bluuebunny/crossref_metadata_2025_split huggingface dataset:
Performance of the BIG Score in Predicting Mortality in Normotensive Children With Trauma
Authors: Yoon Tae Jin , Ko Yura , Lee Jisook , Huh Yo , Kim Jung Heon 
Published: June 2020

Objectives
Children have a larger reserve for traumatic hemorrhagic shock, requiring a score that uses physiologic variables other than hypotension. Recently, the BIG score comprising admission base deficit, international normalized ratio, and the Glasgow Coma Scale has been reported to predict traumatic mortality. We aimed to validate the performance of the BIG score in mortality prediction of normotensive children with trauma.

Methods
We reviewed 1046 injured children (<18 years) who visited a Korean academic hospital from 2010 to 2018, excluding those with age-adjusted hypotension. In-hospital mortality, the BIG score and its predicted mortality, Revised Trauma Score, and Pediatric Trauma Score were calculated. We compared areas under the curve (AUCs) for in-hospital mortality of the 3 scores and did in-hospital and BIG-predicted mortalities.

Results
Of the 1046 children, 554 were enrolled with a 4.9% in-hospital mortality rate. The median BIG score was higher in the nonsurvivors (6.4 [interquartile range, 4.4–9.2] vs 20.1 [16.5–24.8]; P < 0.001). The AUC of the BIG score was 0.94 (95% confidence interval [CI], 0.92–0.96), which was higher than that of Pediatric Trauma Score (0.87 [95% CI, 0.84–0.90]; P < 0.001). The AUC of the BIG score tended to be higher than that of Revised Trauma Score without statistical significance (0.90 [95% CI, 0.87–0.92]; P = 0.130). We noted a parallel between in-hospital and BIG-predicted mortalities. The hemorrhage-related nonsurvivors showed higher median base deficit and BIG score than did the isolated traumatic brain injury-related ones.

Conclusions
The BIG score can predict mortality with excellent accuracy in normotensive children with trauma.
Outcomes and Factors Associated With Prehospital Treatment of Pediatric Anaphylaxis
Authors: Trainor Jennifer L. , Pittsenbarger Zachary E. , Joshi Deepa , Adler Mark D. , Smith Bridget , Gupta Ruchi S. 
Published: June 2020

Objective
Anaphylaxis is a potentially life-threatening reaction requiring prompt treatment with intramuscular epinephrine (EPI). We sought to describe presenting features of pediatric anaphylaxis and compare patient characteristics and outcomes of children treated with prehospital EPI with those untreated.

Methods
We abstracted data from emergency department (ED) records for children meeting the National Institute of Allergy & Infectious Disease criteria for anaphylaxis (2015–2017) in one tertiary care children's hospital. We analyzed associations between patient characteristics and outcomes and receipt of prehospital EPI using descriptive statistics and multivariate logistic regression.

Results
Of 414 children presenting with anaphylaxis, 39.4% received IM EPI and 62.1% received antihistamines before hospital arrival. Children with Medicaid received pre–emergency department EPI less frequently than did children with private insurance (24.5% vs 43.8%, P = 0.001). Factors positively associated with prehospital EPI administration were history of food allergy (odds ratio [OR], 4.4 [95% confidence interval {CI}, 2.4–8.2]) or arrival by emergency medical services (OR, 8.0 [95% CI, 4.2–15.0]). Medicaid insurance was associated with decreased odds of prehospital EPI (OR, 0.33 [95% CI, 0.16–0.66]) and prehospital H1-antihistamine use (OR, 0.30 [95% CI, 0.17–0.56]). Prehospital EPI treatment was also associated with decreased rates of observation (37% vs 63%), inpatient admission (38% vs 62%), and intensive care unit admission (20% vs 80%) compared with no pretreatment (P = 0.03).

Conclusions
Prehospital treatment with EPI remains low, and barriers to optimal treatment are more pronounced in children with public insurance. Prehospital treatment with EPI was associated with decreased morbidity including hospitalization and intensive care unit admission.
Characteristics of Diagnosed Concussions in Children Aged 0 to 4 Years Presenting to a Large Pediatric Healthcare Network
Authors: Podolak Olivia E. , Chaudhary Sofia , Haarbauer-Krupa Juliet , Metzger Kristina B. , Curry Allison E. , Kessler Ronni S. , Pfeiffer Melissa R. , Breiding Matthew J. , Master Christina L. , Arbogast Kristy B. 
Published: June 2020

ObjectiveThe aim of the study was to comprehensively describe the natural history of concussion in early childhood between 0 and 4 years.MethodsRetrospective cohort study of 329 patients aged 0 to 4 years, with anInternational Classification of Diseases,Ninth Revision, concussion diagnosis in the Children's Hospital of Philadelphia healthcare network from October 1, 2013, to September 30, 2015. Clinical data were abstracted from the Children's Hospital of Philadelphia electronic health record, which captured all clinical care visits and injury characteristics.ResultsNearly 9 (86.6%) of 10 patients sought care in the emergency department or urgent care setting, most commonly on the day of injury (56.2%) and as a result of a fall (64.4%). More than two-thirds (64.4%) of patients or their parent/caregiver reported somatic symptoms (ie, vomiting or headache), whereas close to half (49.2%) reported sleep issues. One of 5 patients identified emotional symptoms (21.9%) or visio-vestibular dysfunction (20.4%). Many patients also experienced symptoms not included in standard assessment tools including personality changes (34.0%) and change in appetite (12.8%).ConclusionsThese results provide insight into the clinical characteristics of concussion in early childhood up to 4 years of age. Because assessment in this group relies heavily on parent/caregiver symptom reporting, rather than patient self-report, these results will aid clinicians with the challenge of diagnosing concussions in this population. These findings highlight the need to develop additional tools to adequately and systematically assess common signs and symptoms of concussion in early childhood that may not be included in standard assessment scales routinely used in older adolescents and adults.
The Role of Helicobacter pylori and Serum Pepsinogen Levels in Metachronous Gastric Cancer After Endoscopic Gastrectomy
Authors: Wang Zhen-Yu , Zhang Jian-Guo 
Published: June 2020

Purpose:
The current study aimed to explore the role of Helicobacter pylori (Hp) infection and serum pepsinogen (PG) levels in the occurrence of metachronous gastric cancer after endoscopic gastrectomy.

Materials and Methods:
Totally, 50 patients with metachronous gastric cancer, 50 patients with chronic atrophic gastritis and 50 healthy subjects were collected from October 2015 to October 2018. Patients in the gastric cancer group underwent endoscopic gastrectomy. Serum samples were collected for detection and correlation analysis of serum PG I, PG II, and Hp. In addition, the contents of serum PG and gastrin and postoperative adverse events were statistically analyzed.

Results:
There was a statistically significant difference in serum PG I levels, positive Hp infection rate, the number of mast cells, plasma motilin levels and postoperative adverse events among the 3 groups (P<0.01). There was also a significant difference in PG II levels among the groups (P<0.05). On the basis of the results, the amount of inflammatory cells in the gastric cancer group was significantly higher than that in the gastritis group, and there was a remarkable difference in gastric cancer patients before and after operation. Through data analysis, it was found that the levels of PG I and II were the highest in the healthy control group and the lowest in the gastric cancer group, the number of mast cells was the largest in the gastric cancer group, and the level of motilin was the highest in the healthy control group.

Conclusion:
Hp infection and serum PG levels are associated with metachronous gastric cancer.
Topological Aberrance of Structural Brain Network Provides Quantitative Markers of post-TBI Attention Deficits in Children
Authors: Cao Meng , Luo Yuyang , Wu Ziyan , Mazzola Catherine A. , Goodman Arlene , Catania Lori , Alvarez Tara L. , Halperin Jeffrey M. , Li Xiaobo 
Published: June 2020

ABSTRACTTraumatic brain injury (TBI)-induced attention deficits are among the most common long-term cognitive consequences in children. Most of the existing studies attenpting to understand the neuropathological underpinnings of cognitive and behavioral impairments in TBI have utilized heterogeneous samples and resulted in inconsistent findings. The current research proposed to investigate topological properties of the structural brain network in children with TBI and their associations with TBI-induced attention problems in a more homogeneous subgroup of children who had severe post-TBI attention deficits (TBI-A).A total of 31 children with TBI-A and 35 group-matched controls were involved in the study. Diffusion tensor imaging-based probabilistic tractography and graph theoretical techniques were used to construct the structural brain network in each subject. Network topological properties were calculated in both global level and regional (nodal) level. Between-group comparisons among the topological network measures and analyses for searching brain-behavioral associations were all corrected for multiple comparisons using Bonferroni method.Compare to controls, the TBI-A group showed significantly higher nodal local efficiency and nodal clustering coefficient in left inferior frontal gyrus and right transverse temporal gyrus, while significantly lower nodal clustering coefficient in left supramarginal gyrus as well as lower nodal local efficiency in left parahippocampal gyrus. The temporal lobe topological alterations were significantly associated with the post-TBI inattentive and hyperactive symptoms in the TBI-A group.The results suggest that TBI-related structural re-modularity in the WM subnetworks associated with temporal lobe may play a critical role in the onset of severe post-TBI attention deficits in children. These findings provide valuable input for understanding the neurobiological substrates of TBI-A, and have the potential to serve as a biomarker guiding the development of more timely and tailored strategies for diagnoses and treatments to the affected individuals.
Dissecting Response to Cancer Immunotherapy by Applying Bayesian Network Analysis to Flow Cytometry Data
Authors: Rodin Andrei S. , Gogoshin Grigoriy , Hilliard Seth , Wang Lei , Egelston Colt , Rockne Russel C. , Chao Joseph , Lee Peter P. 
Published: June 2020

AbstractCancer immunotherapy, specifically immune checkpoint blockade therapy, has been found to be effective in the treatment of metastatic cancers. However, only a subset of patients achieve clinical responses. Consequently, elucidating immune system-related pre-treatment biomarkers that are predictive with respect to sustained clinical response is a major research priority. Another research priority is evaluating changes in the immune system before and after treatment in responders and non-responders. Our group has been studying immune signaling networks as an accurate reflection of the global immune state. Flow cytometry (FACS, Fluorescence-activated cell sorting) data characterizing immune signaling in peripheral blood mononuclear cells (PBMC) from gastroesophageal adenocarcinoma (GEA) patients were used to analyze changes in immune signaling networks in this setting. Here, we describe a novel computational pipeline developed by us to perform secondary analyses of FACS data using systems biology / machine learning techniques and concepts. It is centered around comparative Bayesian network analyses of immune signaling networks and is capable of detecting true positive signals that conventional methods (such as FlowJo manual gating) might miss. Future studies are planned to validate and follow up immune markers (and combinations / interactions thereof) associated with clinical responses that were identified by this computational pipeline.
GluD2- and Cbln1-mediated Competitive Synaptogenesis Shapes the Dendritic Arbors of Cerebellar Purkinje Cells
Authors: Takeo Yukari H. , Shuster S. Andrew , Jiang Linnie , Hu Miley , Luginbuhl David J. , Rülicke Thomas , Contreras Ximena , Hippenmeyer Simon , Wagner Mark J. , Ganguli Surya , Luo Liqun 
Published: June 2020

SUMMARYThe synaptotrophic hypothesis posits that synapse formation stabilizes dendritic branches, yet this hypothesis has not been causally testedin vivoin the mammalian brain. Presynaptic ligand cerebellin-1 (Cbln1) and postsynaptic receptor GluD2 mediate synaptogenesis between granule cells and Purkinje cells in the molecular layer of the cerebellar cortex. Here we show that sparse but not global knockout ofGluD2causes under-elaboration of Purkinje cell dendrites in the deep molecular layer and overelaboration in the superficial molecular layer. Developmental, overexpression, structure-function, and genetic epistasis analyses indicate that dendrite morphogenesis defects result from competitive synaptogenesis in a Cbln1/GluD2-dependent manner. A generative model of dendritic growth based on competitive synaptogenesis largely recapitulatesGluD2sparse and global knockout phenotypes. Our results support the synaptotrophic hypothesis at initial stages of dendrite development, suggest a second mode in which cumulative synapse formation inhibits further dendrite growth, and highlight the importance of competition in dendrite morphogenesis.
Reconstitution of Alveolar Regeneration via novel DATPs by Inflammatory Niches
Authors: Choi Jinwook , Park Jong-Eun , Tsagkogeorga Georgia , Yanagita Motoko , Koo Bon-Kyoung , Han Namshik , Lee Joo-Hyeon 
Published: June 2020

SummaryTissue regeneration involves a multi-step process composed of diverse cellular hierarchies and states that are also implicated in tissue dysfunction and pathogenesis. Here, we leveraged single-cell RNA sequencing analysis in combination within vivolineage tracing and organoid models to fine-map trajectories of alveolar lineage cells during injury repair and regeneration. We identified Damage-Associated Transient Progenitors (DATPs) as a distinct AT2-lineaged population arising during alveolar regeneration. Specifically, we found that IL-1β, secreted by interstitial macrophages, primes a subset ofIl1r1+AT2 cells for conversion into DATPs, via aHif1a-mediated glycolysis pathway, that are functional mediators for mature AT1 cell differentiation. Importantly, we show that chronic inflammation mediated by IL-1β prevents differentiation into AT1 cells, leading to aberrant accumulation of DATPs and impaired alveolar differentiation. Our step-wise fine-mapping of cell fate transitions demonstrates how the inflammatory niche impedes alveolar regeneration by directing stem cell fate behavior.
Pulmonary toxicity and inflammatory response of e-cigarettes containing medium-chain triglyceride oil and vitamin E acetate: Implications in the pathogenesis of EVALI but independent of SARS-COV-2 COVID-19 related proteins
Authors: Muthumalage Thivanka , Lucas Joseph H. , Wang Qixin , Lamb Thomas , McGraw Matthew D. , Rahman Irfan 
Published: June 2020

AbstractRecently, there has been an outbreak associated with the use of e-cigarette or vaping products, associated lung injury (EVALI). The primary components of vaping products, vitamin E acetate (VEA) and medium-chain triglycerides (MCT) may be responsible for acute lung toxicity. Currently, little information is available on the physiological and biological effects of exposure to these products. We hypothesized that these e-cig cartridges and their constituents (VEA and MCT) induce pulmonary toxicity, mediated by oxidative damage and inflammatory responses, leading to acute lung injury. We studied the potential mechanisms of cartridge aerosol induced inflammatory response by evaluating the generation of reactive oxygen species by MCT, VEA, and cartridges, and their effects on the inflammatory state of pulmonary epithelium and immune cells both in vitro and in vivo. Cells exposed to these aerosols generated reactive oxygen species, caused cytotoxicity, induced epithelial barrier dysfunction, and elicited an inflammatory response. Using a murine model, the parameters of acute toxicity to aerosol inhalation were assessed. Infiltration of neutrophils and lymphocytes was accompanied by significant increases in IL-6, eotaxin, and G-CSF in the bronchoalveolar lavage fluid (BALF). In mouse plasma, eicosanoid inflammatory mediators, leukotrienes, were significantly increased. Plasma from e-cig users also showed increased levels of hydroxyeicosatetraenoic acid (HETEs) and various eicosanoids. Exposure to e-cig cartridge aerosols showed the most significant effects and toxicity compared to MCT and VEA. In addition, we determined at SARS-COV-2 related proteins and found no impact associated with aerosol exposures from these tested cartridges. Overall, this study demonstrates acute exposure to specific e-cig cartridges induces in vitro cytotoxicity, barrier dysfunction, and inflammation and in vivo mouse exposure induces acute inflammation with elevated pro-inflammatory markers in the pathogenesis of EVALI.
HMGXB4 TargetsSleeping BeautyTransposition to Vertebrate Germinal Stem Cells
Authors: Devaraj Anantharam , Singh Manvendra , Narayanavari Suneel , Yong Guo , Wang Jiaxuan , Wang Jichang , Becker Mareike , Walisko Oliver , Schorn Andrea , Cseresznyés Zoltán , Grzela Dawid , Raskó Tamás , Selbach Matthias , Ivics Zoltán , Izsvák Zsuzsanna 
Published: June 2020

AbstractTransposons are parasitic genetic elements that frequently hijack key cellular processes of the host. HMGXB4 is a Wnt signalling-associated HMG-box protein, previously identified as a transcriptional regulating host factor ofSleeping Beauty(SB) transposition. Here, we establish that HMGXB4 is highly expressed from the zygote stage, and declines after transcriptional genome activation. Nevertheless, HMGXB4 is activated by its own promoter at 4-cell stage, responding to the parental-to-zygotic transition, marks stemness, and maintains its expression during germ cell specification. The HMGXB4 promoter is located at an active chromatin domain boundary. As a vertebrate-specific modulator of SETD1A and NuRF complexes, HMGXB4 links histone H3K4 methyltransferase- and ATP-dependent nucleosome remodelling activities. The expression of HMGXB4 is regulated by the KRAB-ZNF/TRIM28 epigenetic repression machinery. A post-transcriptional modification by SUMOylation diminishes its transcriptional activator function and regulates its nucleolar trafficking. Collectively, HMGXB4 positions SB transposition into an elaborate stem cell-specific transcriptional regulatory mechanism that is active during early embryogenesis and germline development, thereby potentiating heritable transposon insertions in the germline.
Formin FHOD1 regulates the size of EPEC pedestals
Authors: Liu Xuyao Priscilla , Shah Mrinal , Kenney Linda J. 
Published: June 2020

SummaryEnteropathogenicE. coli(EPEC) is an extracellular pathogen that causes polymerization of actin filaments at the site of bacterial attachment, referred to as ‘actin pedestals’. Actin polymerization in the pedestal was believed to be solely regulated via the Nck-WASp-Arp2/3 pathway before formins were recently discovered to be associated with pedestals. Herein, we explored the collaborative role of formins in contributing to EPEC pedestal formation. In particular, we discovered that the formin FHOD1 preferentially localized to the pedestal base and its knockdown drastically reduced pedestal surface area. The pedestal localization of formin FHOD1 was found to be dependent on Tir phosphorylation at Y474, and on FHOD1 phosphorylation at Y99 from host Src family kinases (SFKs). Interestingly, differences in Arp2/3 and FHOD1 dynamics were observed. In large pedestals, Arp3 was nearly absent, but FHOD1 levels were high, suggesting that Arp2/3 and formins were segregated temporally. In line with this observation, as the pedestals grew in size, FHOD1 localization increased, while Arp3 localization decreased along the pedestals. Together, our results suggest that EPEC employs multiple actin nucleators that act at different stages of pedestal formation.Graphical abstract
A neural circuit mechanism of categorical perception: top-down signaling in the primate cortex
Authors: Min Bin , Bliss Daniel P. , Sarma Arup , Freedman David J. , Wang Xiao-Jing 
Published: June 2020

AbstractIn contrast to feedforward architecture commonly used in deep networks at the core of today’s AI revolution, the biological cortex is endowed with an abundance of feedback projections. Feedback signaling is often difficult to differentially identify, and its computational roles remain poorly understood. Here, we investigated a cognitive phenomenon, called categorical perception (CP), that reveals the influences of high-level category learning on low-level feature-based perception, as a putative signature of top-down signaling. By examining behavioral data from a visual motion delayed matching experiment in non-human primates, we found that, after categorization training, motion directions closer to (respectively, away from) a category center became more (less) difficult to discriminate. This distance-dependent discrimination performance change along the dimension relevant to the learned categories provides direct evidence for the CP phenomenon. To explain this experimental finding, we developed a neural circuit model that incorporated key neurophysiological findings in visual categorization, working memory and decision making. Our model accounts for the behavioral data indicative of CP, pinpoints its circuit basis, suggests novel experimentally testable predictions and provides a functional explanation for its existence. Our work shows that delayed matching paradigms in non-human primates combined with biologically-based modeling can serve as a promising model system for elucidating the neural mechanisms of CP, as a manifestation of top-down signaling in the cortex.Significant StatementCategorical perception is a cognitive phenomenon revealing the influences of high-level category learning on low-level feature-based perception. However, its underlying neural mechanisms are largely unknown. Here, we found behavioral evidence for this phenomenon from a visual motion delayed matching experiment in non-human primates. We developed a neural circuit model that can account for this behavioral data, pinpoints its circuit basis, suggests novel experimentally testable predictions and provides a functional explanation for its existence. Our work shows that delayed matching paradigms in non-human primates combined with biologically-based modeling can serve as a promising model system for elucidating the neural mechanisms of categorical perception, as a manifestation of top-down signaling in the cortex.