bluuebunny/crossref_metadata_2025_split huggingface dataset:
International travel to obtain medical treatment for primary retinoblastoma: A global cohort study
Authors: Bowman Richard J. C. , Foster Allen , Stacey Andrew , Keren‐Froim Naama , Bascaran Cova , Kivelä Tero T. , Munier Francis , Fabian Ido Didi 
Published: October 2020

AbstractEarly diagnosis and treatment of retinoblastoma (Rb), the most common intraocular malignancy, can save both the child's life and vision. However, access to services and hence chances for survival and preserving the eye and its vision vary widely across the globe. Some families have to, or make a choice to, leave their home country to seek planned medical treatment abroad. We aimed to investigate how frequently this cross‐border travel occurs and the factors associated with it. A total of 278 Rb centres in 153 countries were recruited to participate in a global cross‐sectional analysis of newly diagnosed Rb patients in 2017. Number and proportions of children who travelled from their home country for treatment were analysed by country, continent, socioeconomic stratum and clinical and demographic features. The cohort included 4351 new patients of whom 223 [5.1%, 95% confidence interval 4.5‐5.8] were taken across country borders for planned medical treatment. Independently significant predictors of travelling across borders included: being from a country with a smaller population, being from a country classified as low socioeconomic status, having bilateral Rb and having intraocular disease without extraocular spread. The factors that determine international travel for Rb treatment are complex and deserve further investigation. We may need to rethink the way services are delivered in the light of the threat of severe curtailment of international travel from pandemics like corona virus disease 2019.
Effect of bioactive Biosilicate®/F18 glass scaffolds on osteogenic differentiation of human adipose stem cells
Authors: Marin Claudia P. , Santana Geovana L. , Robinson Meghan , Willerth Stephanie M. , Crovace Murilo C. , Zanotto Edgar D. 
Published: October 2020

AbstractThis study evaluated the gene expression profile of the human adipose‐derived stem cells (hASCs) grown on the Biosilicate®/F18 glass (BioS‐2P/F18) scaffolds. hASCs were cultured using the osteogenic medium (control), the scaffolds, and their ionic extract. We observed that ALP activity was higher in hASCs grown on the BioS‐2P/F18 scaffolds than in hASCs cultured with the ionic extract or the osteogenic medium on day 14. Moreover, the dissolution product group and the control exhibited deposited calcium, which peaked on day 21. Gene expression profiles of cell cultured using the BioS‐2P/F18 scaffolds and their extract were evaluated in vitro using the RT2 Profiler polymerase chain reaction (PCR) microarray on day 21. Mineralizing tissue‐associated proteins, differentiation factors, and extracellular matrix enzyme expressions were measured using quantitative PCR. The gene expression of different proteins involved in osteoblast differentiation was significantly up‐regulated in hASCs grown on the scaffolds, especially BMP1, BMP2, SPP1, BMPR1B, ITGA1, ITGA2, ITGB1, SMAD1, and SMAD2, showing that both the composition and topographic features of the biomaterial could stimulate osteogenesis. This study demonstrated that gene expression of hASCs grown on the scaffold surface showed significantly increased gene expression related to hASCs cultured with the ionic extract or the osteogenic medium, evidencing that the BioS‐2P/F18 scaffolds have a substantial effect on cellular behavior of hASCs.
Virulence factors impair epithelial junctions during bacterial infection
Authors: Zheng Manxi , Sun Shuang , Zhou Jun , Liu Min 
Published: October 2020

AbstractEpithelial cells are typically connected through different types of cell junctions that are localized from the apical membrane to the basal surface. In this way, epithelium cells form the first barrier against pathogenic microorganisms and prevent their entry into internal organs and the circulatory system. Recent studies demonstrate that bacterial pathogens disrupt epithelial cell junctions through targeting junctional proteins by secreted virulence factors. In this review, we discuss the diverse strategies used by common bacterial pathogens, includingPseudomonas aeruginosa,Helicobacter pylori, and enteropathogenicEscherichia coli, to disrupt epithelial cell junctions during infection. We also discuss the potential of targeting the pathogenic mechanisms in the treatment of pathogen‐associated diseases.
Cytokine profiles and clinical characteristics in primary Sjögren´s syndrome patient groups
Authors: López‐Villalobos Erika Fabiola , Muñoz‐Valle José Francisco , Palafox‐Sánchez Claudia Azucena , García‐Arellano Samuel , Martínez‐Fernández Diana Emilia , Orozco‐Barocio Gerardo , García‐Espinoza José Antonio , Oregon‐Romero Edith 
Published: October 2020

AbstractBackgroundPrimary Sjögren's syndrome (pSS) is an autoimmune disease characterized by a lymphocytic infiltrate in salivary glands driving to epithelial damage. The pSS patients present heterogenic clinical and serological characteristics. This heterogenicity could be due to the cytokine microenvironment. Cytokine levels have been analyzed and reported individually, showing controversial results; for that reason, we considered essential to evaluate a cluster of cytokines and relate them with antibody levels and clinical characteristics to find pSS subgroups.MethodsNinety‐nine pSS patients, diagnosed by the 2016 ACR/EULAR classification criteria, and 76 control subjects (CS) were included. Cytokine quantification was performed by Multiplex assay. Principal component analysis (PCA) was realized, and the K‐mean test was used to identify clusters/groups. Groups were analyzed by the Kruskal‐Wallis test and the Bonferroni test.ResultsHigher IFN‐γ, IL‐17F, IL‐21, IL‐23, IL‐4, and IL‐31 levels were observed in pSS patients in comparison with control subjects. PCA analysis showed three groups. The severe group was characterized by higher cytokine concentrations as well as an increase in clinical parameters such as antibody levels, damage index score, and others. The moderate group presented intermediate severity; meanwhile, the mild group presented the lowest severity.ConclusionCluster analysis revealed three groups that were different in cytokine levels and clinical parameters in which the mild group was defined by lower severity, the moderate group with intermediate severity, and the severe group with higher severity. This analysis could help subclassify the primary Sjögren syndrome patients for a better understanding of the clinical phenotype that impacts the treatment approach.
Peripheral leptin signaling persists in innate immune cells during diet-induced obesity
Authors: Souza-Almeida Glaucia , Palhinha Lohanna , Liechocki Sally , da Silva Pereira Jéssica Aparecida , Reis Patrícia Alves , Dib Paula Ribeiro Braga , Hottz Eugenio D , Gameiro Jacy , Vallochi Adriana Lima , de Almeida Cecília Jacques , Castro-Faria-Neto Hugo , Bozza Patrícia T , Maya-Monteiro Clarissa Menezes 
Published: October 2020

Abstract
Leptin is a pleiotropic adipokine that regulates immunometabolism centrally and peripherally. Obese individuals present increased levels of leptin in the blood and develop hypothalamic resistance to this adipokine. Here we investigated whether leptin effects on the periphery are maintained despite the hypothalamic resistance. We previously reported that leptin injection induces in vivo neutrophil migration and peritoneal macrophage activation in lean mice through TNF-α- and CXCL1-dependent mechanisms. However, leptin effects on leukocyte biology during obesity remain unclear. In this study, we investigated the in vivo responsiveness of leukocytes to i.p. injected leptin in mice with diet-induced obesity (DIO). After 14–16 wk, high-sucrose, high-fat diet (HFD)-fed mice showed hyperglycemia, hyperleptinemia, and dyslipidemia compared to normal-sucrose, normal-fat diet (ND). Exogenous leptin did not reduce food intake in DIO mice in contrast to control mice, indicating that DIO mice were centrally resistant to leptin. Regardless of the diet, we found increased levels of TNF-α and CXCL1 in the animals injected with leptin, alongside a pronounced neutrophil migration to the peritoneal cavity and enhanced biogenesis of lipid droplets in peritoneal macrophages. Supporting our in vivo results, data from ex vivo leptin stimulation experiments confirmed hypothalamic resistance in DIO mice, whereas bone marrow cells responded to leptin stimulation through mTOR signaling despite obesity. Altogether, our results show that leukocytes responded equally to leptin in ND- or HFD-fed mice. These results support a role for leptin in the innate immune response also in obesity, contributing to the inflammatory status that leads to the development of metabolic disease.
Frontline Science: Extracellular CIRP generates a proinflammatory Ly6G+CD11bhi subset of low-density neutrophils in sepsis
Authors: Takizawa Satoshi , Murao Atsushi , Ochani Mahendar , Aziz Monowar , Wang Ping 
Published: October 2020

AbstractExtracellular cold-inducible RNA-binding protein (eCIRP) is a damage-associated molecular pattern. Neutrophils present in the mononuclear cell fraction of Ficoll gradient separation are called low-density neutrophils (LDNs). Here we report the novel role of eCIRP on LDNs’ heterogeneity in sepsis. Sepsis was induced in male C57BL/6 wild-type (WT) and CIRP−/− mice by cecal ligation and puncture (CLP). At 20 h after CLP, LDNs in the blood were isolated by Ficoll gradient separation, followed by staining the cells with anti-Ly6G and anti-CD11b Abs and detection by flow cytometry. Sepsis or recombinant murine CIRP (rmCIRP) injection in mice resulted in significant increase in the frequency (%) and number of Ly6G+CD11bhi and Ly6G+CD11blo LDNs in the blood compared to sham- or vehicle-treated mice. At 20 h of CLP, CIRP−/− mice had significantly lower frequency and number of Ly6G+CD11bhi and Ly6G+CD11blo LDNs in the blood compared to WT mice. In sepsis mice or rmCIRP-injected mice, compared to Ly6G+CD11blo LDNs, the expression of CXCR4, ICAM-1, and iNOS and formation of reactive oxygen species, and neutrophil extracellular traps in Ly6G+CD11bhi LDNs in the blood were significantly increased. Treatment of WT bone marrow-derived neutrophils (BMDNs) with rmCIRP increased Ly6G+CD11bhi LDN frequency, whereas treatment of TLR4−/− BMDNs with rmCIRP significantly decreased the frequency of Ly6G+CD11bhi LDNs. BMDNs’ stimulation with rmCIRP increased the expression of transcription factors in LDNs. eCIRP induces the formation of a proinflammatory phenotype Ly6G+CD11bhi of LDNs through TLR4. Targeting eCIRP may provide beneficial outcomes in sepsis by decreasing proinflammatory Ly6G+CD11bhi LDNs.
Hypoxia-inducible factors not only regulate but also are myeloid-cell treatment targets
Authors: Kling Lovis , Schreiber Adrian , Eckardt Kai-Uwe , Kettritz Ralph 
Published: October 2020

AbstractHypoxia describes limited oxygen availability at the cellular level. Myeloid cells are exposed to hypoxia at various bodily sites and even contribute to hypoxia by consuming large amounts of oxygen during respiratory burst. Hypoxia-inducible factors (HIFs) are ubiquitously expressed heterodimeric transcription factors, composed of an oxygen-dependent α and a constitutive β subunit. The stability of HIF-1α and HIF-2α is regulated by oxygen-sensing prolyl-hydroxylases (PHD). HIF-1α and HIF-2α modify the innate immune response and are context dependent. We provide a historic perspective of HIF discovery, discuss the molecular components of the HIF pathway, and how HIF-dependent mechanisms modify myeloid cell functions. HIFs enable myeloid-cell adaptation to hypoxia by up-regulating anaerobic glycolysis. In addition to effects on metabolism, HIFs control chemotaxis, phagocytosis, degranulation, oxidative burst, and apoptosis. HIF-1α enables efficient infection defense by myeloid cells. HIF-2α delays inflammation resolution and decreases antitumor effects by promoting tumor-associated myeloid-cell hibernation. PHDs not only control HIF degradation, but also regulate the crosstalk between innate and adaptive immune cells thereby suppressing autoimmunity. HIF-modifying pharmacologic compounds are entering clinical practice. Current indications include renal anemia and certain cancers. Beneficial and adverse effects on myeloid cells should be considered and could possibly lead to drug repurposing for inflammatory disorders.
Single-cell transcriptomics uncover distinct innate and adaptive cell subsets during tissue homeostasis and regeneration
Authors: Yang Kevin Y , Ku Manching , Lui Kathy O 
Published: October 2020

Abstract
Recently, immune cell-mediated tissue repair and regeneration has been an emerging paradigm of regenerative medicine. Immune cells form an essential part of the wound as induction of inflammation is a necessary step to elicit tissue healing. Rapid progress in transcriptomic analyses by high-throughput next-generation sequencing has been developed to study gene regulatory network and establish molecular signatures of immune cells that could potentially predict their functional roles in tissue repair and regeneration. However, the identification of cellular heterogeneity especially on the rare cell subsets has been limited in transcriptomic analyses of bulk cell populations. Therefore, genome-wide, single-cell RNA sequencing (scRNA-Seq) has offered an unprecedented approach to unravel cellular diversity and to study novel immune cell populations involved in tissue repair and regeneration through unsupervised sampling of individual cells without the need to rely on prior knowledge about cell-specific markers. The analysis of gene expression patterns at a single-cell resolution also holds promises to uncover the mechanisms and therefore the development of therapeutic strategy promoting immunoregenerative medicine. In this review, we will discuss how scRNA-Seq facilitates the characterization of immune cells, including macrophages, innate lymphoid cells and T and B lymphocytes, discovery of immune cell heterogeneity, identification of novel subsets, and tracking of developmental trajectories of distinct immune cells during tissue homeostasis, repair, and regeneration.
Pivots and pirouettes: adapting a robust departmental CPD and training program to the COVID‐19 crisis
Authors: Besson Jacqueline , McNamara Clare , Brown Elizabeth 
Published: October 2020

AbstractThe onset of the COVID‐19 pandemic caused swift change in society, affecting both personal and professional lives. In radiation therapy (RT), professional and social interactions are highly important to maintaining team culture and effective patient care. Continuing Professional Development (CPD) is also an integral part of maintaining professional and personal competence and growth for healthcare professionals. This article examines the rationale for and methods of swiftly adapting a robust CPD program and training calendar to an online offering for radiation therapists (RTs) at the Princess Alexandra Hospital Radiation Oncology Department, Brisbane, Australia. Reasons for the change, how it was achieved quickly, and the opportunity to build resilience in the staff group are discussed. Successes and challenges of achieving meaningful change in a short timeframe are described, ensuring RTs maintained access to both CPD and social support during the crisis. Initial feedback suggested a positive response from RTs, but the situation remains dynamic and will need to be monitored and adapted as the pandemic continues.
Cardiovascular risk factors and APOE‐ε4 status affect memory functioning in aging via changes to temporal stem diffusion
Authors: McKinnon Andrew C. , Stickel Ariana , Ryan Lee 
Published: October 2020

AbstractPrior research investigating associations between hypertension, obesity, and apolipoprotein (APOE) genotype status with memory performance among older adults has yielded inconsistent results. This may reflect, in part, a lack of first accounting for the effects these variables have on structural brain changes, that in turn contribute to age‐related memory impairment. The current study sought to clarify the relationships between these factors via path modeling. We hypothesized that higher body mass index (BMI), hypertension, and being an APOE‐ε4 allele carrier would predict poorer memory scores, with much of these effects accounted for by indirect effects operating via differences in the integrity of temporal stem white matter. Participants included 125 healthy older adults who underwent neuropsychological assessment and diffusion‐weighted MRI scanning. Direct effects were found for hypertension and demographic variables including age, sex, and education. Importantly, indirect effects were found for BMI, hypertension, APOE‐ε4 status, age, and sex, where these factors predicted memory scores via their impact on temporal stem diffusion measures. There was also a dual effect of sex, with a direct effect indicating that females had better memory performance overall, and an indirect effect indicating that females with greater temporal stem diffusion had poorer memory performance. Results suggest that changes to the integrity of temporal white matter in aging may underpin reduced memory performance. These results highlight that accounting for variables that not only directly impact cognition, but also for those that indirectly impact cognition via structural brain changes, is crucial for understanding the impact of risk factors on cognition.
Time‐to‐contact perception in the brain
Authors: Baurès Robin , Fourteau Marie , Thébault Salomé , Gazard Chloé , Pasquio Léa , Meneghini Giulia , Perrin Juliette , Rosito Maxime , Durand Jean‐Baptiste , Roux Franck‐Emmanuel 
Published: October 2020

AbstractTime‐to‐contact (TTC) perception refers to the ability of an observer to estimate the remaining time before an object reaches a point in the environment, and is of crucial importance in daily life. Noninvasive correlational approaches have identified several brain areas sensitive to TTC information. Here we report the results of two studies, including one during an awake brain surgery, that aimed to identify the specific areas causally engaged in the TTC estimation process. In Study 1, we tested 40 patients with brain tumor in a TTC estimation task. The results showed that four of the six patients with impaired performance had tumors in right upper parietal cortex, although this tumoral location represented only six over 40 patients. In Study 2, 15 patients underwent awake brain surgery electrostimulation mapping to examine the implication of various brain areas in the TTC estimation process. We acquired and normalized to MNI space the coordinates of the functional areas that influenced task performance. Our results seem to demonstrate that the early stage of the TTC estimation process involved specific cortical territories in the ventral region of the right intraparietal sulcus. Downstream processing of TTC could also involve the frontal eye field (middle frontal gyrus) related to ocular search. We also found that deactivating language areas in the left hemisphere interfered with the TTC estimation process. These findings demonstrate a fine grained, cortical representation of TTC processing close to the ventral right intraparietal sulcus and complement those described in other human studies.
Network meta‐analysis results against a fictional treatment of average performance: Treatment effects and ranking metric
Authors: Nikolakopoulou Adriani , Mavridis Dimitris , Chiocchia Virginia , Papakonstantinou Theodoros , Furukawa Toshi A. , Salanti Georgia 
Published: October 2020

BackgroundNetwork meta‐analysis (NMA) produces complex outputs as many comparisons between interventions are of interest. The estimated relative treatment effects are usually displayed in a forest plot or in a league table and several ranking metrics are calculated and presented.MethodsIn this article, we estimate relative treatment effects of each competing treatment against a fictional treatment of average performance using the “deviation from the means” coding that has been used to parametrize categorical covariates in regression models. We then use this alternative parametrization of the NMA model to present a ranking metric (PreTA: Preferable Than Average) interpreted as the probability that a treatment is better than a fictional treatment of average performance.ResultsWe illustrate the alternative parametrization of the NMA model using two networks of interventions, a network of 18 antidepressants for acute depression and a network of four interventions for heavy menstrual bleeding. We also use these two networks to highlight differences among PreTA and existing ranking metrics. We further examine the agreement between PreTA and existing ranking metrics in 232 networks of interventions and conclude that their agreement depends on the precision with which relative effects are estimated.ConclusionsA forest plot with NMA relative treatment effects using “deviation from means” coding could complement presentation of NMA results in large networks and in absence of an obvious reference treatment. PreTA is a viable alternative to existing probabilistic ranking metrics that naturally incorporates uncertainty.
Agricultural practices modulate the bacterial communities, and nitrogen cycling bacterial guild in rhizosphere: field experiment with soybean
Authors: Singh Upma , Choudhary Anil K , Sharma Shilpi 
Published: October 2020

AbstractBACKGROUNDModern agricultural management approaches are often dependent on the application of chemicals, resulting in adverse impacts on human and environmental health. Therefore, for sustainable agriculture, there is a need to implement integrated agriculture practices that can maintain natural soil microbiome and enhance crop production. Various agricultural approaches influence crop production by impacting the functional bacterial community entailed in biogeochemical cycles, for example, nitrogen (N) cycle. This study aimed to assess the rhizospheric N cycling community of soybean under three agricultural practices, namely, conservation agriculture (CA), conventional treatment (CT), and organic agriculture (OA) for two consecutive years (2017 and 2018).RESULTSA field experiment was designed under soybean–wheat cropping system employing CA, CT, and OA modules that included different practices of tillage, crop bedding pattern, crop residue retention, and nutrient application. Assessment of bacterial communities contributing to N transformation was performed with quantitative polymerase chain reaction (qPCR) of important markers (nifH, amoA, narG, and nirK).CONCLUSIONResults concluded that the practice of conservation agriculture comprising of raised bed, zero tillage, crop residue retention, and application of NPK (nitrogen, phosphorus, potassium) nutrients favorably affected the plant attributes and the abundance of N cycling bacterial community over the two consecutive years. The outcome revealed the mechanistic principle behind enhanced plant growth under conservation agriculture, and opened up the possibility of regulating the N cycling bacterial community to develop sustainable and productive agro‐ecosystems. © 2020 Society of Chemical Industry