bluuebunny/crossref_metadata_2025_split huggingface dataset:
Frontline Science: Conversion of neutrophils into atypical Ly6G+SiglecF+ immune cells with neurosupportive potential in olfactory neuroepithelium
Authors: Ogawa Kei , Asano Kenichi , Yotsumoto Satoshi , Yamane Tsuyoshi , Arita Makoto , Hayashi Yoshihiro , Harada Hironori , Makino-Okamura Chieko , Fukuyama Hidehiro , Kondo Kenji , Yamasoba Tatsuya , Tanaka Masato 
Published: July 2020

Abstract
Neutrophils are generally considered as short-lived, homogenous, and terminally differentiated phagocytes that play crucial roles in conquering infection, although they occasionally cause severe collateral tissue damage or chronic inflammation. Recent reports have indicated that neutrophils also play a protective role in inflammation resolution and tissue repair. However, how terminally differentiated neutrophils have diverse functions remains unclear. Here, we show that neutrophils undergo conversion into Ly6G+SiglecF+ double-positive cells expressing neurosupportive genes in the olfactory neuroepithelium (OE) under an inflammatory state. Through comprehensive flow cytometric analysis of murine nose, we identified Ly6G+SiglecF+ double-positive cells that reside only in the OE under steady-state conditions. Double-positive cells were neutrophil-derived cells and increased by more than 10-fold during inflammation or tissue injury. We found that neutrophils infiltrate into the nose to express proinflammatory genes in the acute phase of inflammatory state, and they gradually change their surface markers and gene expression, expressing some neurogenesis-related genes in addition to inflammation related genes in the later phase. As the OE is known to have exceptionally high regeneration capacity as a nervous system, these findings suggest that neutrophils have the potential to contribute neurogenesis after conversion in peripheral nervous tissues, providing a challenge on a classic view of neutrophils as terminally differentiated leukocytes.
Multifunctional T cell response in convalescent patients two years after ZIKV infection
Authors: Pereira Neto Tertuliano Alves , Gonçalves-Pereira Marcela Helena , de Queiroz Camila Pereira , Ramos Michele Faria , de Oliveira Fernanda de Fátima Souza , Oliveira-Prado Roberta , do Nascimento Valdinete Alves , Abdalla Ligia Fernandes , Santos João Hugo Abdalla , Martins-Filho Olindo Assis , Naveca Felipe Gomes , Teixeira-Carvalho Andrea , Santiago Helton da Costa 
Published: July 2020

Abstract
Zika is an important emerging infectious disease in which the role of T cells remains elusive. This study aimed to evaluate the phenotype of multifunctional T cells in individuals 2 yr after exposure to Zika virus (ZIKV). We used a library of 671 synthetic peptides covering the whole polyprotein of ZIKV in pools corresponding to each viral protein (i.e., capsid, membrane precursor or prM, envelope, NS1 [nonstructural protein], NS2A + NS2B, NS3, NS4A + NS4B, and NS5) to stimulate PBMCs from individuals previously exposed to ZIKV. We observed an increased frequency of ZIKV-specific IFNγ, IL-17A, TNF, and IL-10 production by T cell populations. IFNγ and TNF production were especially stimulated by prM, capsid, or NS1 in CD8+ T cells and by capsid or prM in CD4+ T cells. In addition, there was an increase in the frequency of IL-10+ CD8+ T cells after stimulation with prM, capsid, NS1, NS3, or NS5. Multifunctional properties were observed in ZIKV-specific T cells responding especially to prM, capsid, NS1 or, to a smaller extent, NS3 antigens. For example, we found a consistent IFNγ + TNF+ CD8+ T cell population in response to most virus antigens and CD4+ and CD8+ T cells that were IFNγ + IL-17A+ and IL-17A+IL-10+, which could also produce TNF, in response to capsid, prM, NS1, or NS3 stimulation. Interestingly, CD8+ T cells were more prone to a multifunctional phenotype than CD4+ T cells, and multifunctional T cells were more efficient at producing cytokines than single-function cells. This work provides relevant insights into the quality of ZIKV-specific T cell responses and ZIKV immunity.
16‐O‐Methylated diterpenes in green Coffea arabica: ultra‐high‐performance liquid chromatography‐tandem mass spectrometry method optimization and validation
Authors: Guercia Elena , Colomban Silvia , Navarini Luciano 
Published: July 2020

AbstractCoffee diterpenes are the main constituents of the coffee oil unsaponifiable fraction. The three most important diterpenes are cafestol, kahweol, and 16‐O‐methylcafestol (16‐OMC), and they are produced, except for cafestol, only by plants of the Coffea genus. Recently, in addition to these three major diterpenes, another 16‐O‐methylated diterpene (16‐O‐methylkahweol: 16‐OMK) has been identified and quantified, for the first time, in Robusta coffee. For many years, 16‐OMC has been considered present exclusively in Robusta, and so it has been reputed an excellent authenticity marker for the presence of Robusta in coffee products. For its quantification, nuclear magnetic resonance (NMR) has proved very useful when compared with other methods. Quite recently, the detection of very low levels of the two 16‐O‐methylated diterpenes (16‐OMD) 16‐OMC and 16‐OMK in roasted Arabica was reported. This finding makes the use of NMR methods in 16‐OMD quantification in Arabica coffee particularly challenging in view of both the trace amounts of 16‐OMD and the impossibility to discriminate between 16‐OMC and 16‐OMK. The ultra‐high performance liquid chromatography mass spectrometry (UHPLC‐MS) method, already used to detect 16‐OMC and 16‐OMK in Arabica roasted coffee, is then more suitable for quantitative analyses. Up to now however, no quantification of coffee 16‐OMD via ultra‐high performance liquid chromatography tandem mass spectrometry (UHPLC‐MS/MS) has been carried out; this largely stimulated the present study. For the first time, a simple procedure for the quantitative detection of 16‐OMD in Arabica coffee has been developed, and as far as 16‐OMC is concerned, fully validated in terms of specificity, linearity, concentration range, limit of detection (LOD), limit of quantification (LOQ), and repeatability following the criteria specified in the EU Commission Decision 2002/675/EC. This method proved to be very specific and sensitive. In order to avoid the chemical complexity generated by the roasting process, the method was optimized and validated on several green Arabica samples from different geographical origins.
First molecular epidemiological study of hepatitis B and D in individuals infected with human T‐lymphotropic virus 1/2 from Argentina
Authors: Pataccini Gabriela , Berini Carolina Andrea , Pedrozo Williams René , Biglione Mirna Marcela , Delfino Cecilia María 
Published: July 2020

AbstractHuman T‐lymphotropic virus 1/2 (HTLV‐1/2), hepatitis B virus (HBV), and hepatitis D virus (HDV) share transmission routes. Argentina shows low prevalence of HTLV‐1/2, HBV, and HDV infections; however, this situation may vary according to the geographic region and group studied. The aim of this study was to estimate the prevalence of HBV and HDV infections and detect both viral genotypes in HTLV‐1/2 individuals from Argentina. A total of 202 HTLV‐1/2 confirmed samples (blood donors [BD] and individuals with risk factors for HTLV‐1/2 [RF]) were tested for HBsAg and total anti‐HBc by enzyme‐linked immunosorbent assay. All reactive samples for some HBV markers were analyzed for HBV DNA characterization and HDV serological and molecular analysis. Total prevalence was 1.5% for HBsAg and 6.4% for anti‐HBc. Prevalence was 23.1% for anti‐HDV in all HBV‐reactive samples. No significant difference was observed for HBV and HDV prevalence within HTLV subtypes. The population study showed that prevalence of anti‐HBc was higher in the RF than in the BD population, with no significant differences between them. The HBsAg marker and anti‐HDV were only found in RF, showing significant differences when compared to BD. Regarding molecular detection, one sample amplified for HBV DNA and none for HDV RNA. HBV sequence was classified as subgenotype F1b. New and updated background on serological markers of HBV and HDV infection in patients with HTLV‐1/2 was provided.
Plasma endothelial microvesicles and their carrying miRNA‐155 serve as biomarkers for ischemic stroke
Authors: Zhang Huiting , Chen Guanghua , Qiu Wenji , Pan Qunwen , Chen Yanfang , Chen Yusen , Ma Xiaotang 
Published: July 2020

AbstractEndothelial microvesicles (EMVs) could reflect the status of endothelial cells (ECs) which are involved in the pathogenesis of ischemic stroke (IS). MiR‐155 could regulate EC functions. However, their roles in IS remain unclear. This study aimed to investigate the levels of plasma EMVs and EMVs carrying miRNA‐155 (EMVs‐miR‐155) in IS patients to explore their potential roles as biomarkers. Ninety‐three IS patients and 70 controls were recruited in this study. The levels of circulating EMVs and EMVs‐miR‐155 were detected by fluorescence nanoparticle tracking analysis and quantitative real‐time PCR, respectively. The correlations between level of EMVs/EMVs‐miR‐155 and the onset time, severity, infarct volume, and subtypes of IS were analyzed. The severity and infarct volume were assessed by NIHSS and magnetic resonance imaging, respectively. Multivariate logistic regression analysis was used to investigate the risk factors of IS. The ROC curve and area under ROC curve (AUC) of EMVs and EMVs‐miR‐155 were determined. The levels of plasma EMVs and EMVs‐miR‐155 were increased significantly in acute and subacute stages of IS and remained unchanged in chronic stage, and were positively related to the infarct volume and NIHSS scores and were associated with large artery atherosclerosis and cardioembolism subtypes defined by Trial of Org 10 172 in acute stroke treatment (TOAST) classification. Multivariate logistic regression analysis demonstrated that plasma EMVs and EMVs‐miR‐155 were significant and independent risk factors of IS and their AUC were 0.778 and 0.851, respectively, and increased to 0.892 after combination. Our study suggests that plasma EMVs and EMVs‐miR‐155 are promising biomarkers for IS. The diagnostic value of EMVs‐miR‐155 is higher and their combination is the best.
Injury Mechanism of Button Batteries in the Nasal Cavity and Possible Mitigation Strategies During Impaction
Authors: Sancaktar Mehmet Eser , Bayraktar Cem , Bakırtaş Mustafa 
Published: July 2020

Objective/HypothesisButton batteries (BBs) impacted in the nasal cavity can cause several complications. Understanding the injury mechanism and developing possible mitigation strategies can reduce these complications.Study designCadaveric sheep nasal septum model.MethodsLithium, alkaline, silver oxide, and zinc‐air BBs were placed on segments of the nasal septum of cadaveric sheep. The BB voltage, tissue temperatures, and pH were measured every 30 minutes for 6 hours. Subsequently, 5 drops of lemon juice, apple cider vinegar, tea, Coke (Coca‐Cola Co., Atlanta, GA), tap water, and normal saline were applied separately to the other segments with the lithium BBs every 10 minutes for 3 hours. The visible injuries and the necrosis depths were assessed through the tissue temperatures, pH, and the voltage changes.ResultsBoth nonlithium and lithium BBs increased tissue pH without significant temperature changes. The 3V lithium BBs led to the greatest depth of necrosis, with a voltage loss of approximately 50% within the first 2 hours. Lemon juice and apple cider vinegar were the most effective liquids for reducing visible injury, pH, and necrosis without increasing the temperature during pre‐removal time period.ConclusionNonlithium and lithium BBs caused alkaline tissue injury in a nasal septal model. Given the hazard severity, expedited BB removal is critical. For situations when removal cannot be immediately performed, further in vivo study is needed prior to considering human use of any pre‐removal mitigation strategies in the nasal cavity.Level of EvidenceNA Laryngoscope, 130:2487–2493, 2020
Center Variation in Intention‐to‐Treat Survival Among Patients Listed for Liver Transplant
Authors: Kwong Allison J. , Flores Avegail , Saracino Giovanna , Boutté Jodi , McKenna Greg , Testa Giuliano , Bahirwani Ranjeeta , Wall Anji , Kim W. Ray , Klintmalm Göran , Trotter James F. , Asrani Sumeet K. 
Published: July 2020

In the United States, centers performing liver transplant (LT) are primarily evaluated by patient survival within 1 year after LT, but tight clustering of outcomes allows only a narrow window for evaluation of center variation for quality improvement. Alternate measures more relevant to patients and the transplant community are needed. We examined adults listed for LT in the United States, using data submitted to the Scientific Registry of Transplant Recipients. Intention‐to‐treat (ITT) survival was defined as survival within 1 year from listing, regardless of transplant. Mixed effects/frailty models were used to assess center variation in ITT survival. Between January 2010 and December 2016, there were 66,428 new listings at 113 centers. Overall, median 1‐year ITT survival was 79.8% (interquartile range [IQR], 76.1%‐83.4%), whereas 1‐year waiting‐list (WL) survival was 75.8% (IQR, 71.2%‐79.4%), and 1‐year post‐LT survival was 90.0% (IQR, 87.9%‐91.8%). Higher rates of ITT mortality were correlated with increased WL mortality (correlation, r = 0.76), increased post‐LT mortality (r = 0.31), lower volume centers (r = −0.34), and lower transplant rate ratio (r = −0.25). Similar patterns were observed in the subgroup of WL candidates listed with Model for End‐Stage Liver Disease (MELD) ≥25: median 1‐year ITT survival was 65.2% (IQR, 60.2%‐72.6%), whereas 1‐year post‐LT survival was 87.5% (IQR, 84.0%‐90.9%), and 1‐year WL survival was 36.6% (IQR, 27.9%‐47.0%). In mixed effects modeling, the transplant center was an independent predictor of ITT survival even after adjustment for age, sex, MELD, and sociodemographic variables. Center variation for ITT survival was larger compared with post‐LT survival. The measurement of ITT outcome offers a complementary method to assess center performance. This is a first step toward understanding differences in program quality beyond patient and graft survival after LT.
Error detection and classification in patient‐specific IMRT QA with dual neural networks
Authors: Potter Nicholas J. , Mund Karl , Andreozzi Jacqueline M. , Li Jonathan G. , Liu Chihray , Yan Guanghua 
Published: July 2020

PurposeDespite being the standard metric in patient‐specific quality assurance (QA) for intensity‐modulated radiotherapy (IMRT), gamma analysis has two shortcomings: (a) it lacks sensitivity to small but clinically relevant errors (b) it does not provide efficient means to classify the error sources. The purpose of this work is to propose a dual neural network method to achieve simultaneous error detection and classification in patient‐specific IMRT QA.MethodsFor a pair of dose distributions, we extracted the dose difference histogram (DDH) for the low dose gradient region and two signed distance‐to‐agreement (sDTA) maps (one in x direction and one in y direction) for the high dose gradient region. An artificial neural network (ANN) and a convolutional neural network (CNN) were designed to analyze the DDH and the two sDTA maps, respectively. The ANN was trained to detect and classify six classes of dosimetric errors: incorrect multileaf collimator (MLC) transmission (±1%) and four types of monitor unit (MU) scaling errors (±1% and ±2%). The CNN was trained to detect and classify seven classes of spatial errors: incorrect effective source size, 1 mm MLC leaf bank overtravel or undertravel, 2 mm single MLC leaf overtravel or undertravel, and device misalignment errors (1 mm in x‐ or y direction). An in‐house planar dose calculation software was used to simulate measurements with errors and noise introduced. Both networks were trained and validated with 13 IMRT plans (totaling 88 fields). A fivefold cross‐validation technique was used to evaluate their accuracy.ResultsDistinct features were found in the DDH and the sDTA maps. The ANN perfectly identified all four types of MU scaling errors and the specific accuracies for the classes of no error, MLC transmission increase, MLC transmission decrease were 98.9%, 96.6%, and 94.3%, respectively. For the CNN, the largest confusion occurred between the 1‐mm‐MLC bank overtravel class and the 1‐mm‐device alignment error in x‐direction class, which brought the specific accuracies down to 90.9% and 92.0%, respectively. The specific accuracy for the 2‐mm‐single MLC leaf undertravel class was 93.2% as it misclassified 5.7% of the class as being error free (false negative). Otherwise, the specific accuracy was above 95%. The overall accuracies across the fivefold were 98.3 ± 0.7% and 95.6% ± 1.5% for the ANN and the CNN, respectively.ConclusionsBoth the DDH and the sDTA maps are suitable features for error classification in IMRT QA. The proposed dual neural network method achieved simultaneous error detection and classification with excellent accuracy. It could be used in complement with the gamma analysis to potentially shift the IMRT QA paradigm from passive pass/fail analysis to active error detection and root cause identification.
Synthetic generation of DSC‐MRI‐derived relative CBV maps from DCE MRI of brain tumors
Authors: Sanders Jeremiah W. , Chen Henry Szu‐Meng , Johnson Jason M. , Schomer Donald F. , Jimenez Jorge E. , Ma Jingfei , Liu Ho‐Ling 
Published: July 2020

PurposePerfusion MRI with gadolinium‐based contrast agents is useful for diagnosis and treatment response evaluation of brain tumors. Dynamic susceptibility contrast (DSC) MRI and dynamic contrast enhanced (DCE) MRI are two gadolinium‐based contrast agent perfusion imaging techniques that provide complementary information about the tumor vasculature. However, each requires a separate administration of a gadolinium‐based contrast agent. The purpose of this retrospective study was to determine the feasibility of synthesizing relative cerebral blood volume (rCBV) maps, as computed from DSC MRI, from DCE MRI of brain tumors.MethodsOne hundred nine brain‐tumor patients underwent both DCE and DSC MRI. Relative CBV maps were computed from the DSC MRI, and blood plasma volume fraction maps were computed from the DCE MRIs. Conditional generative adversarial networks were developed to synthesize rCBV maps from the DCE MRIs. Tumor–to–white matter ratios were calculated from real rCBV, synthetic rCBV, and plasma volume fraction maps and compared using correlation analysis. Real and synthetic rCBV in white and gray matter regions were also compared.ResultsPearson correlation analysis showed that both the tumor rCBV and tumor–to–white matter ratios in the synthetic and real rCBV maps were strongly correlated (ρ = 0.87, P < .05 and ρ = 0.86, P < .05, respectively). Tumor plasma volume fraction and real rCBV were not strongly correlated (ρ = 0.47). Bland‐Altman analysis showed a mean difference between the synthetic and real rCBV tumor–to–white matter ratios of 0.20 with a 95% confidence interval of ±0.47.ConclusionRealistic rCBV maps can be synthesized from DCE MRI and contain quantitative information, enabling robust brain‐tumor perfusion imaging of DSC and DCE parameters with a single gadolinium‐based contrast agent administration.
A crisis in US drug pricing: Consequences for patients with neuromuscular diseases, physicians, and society, part 2
Authors: Burns Ted M. , Crowell Jason L. , Smith A. Gordon 
Published: July 2020

AbstractEscalating drug costs place patients at risk for financial toxicity and demand that physicians understand and act on the ethical and economic principles related to drug pricing. This manuscript reviews these principles and provides clinicians with a framework to think about the value of the drugs prescribed for patients with neuromuscular diseases. A key component of addressing the drug pricing crisis will be establishing a value based (benefit/cost) drug pricing framework. Determining the value of a drug is difficult and requires estimating the benefit and costs to patients and society while integrating indirect and contextual variables. Other considerations in drug pricing include “externality,” the value to society derived from innovation. The Institute for Clinical and Economic Review (ICER) is a leading independent research organization providing clinicians with value‐based price “benchmarks.” All physicians must educate themselves in drug pricing principles and be prepared to have conversations regarding individual and societal value with the patients they serve.
Weak aging properties for coherent systems with statistically dependent component lifetimes
Authors: Li Chen , Li Xiaohu 
Published: July 2020

AbstractAs a relevant topic in reliability theory, the preservation of aging properties under the formation of various coherent structures contributes to improving system performance through better structure design and more effective system maintenance. The classical research in this line usually focuses upon coherent systems with independent component lifetimes. Recently, some authors discussed the preservation of IFR, NBU, and DMRL in the setting of dependent component lifetimes. This paper further investigates sufficient conditions for coherent systems with dependent component lifetimes to preserve aging properties including NBUC, NBU (2), DMRL, and their dual versions. Some examples are presented to illustrate coherent structures and typical copula functions fulfilling the present sufficient conditions as well.
Phospholipase D1 inhibition sensitizes glioblastoma to temozolomide and suppresses its tumorigenicity
Authors: Kang Dong Woo , Hwang Won Chan , Noh Yu Na , Park Kang Seo , Min Do Sik 
Published: July 2020

AbstractResistance of glioblastoma to the chemotherapeutic compound temozolomide is associated with the presence of glioblastoma stem cells in glioblastoma and is a key obstacle for the poor prognosis of glioblastoma. Here, we show that phospholipase D1 is elevated in CD44High glioblastoma stem cells and in glioblastoma, especially recurring glioblastoma. Phospholipase D1 elevation positively correlated with the level of CD44 and poor prognosis in glioblastoma patients. Temozolomide significantly upregulated the expression of phospholipase D1 in the low and moderate CD44 populations of glioblastoma stem cells, but not in the CD44High population in which phospholipase D1 is highly expressed. Phospholipase D1 conferred resistance to temozolomide in CD44High glioblastoma stem cells and increased their self‐renewal capacity and maintenance. Phospholipase D1 expression significantly correlated with levels of temozolomide resistance factors, which were suppressed by microRNA‐320a and ‐4496 induced by phospholipase D1 inhibition. Genetic and pharmacological targeting of phospholipase D1 attenuated glioblastoma stem cell‐derived intracranial tumors of glioblastoma using the microRNAs, and improved survival. Treatment solely with temozolomide produced no benefits on the glioblastoma, whereas in combination, phospholipase D1 inhibition sensitized glioblastoma stem cells to temozolomide and reduced glioblastoma tumorigenesis. Together, these findings indicate that phospholipase D1 inhibition might overcome resistance to temozolomide and represents a potential treatment strategy for glioblastoma. © 2020 The Authors. The Journal of Pathology published by John Wiley & Sons, Ltd. on behalf of The Pathological Society of Great Britain and Ireland.