bluuebunny/crossref_metadata_2025 huggingface dataset:
Differential Expression and Bioinformatics Analysis of circRNA in Non-small Cell Lung Cancer
Authors: Sun Qiuwen , Li Xia , Xu Muchen , Zhang Li , Zuo Haiwei , Xin Yong , Zhang Longzhen , Gong Ping
Published: November 2020

Circular RNA (CircRNA) plays an important role in tumorigenesis and progression of non-small cell lung cancer (NSCLC), but the pathogenesis of NSCLC caused by circRNA has not been fully elucidated. This study aimed to investigate differentially expressed circRNAs and identify the underlying pathogenesis hub genes of NSCLC by comprehensive bioinformatics analysis. Data of gene expression microarrays (GSE101586, GSE101684, and GSE112214) were downloaded from Gene Expression Omnibus (GEO) database. Differentially expressed circRNAs (DECs) were obtained by the “limma” package of R programs and the overlapping operation was implemented of DECs. CircBase database and Cancer-Specific CircRNA database (CSCD) were used to find miRNAs binding to DECs. Target genes of the found miRNAs were identified utilizing Perl programs based on miRDB, miRTarBase, and TargetScan databases. Functional and enrichment analyses of selected target genes were performing using the “cluster profiler” package. Protein-protein interaction (PPI) network was constructed by the Search Tool for the STRING database and module analysis of selected hub genes was performed by Cytoscape 3.7.1. Survival analysis of hub genes were performed by Gene Expression Profiling Interactive Analysis (GEPIA). Respectively, 1 DEC, 249 DECs, and 101 DECs were identified in GSE101586, GSE101684, and GSE112214. A total of eight overlapped circRNAs, 43 miRNAs and 427 target genes were identified. Gene Ontology (GO) enrichment analysis showed these target genes were enriched in biological processes of regulation of histone methylation, Ras protein signal transduction and covalent chromatin modification etc. Pathway enrichment analysis showed these target genes are mainly involved in AMPK signaling pathway, signaling pathways regulating pluripotency of stem cells and insulin signaling pathway etc. A PPI network was constructed based on 427 target genes of the 43 miRNAs. Ten hub genes were found, of which the expression of MYLIP, GAN, and CDC27 were significantly related to NSCLC patient prognosis. Our study provide a deeper understanding the circRNAs-miRNAs-target genes by bioinformatics analysis, which may provide novel insights for unraveling pathogenesis of NSCLC. MYLIP, GAN, and CDC27 genes might serve as novel biomarker for precise treatment and prognosis of NSCLC in the future.
3D Ensemble Simulation of Seawater Temperature – An Application for Aquaculture Operations
Authors: Shettigar Nithin Achutha , Bhattacharya Biswa , Mészáros Lörinc , Spinosa Anna , El Serafy Ghada
Published: November 2020

During the past decades, the aquaculture industry has developed rapidly, due to drop in wild fish catch. Water quality variables play major role in aquaculture operations, specifically seawater temperature has major impact on the metabolism of the fish species and therefore on the growth rate too. Since the fish farming business relies on the growth rate of the species to plan and operate the farm, seawater temperature becomes crucial information. With the availability of hydrodynamic modeling tools and global ocean information source such as Copernicus Marine Environment Monitoring Service (CMEMS), seawater temperature can be simulated for practically any coast with dynamic downscaling approach. However, the simulated data needs to be assessed for uncertainties for enabling informed decision making using such model predictions. In this paper, a coastal 3D hydrodynamic model aiming at simulating seawater temperature is developed for the southern Aegean Sea, Greece using the Delft3D Flexible Mesh modeling tool. Seawater temperature is impacted by atmospheric forces; therefore, uncertainties are assessed for seawater temperature using ensemble atmospheric forcing functions of the European Centre for Medium-Range Weather Forecasts (ECMWF) ERA5. Spatial analysis of the uncertainty indicates regions of different seawater temperature behavior within the model domain. Seasonal behavior of the vertical temperature gradient suggests that farms need to adapt different operational strategies in different seasons to make best use of the seawater temperature. The application of CMEMS data along with ECMWF ERA5 ensemble atmospheric forcing members proves to be beneficial in analyzing the uncertainties both in spatial and vertical gradient of seawater temperature.
Sarcoidosis and Cancer: A Complex Relationship
Authors: El Jammal Thomas , Pavic Michel , Gerfaud-Valentin Mathieu , Jamilloux Yvan , Sève Pascal
Published: November 2020

Sarcoidosis is a systemic disease of unknown etiology, characterized by the presence of non-caseating granulomas in various organs, mainly the lungs, and the lymphatic system. Since the individualization of sarcoidosis-lymphoma association by Brincker et al., the relationship between sarcoidosis or granulomatous syndromes and malignancies has been clarified through observational studies worldwide. Two recent meta-analyses showed an increased risk of neoplasia in sarcoidosis. The granulomatosis can also reveal malignancy, either solid or hematological, defining paraneoplastic sarcoidosis. Recent cancer immunotherapies, including immune checkpoint inhibitors (targeting PD-1, PD-L1, or CTLA-4) and BRAF or MEK inhibitors were also reported as possible inducers of sarcoidosis-like reactions. Sarcoidosis and neoplasia, especially lymphoma, can show overlapping presentations, thus making the diagnosis and treatment harder to deal with. There are currently no formal recommendations to guide the differential diagnosis workup between the evolution of lymphoma or a solid cancer and a granulomatous reaction associated with neoplasia. Thus, in atypical presentations (e.g., deeply impaired condition, compressive lymphadenopathy, atypical localization, unexplained worsening lymphadenopathy, or splenomegaly), and treatment-resistant disease, targeted biopsies on suspect localizations with histological examination could help the clinician to differentiate neoplasia from sarcoidosis. Pathological diagnosis could sometimes be challenging since very few tumor cells may be surrounded by massive granulomatous reaction. The sensitization of currently available diagnostic tools should improve the diagnostic accuracy, such as the use of more “cancer-specific” radioactive tracers coupled with Positron Emission Tomography scan.
Variations of Indole Metabolites and NRPS-PKS Loci in Two Different Virulent Strains of Xenorhabdus hominickii
Authors: Mollah Md. Mahi Imam , Roy Miltan Chandra , Choi Doo-Yeol , Hasan Md. Ariful , Al Baki Md. Abdullah , Yeom Hyun-Suk , Kim Yonggyun
Published: November 2020

Xenorhabdus hominickii ANU1 is known to be an entomopathogenic bacterium symbiotic to nematode Steinernema monticolum. Another bacterial strain X. hominickii DY1 was isolated from a local population of S. monticolum. This bacterial strain X. hominickii DY1 was found to exhibit high insecticidal activities against lepidopteran and coleopteran species after hemocoelic injection. However, these two X. hominickii strains exhibited significant variations in insecticidal activities, with ANU1 strain being more potent than DY1 strain. To clarify their virulence difference, bacterial culture broths of these two strains were compared for secondary metabolite compositions. GC-MS analysis revealed that these two strains had different compositions, including pyrrolopyrazines, piperazines, cyclopeptides, and indoles. Some of these compounds exhibited inhibitory activities against phospholipase A2 to block eicosanoid biosynthesis and induce significant immunosuppression. They also exhibited significant insecticidal activities after oral feeding, with indole derivatives being the most potent. More kinds of indole derivatives were detected in the culture broth of ANU1 strain. To investigate variations in regulation of secondary metabolite production, expression level of leucine-responsive regulatory protein (Lrp), a global transcription factor, was compared. ANU1 strain exhibited significantly lower Lrp expression level than DY1 strain. To assess genetic variations associated with secondary metabolite synthesis, bacterial loci encoding non-ribosomal protein synthase and polyketide synthase (NRPS-PKS) were compared. Three NRPS and four PKS loci were predicted from the genome of X. hominickii. The two bacterial strains exhibited genetic variations (0.12∼0.67%) in amino acid sequences of these NRPS-PKS. Most NRPS-PKS genes exhibited high expression peaks at stationary phase of bacterial growth. However, their expression levels were significantly different between the two strains. These results suggest that differential virulence of the two bacterial strains is caused by the difference in Lrp expression level, leading to difference in the production of indole compounds and other NRPS-PKS-associated secondary metabolites.
Mapping the Multi-Organ miRNA-mRNA Regulatory Network in LPS-Mediated Endotoxemic Mice: Exploring the Shared Underlying Key Genes and Mechanisms
Authors: Zhang Cong , Liao Ying , Liu Zhihao , Zeng Lijin , Peng Zhihua , Liao Jinli , Yang Zhen
Published: November 2020

Background

To this day, the molecular mechanism of endotoxin-induced multi-organ failure has not been completely clarified. This study aimed to construct an miRNA-mRNA regulatory network and identify main pathways and key genes in multi-organ of LPS-mediated endotoxemic mice.

Methods

Public datasets from six mRNA and three miRNA microarray datasets were downloaded from the GEO website to screen final differentially expressed genes (FDEGs) and hub genes in the heart, lung, liver, and kidney of LPS-mediated endotoxemic mice. Functional and pathway enrichment analysis of FDEGs was used to identify the main pathways in multi-organ damage of LPS-treated mice. Finally, hub genes of each organ were intersected to obtain the key genes of multi-organ.

Results

Firstly, 158, 358, 299, and 91 FDEGs were identified in the heart, lung, liver, and kidney, respectively. The pathway enrichment analysis of the FDEGs then showed that the TNF signaling pathway, Toll-like receptor signaling pathway, and some viral-infection-related pathways (influenza A, measles, and herpes simplex) were the main pathways in multi-organ damage of LPS-mediated endotoxemic mice. Moreover, miRNA-mRNA or PPI regulatory networks were constructed based on FDEGs. According to these networks, 31, 34, 34, and 31 hub genes were identified in the heart, lung, liver, and kidney, respectively. Among them, nine key genes (Cd274, Cxcl1, Cxcl9, Icam1, Ifit2, Isg15, Stat1, Tlr2, and Usp18) were enriched in Toll-like receptor signaling pathway and chemokine signaling pathway. Finally, seven potential drugs were predicted based on these key genes.

Conclusion

The shared underlying molecular pathways in endotoxin-induced multi-organ damage that have been identified include Toll-like receptor signaling pathway and TNF signaling pathway. Besides, nine key genes (Cd274, Cxcl1, Cxcl9, Icam1, Ifit2, Isg15, Stat1, Tlr2, and Usp18) and seven potential drugs were identified. Our data provide a new sight and potential target for future therapy in endotoxemia-induced multi-organ failure.
Delivery of Periodontopathogenic Extracellular Vesicles to Brain Monocytes and Microglial IL-6 Promotion by RNA Cargo
Authors: Ha Jae Yeong , Choi Song-Yi , Lee Ji Hye , Hong Su-Hyung , Lee Heon-Jin
Published: November 2020

Gram-negative bacterial extracellular vesicles (EVs), also known as outer membrane vesicles (OMVs), are secreted from bacterial cells and have attracted research attention due to their role in cell-to-cell communication. During OMV secretion, a variety of cargo such as extracellular RNA (exRNA) is loaded into the OMV. The involvement of exRNAs from a range of bacteria has been identified in several diseases, however, their mechanism of action has not been elucidated. We have recently demonstrated that OMVs secreted by the periodontopathogen Aggregatibacter actinomycetemcomitans can cross the blood–brain barrier (BBB) and that its exRNA cargo could promote the secretion of proinflammatory cytokines in the brain. However, it was unclear whether the brain immune cells could actually take up bacterial OMVs, which originate outside of the brain, in an appropriate immune response. In the present study, using monocyte-specific live CX3CR1-GFP mice, we visualized OMV-colocalized meningeal macrophages and microglial cells into which bacterial OMVs had been loaded and intravenously injected through tail veins. Our results suggested that meningeal macrophages uptake BBB-crossed OMVs earlier than do cortex microglia. BV2 cells (a murine microglia cell line) and exRNAs were also visualized after OMV treatment and their proinflammatory cytokine levels were observed. Interleukin (IL)-6 and NF-κB of BV2 cells were activated by A. actinomycetemcomitans exRNAs but not by OMV DNA cargo. Altogether, these findings indicate that OMVs can successfully deliver exRNAs into brain monocyte/microglial cells and cause neuroinflammation, implicating a novel pathogenic mechanism in neuroinflammatory diseases.
Differential Changed Excitability of Spinal Motor Neurons Innervating Tibialis Anterior and Peroneus Muscles Cause Foot Inversion After Stroke
Authors: Liu Gang , Chia Chin-hsuan , Cao Yue , Tang Xin-wei , Tian Shan , Shen Xue-yan , Chen Ying , Lu Rong-rong , Wu Jun-fa , Wu Yi
Published: November 2020

Objective: To study differential post-stroke changes of excitability of spinal motor neurons innervating a group of antagonist muscles of ankle and their effects on foot inversion.

Methods: F waves in tibialis anterior (TA) and peroneus muscles (PN) were recorded. The condition of spasticity and foot inversion in stroke patients were also evaluated. The differences of F wave parameters between patients and healthy controls (HC), as well as TA and PN, were investigated.

Results: There were natural differences in the persistence of the F waves (Fp) and F/M amplitude ratio (F/M) between TA and PN in HC. Stroke patients showed significantly higher F/M in TA and PN, while there was no difference in Fp comparing to HC. The natural differences in F wave parameters between TA and PN were differentially retained after stroke. The natural difference of the two muscles in Fp remained unchanged and the F/M difference disappeared in those without spasticity or foot inversion, while the Fp difference disappeared and the F/M difference remained in those with spasticity or foot inversion.

Conclusion: Based on the natural difference of the number and size of spinal motor neurons innervating TA and PN, their excitability may change differently according to the severity of the stroke, which may be the reason of foot inversion.
Distinguishing Focal Cortical Dysplasia From Glioneuronal Tumors in Patients With Epilepsy by Machine Learning
Authors: Guo Yi , Liu Yushan , Ming Wenjie , Wang Zhongjin , Zhu Junming , Chen Yang , Yao Lijun , Ding Meiping , Shen Chunhong
Published: November 2020

Purpose: We are aiming to build a supervised machine learning-based classifier, in order to preoperatively distinguish focal cortical dysplasia (FCD) from glioneuronal tumors (GNTs) in patients with epilepsy.

Methods: This retrospective study was comprised of 96 patients who underwent epilepsy surgery, with the final neuropathologic diagnosis of either an FCD or GNTs. Seven classical machine learning algorithms (i.e., Random Forest, SVM, Decision Tree, Logistic Regression, XGBoost, LightGBM, and CatBoost) were employed and trained by our dataset to get the classification model. Ten features [i.e., Gender, Past history, Age at seizure onset, Course of disease, Seizure type, Seizure frequency, Scalp EEG biomarkers, MRI features, Lesion location, Number of antiepileptic drug (AEDs)] were analyzed in our study.

Results: We enrolled 56 patients with FCD and 40 patients with GNTs, which included 29 with gangliogliomas (GGs) and 11 with dysembryoplasic neuroepithelial tumors (DNTs). Our study demonstrated that the Random Forest-based machine learning model offered the best predictive performance on distinguishing the diagnosis of FCD from GNTs, with an F1-score of 0.9180 and AUC value of 0.9340. Furthermore, the most discriminative factor between FCD and GNTs was the feature “age at seizure onset” with the Chi-square value of 1,213.0, suggesting that patients who had a younger age at seizure onset were more likely to be diagnosed as FCD.

Conclusion: The Random Forest-based machine learning classifier can accurately differentiate FCD from GNTs in patients with epilepsy before surgery. This might lead to improved clinician confidence in appropriate surgical planning and treatment outcomes.
Predicting Response to Group Cognitive Behavioral Therapy in Asthma by a Small Number of Abnormal Resting-State Functional Connections
Authors: Zhang Yuqun , Ma Kai , Yang Yuan , Yin Yingying , Hou Zhenghua , Zhang Daoqiang , Yuan Yonggui
Published: November 2020

Group cognitive behavioral therapy (GCBT) is a successful psychotherapy for asthma. However, response varies considerably among individuals, and identifying biomarkers of GCBT has been challenging. Thus, the aim of this study was to predict an individual’s potential response by using machine learning algorithms and functional connectivity (FC) and to improve the personalized treatment of GCBT. We use the lasso method to make the feature selection in the functional connections between brain regions, and we utilize t-test method to test the significant difference of these selected features. The feature selections are performed between controls (size = 20) and pre-GCBT patients (size = 20), pre-GCBT patients (size = 10) and post-GCBT patients (size = 10), and post-GCBT patients (size = 10) and controls (size = 10). Depending on these features, support vector classification was used to classify controls and pre- and post-GCBT patients. Pearson correlation analysis was employed to analyze the associations between clinical symptoms and the selected discriminated FCs in post-GCBT patients. At last, linear support vector regression was applied to predict the therapeutic effect of GCBT. After feature selection and significant analysis, five discriminated FC regarding neuroimaging biomarkers of GCBT were discovered, which are also correlated with clinical symptoms. Using these discriminated functional connections, we could accurately classify the patients before and after GCBT (classification accuracy, 80%) and predict the therapeutic effect of GCBT in asthma (predicted accuracy, 67.8%). The findings in this study would provide a novel sight toward GCBT response prediction and further confirm neural underpinnings of asthma. Moreover, our findings had clinical implications for personalized treatment by identifying asthmatic patients who will be appropriate for GCBT.

Clinical Trial Registration

The brain mechanisms of group cognitive behavioral therapy to improve the symptoms of asthma (Registration number: Chi-CTR-15007442, http://www.chictr.org.cn/index.aspx).
Refinement of High-Gamma EEG Features From TBI Patients With Hemicraniectomy Using an ICA Informed by Simulated Myoelectric Artifacts
Authors: Li Yongcheng , Wang Po T. , Vaidya Mukta P. , Flint Robert D. , Liu Charles Y. , Slutzky Marc W. , Do An H.
Published: November 2020

Recent studies have shown the ability to record high-γ signals (80–160 Hz) in electroencephalogram (EEG) from traumatic brain injury (TBI) patients who have had hemicraniectomies. However, extraction of the movement-related high-γ remains challenging due to a confounding bandwidth overlap with surface electromyogram (EMG) artifacts related to facial and head movements. In our previous work, we described an augmented independent component analysis (ICA) approach for removal of EMG artifacts from EEG, and referred to as EMG Reduction by Adding Sources of EMG (ERASE). Here, we tested this algorithm on EEG recorded from six TBI patients with hemicraniectomies while they performed a thumb flexion task. ERASE removed a mean of 52 ± 12% (mean ± S.E.M) (maximum 73%) of EMG artifacts. In contrast, conventional ICA removed a mean of 27 ± 19% (mean ± S.E.M) of EMG artifacts from EEG. In particular, high-γ synchronization was significantly improved in the contralateral hand motor cortex area within the hemicraniectomy site after ERASE was applied. A more sophisticated measure of high-γ complexity is the fractal dimension (FD). Here, we computed the FD of EEG high-γ on each channel. Relative FD of high-γ was defined as that the FD in move state was subtracted by FD in idle state. We found relative FD of high-γ over hemicraniectomy after applying ERASE were strongly correlated to the amplitude of finger flexion force. Results showed that significant correlation coefficients across the electrodes related to thumb flexion averaged ~0.76, while the coefficients across the homologous electrodes in non-hemicraniectomy areas were nearly 0. After conventional ICA, a correlation between relative FD of high-γ and force remained high in both hemicraniectomy areas (up to 0.86) and non-hemicraniectomy areas (up to 0.81). Across all subjects, an average of 83% of electrodes significantly correlated with force was located in the hemicraniectomy areas after applying ERASE. After conventional ICA, only 19% of electrodes with significant correlations were located in the hemicraniectomy. These results indicated that the new approach isolated electrophysiological features during finger motor activation while selectively removing confounding EMG artifacts. This approach removed EMG artifacts that can contaminate high-gamma activity recorded over the hemicraniectomy.
Potential Application of Essential Oils for Mitigation of Listeria monocytogenes in Meat and Poultry Products
Authors: Yousefi Mojtaba , Khorshidian Nasim , Hosseini Hedayat
Published: November 2020

One of the most important challenges in the food industry is to provide healthy and safe food. Therefore, it is not possible to achieve this without different processes and the use of various additives. In order to improve safety and extend the shelf life of food products, various synthetic preservatives have been widely utilized by the food industry to prevent growth of spoilage and pathogenic microorganisms. On the other hand, consumers' preference to consume food products with natural additives induced food industries to use natural-based preservatives in their production. It has been observed that herbal extracts and their essential oils could be potentially considered as a replacement for chemical antimicrobials. Antimicrobial properties of plant essential oils are derived from some main bioactive components such as phenolic acids, terpenes, aldehydes, and flavonoids that are present in essential oils. Various mechanisms such as changing the fatty acid profile and structure of cell membranes and increasing the cell permeability as well as affecting membrane proteins and inhibition of functional properties of the cell wall are effective in antimicrobial activity of essential oils. Therefore, our objective is to revise the effect of various essential oils and their bioactive components against Listeria monocytogenes in meat and poultry products.
Sector Irradiation vs. Whole Brain Irradiation After Resection of Singular Brain Metastasis—A Prospective Randomized Monocentric Trial
Authors: Kerschbaumer Johannes , Pinggera Daniel , Holzner Bernhard , Delazer Margarete , Bodner Thomas , Karner Elfriede , Dostal Lucie , Kvitsaridze Irma , Minasch Danijela , Thomé Claudius , Seiz-Rosenhagen Marcel , Nevinny-Stickel Meinhard , Freyschlag Christian F.
Published: November 2020

To minimize recurrence following resection of a cerebral metastasis, whole-brain irradiation therapy (WBRT) has been established as the adjuvant standard of care. With prolonged overall survival in cancer patients, deleterious effects of WBRT gain relevance. Sector irradiation (SR) aims to spare uninvolved brain tissue by applying the irradiation to the resection cavity and the tumor bed. 40 were randomized to receive either WBRT (n = 18) or SR (n = 22) following resection of a singular brain metastasis. Local tumor control was satisfactory in both groups. Recurrence was observed earlier in the SR (median 3 months, 1–6) than in the WBRT cohort (median 8 months, 7–9) (HR, 0.63; 95% CI, 0.03–10.62). Seventeen patients experienced a distant intracranial recurrence. Most relapses (n = 15) occurred in the SR cohort, whereas only two patients in the WBRT group had new distant tumor manifestation (HR, 6.59; 95% CI, 1.71–11.49; p = 0.002). Median overall survival (OS) was 15.5 months (range: 1–61) with longer OS in the SR group (16 months, 1–61) than in the WBRT group (13 months, 3–52), without statistical significance (HR, 0.55; 95% CI, 0.69–3.64). Concerning neurocognition, patients in the SR group improved in the follow-up assessments, while this was not observed in the WBRT group. There were positive signals in terms of QOL within the SR group, but no significant differences in the global QLQ and QLQ-C30 summary scores were found. Our results indicate comparable efficacy of SR in terms of local control, with better maintenance of neurocognitive function. Unsurprisingly, more distant intracranial relapses occurred.

Clinical Trial Registration:ClinicalTrials.gov, identifier NCT01667640.
Anti-Angiogenic Agents in Management of Sarcoma Patients: Overview of Published Trials
Authors: Cren Pierre-Yves , Lebellec Loïc , Ryckewaert Thomas , Penel Nicolas
Published: November 2020

We reviewed all fully published clinical trials assessing anti-angiogenic agents in sarcoma patients (last issue, January 13, 2020). Anti-angiogenic macromolecules (e.g., bevacizumab or ombrabulin) provide disappointing results. Many multikinase inhibitors have been assessed with non-randomized phase II trials with limited samples and without stratification according to histological subtypes, therefore interpretation of such trials is very challenging. On the contrary, pazopanib, regorafenib, and sorafenib have been assessed using double-blind placebo-controlled randomized phase II or phase III trials. Compared to placebo, sorafenib demonstrates activity in desmoid-type fibromatosis patients. Based on results of phase 3 trial, pazopanib had obtained approval for treatment of pretreated non-adipocytic soft tissue sarcoma. Regorafenib is currently assessed in several clinical settings and provides significant improvement of progression-free survival in pre-treated non-adipocytic soft tissue sarcoma and in advanced pretreated osteosarcoma. Multikinase inhibitors are a breakthrough in sarcoma management. Many trials are ongoing. Nevertheless, predictive factors are still missing.
Higher Hospitalization Rate for Lower Airway Infection in Transfusion-Naïve Thalassemia Children
Authors: Tsai Ti-An , Tsai Chang-Ku , Yang Yao-Hsu , Lee Zon-Min , Sheen Jiunn-Ming , Lee Yi-Chen , Tsai Chih-Min , Chen Chih-Cheng , Chang Chih-Hao , Niu Chen-Kuang , Yu Hong-Ren
Published: November 2020

Few studies have addressed the risk of infection in transfusion-naïve thalassemia patients. We aimed to investigate whether transfusion-naïve thalassemia population has higher hospitalization rates for lower airway infection-related diseases than non-thalassemia population in children. A nationwide population-based retrospective cohort study was conducted using detailed medical records of the Taiwan National Health Insurance Research Database. Transfusion-naïve thalassemia patients were compared with a matched cohort at a ratio of 1:4. Data of the selected patients were adjusted for age, sex, and related comorbidities. We recorded the frequency of admissions or outpatient clinic visits for patients with a diagnosis of pneumonia or acute bronchitis/bronchiolitis. Based on our results, the hospitalization rates and incidence rate ratios of bronchitis/bronchiolitis and pneumonia for transfusion-naïve thalassemia children were all higher than those for non-thalassemia controls. Therefore, we conclude that transfusion-naïve thalassemia children are more likely to experience lower airway infections and have a higher probability of hospitalization for these conditions.
Response to Zoledronic Acid Infusion in Children With Fibrous Dysplasia
Authors: Tripathy Sujit Kumar , Swaroop Shakti , Velagada Sandeep , Priyadarshini Debashree , Das Rashmi Ranjan , Satpathy Amit Kumar , Agrawal Kanhaiyalal
Published: November 2020

Objective: This retrospective study evaluated the outcome and safety of long-term treatment with zoledronic acid, in both polyostotic and mono-ostotic fibrous dysplasia (FD) of children.

Methods: The case records of children and adolescents with symptomatic FD who received zoledronic acid (0.1 mg/kg IV infusion over 1 h) and have completed at least 2 years follow-up were analyzed. The relevant details were recorded in a predesigned chart. Clinical assessment [pain assessment by visual analog scale (VAS) and incidence of new fracture], radiological changes (cortical thickening, ossification, and decrease in the diameter of the osteolytic lesions) and biochemical parameters [alkaline phosphatase (ALP)] were used to evaluate the improvement.

Results: The mean age of presentation was 9.1 years, with four males and six females. All patients had symptomatic FD in the lower limb with complaints of pain, tenderness, swelling, or deformity. Four children had associated pathological fracture. The radiological evaluation with bone scan revealed polyostotic involvement in eight patients and mono-ostotic involvement in two patients. Three patients had associated systemic features like café-au-lait spots or precocious puberty. The fracture united within 3 months and the radiological improvement was evident in the form of filling of the osteolytic defect. The pain score in six patients showed significant improvement (VAS < 3). The ALP level decreased to 544.12 ± 47.35 IU/L from an initial value of 895.75 ± 79.64 IU/L (p = 0.04) at 12 months. One patient had symptomatic hypocalcaemia after zoledronic acid infusion.

Conclusion: The clinical and radiological response of zoledronic acid treatment in FD of children is promising. Further randomized control trials with a larger sample size are required to establish this drug as a first-line medical treatment in FD.
Dose Effect of Poractant Alfa in Neonatal RDS: Analysis of Combined Data from Three Prospective Studies
Authors: Królak-Olejnik Barbara , Hożejowski Roman , Szczapa Tomasz
Published: November 2020

Aim: To evaluate the effect of the initial dose of poractant alfa on clinical outcomes in neonatal respiratory distress syndrome (RDS) and to assess adherence to treatment guidelines recommending a dose of 200 mg/kg.

Methods: Records of neonates who received poractant alfa with a less invasive technique (LISA) or with the INtubate-SURfactant-Extubate (INSURE) technique were retrieved from the aggregated datasets of three prospective RDS studies conducted between 2015 and 2019. The impact of poractant dose on neonatal outcomes was analyzed by multivariate logistic regression. The primary endpoint was the need for early (<72 h of life) mechanical ventilation (MV). Typical complications of prematurity and the need for surfactant retreatment were secondary endpoints. Deviation from the 200 mg/kg dose of surfactant was a measure of compliance with the treatment guidelines. As a complementary analysis, the rates of adverse outcomes were compared for infants receiving high (200 mg/kg ±10%) and low (100 mg/kg ±10%) doses of poractant.

Results: Of 994 eligible infants, 574 received poractant alfa with LISA, and 420 received poractant with INSURE. A logistic regression model using data from all 994 infants showed that the surfactant dose had a significant effect on reducing the need for MV and retreatment; the respective odds ratios were 0.92 (95% CI: 0.90–0.95) and 0.93 (95% CI: 0.90–0.96) per 10-mg/kg dose increment of poractant alfa. This dose effect was observed across all gestational age ranges and in infants treated with LISA. In newborns treated with INSURE, the dose of surfactant only influenced the rates of retreatment (p = 0.036) but not MV (p = 0.170). No impact on other neonatal outcomes was observed. In the subset of infants who received high (N = 502) and low (N = 58) doses of poractant, the high-dose group had lower rates of MV (34 vs. 48%, p = 0.042) and lower rates of retreatment (11 vs. 21%, p = 0.045). Surfactant underdosage increased with gestational age and ranged from a minimum of −3 mg/kg in <26 weeks to a maximum of −23.5 mg/kg in >32 weeks.

Conclusions: The initial dose of poractant alfa significantly impacts the need for invasive ventilation and retreatment. More mature newborns are at a greater risk of underdosing.
Regional Differences in the Gut Microbiota and Gut-Associated Immunologic Factors in the Ileum and Cecum of Rats With Collagen-Induced Arthritis
Authors: Xu Huihui , Cao Jinfeng , Li Xiaoya , Lu Xiangchen , Xia Ya , Fan Danping , Zhao Hongyan , Ju Dahong , Xiao Cheng
Published: November 2020

Rheumatoid arthritis (RA) is a common autoimmune disease characterized by chronic inflammation and a multifactorial etiology. We previously showed that gut microbiota dysbiosis in the rat ileum is involved in the development of collagen-induced arthritis (CIA). The gut microbiota in the distinct gastrointestinal tract (GIT) plays region-specific roles, but information on the different roles of the microbiota in distinct GIT compartments of CIA rats is limited. This study aimed to evaluate the region-specific differences in the gut microbial communities and certain gut-associated immunologic factors in the ileum and cecum of CIA rats. Ileal and cecal digesta were collected from CIA and control rats for microbiome analysis. We determined the microbial richness, diversity and taxa as well as the expression of interleukin (IL)-1β and IL-17A in the epithelium and lamina propria of the ileum and cecum mucosal layers. The CIA-induced microbiota alterations in the ileum differed from those in the cecum. The ileal microbiota were more markedly influenced in CIA, as revealed by sharp reductions in the abundances of the families Enterococcaceae, Lactobacillaceae and Streptococcaceae and the genera Lactobacillus and Lactococcus. Moreover, significant increases in IL-1β, and IL-17A mRNA expression were detected in only the ileal epithelium and lamina propria of the mucosal layer. Therefore, the microbial characteristics in the ileum were consistent with the immune-mediated inflammatory features of CIA, suggesting that the ileal microbiota might better represent the CIA-induced inflammatory responses than the cecal microbiota and that these responses might partially impact the progression of RA by regulating intestinal mucosal immunity.
Mitochondrial DNA Affects the Expression of Nuclear Genes Involved in Immune and Stress Responses in a Breast Cancer Model
Authors: Grasso Carole , Eccles David A. , Boukalova Stepana , Fabre Marie-Sophie , Dawson Rebecca H. , Neuzil Jiri , Herst Patries M. , Berridge Michael V.
Published: November 2020

Tumor cells without mitochondrial (mt) DNA (ρ0cells) are auxotrophic for uridine, and their growth is supported by pyruvate. While ATP synthesis in ρ0cells relies on glycolysis, they fail to form tumors unless they acquire mitochondria from stromal cells. Mitochondrial acquisition restores respiration that is essential forde novopyrimidine biosynthesis and for mitochondrial ATP production. The physiological processes that underpin intercellular mitochondrial transfer to tumor cells lacking mtDNA and the metabolic remodeling and restored tumorigenic properties of cells that acquire mitochondria are not well understood. Here, we investigated the changes in mitochondrial and nuclear gene expression that accompany mtDNA deletion and acquisition in metastatic murine 4T1 breast cancer cells. Loss of mitochondrial gene expression in 4T1ρ0cells was restored in cells recovered from subcutaneous tumors that grew from 4T1ρ0cells following acquisition of mtDNA from host cells. In contrast, the expression of most nuclear genes that encode respiratory complex subunits and mitochondrial ribosomal subunits was not greatly affected by loss of mtDNA, indicating ineffective mitochondria-to-nucleus communication systems for these nuclear genes. Further, analysis of nuclear genes whose expression was compromised in 4T1ρ0cells showed that immune- and stress-related genes were the most highly differentially expressed, representing over 70% of those with greater than 16-fold higher expression in 4T1 compared with 4T1ρ0cells. The monocyte recruiting chemokine, Ccl2, and Psmb8, a subunit of the immunoproteasome that generates MHCI-binding peptides, were the most highly differentially expressed. Early monocyte/macrophage recruitment into the tumor mass was compromised in 4T1ρ0cells but recovered before mtDNA could be detected. Taken together, our results show that mitochondrial acquisition by tumor cells without mtDNA results in bioenergetic remodeling and re-expression of genes involved in immune function and stress adaptation.
Conditioned Variation in Heart Rate During Static Breath-Holds in the Bottlenose Dolphin (Tursiops truncatus)
Authors: Fahlman Andreas , Cozzi Bruno , Manley Mercy , Jabas Sandra , Malik Marek , Blawas Ashley , Janik Vincent M.
Published: November 2020

Previous reports suggested the existence of direct somatic motor control over heart rate (fH) responses during diving in some marine mammals, as the result of a cognitive and/or learning process rather than being a reflexive response. This would be beneficial for O2storage management, but would also allow ventilation-perfusion matching for selective gas exchange, where O2and CO2can be exchanged with minimal exchange of N2. Such a mechanism explains how air breathing marine vertebrates avoid diving related gas bubble formation during repeated dives, and how stress could interrupt this mechanism and cause excessive N2exchange. To investigate the conditioned response, we measured thefH-response before and during static breath-holds in three bottlenose dolphins (Tursiops truncatus) when shown a visual symbol to perform either a long (LONG) or short (SHORT) breath-hold, or during a spontaneous breath-hold without a symbol (NS). The averagefH(ifHstart), and the rate of change infH(difH/dt) during the first 20 s of the breath-hold differed between breath-hold types. In addition, the minimum instantaneousfH(ifHmin), and the average instantaneousfHduring the last 10 s (ifHend) also differed between breath-hold types. The difH/dt was greater, and the ifHstart, ifHmin, and ifHendwere lower during a LONG as compared with either a SHORT, or an NS breath-hold (P< 0.05). Even though the NS breath-hold dives were longer in duration as compared with SHORT breath-hold dives, the difH/dt was greater and the ifHstart, ifHmin, and ifHendwere lower during the latter (P< 0.05). In addition, when the dolphin determined the breath-hold duration (NS), thefHwas more variable within and between individuals and trials, suggesting a conditioned capacity to adjust thefH-response. These results suggest that dolphins have the capacity to selectively alter thefH-response during diving and provide evidence for significant cardiovascular plasticity in dolphins.
Biodiversity in Tomatoes: Is It Reflected in Nutrient Density and Nutritional Yields Under Organic Outdoor Production?
Authors: Erika Cut , Griebel Stefanie , Naumann Marcel , Pawelzik Elke
Published: November 2020

In many regions of the world, human nutrition is still characterized by an insufficient intake of essential nutrients like minerals such as iron (Fe) and zinc (Zn). In view of decreasing resources and a growing world population, the efficiency and the sustainability of cultivation systems should be considered not only in terms of crop yield and profit margin but also in terms of the yield of essential nutrients. Tomatoes are the most consumed vegetable in the world. Organic outdoor tomato cultivation is generally characterized by a higher diversity of varieties and lower fertilization input compared to conventional production. A 2-year field experiment with a set of 20 cultivars was performed to evaluate their variation regarding fruit mineral concentrations [potassium (K), calcium (Ca), magnesium (Mg), phosphorous (P), Fe, and Zn], their contribution to the dietary reference intake (DRI), and the nutritional yields (adults ha–1 year–1). Results show that mineral concentrations differed significantly by cultivar and by year. However, even though significant genotype-by-year effects appear, several cultivars exhibit high genotype stability across years for the single traits studied. Taking this together with medium-to-high heritability, genetics strongly controls most studied traits. Among the cultivars, the contribution of 100 g fresh fruits varied from 4.5 to 7.7% for K, 0.8 to 1.8% for Ca, 2.3 to 4.4% for Mg, 3 to 6.6% for P, 3.1 to 6.9% for Fe, and 1.9 to 4.2% for Zn to meet daily requirements. Based on average fruit yields per hectare, the cultivars varied with regard to the nutritional yields for all the studied minerals, but most strongly for Fe (44–120 adults ha–1 year–1) and Zn (22–84 adults ha–1 year–1). In terms of contribution to the DRI and nutritional yield for Fe, the cocktail cultivar “Bartelly F1” produced the highest results, while for Zn the salad cultivar “Bocati F1” showed the highest values. Our results show that the targeted use of tomato biodiversity in organic outdoor production can be suitable to achieve high fruit yields as well as to produce high nutritional yields per unit area, thus contributing to more effective land use and improved food security. These findings also provide valuable insights for tomato breeders to improve the tomato fruit quality while maintaining yield.
Detecting Authoritarianism Efficiently: Psychometric Properties of the Screening Instrument Authoritarianism – Ultra Short (A-US) in a German Representative Sample
Authors: Heller Ayline , Decker Oliver , Schmalbach Bjarne , Beutel Manfred , Fegert Jörg M. , Brähler Elmar , Zenger Markus
Published: November 2020

With right-wing-extremist and -populist parties and movements on the rise throughout the world, the concept of authoritarianism has proven to be particularly valuable to explain the psychological underpinnings of these tendencies. Even though many scales to measure the different dimensions of authoritarianism exist, no short screening instrument has been tested and validated on a large scale so far. The present study examines the psychometric properties of the screening instrument Authoritarianism – Ultrashort (A-US) in three representative German samples (n = 2,524, n = 2,478, and n = 2,495). Using exploratory and confirmatory factor analysis, the A-US demonstrated acceptable internal consistency. Model fit was good and correlations with related constructs indicated convergent validity in both samples. Construct validity was demonstrated using the original version of the scale. The instrument proved to be invariant across sex, employment status, and education, but not across different age groups. Finally, the analyses showed that differences in the A-US are associated with sociodemographic variables. Potential causes and effects of these findings are discussed. Based on these results, the A-US proved to be a valuable and highly efficient tool to screen for authoritarian tendencies.
How to Solve the Social Norm Conflict Dilemma of Green Consumption: The Moderating Effect of Self-Affirmation
Authors: Ge Wanda , Sheng Guanghua , Zhang Hongli
Published: November 2020

Social norms are important social factors that affect individual behavioral change. Using social norms to promote green consumption is receiving increasing attention. However, due to the different formation processes and mechanisms of the behavioral influence of the different types of social norms, using social norms to promote green consumption often has social norm conflict situations (injunctive norms + negative descriptive norms). Thus, it is difficult to attain the maximum utility of social norms. The present research found that social norm conflict weakens the role of injunctive norms in promoting green consumption. Specifically, negative descriptive norms weaken the role of injunctive norms in promoting green consumption. Alienation, which manifests through powerlessness and meaninglessness, plays a mediating role in the relationship between social norm conflict and green consumption. Self-affirmation moderates the mediating role of alienation between social norm conflicts and green consumption. Self-affirmation reduces the alienation caused by social norm conflict, thereby alleviating the weakening effect of social norm conflict on green consumption.
Human Cognitive Neuroscience as It Is Taught
Authors: Hauk Olaf
Published: November 2020

Cognitive neuroscience increasingly relies on complex data analysis methods. Researchers in this field come from highly diverse scientific backgrounds, such as psychology, engineering, and medicine. This poses challenges with respect to acquisition of appropriate scientific computing and data analysis skills, as well as communication among researchers with different knowledge and skills sets. Are researchers in cognitive neuroscience adequately equipped to address these challenges? Here, we present evidence from an online survey of methods skills. Respondents (n= 307) mainly comprised students and post-doctoral researchers working in the cognitive neurosciences. Multiple choice questions addressed a variety of basic and fundamental aspects of neuroimaging data analysis, such as signal analysis, linear algebra, and statistics. We analyzed performance with respect to the following factors: undergraduate degree (grouped into Psychology, Methods, and Biology), current researcher status (undergraduate student, PhD student, and post-doctoral researcher), gender, and self-rated expertise levels. Overall accuracy was 72%. Not surprisingly, the Methods group performed best (87%), followed by Biology (73%) and Psychology (66%). Accuracy increased from undergraduate (59%) to PhD (74%) level, but not from PhD to post-doctoral (74%) level. The difference in performance for the Methods vs. non-methods (Psychology/Biology) groups was especially striking for questions related to signal analysis and linear algebra, two areas particularly relevant to neuroimaging research. Self-rated methods expertise was not strongly predictive of performance. The majority of respondents (93%) indicated they would like to receive at least some additional training on the topics covered in this survey. In conclusion, methods skills among junior researchers in cognitive neuroscience can be improved, researchers are aware of this, and there is strong demand for more skills-oriented training opportunities. We hope that this survey will provide an empirical basis for the development of bespoke skills-oriented training programs in cognitive neuroscience institutions. We will provide practical suggestions on how to achieve this.