bluuebunny/crossref_metadata_2025_split huggingface dataset:
Treatment of an aggressive orthotopic murine glioblastoma model with combination checkpoint blockade and a multivalent neoantigen vaccine
Authors: Liu Connor J , Schaettler Maximilian , Blaha Dylan T , Bowman-Kirigin Jay A , Kobayashi Dale K , Livingstone Alexandra J , Bender Diane , Miller Christopher A , Kranz David M , Johanns Tanner M , Dunn Gavin P 
Published: February 2020

AbstractBackgroundAlthough clinical trials testing immunotherapies in glioblastoma (GBM) have yielded mixed results, new strategies targeting tumor-specific somatic coding mutations, termed “neoantigens,” represent promising therapeutic approaches. We characterized the microenvironment and neoantigen landscape of the aggressive CT2A GBM model in order to develop a platform to test combination checkpoint blockade and neoantigen vaccination.MethodsFlow cytometric analysis was performed on intracranial CT2A and GL261 tumor-infiltrating lymphocytes (TILs). Whole-exome DNA and RNA sequencing of the CT2A murine GBM was employed to identify expressed, somatic mutations. Predicted neoantigens were identified using the pVAC-seq software suite, and top-ranking candidates were screened for reactivity by interferon-gamma enzyme linked immunospot assays. Survival analysis was performed comparing neoantigen vaccination, anti-programmed cell death ligand 1 (αPD-L1), or combination therapy.ResultsCompared with the GL261 model, CT2A exhibited immunologic features consistent with human GBM including reduced αPD-L1 sensitivity and hypofunctional TILs. Of the 29 CT2A neoantigens screened, we identified neoantigen-specific CD8+ T-cell responses in the intracranial TIL and draining lymph nodes to two H2-Kb restricted (Epb4H471L and Pomgnt1R497L) and one H2-Db restricted neoantigen (Plin2G332R). Survival analysis showed that therapeutic neoantigen vaccination with Epb4H471L, Pomgnt1R497L, and Plin2G332R, in combination with αPD-L1 treatment was superior to αPD-L1 alone.ConclusionsWe identified endogenous neoantigen specific CD8+ T cells within an αPD-L1 resistant murine GBM and show that neoantigen vaccination significantly augments survival benefit in combination with αPD-L1 treatment. These observations provide important preclinical correlates for GBM immunotherapy trials and support further investigation into the effects of multimodal immunotherapeutic interventions on antiglioma immunity.Key Points1. Neoantigen vaccines combined with checkpoint blockade may be promising treatments.2. CT2A tumors exhibit features of human GBM microenvironments.3. Differential scanning fluorimetry assays may complement in silico neoantigen prediction tools.
Simulating the Impact of a Cigarette Minimum Floor Price Law on Adult Smoking Prevalence in California
Authors: Golden Shelley D , Kim KyungSu , Kong Amanda Y , Tao Vivian Qingzi , Carr Derek , Musburger Pratima 
Published: February 2020

Abstract

Introduction
Minimum floor price laws (MFPLs) are an emerging tobacco control policy that sets a minimum price below which a specific tobacco product cannot be sold. MFPLs target cheaper products and may disproportionately impact consumers choosing low price brands or using discounts to reduce prices. We developed a static microsimulation model for California, United States to project short-term effects of different MFPL options for a 20-stick pack of cigarettes on adult smoking behaviors.

Aims and Methods
We simulated 300 000 individuals defined by race and ethnicity, sex, age, and poverty status. Smoking behaviors and cigarette prices were assigned based on demographic distributions in the 2014–2016 California Behavioral Risk Factor Surveillance System. We drew 100 random samples (n = 30 000), weighted to state-level California demographic characteristics. We simulated six MFPL options and modeled impacts on smoking prevalence and cigarette consumption, in general, and separately for those in households below or above 250% of the federal poverty level, assuming a price elasticity of −0.4.

Results
Predicted changes in prices, prevalence, and consumption increased exponentially as the floor price increased from $7.00 to $9.50. Assuming 15% policy avoidance, projected increases in average cigarette prices ranged from $0.19 to $1.61. Decreases in smoking prevalence ranged from 0.05 to 0.43 percentage points, and decreases in average monthly cigarette consumption ranged from 1.4 to 12.3 cigarettes. Projected prices increased, and prevalence and consumption decreased, more among individuals in households below 250% federal poverty level.

Conclusions
MFPLs are a promising tobacco control strategy with the potential to reduce socioeconomic disparities in cigarette smoking prevalence and consumption.

Implications
Despite reductions in adult smoking prevalence, significant socioeconomic disparities remain, with lower-income groups smoking at substantially higher levels than higher-income groups. Policies that set a floor price below which a tobacco product cannot be sold could reduce socioeconomic disparities in smoking, depending on variation in prices paid by smokers prepolicy. By using a microsimulation model to predict changes in smoking for different population groups in California under several floor price scenarios, this study demonstrates that MFPLs have the potential to reduce adult smoking prevalence overall, and especially for lower-income tobacco users.
Functional feeding response of Nordic and Arctic krill on natural phytoplankton and zooplankton
Authors: Cabrol Jory , Fabre Anaïs , Nozais Christian , Tremblay Réjean , Starr Michel , Plourde Stéphane , Winkler Gesche 
Published: February 2020

Abstract
Krill species play a pivotal role in energetic transfer from lower to upper trophic levels. However, functional feeding responses, which determine how food availability influences ingestion rates, are still not well defined for northern krill species. Here, we estimated and compared the functional feeding responses on natural communities of phytoplankton and mesozooplankton of two coexisting species, Meganyctiphanes norvegica and Thysanoessa raschii. We tested the influence of the presence of phytoplankton on the ingestion rate and the selectivity of both krill species when feeding on zooplankton prey. We performed a series of feeding experiments using increasing concentrations of natural phytoplankton (64 taxa; 2 to &gt;50 μm) and mesozooplankton (28 taxa; ~100–2000 μm) assemblages and the latter in presence and absence of phytoplankton. Results revealed that both krill species exhibited a Holling type III feeding response on phytoplankton. However, T. raschii was able to exploit efficiently the highest phytoplankton concentrations. Our experiments highlighted that the presence of phytoplankton modified the functional feeding response on mesozooplankton preys of M. norvegica, but not that of T. raschii. Similarly, the presence of phytoplankton influenced the feeding selectivity on mesozooplankton preys, although both species showed contrasting selectivity patterns. In addition, we estimated the energy needs in relation to the daily rations. T. raschii satisfied its energy needs by feeding either on high phytoplankton concentrations or on low mesozooplankton densities, whereas M. norvegica did not cover its metabolic costs efficiently by feeding on phytoplankton only, even at high phytoplankton concentrations.
Tournament Incentives and Acquisition Performance
Authors: Hasan Iftekhar , Navone Marco , To Thomas Y , Wu Eliza 
Published: February 2020

Abstract
This paper examines the impact of promotion-based tournament incentives on corporate acquisition performance. Measuring tournament incentives as the compensation ratio between the CEO and other senior executives, we show that acquirers with greater tournament incentives experience lower announcement returns. Further analysis shows that the negative effect is driven by the risk-seeking behavior of senior executives induced by tournament incentives. Our results are robust to alternative identification strategies. Our evidence highlights that senior executives, in addition to the CEO, play an influential role in acquisition decisions. (JEL G30, G34, G41, J31, J33, J62)
Received: November 5, 2018; editorial decision January 6, 2020 by Editor Isil Erel.
Exogenous melatonin alleviates cadmium uptake and toxicity in apple rootstocks
Authors: He Jiali , Zhuang Xiaolei , Zhou Jiangtao , Sun Luyang , Wan Huixue , Li Huifeng , Lyu Deguo 
Published: February 2020

Abstract
To examine the potential roles of melatonin in cadmium (Cd) uptake, accumulation and detoxification in Malus plants, we exposed two different apple rootstocks varying greatly in Cd uptake and accumulation to either 0 or 30 μM Cd together with 0 or 100 μM melatonin. Cadmium stress stimulated endogenous melatonin production to a greater extent in the Cd-tolerant Malus baccata Borkh. than in the Cd-susceptible Malus micromalus ‘qingzhoulinqin’. Melatonin application attenuated Cd-induced reductions in growth, photosynthesis and enzyme activity, as well as reactive oxygen species (ROS) and malondialdehyde accumulation. Melatonin treatment more effectively restored photosynthesis, photosynthetic pigments and biomass in Cd-challenged M. micromalus ‘qingzhoulinqin’ than in Cd-stressed M. baccata. Exogenous melatonin lowered root Cd2+ uptake, reduced leaf Cd accumulation, decreased Cd translocation factors and increased root, stem and leaf melatonin contents in both Cd-exposed rootstocks. Melatonin application increased both antioxidant concentrations and enzyme activities to scavenge Cd-induced ROS. Exogenous melatonin treatment altered the mRNA levels of several genes regulating Cd uptake, transport and detoxification including HA7, NRAMP1, NRAMP3, HMA4, PCR2, NAS1, MT2, ABCC1 and MHX. Taken together, these results suggest that exogenous melatonin reduced aerial parts Cd accumulation and mitigated Cd toxicity in Malus plants, probably due to the melatonin-mediated Cd allocation in tissues, and induction of antioxidant defense system and transcriptionally regulated key genes involved in detoxification.
Severity of Traumatic Brain Injury in Older Adults and Risk of Ischemic Stroke and Depression
Authors: Vadlamani Aparna , Albrecht Jennifer S. 
Published: February 2020

Objective:
Risk of ischemic stroke and depression is elevated among older adults following traumatic brain injury (TBI), yet little is known about how the severity of TBI influences risk. Thus, our objective was to assess the association between severity of the index TBI and risk of ischemic stroke and depression in a sample of older adults treated for TBI.

Design:
Retrospective cohort study.

Setting:
R Adams Cowley Shock Trauma Center.

Participants:
Adults 65 years and older treated for TBI between 2006 and 2010 who survived to hospital discharge and could be linked to their Medicare administrative claims data with continuous enrollment for at least 6 months pre-TBI and 12 months post-TBI.

Main Measures:
First dates of ischemic stroke and depression available in Medicare claims were used to exclude individuals with a history. Next, we separately assessed the association between TBI severity and time to first stroke and depression using Cox proportional hazards models.

Results:
Among 132 patients without preexisting history of stroke, high TBI severity was associated with increased risk of stroke compared with low TBI severity (adjusted hazard ratio 6.68, 95% confidence interval 2.49-17.94). Among 163 patients without preexisting history of depression, high TBI severity was not significantly associated with increased risk of depression compared with low TBI severity (adjusted hazard ratio 1.90, 95% confidence interval 0.94-3.84).

Conclusion:
In this group of older adults with TBI, higher TBI severity was associated with increased risk of ischemic stroke, but not depression. These results suggest that increased monitoring of older adults with moderate-severe TBI for stroke may be warranted.
Sleep Disturbances Following Traumatic Brain Injury in Older Adults: A Comparison Study
Authors: Wei Li , Wen Ya-Ting , Thompson Hilaire J. , Liu Cyong-Yi , Su Yu-Kai , Chen Pin-Yuan , Chen Ching-Yi , Chuang Yeu-Hui , Lin Ya-Jui , Chen Chun-Ting , Chen Ching-Chang , Chiu Hsiao-Ting , Chiu Hsiao-Yean 
Published: February 2020

Objectives:
To compare the prevalence of sleep disturbances in older adults with traumatic brain injury (TBI) with that of age- and gender-matched controls and to determine the risk factors for post-TBI sleep disturbances and the effects of post-TBI disturbances on quality of life (QOL).

Design:
Cross-sectional case-comparison study.

Participants:
Eighty older adults (aged ≥65 years) with first-time TBI more than 3 months since injury and 80 older adults controls without TBI who completed sleep and health-related QOL questionnaires.

Results:
Older adults with TBI showed a higher prevalence of obstructive sleep apnea (OSA), insomnia, and daytime sleepiness than older adult controls. Being male, having higher levels of depression and pain, and the presence of insomnia were significantly correlated with the risks of OSA, insomnia, and daytime sleepiness following TBI, respectively. Both OSA and insomnia were significantly correlated with low QOL in older adults with TBI.

Conclusions:
Sleep disturbances are highly prevalent in older adults with TBI. Gender differences, depression severity, and pain level are correlated with the occurrence of post-TBI sleep disturbances. Both OSA and insomnia are regarded as major contributors to low QOL in older people with TBI. Interventions targeted at post-TBI sleep disturbances may improve QOL of older adults.
Evidence-Based Care of Children With Tracheostomies: Hospitalization to Home Care
Authors: Lawrence Patricia R. , Chambers Rebecca , Faulkner Melissa Spezia , Spratling Regena 
Published: February 2020

Abstract
Routine tracheostomy care in children maintains airway patency, minimizes infection, and ensures skin integrity around the tracheostomy stoma to prevent complications. Using evidence-based recommendations for care of the mature tracheostomy limits variation in practice and leads to better patient outcomes in all care settings. Incorporating evidence-based care into practice is especially important because children with tracheostomies are at high risk for morbidity and mortality. The purpose of this review is to summarize the most current, evidence-based literature for pediatric tracheostomy care, including stoma care and tracheostomy suctioning. Rehabilitation nurses can then include these best practices when caring for children with tracheostomies and when educating caregivers who provide tracheostomy care to children at home.
The Association Between ABO Blood Type and Mortality Among Severely Injured Trauma Patients
Authors: Griffin Russell L. , Jansen Jan O. , Bosarge Patrick L. , Marques Marisa B. , Kerby Jeffrey D. 
Published: February 2020

ABSTRACT

Background:
Prior research has reported an association among trauma patients between blood type O and adverse events. More recently, another study reported that severely injured trauma patients of mostly O Rh positive blood type were more likely to die.

Objective:
The objective of the current study is to examine whether the same increased association is observed for blood type O severely injured patients in a more generalizable population comprised of Rh positive and Rh negative individuals.

Methods:
Patients admitted to a Level-I academic trauma center between 2015 and 2018 with severe injury (Injury Severity Score >15) were included in this retrospective cohort study. Logistic regression estimated odds ratios (ORs) and 95% confidence intervals (CIs) for the association between blood type and mortality.

Results:
Among 3,913 patients, a majority were either blood type O (47.5%) or A (34.7%) and 60% were Rh positive. There was no observed difference in complication rates by blood type, and there was no observed significant association with death overall or by cause of death. There were weak, increased associations for blood type B (OR 1.61, 95% CI 0.74–3.53) and type O (OR 1.57, 95% CI 0.90–2.76) compared with blood type A patients.

Conclusion:
Contrary to prior research, the current results suggest no association between blood type and mortality among severely injured trauma patients.
A simple magnetic nanoparticles-based viral RNA extraction method for efficient detection of SARS-CoV-2
Authors: Zhao Zhen , Cui Haodong , Song Wenxing , Ru Xiaoling , Zhou Wenhua , Yu Xuefeng 
Published: February 2020

1AbstractThe ongoing outbreak of the novel coronavirus disease 2019 (COVID-19) originating from Wuhan, China, draws worldwide concerns due to its long incubation period and strong infectivity. Although RT-PCR-based molecular diagnosis techniques are being widely applied for clinical diagnosis currently, timely and accurate diagnosis are still limited due to labour intensive and time-consuming operations of these techniques. To address the issue, herein we report the synthesis of poly (amino ester) with carboxyl groups (PC)-coated magnetic nanoparticles (pcMNPs), and the development of pcMNPs-based viral RNA extraction method for the sensitive detection of COVID-19 causing virus, the SARS-CoV-2. This method combines the lysis and binding steps into one step, and the pcMNPs-RNA complexes can be directly introduced into subsequent RT-PCR reactions. The simplified process can purify viral RNA from multiple samples within 20 min using a simple manual method or an automated high-throughput approach. By identifying two different regions (ORFlabandNgene) of viral RNA, a 10-copy sensitivity and a strong linear correlation between 10 and 105copies of SARS-CoV-2 pseudovirus particles are achieved. Benefitting from the simplicity and excellent performances, this new extraction method can dramatically reduce the turn-around time and operational requirements in current molecular diagnosis of COVID-19, in particular for the early clinical diagnosis.
Temporal dynamics of visual representations in the infant brain
Authors: Bayet Laurie , Zinszer Benjamin D. , Reilly Emily , Cataldo Julia K. , Pruitt Zoe , Cichy Radoslaw M. , Nelson Charles A. , Aslin Richard N. 
Published: February 2020

AbstractTools from computational neuroscience have facilitated the investigation of the neural correlates of mental representations. However, access to the representational content of neural activations early in life has remained limited. We asked whether patterns of neural activity elicited by complex visual stimuli (animals, human body) could be decoded from EEG data gathered from 12-15-month-old infants and adult controls. We assessed pairwise classification accuracy at each time-point after stimulus onset, for individual infants and adults. Classification accuracies rose above chance in both groups, within 500 ms. In contrast to adults, neural representations in infants were not linearly separable across visual domains. Representations were similar within, but not across, age groups. These findings suggest a developmental reorganization of visual representations between the second year of life and adulthood and provide a promising proof-of-concept for the feasibility of decoding EEG data within-subject to assess how the infant brain dynamically represents visual objects.
A plasmid locus associated withKlebsiellaclinical infections encodes a microbiome-dependent gut fitness factor
Authors: Vornhagen Jay , Bassis Christine M. , Ramakrishnan Srividya , Hein Robert , Mason Sophia , Bergman Yehudit , Sunshine Nicole , Fan Yunfan , Timp Winston , Schatz Michael C. , Young Vincent B. , Simner Patricia J. , Bachman Michael A. 
Published: February 2020

Introductory paragraphGut colonization by the pathogenKlebsiella pneumoniae(Kp) is consistently associated with subsequent Kp disease1-5, and patients are predominantly infected with their colonizing strain1,2. However, colonizing strains likely vary in their potential to cause infection. We previously identified the plasmid-encoded tellurium resistance (ter) operon as highly associated with infection when compared to asymptomatic colonization in hospitalized patients1. Theteroperon bestows resistance to the toxic compound tellurite oxide (TeO3−2), but this is unlikely to be its physiological function, as tellurium and TeO3−2are exceedingly rare. Here we show thatterCis necessary andterZABCDEFis sufficient for phenotypic TeO3−2resistance. Next, we demonstrate thatteris encoded on a diverse group of plasmids without known plasmid-encoded virulence genes, suggesting an independent role in infection. Finally, our studies indicate thatteris a gut fitness factor, and its fitness advantage is conferred only when specific gut microbiota constituents are present. Collectively, these data reveal the Kpteroperon that is highly associated with human infection likely acts early in pathogenesis as a horizontally-transferrable fitness factor promoting robust gut colonization in the presence of the indigenous microbiota.
Structure of Mprofrom COVID-19 virus and discovery of its inhibitors
Authors: Jin Zhenming , Du Xiaoyu , Xu Yechun , Deng Yongqiang , Liu Meiqin , Zhao Yao , Zhang Bing , Li Xiaofeng , Zhang Leike , Peng Chao , Duan Yinkai , Yu Jing , Wang Lin , Yang Kailin , Liu Fengjiang , Jiang Rendi , Yang Xinglou , You Tian , Liu Xiaoce , Yang Xiuna , Bai Fang , Liu Hong , Liu Xiang , Guddat Luke W. , Xu Wenqing , Xiao Gengfu , Qin Chengfeng , Shi Zhengli , Jiang Hualiang , Rao Zihe , Yang Haitao 
Published: February 2020

SUMMARYA new coronavirus (CoV) identified as COVID-19 virus is the etiological agent responsible for the 2019-2020 viral pneumonia outbreak that commenced in Wuhan1–4. Currently there is no targeted therapeutics and effective treatment options remain very limited. In order to rapidly discover lead compounds for clinical use, we initiated a program of combined structure-assisted drug design, virtual drug screening and high-throughput screening to identify new drug leads that target the COVID-19 virus main protease (Mpro). Mprois a key CoV enzyme, which plays a pivotal role in mediating viral replication and transcription, making it an attractive drug target for this virus5,6. Here, we identified a mechanism-based inhibitor, N3, by computer-aided drug design and subsequently determined the crystal structure of COVID-19 virus Mproin complex with this compound. Next, through a combination of structure-based virtual and high-throughput screening, we assayed over 10,000 compounds including approved drugs, drug candidates in clinical trials, and other pharmacologically active compounds as inhibitors of Mpro. Six of these inhibit Mprowith IC50values ranging from 0.67 to 21.4 μM. Ebselen also exhibited promising antiviral activity in cell-based assays. Our results demonstrate the efficacy of this screening strategy, which can lead to the rapid discovery of drug leads with clinical potential in response to new infectious diseases where no specific drugs or vaccines are available.