level, diagnostic specificity among similar appearing, pathological LUS images.DesignA convolutional neural network was trained on LUS images with B lines of different etiologies. CNN diagnostic performance, as validated using a 10% data holdback set was compared to surveyed LUS-competent physicians.SettingTwo tertiary Canadian hospitals.Participants600 LUS videos (121,381 frames) of B lines from 243 distinct patients with either 1) COVID-19, Non-COVID acute respiratory distress syndrome (NCOVID) and 3) Hydrostatic pulmonary edema (HPE).ResultsThe trained CNN performance on the independent dataset showed an ability to discriminate between COVID (AUC 1.0), NCOVID (AUC 0.934) and HPE (AUC 1.0) pathologies. This was significantly better than physician ability (AUCs of 0.697, 0.704, 0.967 for the COVID, NCOVID and HPE classes, respectively), p < 0.01.ConclusionsA deep learning model can distinguish similar appearing LUS pathology, including COVID-19, that cannot be distinguished by humans. The performance gap between humans and the model suggests that subvisible biomarkers within ultrasound images could exist and multi-center research is merited.
Longitudinal survey reveals delayed effects of forager gene expression on stingless bee colony health
Authors: Caesar Lílian , Lopes Anelise Martins Correa , Radaeski Jefferson Nunes , Bauermann Soraia Girardi , Konzen Enéas Ricardo , Pombert Jean-François , Sattler Aroni , Blochtein Betina , Carvalho Airton Torres , Haag Karen Luisa 
Published: October 2020

AbstractBee populations are declining globally due to different environmental stressors, such as pathogens, malnutrition, and agrochemicals. Brazil is the home of hundreds of stingless bee species, some of them now considered endangered, though very little is known about the impact of disease on native bees. In Southern Brazil the endangered stingless beeMelipona quadrifasciatais affected by an annual syndrome that causes sudden death of workers, eventually leading colonies to collapse. Although novel viruses were found in foragers from diseased colonies, none has been consistently implicated in the outbreak. Here we used transcriptomics in combination with an integrative longitudinal survey on managed colonies to identify predictors for preventingM. quadrifasciatacolony failures. We found that key genes related to xenobiotic metabolization, nutrition and immune responses are downregulated in foragers from colonies that became diseased three months later. The period that preceded the outbreak was marked by pronounced forager weight loss as well as behavioural changes. Our findings support the proposition that worldwide bee mortality is influenced by a combination of diverse sublethal factors, and increase awareness of the long-term effects of genetic diversity erosion in stingless bee species, which enhances their vulnerability to environmental stressors.
DNA Methyltransferase Inhibitors with Novel Chemical Scaffolds
Authors: Juárez-Mercado K. Eurídice , Prieto-Martínez Fernando D. , Sánchez-Cruz Norberto , Peña-Castillo Andrea , Prada-Gracia Diego , Medina-Franco José L. 
Published: October 2020

AbstractInhibitors of DNA methyltransferases (DNMTs) are attractive compounds for epigenetic drug discovery. They are also chemical tools to understand the biochemistry of epigenetic processes. Herein, we report five distinct inhibitors of DNMT1 characterized in enzymatic inhibition assays that did not show activity with DNMT3B. It was concluded that the dietary component theaflavin is an inhibitor of DNMT1. Two additional novel inhibitors of DNMT1 are the approved drugs glyburide and panobinostat. The DNMT1 enzymatic inhibitory activity of panobinostat, a known pan inhibitor of histone deacetylases, agrees with experimental reports of its ability to reduce DNMT1 activity in liver cancer cell lines. Molecular docking of the active compounds with DNMT1, and re-scoring with the recently developed Extended Connectivity Interaction Features approach, had an excellent agreement between the experimental IC50values and docking scores.
High-resolution architecture of human epiphysis formation
Authors: Sun Heng , Wen Ya , Wu Weiliang , Qin Tian , An Chengrui , Fan Chunmei , Chen Yishan , Ji Junfeng , Chew Ting Gang , Chen Jiansong , Ouyang Hongwei 
Published: October 2020

SummaryHuman limb skeletal system consists of both bone and cartilage which originated from fetal cartilage. However, the roadmap of chondrocyte divergent differentiation to bone and articular cartilage has yet to be established. Epiphysis possesses articular cartilage, growth plate and the secondary ossification center (SOC), making it an ideal model to uncover the trajectory of chondrocyte divergent differentiation. Here, we mapped differentiation trajectory of human chondrocyte during postnatal finger epiphysis development by using single-cell RNA sequencing. Our results uncovered that chondroprogenitors have two differentiation pathways to hypertrophic chondrocytes during ossification, and one pathway to articular chondrocytes for formation of cartilages. Interestingly, we found that, as an addition to the known typical endochondral ossification path from resting, proliferative to hypertrophic chondrocytes, there was a bypass by which chondroprogenitors differentiate into hypertrophic chondrocytes without proliferative stage. Furthermore, our results revealed two new chondrocyte subpopulations (bypass chondrocytes as it appeared in the ossification bypass, andID1+chondroblasts in articular chondrocyte path) during postnatal epiphysis development in addition to six well-known subpopulations. Overall, our study provides a comprehensive roadmap of chondrocyte differentiation in human epiphysis thereby expanding the knowledge of bone and articular cartilage, which could be utilized to design biotherapeutics for bone and articular cartilage regeneration.
The ubiquitylome of developing cortical neurons
Authors: Menon Shalini , Goldfarb Dennis , Cousins Emily M. , Major M. Ben , Gupton Stephanie L. 
Published: October 2020

AbstractTRIM9 and TRIM67 are neuronally-enriched E3 ubiquitin. Both genes are required for neuronal morphological responses to the axon guidance cue netrin-1. For example, our previously published work demonstrated that the actin polymerase VASP and the netrin receptor DCC exhibit TRIM9 dependent ubiquitylation that is lost upon netrin stimulation. Deletion of either gene in the mouse results in subtle neuroanatomical anomalies yet overt deficits in spatial learning and memory. Despite their role in neuronal form and function, the identity of few TRIM9 or TRIM67 substrates are known. Here we performed ubiquitin remnant profiling approach in cultured wildtype and knockout murine embryonic cortical neurons to identify ubiquitylated peptides and proteins, with the ultimate goal of identifying substrates of TRIM9 and TRIM67 that exhibited reduced ubiquitylation in the absence of the ligase. This work reveals the ubiquitylome of developing cortical neurons.
Higher temperatures worsen the effects of mutations on protein stability
Authors: Kontopoulos Dimitrios - Georgios , Patmanidis Ilias , Barraclough Timothy G. , Pawar Samraat 
Published: October 2020

AbstractUnderstanding whether and how temperature increases alter the effects of mutations on protein stability is crucial for understanding the limits to thermal adaptation by organisms. Currently, it is generally assumed that the stability effects of mutations are independent of temperature. Yet, mutations should become increasingly destabilizing as temperature rises due to the increase in the energy of atoms. Here, by performing an extensive computational analysis on the essential enzyme adenylate kinase in prokaryotes, we show, for the first time, that mutations become more destabilizing with temperature both across and within species. Consistent with these findings, we find that substitution rates of prokaryotes decrease nonlinearly with temperature. Our results suggest that life on Earth likely originated in a moderately thermophilic and thermally fluctuating environment, and indicate that global warming should decrease the per-generation rate of molecular evolution of prokaryotes.
Connecting high-resolution 3D chromatin organization with epigenomics
Authors: Feng Fan , Yao Yuan , Wang Xue Qing David , Zhang Xiaotian , Liu Jie 
Published: October 2020

AbstractThe resolution of chromatin conformation capture technologies keeps increasing, and the recent nucleosome resolution chromatin contact maps allow us to explore how fine-scale 3D chromatin organization is related to epigenomic states in human cells. Using publicly available Micro-C datasets, we have developed a deep learning model, CAESAR, to learn a mapping function from epigenomic features to 3D chromatin organization. The model accurately predicts fine-scale structures, such as short-range chromatin loops and stripes, that Hi-C fails to detect. With existing epigenomic datasets from ENCODE and Roadmap Epigenomics Project, we successfully imputed high-resolution 3D chromatin contact maps for 91 human tissues and cell lines. In the imputed high-resolution contact maps, we identified the spatial interactions between genes and their experimentally validated regulatory elements, demonstrating CAESAR’s potential in coupling transcriptional regulation with 3D chromatin organization at high resolution.
The emergence of inter-clade hybrid SARS-CoV-2 lineages revealed by 2D nucleotide variation mapping
Authors: Wang Hai-Long 
Published: October 2020

ABSTRACTI performed whole-genome sequencing on SARS-CoV-2 collected from COVID-19 samples at Mayo Clinic Rochester in mid-April, 2020, generated 85 consensus genome sequences and compared them to other genome sequences collected worldwide. I proposed a novel illustrating method using a 2D map to display populations of co-occurring nucleotide variants for intra- and inter-viral clades. This method is highly advantageous for the new era of “big-data” when high-throughput sequencing is becoming readily available. Using this method, I revealed the emergence of inter-clade hybrid SARS-CoV-2 lineages that are potentially caused by homologous genetic recombination.