bluuebunny/crossref_metadata_2025 huggingface dataset:
Prediction of Sediment Yield in the Middle Reaches of the Yellow River Basin Under Extreme Precipitation
Authors: Dang Suzhen , Liu Xiaoyan , Yin Huijuan , Guo Xinwei
Published: December 2020

The Yellow River is one of the rivers with the largest amount of sediment in the world. The amount of incoming sediment has an important impact on water resources management, sediment regulation schemes, and the construction of water conservancy projects. The Loess Plateau is the main source of sediment in the Yellow River Basin. Floods caused by extreme precipitation are the primary driving forces of soil erosion in the Loess Plateau. In this study, we constructed the extreme precipitation scenarios based on historical extreme precipitation records in the main sediment-yielding area in the middle reaches of the Yellow River. The amount of sediment yield under current land surface conditions was estimated according to the relationship between extreme precipitation and sediment yield observations in the historical period. The results showed that the extreme rainfall scenario of the study area reaches to 159.9 mm, corresponding to a recurrence period of 460 years. The corresponding annual sediment yield under the current land surface condition was range from 0.821 billion tons to 1.899 billion tons, and the median annual sediment yield is 1.355 billion tons, of which more than 91.9% of sediment yields come from the Hekouzhen to Longmen sectionand the Jinghe River basin. Therefore, even though the vegetation of the Loess Plateau has been greatly improved, and a large number of terraces and check dams have been built, the flood control and key project operation of the Yellow River still need to be prepared to deal with the large amount of sediment transport.
A Social Learning Approach for Stakeholder Engagement in Large Carnivore Conservation and Management
Authors: Hovardas Tasos
Published: December 2020

The present paper reports on a methodology for stakeholder engagement in large carnivore conservation and management, which was implemented in a LIFE project in Greece (LIFE AMYBEAR: Improving Human-Bear Coexistence Conditions in Municipality of Amyntaio–LIFE15 NAT/GR/001108). The methodology was employed within the frame of human dimension actions in that project and included three different stages planned in a modular sequence (stakeholder analysis, stakeholder consultation and involvement, and participatory scenario development). Each stage was operationalized by means of a template (Strengths, Weaknesses, Opportunities, and Threats analysis template; mixed-motive template; template for participatory scenario development), which was designed to structure stakeholder input and interaction and scaffold social learning. The templates were completed by standard methods and procedures in social science, namely, interviews, focus groups, and workshops. The presentation of the methodology in this paper has a demonstration character. The main aim is to showcase its heuristic value in steering stakeholder collaboration and tracking change as a result of stakeholder joint action. The paper will demonstrate the benefits and added value of innovation and change initiated by actions in the LIFE project, as well as the costs or unintended consequences of that innovation and change, which need to be tackled by future stakeholder collaboration. The beginnings of an institutionalization of stakeholder involvement revealed features of both formal (e.g., new institutions established such as a Bear Emergency Team) and informal institutions (e.g., social norms). These features illustrated a departure from the current condition, where social learning may already be traceable. At the same time, however, stakeholder interaction has also delineated additional aspects that need to be addressed by stakeholders. The added value of the methodology is that it can be enacted by stakeholders themselves, provided that they are empowered to take ownership of the social learning process. Therefore, it can be exploited in after-LIFE plans. The approach can also be used in other multi-stakeholder arrangements, such as platforms concentrated on wildlife conservation and management. Finally, it should be noted that the methodology and templates fill an important gap, often highlighted in the social learning literature, in that they offer a toolkit for monitoring and assessment.
Th17/Treg-Related Transcriptional Factor Expression and Cytokine Profile in Patients With Rheumatoid Arthritis
Authors: Paradowska-Gorycka Agnieszka , Wajda Anna , Romanowska-Próchnicka Katarzyna , Walczuk Ewa , Kuca-Warnawin Ewa , Kmiolek Tomasz , Stypinska Barbara , Rzeszotarska Ewa , Majewski Dominik , Jagodzinski Pawel Piotr , Pawlik Andrzej
Published: December 2020

Objectives

The aim of our study was to determine whether there is a correlation between transcription factors expression and Th17/Treg ratio, cytokine profile in the RA phenotype as well as to identify transcription factors that could be a potential biomarker for RA.

Methods

The study was conducted on 45 patients with RA, 27 patients with OA and 46 healthy controls (HCs). Th17 and Treg frequency was determined by flow cytometry (15 patients with RA/OA and 15 subjects of HC). Gene expression was estimated by qPCR, and the serum cytokine levels were determined by ELISA.

Results

The percentage of Treg (CD4+CD25highCD127-) cells in RA patients was lower than in OA patients or HCs. Proportions of Th17 (CD4+CCR6+CXCR3-) cells were higher in RA and OA in comparison to HCs. STAT5 showed a very high expression in the blood of RA patients compared to healthy subjects. The expression of STAT5 and HELIOS was not detected in Th17 cells. A positive correlation between SMAD3 and STAT3 in RA patients was observed. Negative correlations between HIF-1A and SMAD2 in RA Treg cells and DAS-28 score were observed. The range of serum of IL-17 and IL-21 were higher in RA patients than in OA patients. Concentrations of serum IL-2 and IFN-γ were higher in RA and OA patients than in healthy subjects. Based on the ROC analysis, the diagnostic potential of the combination of HIF1A, SMAD3 and STAT3, was determined at AUC 0.95 for distinguishing RA patients from HCs. For distinguishing RA patients from OA patients the diagnostic potential of the combination of SMAD2, SMAD3, SMAD4 and STAT3, was determined at AUC 0.95.

Conclusion

Based on our study, we conclude that SMAD3 and STAT3 could be potential diagnostic biomarkers for RA.
NLRX1 Deletion Increases Ischemia-Reperfusion Damage and Activates Glucose Metabolism in Mouse Heart
Authors: Zhang Hong , Xiao Yang , Nederlof Rianne , Bakker Diane , Zhang Pengbo , Girardin Stephen E. , Hollmann Markus W. , Weber Nina C. , Houten Sander M. , van Weeghel Michel , Kibbey Richard G. , Zuurbier Coert J.
Published: December 2020

Background

NOD-like receptors (NLR) are intracellular sensors of the innate immune system, with the NLRP3 being a pro-inflammatory member that modulates cardiac ischemia-reperfusion injury (IRI) and metabolism. No information is available on a possible role of anti-inflammatory NLRs on IRI and metabolism in the intact heart. Here we hypothesize that the constitutively expressed, anti-inflammatory mitochondrial NLRX1, affects IRI and metabolism of the isolated mouse heart.

Methods

Isolated C57Bl/6J and NLRX1 knock-out (KO) mouse hearts were perfused with a physiological mixture of the essential substrates (lactate, glucose, pyruvate, fatty acid, glutamine) and insulin. For the IRI studies, hearts were subjected to either mild (20 min) or severe (35 min) ischemia and IRI was determined at 60 min reperfusion. Inflammatory mediators (IL-6, TNFα) and survival pathways (mito-HKII, p-Akt, p-AMPK, p-STAT3) were analyzed at 5 min of reperfusion. For the metabolism studies, hearts were perfused for 35 min with either 5.5 mM 13C-glucose or 0.4 mM 13C-palmitate under normoxic conditions, followed by LC-MS analysis and integrated, stepwise, mass-isotopomeric flux analysis (MIMOSA).

Results

NLRX1 KO significantly increased IRI (infarct size from 63% to 73%, end-diastolic pressure from 59 mmHg to 75 mmHg, and rate-pressure-product recovery from 15% to 6%), following severe, but not mild, ischemia. The increased IRI in NLRX1 KO hearts was associated with depressed Akt signaling at early reperfusion; other survival pathways or inflammatory parameters were not affected. Metabolically, NLRX1 KO hearts displayed increased lactate production and glucose oxidation relative to fatty acid oxidation, associated with increased pyruvate dehydrogenase flux and 10% higher cardiac oxygen consumption.

Conclusion

Deletion of the mitochondrially-located NOD-like sensor NLRX1 exacerbates severe cardiac IR injury, possibly through impaired Akt signaling, and increases cardiac glucose metabolism.
Intestinal Transcriptome Analysis Reveals Soy Derivative-Linked Changes in Atlantic Salmon
Authors: Kiron Viswanath , Park Youngjin , Siriyappagouder Prabhugouda , Dahle Dalia , Vasanth Ghana K. , Dias Jorge , Fernandes Jorge M. O. , Sørensen Mette , Trichet Viviane Verlhac
Published: December 2020

Intestinal inflammation in farmed fish is a non-infectious disease that deserves attention because it is a major issue linked to carnivorous fishes. The current norm is to formulate feeds based on plant-derived substances, and the ingredients that have antinutritional factors are known to cause intestinal inflammation in fishes such as Atlantic salmon. Hence, we studied inflammatory responses in the distal intestine of Atlantic salmon that received a feed rich in soybean derivatives, employing histology, transcriptomic and flow cytometry techniques. The fish fed on soy products had altered intestinal morphology as well as upregulated inflammation-associated genes and aberrated ion transport-linked genes. The enriched pathways for the upregulated genes were among others taurine and hypotaurine metabolism, drug metabolism—cytochrome P450 and steroid biosynthesis. The enriched gene ontology terms belonged to transmembrane transporter- and channel-activities. Furthermore, soybean products altered the immune cell counts; lymphocyte-like cell populations were significantly higher in the whole blood of fish fed soy products than those of control fish. Interestingly, the transcriptome of the head kidney did not reveal any differential gene expression, unlike the observations in the distal intestine. The present study demonstrated that soybean derivatives could evoke marked changes in intestinal transport mechanisms and metabolic pathways, and these responses are likely to have a significant impact on the intestine of Atlantic salmon. Hence, soybean-induced enteritis in Atlantic salmon is an ideal model to investigate the inflammatory responses at the cellular and molecular levels.
Importance of Type I and III Interferons at Respiratory and Intestinal Barrier Surfaces
Authors: Stanifer Megan L. , Guo Cuncai , Doldan Patricio , Boulant Steeve
Published: December 2020

Interferons (IFNs) constitute the first line of defense against microbial infections particularly against viruses. They provide antiviral properties to cells by inducing the expression of hundreds of genes known as interferon-stimulated genes (ISGs). The two most important IFNs that can be produced by virtually all cells in the body during intrinsic innate immune response belong to two distinct families: the type I and type III IFNs. The type I IFN receptor is ubiquitously expressed whereas the type III IFN receptor’s expression is limited to epithelial cells and a subset of immune cells. While originally considered to be redundant, type III IFNs have now been shown to play a unique role in protecting mucosal surfaces against pathogen challenges. The mucosal specific functions of type III IFN do not solely rely on the restricted epithelial expression of its receptor but also on the distinct means by which type III IFN mediates its anti-pathogen functions compared to the type I IFN. In this review we first provide a general overview on IFNs and present the similarities and differences in the signal transduction pathways leading to the expression of either type I or type III IFNs. By highlighting the current state-of-knowledge of the two archetypical mucosal surfaces (e.g.the respiratory and intestinal epitheliums), we present the differences in the signaling cascades used by type I and type III IFNs to uniquely induce the expression of ISGs. We then discuss in detail the role of each IFN in controlling pathogen infections in intestinal and respiratory epithelial cells. Finally, we provide our perspective on novel concepts in the field of IFN (stochasticity, response heterogeneity, cellular polarization/differentiation and tissue microenvironment) that we believe have implications in driving the differences between type I and III IFNs and could explain the preferences for type III IFNs at mucosal surfaces.
How to Estimate the Binder: Aggregate Ratio From Lime-Based Historic Mortars for Restoration?
Authors: Loureiro Alexandre Máximo Silva , Paz Simone Patrícia Aranha da , Angélica Rômulo Simões
Published: December 2020

One of the most important studies from historic mortars is the binder:aggregate ratio, which is usually obtained through wet chemical analysis. Instrumental techniques and benchtop equipment have become increasingly important tools in the characterization of historic materials. The analysis of such materials has become more practical, faster and more accurate, and the sample preparation methods require less and less material. Thus, this article aims to investigate the validity of the results obtained by some of the methods and techniques used in historic materials analysis and determine the possibility of estimating the binder:aggregate ratio with adequate accuracy and precision. For this purpose, historic mortars from Belém do Pará, in northern Brazil, were selected, and the following quantification techniques were employed: wet chemical analysis, XRD, DSC and XRF. The results showed that the amounts of the components in the mortars could be quantified with the use of approximately 3 g of sample, thus providing one of the main pieces of information needed for the production of a restoration mortar: the binder:aggregate ratio.
A Potential Peptide From Soy Cheese Produced Using Lactobacillus delbrueckii WS4 for Effective Inhibition of SARS-CoV-2 Main Protease and S1 Glycoprotein
Authors: Chourasia Rounak , Padhi Srichandan , Chiring Phukon Loreni , Abedin Md Minhajul , Singh Sudhir P. , Rai Amit Kumar
Published: December 2020

The COVID-19 pandemic caused by novel SARS-CoV-2 has resulted in an unprecedented loss of lives and economy around the world. In this study, search for potential inhibitors against two of the best characterized SARS-CoV-2 drug targets: S1 glycoprotein receptor-binding domain (RBD) and main protease (3CLPro), was carried out using the soy cheese peptides. A total of 1,420 peptides identified from the cheese peptidome produced using Lactobacillus delbrueckii WS4 were screened for antiviral activity by employing the web tools, AVPpred, and meta-iAVP. Molecular docking studies of the selected peptides revealed one potential peptide “KFVPKQPNMIL” that demonstrated strong affinity toward significant amino acid residues responsible for the host cell entry (RBD) and multiplication (3CLpro) of SARS-CoV-2. The peptide was also assessed for its ability to interact with the critical residues of S1 RBD and 3CLpro of other β-coronaviruses. High binding affinity was observed toward critical amino acids of both the targeted proteins in SARS-CoV, MERS-CoV, and HCoV-HKU1. The binding energy of KFVPKQPNMIL against RBD and 3CLpro of the four viruses ranged from −8.45 to −26.8 kcal/mol and −15.22 to −22.85 kcal/mol, respectively. The findings conclude that cheese, produced by using Lb. delbrueckii WS4, could be explored as a prophylactic food for SARS-CoV-2 and related viruses. In addition, the multi-target inhibitor peptide, which effectively inhibited both the viral proteins, could further be used as a terminus a quo for the in vitro and in vivo function against SARS-CoV-2.
Exploring the Neural Structures Underlying the Procedural Memory Network as Predictors of Language Ability in Children and Adolescents With Autism Spectrum Disorder and Attention Deficit Hyperactivity Disorder
Authors: Sanjeevan Teenu , Hammill Christopher , Brian Jessica , Crosbie Jennifer , Schachar Russell , Kelley Elizabeth , Liu Xudong , Nicolson Robert , Iaboni Alana , Day Fragiadakis Susan , Ristic Leanne , Lerch Jason P. , Anagnostou Evdokia
Published: December 2020

Introduction: There is significant overlap in the type of structural language impairments exhibited by children with autism spectrum disorder (ASD) and children with attention deficit hyperactivity disorder (ADHD). This similarity suggests that the cognitive impairment(s) contributing to the structural language deficits in ASD and ADHD may be shared. Previous studies have speculated that procedural memory deficits may be the shared cognitive impairment. The procedural deficit hypothesis (PDH) argues that language deficits can be explained by differences in the neural structures underlying the procedural memory network. This hypothesis is based on the premise that the neural structures comprising the procedural network support language learning. In this study, we aimed to test the PDH in children with ASD, ADHD, and typical development (TD).

Methods: One hundred and sixty-three participants (ages 10–21): 91 with ASD, 26 with ADHD, and 46 with TD, completed standardized measures of cognitive and language ability as well as structural magnetic resonance imaging. We compared the structural language abilities, the neural structures underlying the procedural memory network, and the relationship between structural language and neural structure across diagnostic groups.

Results: Our analyses revealed that while the structural language abilities differed across ASD, ADHD, and TD groups, the thickness, area, and volume of the structures supporting the procedural memory network were not significantly different between diagnostic groups. Also, several neural structures were associated with structural language abilities across diagnostic groups. Only two of these structures, the inferior frontal gyrus, and the left superior parietal gyrus, are known to be linked to the procedural memory network.

Conclusions: The inferior frontal gyrus and the left superior parietal gyrus, have well-established roles in language learning independent of their role as part of the procedural memory system. Other structures such as the caudate and cerebellum, with critical roles in the procedural memory network, were not associated with structural language abilities across diagnostic groups. It is unclear whether the procedural memory network plays a fundamental role in language learning in ASD, ADHD, and TD.
Changes in Electroencephalography and Cardiac Autonomic Function During Craft Activities: Experimental Evidence for the Effectiveness of Occupational Therapy
Authors: Shiraiwa Keigo , Yamada Sumie , Nishida Yurika , Toichi Motomi
Published: December 2020

Occupational therapy often uses craft activities as therapeutic tools, but their therapeutic effectiveness has not yet been adequately demonstrated. The aim of this study was to examine changes in frontal midline theta rhythm (Fmθ) and autonomic nervous responses during craft activities, and to explore the physiological mechanisms underlying the therapeutic effectiveness of occupational therapy. To achieve this, we employed a simple craft activity as a task to induce Fmθ and performed simultaneous EEG and ECG recordings. For participants in which Fmθ activities were provoked, parasympathetic and sympathetic activities were evaluated during the appearance of Fmθ and rest periods using the Lorenz plot analysis. Both parasympathetic and sympathetic indices increased with the appearance of Fmθ compared to during resting periods. This suggests that a relaxed-concentration state is achieved by concentrating on craft activities. Furthermore, the appearance of Fmθ positively correlated with parasympathetic activity, and theta band activity in the frontal area were associated with sympathetic activity. This suggests that there is a close relationship between cardiac autonomic function and Fmθ activity.
Parallel Spatial–Temporal Self-Attention CNN-Based Motor Imagery Classification for BCI
Authors: Liu Xiuling , Shen Yonglong , Liu Jing , Yang Jianli , Xiong Peng , Lin Feng
Published: December 2020

Motor imagery (MI) electroencephalography (EEG) classification is an important part of the brain-computer interface (BCI), allowing people with mobility problems to communicate with the outside world via assistive devices. However, EEG decoding is a challenging task because of its complexity, dynamic nature, and low signal-to-noise ratio. Designing an end-to-end framework that fully extracts the high-level features of EEG signals remains a challenge. In this study, we present a parallel spatial–temporal self-attention-based convolutional neural network for four-class MI EEG signal classification. This study is the first to define a new spatial-temporal representation of raw EEG signals that uses the self-attention mechanism to extract distinguishable spatial–temporal features. Specifically, we use the spatial self-attention module to capture the spatial dependencies between the channels of MI EEG signals. This module updates each channel by aggregating features over all channels with a weighted summation, thus improving the classification accuracy and eliminating the artifacts caused by manual channel selection. Furthermore, the temporal self-attention module encodes the global temporal information into features for each sampling time step, so that the high-level temporal features of the MI EEG signals can be extracted in the time domain. Quantitative analysis shows that our method outperforms state-of-the-art methods for intra-subject and inter-subject classification, demonstrating its robustness and effectiveness. In terms of qualitative analysis, we perform a visual inspection of the new spatial–temporal representation estimated from the learned architecture. Finally, the proposed method is employed to realize control of drones based on EEG signal, verifying its feasibility in real-time applications.
The Inferior Colliculus in Alcoholism and Beyond
Authors: Bordia Tanuja , Zahr Natalie M.
Published: December 2020

Post-mortem neuropathological andin vivoneuroimaging methods have demonstrated the vulnerability of the inferior colliculus to the sequelae of thiamine deficiency as occurs in Wernicke-Korsakoff Syndrome (WKS). A rich literature in animal models ranging from mice to monkeys—including our neuroimaging studies in rats—has shown involvement of the inferior colliculi in the neural response to thiamine depletion, frequently accomplished with pyrithiamine, an inhibitor of thiamine metabolism. In uncomplicated alcoholism (i.e., absent diagnosable neurological concomitants), the literature citing involvement of the inferior colliculus is scarce, has nearly all been accomplished in preclinical models, and is predominately discussed in the context of ethanol withdrawal. Our recent work using novel, voxel-based analysis of structural Magnetic Resonance Imaging (MRI) has demonstrated significant, persistent shrinkage of the inferior colliculus using acute and chronic ethanol exposure paradigms in two strains of rats. We speculate that these consistent findings should be considered from the perspective of the inferior colliculi having a relatively high CNS metabolic rate. As such, they are especially vulnerable to hypoxic injury and may be provide a common anatomical link among a variety of disparate insults. An argument will be made that the inferior colliculi have functions, possibly related to auditory gating, necessary for awareness of the external environment. Multimodal imaging including diffusion methods to provide more accuratein vivovisualization and quantification of the inferior colliculi may clarify the roles of brain stem nuclei such as the inferior colliculi in alcoholism and other neuropathologies marked by altered metabolism.
A Nomogram for Pretreatment Prediction of Response to Induction Chemotherapy in Locally Advanced Hypopharyngeal Carcinoma
Authors: Guo Baoliang , Ouyang Fusheng , Ouyang Lizhu , Huang Xiyi , Chen Haixiong , Guo Tiandi , Yang Shao-min , Meng Wei , Liu Ziwei , Zhou Cuiru , Hu Qiu-gen
Published: December 2020

Background

Induction chemotherapy (IC) significantly improves the rate of larynx preservation; however, some patients could not benefit from it. Hence, it is of clinical importance to predict the response to IC to determine the necessity of IC. We aimed to develop a clinical nomogram for predicting the treatment response to IC in locally advanced hypopharyngeal carcinoma.

Methods

We retrospectively include a total of 127 patients with locally advanced hypopharyngeal carcinoma who underwent MRI scans prior to IC between January 2014 and December 2017. The clinical characteristics were collected, which included age, sex, tumor location, invading sites, histological grades, T-stage, N-stage, overall stage, size of the largest lymph node, neutrophil-to-lymphocyte ratio, hemoglobin concentration, and platelet count. Univariate and multivariate logistic regression was used to select the significant predictors of IC response. A nomogram was built based on the results of stepwise logistic regression analysis. The predictive performance and clinical usefulness of the nomogram were determined based on the area under the curve (AUC), calibration curve, and decision curve.

Results

Age, T-stage, hemoglobin, and platelet were four independent predictors of IC treatment response, which were incorporated into the nomogram. The AUC of the nomogram was 0.860 (95% confidence interval [CI]: 0.780-0.940), which was validated using 3-fold cross-validation (AUC, 0.864; 95% CI: 0.755-0.973). The calibration curve demonstrated good consistency between the prediction by the nomogram and actual observation. Decision curve analysis shows that the nomogram was clinically useful.

Conclusion

The proposed nomogram resulted in an accurate prediction of the efficacy of IC for patients with locally advanced hypopharyngeal carcinoma.
Meningiomas in Premenopausal Women: Role of the Hormone Related Conditions
Authors: Maiuri Francesco , Mariniello Giuseppe , Somma Teresa , Guadagno Elia , Corvino Sergio , Pagano Serena , Orlando Valentina , Del Basso De Caro Marialaura
Published: December 2020

Background

Several epidemiological and pathological findings suggest that the female sex hormones may influence the development of meningiomas. However, the role of pregnancy, oral contraceptives, and fertilization therapies is still controversial.

Methods

From the surgical series of 354 patients with meningiomas operated between 2006 and 2019, the group of 72 premenopausal women was separately considered. The tumor location, WHO grade, Ki67-labeling index (LI), progesterone receptor (PR) expression, and histological types were studied in premenopausal women with and without hormone-related conditions were compared.

Results

In this premenopausal group, 24 patients had hormone-related conditions, including use of oral contraceptives in 16, intrauterine fertilization in one, pregnancy in three, and tumors of the female reproductive system in four. The group of patients with hormone-related conditions, as compared to that with no hormone related conditions, showed slightly lower median age (38 versus 43 years) and no significant difference of meningioma location WHO grade, Ki 67-Li, PR expression and histological type. The clinical onset during pregnancy in three patients and tumor growth during contraceptive progesterone therapy in two others were evidenced.

Conclusion

The biological behavior of meningiomas and their pathological findings, including PR expression, are not correlated with the different hormone related conditions in premenopausal female patients. Contraceptives and fertilization therapies, mainly with progesterone, should be avoided in patients with meningiomas.
Altered T-Lymphocyte Biology Following High-Dose Melphalan and Autologous Stem Cell Transplantation With Implications for Adoptive T-Cell Therapy
Authors: Mika Thomas , Ladigan-Badura Swetlana , Maghnouj Abdelouahid , Mustafa Bakr , Klein-Scory Susanne , Baraniskin Alexander , Döhring Sascha , Fuchs Ilka , Ehl Stephan , Hahn Stephan A. , Schroers Roland
Published: December 2020

In relapsed and refractory multiple myeloma (MM), adoptive cell therapies (ACT) including CAR-T-cells are under clinical investigation. However, relapse due to T-cell exhaustion or limited persistence is an obstacle. Before ACT are considered in MM, high-dose (HD) melphalan followed by autologous stem-cell transplantation (autoSCT) has been administered in most clinical situations. Yet, the impact of HD chemotherapy on T-cells in MM with respect to ACT is unclear. In this study, T-lymphocytes’ phenotypes, expansion properties, lentiviral transduction efficacy, and gene expression were examined with special respect to patients following HD melphalan. Significant impairment of T-cells’ expansion and transduction rates could be demonstrated. Expansion was diminished due to inherent disadvantages of the predominant T-cell phenotype but restored over time. The quantitative fraction of CD27−/CD28− T-cells before expansion was predictive of T-cell yield. Following autoSCT, the transduction efficacy was reduced by disturbed lentiviral genome integration. Moreover, an unfavorable T-cell phenotype after expansion was demonstrated. In initial analyses of CD107a degranulation impaired T-cell cytotoxicity was detected in one patient following melphalan and autoSCT. The findings of our study have potential implications regarding the time point of leukapheresis for CAR-T-cell manufacturing. Our results point to a preferred interval of more than 3 months until patients should undergo cell separation for CAR-T therapy in the specific situation post-HD melphalan/autoSCT. Monitoring of CD27−/CD28− T-cells, has the potential to influence clinical decision making before apheresis in MM.
Development and Validation of a Nomogram for Predicting Radiation-Induced Temporal Lobe Injury in Nasopharyngeal Carcinoma
Authors: Guan Wenqiang , Xie Kang , Fan Yixin , Lin Stefan , Huang Rui , Tang Qianlong , Chen Ailin , Song Yanqiong , Lang Jinyi , Zhang Peng
Published: December 2020

Background

The purpose was to develop and validate a nomogram for prediction on radiation-induced temporal lobe injury (TLI) in patients with nasopharyngeal carcinoma (NPC).

Methods

The prediction model was developed based on a primary cohort that consisted of 194 patients. The data was gathered from January 2008 to December 2010. Clinical factors associated with TLI and dose–volume histograms for 388 evaluable temporal lobes were analyzed. Multivariable logistic regression analysis was used to develop the predicting model, which was conducted by R software. The performance of the nomogram was assessed with calibration and discrimination. An external validation cohort contained 197 patients from January 2011 to December 2013.

Results

Among the 391 patients, 77 patients had TLI. Prognostic factors contained in the nomogram were Dmax (the maximum point dose) of temporal lobe, D1cc (the maximum dose delivered to a volume of 1 ml), T stage, and neutrophil-to-lymphocyte ratios (NLRs). The Internal validation showed good discrimination, with a C-index of 0.847 [95%CI 0.800 to 0.893], and good calibration. Application of the nomogram in the external validation cohort still obtained good discrimination (C-index, 0.811 [95% CI, 0.751 to 0.870]) and acceptable calibration.

Conclusions

This study developed and validated a nomogram, which may be conveniently applied for the individualized prediction of TLI.
Immunomodulatory Mechanism and Potential Therapies for Perinatal Hypoxic-Ischemic Brain Damage
Authors: Min Ying-Jun , Ling Eng-Ang , Li Fan
Published: December 2020

Hypoxia-ischemia (HI) is one of the most common causes of death and disability in neonates. Currently, the only available licensed treatment for perinatal HI is hypothermia. However, it alone is not sufficient to prevent the brain injuries and/or neurological dysfunction related to HI. Perinatal HI can activate the immune system and trigger the peripheral and central responses which involve the immune cell activation, increase in production of immune mediators and release of reactive oxygen species. There is mounting evidence indicating that regulation of immune response can effectively rescue the outcomes of brain injury in experimental perinatal HI models such as Rice-Vannucci model of newborn hypoxic-ischemic brain damage (HIBD), local transient cerebral ischemia and reperfusion model, perinatal asphyxia model, and intrauterine hypoxia model. This review summarizes the many studies about immunomodulatory mechanisms and therapies for HI. It highlights the important actions of some widely documented therapeutic agents for effective intervening of HI related brain damage, namely, HIBD, such as EPO, FTY720, Minocycline, Gastrodin, Breviscapine, Milkvetch etc. In this connection, it has been reported that the ameboid microglial cells featured prominently in the perinatal brain represent the key immune cells involved in HIBD. To this end, drugs, chemical agents and herbal compounds which have the properties to suppress microglia activation have recently been extensively explored and identified as potential therapeutic agents or strategies for amelioration of neonatal HIBD.
Chemical Composition of Pterospermum heterophyllum Root and its Anti-Arthritis Effect on Adjuvant-Induced Arthritis in Rats via Modulation of Inflammatory Responses
Authors: Yang Li , Liu Ronghua , Fan Aiguo , Zhao Jingjing , Zhang Yong , He Junwei
Published: December 2020

Rheumatoid arthritis (RA) is a chronic autoimmune inflammatory disease without effective and beneficial drugs. Many traditional folk medicines have been proven to be effective in treating RA. Among these, the root of Pterospermum heterophyllum Hance has been widely used as a traditional remedy against RA in China, but there is no scientific basis yet. The aim of this study was to investigate for the first time the chemical compositions and therapeutic effect of P. heterophyllum on adjuvant-induced arthritis (AIA) model in rats. 73 compounds were identified from P. heterophyllum based on ultra-performance liquid chromatography-quadrupole time-of-flight tandem mass spectrometry (UPLC-qTOF-MS/MS), and flavonoids may be partly responsible for the major anti-arthritic effect. In parallel, the P. heterophyllum extract at 160, 320, and 640 mg/kg/day were orally administered to rats for 22 days after post-administration adjuvant. The results showed that P. heterophyllum remarkably ameliorated histological lesions of the knee joint, increased body weight growth, decreased arthritis score, reduced thymus and spleen indices in model rats. Moreover, P. heterophyllum treatment persuasively downregulated the levels of rheumatoid factor (RF), C-reactive protein (CRP), tumor necrosis factor alpha (TNF-α), interleukin-1β (IL-1β), IL-6, IL-17, cyclooxygenase-2 (COX-2), 5-lipoxygenase (5-LOX) and matrix metalloproteinase-2 (MMP-2), and observably upregulated IL-4 and IL-10 levels in model rats. These findings suggest that P. heterophyllum has a prominent anti-RA effect on AIA rats by modulating the inflammatory responses, and supports the traditional folk use of this plant.
Increasing Trends in Opioid Use From 2010 to 2018 in the Region of Valencia, Spain: A Real-World, Population-Based Study
Authors: Hurtado Isabel , García-Sempere Aníbal , Peiró Salvador , Sanfélix-Gimeno Gabriel
Published: December 2020

Background: The opioid epidemic has been extensively documented in the United States and Canada, but fewer data are available for Europe.

Aim: To describe the trends in opioid use—volume of prescriptions, dosage and number of patients treated—in a Spanish population with more than 4.2 million inhabitants aged 18 years and older.

Patients and Methods: Population-based cross-sectional analysis of opioid prescription in adults (≥18 years) from January 1, 2010 to December 31, 2018 in the region of Valencia, Spain. Outcomes were estimated on an annual basis: number of prescriptions, prescription rate per 100 inhabitants, dosage per capita (morphine mg equivalents, MME/c) and volume of patients treated (overall and by drug).

Results: Over the study period, 2,107,756 unique patients were prescribed more than 35 million total treatments. The yearly number of treatments doubled, and total MME/c showed almost a threefold increase. Fentanyl MME/c more than tripled, accounting for 34.4% of the total MME/c in 2018. Oxycodone MME/c showed a 10-fold increase, while tapentadol, launched in 2011, showed the highest growth rates. The annual number of patients receiving at least one opioid prescription more than doubled, from 335,379 in 2010 to 722,838 in 2018.

Conclusions: Even if proportions still seem far from epidemic, urgent research is warranted on the observed patterns of use, their appropriateness and their association with health and safety outcomes, especially for high-use and high-strength drugs.
Why Does the Face Predict the Brain? Neural Crest Induction, Craniofacial Morphogenesis, and Neural Circuit Development
Authors: LaMantia Anthony-Samuel
Published: December 2020

Mesenchephalic and rhombencephalic neural crest cells generate the craniofacial skeleton, special sensory organs, and subsets of cranial sensory receptor neurons. They do so while preserving the anterior-posterior (A-P) identity of their neural tube origins. This organizational principle is paralleled by central nervous system circuits that receive and process information from facial structures whose A-P identity is in register with that in the brain. Prior to morphogenesis of the face and its circuits, however, neural crest cells act as “inductive ambassadors” from distinct regions of the neural tube to induce differentiation of target craniofacial domains and establish an initial interface between the brain and face. At every site of bilateral, non-axial secondary induction, neural crest constitutes all or some of the mesenchymal compartment for non-axial mesenchymal/epithelial (M/E) interactions. Thus, for epithelial domains in the craniofacial primordia, aortic arches, limbs, the spinal cord, and the forebrain (Fb), neural crest-derived mesenchymal cells establish local sources of inductive signaling molecules that drive morphogenesis and cellular differentiation. This common mechanism for building brains, faces, limbs, and hearts, A-P axis specified, neural crest-mediated M/E induction, coordinates differentiation of distal structures, peripheral neurons that provide their sensory or autonomic innervation in some cases, and central neural circuits that regulate their behavioral functions. The essential role of this neural crest-mediated mechanism identifies it as a prime target for pathogenesis in a broad range of neurodevelopmental disorders. Thus, the face and the brain “predict” one another, and this mutual developmental relationship provides a key target for disruption by developmental pathology.
Lactate Metabolism and Satellite Cell Fate
Authors: Nalbandian Minas , Radak Zsolt , Takeda Masaki
Published: December 2020

Lactate is one of the metabolic products of glycolysis. It is widely accepted as an important energy source for many cell types and more recently has been proposed to actively participate in cell-cell communication. Satellite cells (SCs), which are adult skeletal muscle stem cells, are the main players of the skeletal muscle regeneration process. Recent studies have proposed a metabolic switch to increase glycolysis in activated SCs. Moreover, lactate has been shown to affect SCs and myoblasts in vivo and in vitro. In this short review, we describe how metabolic variations relate with SC fate (quiescence, activation, proliferation, migration, differentiation, fusion, and self-renewal), as well as discuss possible relationships between lactate as a metabolite and as a signaling molecule affecting SC fate.
Targeted Transgene Expression in Rice Using a Callus Strong Promoter for Selectable Marker Gene Control
Authors: Zhou Jie , Li Dongyue , Zheng Chao , Xu Rumeng , Zheng Ersong , Yang Yong , Chen Yang , Yu Chulang , Yan Chengqi , Chen Jianping , Wang Xuming
Published: December 2020

Precise expression of a transgene in the desired manner is important for plant genetic engineering and gene function deciphering, but it is a challenge to obtain specific transgene expression free from the interference of the constitutive promoters used to express the selectable marker gene, such as the Cauliflower mosaic virus (CaMV) 35S promoter. So, the solutions to avoid these inappropriate regulations are largely demanded. In this study, we report the characterization of a callus strong promoter (CSP1) in rice and its application for accurate transgene expression. Our results indicate that the high expression of theCSP1promoter in the callus enables efficient selection of hygromycin equivalent to that provided by the CaMV 35S promoter, whereas its expression in other tissues is low. To evaluate possible leaky effects, the expression of a β-glucuronidase reporter driven by six specific promoters involving hormone signaling, pathogen response, cell fate determination, and proliferation was observed in transgenic rice plants generated byCSP1-mediated selection. Distinct β-glucuronidase expression was found consistently in most of the transgenic lines obtained for each promoter. In addition, we applied these specific marker lines to investigate the root cellular responses to exogenous cytokinin and auxin treatment. The results reveal that the root growth inhibition by cytokinin was differently regulated at high and low concentrations. In summary, we have established the feasibility of using callus-specific promoter-dependent selection to mitigate the transgene misexpression in rice. By enabling efficient transformation, rice plants with reliable transgene expression will be easily acquired for broad applications.
What Makes Musical Prodigies?
Authors: Marion-St-Onge Chanel , Weiss Michael W. , Sharda Megha , Peretz Isabelle
Published: December 2020

Musical prodigies reach exceptionally high levels of achievement before adolescence. Despite longstanding interest and fascination in musical prodigies, little is known about their psychological profile. Here we assess to what extent practice, intelligence, and personality make musical prodigies a distinct category of musician. Nineteen former or current musical prodigies (aged 12–34) were compared to 35 musicians (aged 14–37) with either an early (mean age 6) or late (mean age 10) start but similar amount of musical training, and 16 non-musicians (aged 14–34). All completed a Wechsler IQ test, the Big Five Inventory, the Autism Spectrum Quotient, the Barcelona Music Reward Questionnaire, the Dispositional Flow Scale, and a detailed history of their lifetime music practice. None of the psychological traits distinguished musical prodigies from control musicians or non-musicians except their propensity to report flow during practice. The other aspects that differentiated musical prodigies from their peers were the intensity of their practice before adolescence, and the source of their motivation when they began to play. Thus practice, by itself, does not make a prodigy. The results are compatible with multifactorial models of expertise, with prodigies lying at the high end of the continuum. In summary, prodigies are expected to present brain predispositions facilitating their success in learning an instrument, which could be amplified by their early and intense practice happening at a moment when brain plasticity is heightened.
Understanding the Effects of Antecedents on Continuance Intention to Gather Food Safety Information on Websites
Authors: Tsai Hsinyeh , Lee Yu-Ping , Ruangkanjanases Athapol
Published: December 2020

Virtual community websites are one of the applications that provide a platform for people with common interests to extend their social relations in social media. With the proliferation of food safety incidents in recent years, social media has often been a major channel for public engagement in risk communication because of its social networking and immediate interaction. To understand the users’ needs and satisfaction, this study proposed a model to develop and evaluate the antecedents of continuance intention toward food safety information from social media. Based on the questionnaire collected from 289 Facebook users, this study assessed the integrated model of the expectation-confirmation theory and technology acceptance model with technology readiness as moderator. The results showed that the perceived ease-of-use, usefulness, and confirmation indirectly affected social media continuance usage intention through satisfaction; perceived ease-of-use, usefulness, and satisfaction were the direct determinants that affected the users’ social media continuance intention. Furthermore, positive technology readiness had significant effects on the relationship between the perceived ease-of-use, usefulness, confirmation, satisfaction, and continuance intention toward food safety information. This study contributes some important suggestions and managerial implications for food safety promotion providers, practitioners, and academics in the food industry, and social media environment.
Beyond Stereotypes: Analyzing Gender and Cultural Differences in Nonverbal Rapport
Authors: Bente Gary , Novotny Eric , Roth Daniel , Al-Issa Ahmad
Published: December 2020

The current paper addresses two methodological problems pertinent to the analysis of observer studies in nonverbal rapport and beyond. These problems concern: (1) the production of standardized stimulus materials that allow for unbiased observer ratings and (2) the objective measurement of nonverbal behaviors to identify the dyadic patterns underlying the observer impressions. We suggest motion capture and character animation as possible solutions to these problems and exemplarily apply the novel methodology to the study of gender and cultural differences in nonverbal rapport. We compared a Western, individualistic culture with an egalitarian gender-role conception (Germany) and a collectivistic culture with a more traditional gender role conceptions (Middle East, Gulf States). Motion capture data were collected for five male and five female dyadic interactions in each culture. Character animations based on the motion capture data served as stimuli in the observation study. Female and male observers from both cultures rated the perceived rapport continuously while watching the 1 min sequences and guessed gender and cultural background of the dyads after each clip. Results show that masking of gender and culture in the stimuli was successful, as hit rates for both aspects remained at chance level. Further the results revealed high levels of agreement in the rapport ratings across gender and culture, pointing to universal judgment policies. A 2 × 2 × 2 × 2 ANOVA for gender and culture of stimuli and observers showed that female dyads were rated significantly higher on rapport across the board and that the contrast between female and male dyads was more pronounced in the Arab sample as compared to the German sample. nonverbal parameters extracted from the motion capture protocols were submitted to a series of algorithms to identify dyadic activity levels and coordination patterns relevant to the perception of rapport. The results are critically discussed with regard to the role of nonverbal coordination as a constituent of rapport.