bluuebunny/crossref_metadata_2025 huggingface dataset:
Mechanisms of Invasion in Glioblastoma: Extracellular Matrix, Ca2+ Signaling, and Glutamate
Authors: So Jae-Seon , Kim Hyeono , Han Kyung-Seok
Published: June 2021

Glioblastoma (GBM) is the most common and malignant form of primary brain tumor with a median survival time of 14–16 months in GBM patients. Surgical treatment with chemotherapy and radiotherapy may help increase survival by removing GBM from the brain. However, complete surgical resection to eliminate GBM is almost impossible due to its high invasiveness. When GBM cells migrate to the brain, they interact with various cells, including astrocytes, neurons, endothelial cells, and the extracellular matrix (ECM). They can also make their cell body shrink to infiltrate into narrow spaces in the brain; thereby, they can invade regions of the brain and escape from surgery. Brain tumor cells create an appropriate microenvironment for migration and invasion by modifying and degrading the ECM. During those processes, the Ca2+ signaling pathway and other signaling cascades mediated by various ion channels contribute mainly to gene expression, motility, and invasion of GBM cells. Furthermore, GBM cells release glutamate, affecting migration via activation of ionotropic glutamate receptors in an autocrine manner. This review focuses on the cellular mechanisms of glioblastoma invasion and motility related to ECM, Ca2+ signaling, and glutamate. Finally, we discuss possible therapeutic interventions to inhibit invasion by GBM cells.
Multimodal Medical Supervised Image Fusion Method by CNN
Authors: Li Yi , Zhao Junli , Lv Zhihan , Pan Zhenkuan
Published: June 2021

This article proposes a multimode medical image fusion with CNN and supervised learning, in order to solve the problem of practical medical diagnosis. It can implement different types of multimodal medical image fusion problems in batch processing mode and can effectively overcome the problem that traditional fusion problems that can only be solved by single and single image fusion. To a certain extent, it greatly improves the fusion effect, image detail clarity, and time efficiency in a new method. The experimental results indicate that the proposed method exhibits state-of-the-art fusion performance in terms of visual quality and a variety of quantitative evaluation criteria. Its medical diagnostic background is wide.
Epithelial-Mesenchymal-Transition-Like Circulating Tumor Cell-Associated White Blood Cell Clusters as a Prognostic Biomarker in HR-Positive/HER2-Negative Metastatic Breast Cancer
Authors: Guan Xiuwen , Li Chunxiao , Li Yiqun , Wang Jiani , Yi Zongbi , Liu Binliang , Chen Hongyan , Xu Jiasen , Qian Haili , Xu Binghe , Ma Fei
Published: June 2021

Background

Although positive Circulating tumor cells (CTCs) status has been validated as a prognostic marker in breast cancer, the interaction between immune cells and CTCs during the progress of Epithelial-mesenchymal-transition (EMT), and the clinical implications of CTC-associated white blood cell clusters (CTC-WBC clusters) for metastatic breast cancer are largely uncharacterized.

Methods

We optimized a filter-based method combined with an RNA in situ hybridization technique according to the epithelial- and mesenchymal-markers to analyze EMT in CTC-WBC clusters. Serial peripheral blood samples from 135 patients with Hormone receptor (HR)-positive/HER2-negative metastatic breast cancer receiving first-line chemotherapy with docetaxel plus capecitabine were prospectively collected until disease progression from Nov 2013 to March 2019. Follow-up data collection was conducted until July 2020.

Results

A total of 452 blood samples at all time-points were collected and analyzed. Median age of the cohort was 51.0 years (range, 27 to 73 years), and most of them (76.3%) had visceral metastases. Median progression-free survival (PFS) was 10.6 months (95% CI, 8.8 to 12.3 months). The presence of EMT-like CTC-WBC clusters was more frequently evident among patients with simultaneous bone and lymph node metastases (87.5% vs 36.2%, P=0.006), whereas no associations were observed between CTC-WBC clusters and other clinicopathologic characteristics before chemotherapy. The patients with EMT-like CTC-WBC clusters tended to show a significantly increased number of total CTC count (median,19.0 vs 5.0, P<0.001). The patients with at least one detectable EMT-like CTC-WBC cluster at baseline were characterized by significantly worse PFS, when compared to the patients with no EMT-like CTC-WBC clusters detected (7.0 vs 10.7 months, P=0.023), and those with five or more epithelial-based CTCs detected per 5mL of peripheral blood (7.0 vs 12.7 months, P=0.014). However, the total CTC-WBC clusters were not correlated with patients’ survival in the cohort (8.4 vs 10.6 months, P=0.561).

Conclusions

Our data provide evidence that the emergence of CTC-WBC clusters underwent EMT before treatment is associated with significantly poorer PFS in HR-positive/HER2-negative metastatic breast cancer patients receiving docetaxel plus capecitabine, which may be used as a parameter to predict the clinical outcomes and a potential target for individualized therapy.
Role of Tacrolimus C/D Ratio in the First Year After Pediatric Liver Transplantation
Authors: Prusinskas Benas , Ohlsson Sinja , Kathemann Simone , Pilic Denisa , Kampmann Kristina , Büscher Rainer , Paul Andreas , Pape Lars , Hoyer Peter F. , Lainka Elke
Published: June 2021

Background: The calcineurin inhibitor (CNI) tacrolimus (TAC) is a cornerstone agent in immunosuppressive therapy in pediatric liver transplantation (LTX). Adverse effects limit the use of CNI. In adults, calculating the individual TAC metabolism rate allows to estimate the transplant recipient's risk for therapy-associated complications.

Methods: A retrospective, descriptive data analysis was performed in children who had undergone LTX in 2009–2017 and had received TAC twice daily in the first year after LTX. A weight-adjusted concentration/dose ratio (C/D ratio) was calculated [TAC trough level/(daily TAC dose/body weight)] every 3 months after LTX to estimate the average individual TAC metabolism rate. Depending on the C/D ratio, all patients were divided into two groups: fast metabolizers (FM) and slow metabolizers (SM). Clinical and laboratory parameters were analyzed as risk factors in both groups.

Results: A total of 78 children (w 34, m 44, median age at LTX 2.4; 0.4–17.0 years) were enrolled in the study. FM (SM) had a mean C/D ratio of <51.83 (≥51.83) ng/ml/(mg/kg). FM were younger at the time of LTX (median age 1.7; 0.4–15.8 years) than SM (5.1, 0.4–17.0), p = 0.008. FM were more likely to have biliary atresia (20/39, 51%) compared to SM (11/39, 28%), p = 0.038, whereas SM were more likely to have progressive familial intrahepatic cholestasis (9/39, 23%) vs. in FM (1/39, 3%), p = 0.014. Epstein–Barr virus (EBV) infection occurred more frequently in FM (27/39, 69%) than SM (13/39, 33%), p = 0.002. Three FM developed post-transplant lymphoproliferative disorder. The annual change of renal function did not differ in both groups (slope FM 1.2 ± 0.6; SM 1.4 ± 0.8 ml/min/1.73 m2 per year, and p = 0.841).

Conclusions: Calculation of individual, weight-adjusted TAC C/D ratio is a simple, effective, and cost-efficient tool for physicians to estimate the risk of therapy-associated complications and to initiate individual preventive adjustments after pediatric LTX. Lower TAC levels are tolerable in FM, especially in the presence of EBV infection, reduced renal function, or when receiving a liver transplant in the first 2 years of life.
Systemic Risk Caused by the Overlapping Portfolios of Banks Under a Bilateral Network
Authors: Gao Qianqian , Fan Hong
Published: June 2021

Frequent financial crises and economic globalization have made systemic risk a growing Research Topic. This paper constructs a dynamic banking system model based on the bank-asset bilateral network. By collecting the balance sheet and portfolio data of 47 Chinese listed banks in 2018, the paper firstly empirically analyses the impact of external shocks, the price-cutting effect, and the proportion of various assets held by banks to their total assets on the systemic risk of the banking system. The risk preference coefficient and systemic shock are then introduced to construct the banks' quantitative portfolio strategy model to study its optimal investment. It has been found that the greater the external shock and the stronger the price-cutting effect, the higher the systemic risk. Moreover, the external shock and price-cutting effect will have a superimposed effect within a specific range, and systemic risk will increase significantly. The asset classes of the Chinese banking system have a different sensitivity to external shocks, among which loan assets are the most sensitive. Further studies reveal an inflection point of risk preference, resulting in banks' expected return “increasing first and then decreasing.” The higher the debt-asset ratio and the stronger the banks' risk tolerance, the more aggressive investment strategies banks can choose to achieve high returns. This paper provides a reference for the banking industry to react to shocks and analyze systemic risk.
Event-Chain Monte Carlo: Foundations, Applications, and Prospects
Authors: Krauth Werner
Published: June 2021

This review treats the mathematical and algorithmic foundations of non-reversible Markov chains in the context of event-chain Monte Carlo (ECMC), a continuous-time lifted Markov chain that employs the factorized Metropolis algorithm. It analyzes a number of model applications and then reviews the formulation as well as the performance of ECMC in key models in statistical physics. Finally, the review reports on an ongoing initiative to apply ECMC to the sampling problem in molecular simulation, i.e., to real-world models of peptides, proteins, and polymers in aqueous solution.
OsSPL9 Regulates Grain Number and Grain Yield in Rice
Authors: Hu Li , Chen Weilan , Yang Wen , Li Xiaoling , Zhang Cheng , Zhang Xiaoyu , Zheng Ling , Zhu Xiaobo , Yin Junjie , Qin Peng , Wang Yuping , Ma Bingtian , Li Shigui , Yuan Hua , Tu Bin
Published: June 2021

Rice grain yield consists of several key components, including tiller number, grain number per panicle (GNP), and grain weight. Among them, GNP is mainly determined by panicle branches and spikelet formation. In this study, we identified a gene affecting GNP and grain yield, OsSPL9, which encodes SQUAMOSA-PROMOTER BINDING PROTEIN-LIKE (SPL) family proteins. The mutation of OsSPL9 significantly reduced secondary branches and GNP. OsSPL9 was highly expressed in the early developing young panicles, consistent with its function of regulating panicle development. By combining expression analysis and dual-luciferase assays, we further confirmed that OsSPL9 directly activates the expression of RCN1 (rice TERMINAL FLOWER 1/CENTRORADIALIS homolog) in the early developing young panicle to regulate the panicle branches and GNP. Haplotype analysis showed that Hap3 and Hap4 of OsSPL9 might be favorable haplotypes contributing to high GNP in rice. These results provide new insights on high grain number breeding in rice.
The Self-Regulation of Conformity: Mental Contrasting With Implementation Intentions (MCII)
Authors: von Weichs Vivica , Krott Nora Rebekka , Oettingen Gabriele
Published: June 2021

The self-regulation of conformity has received little attention in previous research. This is surprising because group majorities can exert social strong pressure on people, leading them to overlook the pursuit of their own goals. We investigated if self-regulation by mental contrasting with implementation intentions (MCII) can reduce people’s tendency to conform and facilitate their own goal-pursuit despite deviant majority influence. In a computer-based logical reasoning task, we exposed participants to a conformity manipulation, where we presented bogus diagrams showing the supposedly correct answers of a majority ingroup. Compared to participants who were not given a self-regulation strategy (Studies 1, 2, and 4) or who were in an active control group (Study 3), MCII helped participants to self-regulate conforming behavior in trying to solve the task and to independently solve the logical reasoning task, as indicated by increases in correct answers in the task. The findings suggest that MCII is an effective strategy to regulate people’s tendency to conform and supports them to attain their goal despite deviant majority influence.
Micro-Expressions of Fear During the 2016 Presidential Campaign Trail: Their Influence on Trait Perceptions of Donald Trump
Authors: Stewart Patrick A. , Svetieva Elena
Published: June 2021

The 2016 United States presidential election was exceptional for many reasons; most notably the extreme division between supporters of Donald Trump and Hillary Clinton. In an election that turned more upon the character traits of the candidates than their policy positions, there is reason to believe that the non-verbal performances of the candidates influenced attitudes toward the candidates. Two studies, before Election Day, experimentally tested the influence of Trump’s micro-expressions of fear during his Republican National Convention nomination acceptance speech on how viewers evaluated his key leadership traits of competence and trustworthiness. Results from Study 1, conducted 3 weeks prior to the election, indicated generally positive effects of Trump’s fear micro-expressions on his trait evaluations, particularly when viewers were first exposed to his opponent, Clinton. In contrast, Study 2, conducted 4 days before Election Day, suggests participants had at that point largely established their trait perceptions and were unaffected by the micro-expressions.
The Role of Personal Biological Resource in the Job Demands-Control-Support Model: Evidence From Stress Reactivity
Authors: Deng Huihua , Zhuo Yuli , Qi Xingliang , Wu Hanyao , Liu Yapeng , Li Jianmei , Jin Caixiang
Published: June 2021

Job resources can buffer the deleterious effect of adverse work environments. Extant studies on the interaction pattern between job resources and adverse environments were confined to the diathesis stress model. This traditional perspective has received the challenge from the differential susceptibility model and the vantage sensitivity model. Additionally, stress reactivity may be one of the important job resources at the personal biological level, but its moderating role was short of empirical research. This study aimed to examine how stress reactivity interacts with work environments in predicting job burnouts among 341 Chinese hospital female nurses. This study selected job control and job support representative of supportive environments and psychological demands representative of an adverse environment and the cortisol content in 1-cm hair segment as a biomarker to assess individual’s stress reactivity in 1 month. The nurses self-reported their work environments and job burnouts and provided 1-cm hair segments closest to the scalp. Hair cortisol content was measured with high-performance liquid chromatography-tandem mass spectrometry. The interaction pattern was examined with multiple linear regressions and the analysis of region of significance (RoS). The regression revealed that the interaction of hair cortisol content with job control could positively predict professional efficiency among nurses, with psychological demands could negatively predict emotional exhaustion, and with coworker support could negatively predict professional efficiency. The RoS analysis revealed that nurses with high cortisol levels had not only significantly higher professional efficiency than those with low cortisol levels in high job control but also significantly lower professional efficiency in low job control. Nurses with high cortisol levels had significantly higher emotional exhaustion than those with low cortisol levels in low psychological demands. Nurses with low cortisol levels had not only significantly higher professional efficiency than those with high cortisol levels in high coworker support but also significantly lower professional efficiency in low coworker support. The interaction patterns of stress reactivity with both job control and coworker support were consistent with the differential susceptibility model, but the interaction between stress reactivity and psychological demands supported the vantage sensitivity model.
Self-Regulated Resource Management in Emergency Remote Higher Education: Status Quo and Predictors
Authors: Naujoks Nick , Bedenlier Svenja , Gläser-Zikuda Michaela , Kammerl Rudolf , Kopp Bärbel , Ziegler Albert , Händel Marion
Published: June 2021

Because of the COVID-19 pandemic in the spring term 2020, students faced a sudden change from on-campus learning to online learning with synchronous and asynchronous online courses (emergency remote teaching). To study successfully, students not only needed to be prepared in terms of digital readiness (workspace, IT equipment, previous online learning experiences, and sharing information online), they also faced challenges that pertained to the self-regulated management of external resources (environment structuring, time management, and help-seeking). In the current study, we investigated students’ digital readiness for the sudden switch to online learning; differences between students’ intended and actual use of external resource management strategies; and the influence of students’ digital readiness on their actual use of resource management strategies. Students enrolled in a full-scale, German university (N= 662) answered two online questionnaires (before and in the middle of the term). Descriptive statistics indicated that students seemed to be ready to study online. However, repeated measures ANOVA showed that students were not able to manage their resources during the term as frequently as intended. Finally, separate regression analyses revealed that availability of workspace and IT equipment predicted the use of environment structuring strategies. Additionally, IT equipment and information sharing behavior predicted students’ help-seeking. Based on the current results, we discuss implications for the promotion of student self-regulated learning (SRL) in online emergency remote teaching based on both external resources and digital readiness.
Attitudes Surrounding Music of Patients With Anorexia Nervosa: A Survey-Based Mixed-Methods Analysis
Authors: Krishna Priya Aishwarya , Applewhite Briana , Au Katie , Oyeleye Oyenike , Walton Emma , Norton Caroline , Patsalos Olivia , Cardi Valentina , Himmerich Hubertus
Published: June 2021

Anorexia nervosa (AN) is one of the main eating disorders. It has the highest mortality of all psychiatric disorders, and the success rates of current therapies are not fully satisfactory. Thus, there is a need for novel interventions. We investigated the attitudes surrounding music of 41 patients with clinically-diagnosed AN as well as their thoughts on the potential therapeutic uses of music using a questionnaire of 50 questions. Free text responses were qualitatively analyzed for reoccurring themes with NVivo 12 software. Yes/no questions and questions of best fit were analyzed using the IBM SPSS Statistics version 25. The most prevalent theme was the positive effect of music. Most patients reported that listening to music evokes varying emotions in them (83%) which may be of positive or negative nature. Similarly, patients associated certain music with particular positive, but also with particular negative memories. A majority of patients stated that music helps to distract them (85%), helps with loneliness (59%) and helps them feel more connected to others (58%). This data indicates that people with AN make nonclinical use of music which seems to elicit positive as well as negative emotions and memories. Patients felt music is beneficial with regard to important aspects of AN, such as emotional problems, loneliness, and relationship difficulties. Most of them would also like to attend music therapy.
Diagnostic and Therapeutic Challenges of Catatonia in an Adolescent With High Functioning Autism Spectrum Disorder: A Case Report
Authors: Traverso Annalisa , Ancora Caterina , Zanato Silvia , Raffagnato Alessia , Gatta Michela
Published: June 2021

Catatonia is a psychomotor syndrome with specific clusters of speech, behavioral and motor features. Although potentially life-threatening, especially in its malignant form accompanied with autonomic dysregulation and medical complications, it is a treatable condition, when promptly identified. For a long time catatonia was considered a marker of schizophrenia, thus limiting the possibility of diagnosis and treatment. Due to growing awareness and studies on the subject, it is now known that catatonia can occur in the context of a number of diseases, including psychotic, affective and neurodevelopmental disorders. In recent years, there's been a renewed interest in the recognition and definition of catatonia in neurodevelopmental disorders, such as Autism Spectrum Disorder (ASD), where the differential diagnosis poses great challenges, given the considerable overlapping of signs and symptoms between the conditions. We present the case of a 15 year old boy with High Functioning ASD with a sudden onset of severe catatonic symptoms and the co-existence of psychotic symptoms, whose complex clinical course raises many questions on the differentiation and relation of said disorders.
Knowledge, Attitude, and Self-Reported Practice Towards Measures for Prevention of the Spread of COVID-19 Among Australians: A Nationwide Online Longitudinal Representative Survey
Authors: Enticott Joanne , Slifirski William , Lavoie Kim L. , Bacon Simon L. , Teede Helena J. , Boyle Jacqueline A.
Published: June 2021

Objective: To assess and share learnings on the motivators and behavioural adherence across sex and age to evolving strategies in public policy to prevent the spread of SARS-CoV-2 at the end of a first COVID-19 wave and the beginning of a second COVID-19 wave in Australia.

Design and Setting: A national longitudinal survey using a framework based on evidence-based behaviour change models. The survey was administered to a national sample representative across sex, age and location was undertaken at two time points: May 1st to 5th, 2020, and July 1st to 7th, 2020.

Results: Overall 2,056 surveys were completed across the first and second rounds, with 63% (1,296/2,056) completing both. Age range was 18–99 years (median 53, IQR: 34–64). Suboptimal physical distancing and self-quarantining if unwell/diagnosed was reported in one in four respondents and not getting a test at onset of symptoms reported in one in three. Those non-adherent to all three behaviours (19%, 60/323), were mainly male, younger, lived in major cities and reported fewer concerns or motivators to change behaviour. Overall, government lockdown measures were considered very important by 81% (835/1,032) and appropriate by 75% (772/1,029).

Conclusions: Prior to the suppression of a second COVID-19 wave, a significant minority of Australians reported suboptimal behavioural adherence to vital policy strategies to limit SARS-CoV-2 spread, mostly young adults and men. Successful wave 2 suppression required consistent communication from political and health leaders and supportive public health and economic strategies. Additional lockdown and punitive strategies were needed in Victoria and were generally well-supported and adhered to. To limit subsequent lockdown, this work reinforces the need for a mix of communication around saving lives of the vulnerable, and other strategies targeting high risk groups, facilitation of easy testing and minimisation of financial impacts.
Expectations and Perceptions of Healthcare Professionals for Robot Deployment in Hospital Environments During the COVID-19 Pandemic
Authors: Sierra Marín Sergio D. , Gomez-Vargas Daniel , Céspedes Nathalia , Múnera Marcela , Roberti Flavio , Barria Patricio , Ramamoorthy Subramanian , Becker Marcelo , Carelli Ricardo , Cifuentes Carlos A.
Published: June 2021

Several challenges to guarantee medical care have been exposed during the current COVID-19 pandemic. Although the literature has shown some robotics applications to overcome the potential hazards and risks in hospital environments, the implementation of those developments is limited, and few studies measure the perception and the acceptance of clinicians. This work presents the design and implementation of several perception questionnaires to assess healthcare provider's level of acceptance and education toward robotics for COVID-19 control in clinic scenarios. Specifically, 41 healthcare professionals satisfactorily accomplished the surveys, exhibiting a low level of knowledge about robotics applications in this scenario. Likewise, the surveys revealed that the fear of being replaced by robots remains in the medical community. In the Colombian context, 82.9% of participants indicated a positive perception concerning the development and implementation of robotics in clinic environments. Finally, in general terms, the participants exhibited a positive attitude toward using robots and recommended them to be used in the current panorama.
Effect of Pre-treatment and Processing on Nutritional Composition of Cassava Roots, Millet, and Cowpea Leaves Flours
Authors: Onyango Samwel Ochieng , Abong George Ooko , Okoth Michael Wandayi , Kilalo Dora C. , Mwang'ombe Agnes Wakesho
Published: June 2021

Cassava roots, millet and cowpea leaves have short storage life thus the need for simple post-harvest handling and storage protocol to ensure prolonged availability to fully contribute toward food and nutrition security, a major challenge within Sub-Saharan Africa. The current study sought to investigate the effect of pre-treatment and processing on cyanide safety and nutrition composition of cassava roots, millet and cowpea leaves flours. The study used three popular cassava varieties grown along the Kenyan coast, cowpea leaves (M66) grown as vegetable and pearl millet. The study used analytical techniques as guided by AOAC standard methods, to determine the nutritional composition of the individual crops while subjecting them to pre-treatment processes (blanching, peeling, washing, drying, and fermentation) and optimizing for maximum nutrient composition. The cyanide content ranged 7.8–9.5, 3.4–5.0, and 2.2–2.8 ppb for raw, untreated, and fermented cassava flours, respectively. The carbohydrates content was in the range of 35–37, 81.73–83.49, and 70.28–71.20% for raw cowpea leaves, cassava roots, and millet, respectively; the carbohydrate content for untreated flours was in the range of 35.68–35.19, 66.07–83.49, and 66.07–68.89% for cowpea leaves, cassava roots, and millet, respectively; the carbohydrate content for the fermented flours was in the range of 29.06–28.01, 79.68–84.36, and 69.08–70.12% for cowpea leaves, cassava roots, and millet, respectively. The protein content was in the range of 25.69–26.01, 1.2–18, and 11.1–13.3% for untreated cowpea, cassava, and millet flours, respectively; fermented flours protein content was in the range of 25.7–29.3, 1.3–2.2, and 8.5–11.1% cowpea, cassava, and millet flours, respectively. Iron and zinc contents were in the range of 4.31–9.04, 1.0–1.3; 7.98–7.89, 1.21–1.25; 6.58–8.23, 0.99–1.22 (mg/100 g dwb) for raw, untreated, and fermented cowpea flours, respectively. Pre-treatment had significant effects (P ≤ 0.05) on cyanide content and nutritional composition of each of the flours. Farmers should be trained to utilize such simple processing techniques.
Racial and Ethnic Inequities in Mortality During Hospitalization for Traumatic Brain Injury: A Call to Action
Authors: Richie Emma A. , Nugent Joseph G. , Raslan Ahmed M.
Published: June 2021

The health disparities which drive inequities in health outcomes have long plagued our already worn healthcare system and are often dismissed as being a result of social determinants of health. Herein, we explore the nature of these inequities by comparing outcomes for racial and ethnic minorities patients suffering from traumatic brain injury (TBI). We retrospectively reviewed all patients enrolled in the Trauma One Database at the Oregon Health & Science University Hospital from 2006 to October 2017 with an abbreviated injury scale (AIS) for the head or neck >2. Racial and ethnic minority patients were defined as non-White or Hispanic. A total of 6,352 patients were included in our analysis with 1,504 in the racial and ethnic minority cohort vs. 4,848 in the non-minority cohort. A propensity score (PS) model was generated to account for differences in baseline characteristics between these cohorts to generate 1,500 matched pairs. The adjusted hazard ratio for in-hospital mortality for minority patients was 2.21 [95% Confidence Interval (CI) 1.43–3.41, p < 0.001] using injury type, probability of survival, and operative status as covariates. Overall, this study is the first to specifically look at racial and ethnic disparities in the field of neurosurgical trauma. This research has demonstrated significant inequities in the mortality of TBI patients based on race and ethnicity and indicates a substantive need to reshape the current healthcare system and advocate for safer and more supportive pre-hospital social systems to prevent these life-threatening sequelae.
Biological Mechanisms Induced by Soybean Agglutinin Using an Intestinal Cell Model of Monogastric Animals
Authors: Pan Li , Liu Yan , Lan Hainan , Bao Nan , Zhao Yuan , Sun Hui , Qin Guixin , Farouk Mohammed Hamdy
Published: June 2021

Soybean agglutinin (SBA) has a toxic effect on most animals. The anti-nutritional mechanisms of SBA are not fully understood, in terms of cell survival activity and metabolism of intestinal cells. This study aims to investigate the effects of SBA on the cell cycle, apoptosis, and to verify the mechanism of SBA anti-nutritional characters based on proteomic-based analysis. The IPEC-J2 cell line was cultured with medium containing 0.0, 0.5, or 2.0 mg/mL SBA. With increasing SBA levels, the percentage of the cells at G0/G1 phase, cell apoptosis rates, expressions of Bax and p21, and the activities of Casp-3 and Casp-9 were increased, while cyclin D1 and Bcl-2 expressions were declined (p < 0.05). The proteomic analysis showed that the numbers of differentially expressed proteins, induced by SBA, were mainly enriched in different pathways including DNA replication, base excision repair, nucleus excision repair, mismatch repair, amide and peptide biosynthesis, ubiquitin-mediated proteolysis, as well as structures and functions of mitochondria and ribosome. In conclusion, the anti-nutritional mechanism of SBA is a complex cellular process. Such process including DNA related activities; protein synthesis and metabolism; signal-conducting relation; as well as subcellular structure and function. This study provides comprehensive information to understand the toxic mechanism of SBA in monogastrics.
Biosecurity in Village and Other Free-Range Poultry—Trying to Square the Circle?
Authors: Otte Joachim , Rushton Jonathan , Rukambile Elpidius , Alders Robyn G.
Published: June 2021

Village poultry commonly suffer significant disease related losses and a plethora of biosecurity measures is widely advocated as a means to reduce morbidity and mortality. This paper uses a household economy perspective to assess some “economic” considerations determining biosecurity investments of village poultry keepers. It draws on the 2012/13 Tanzania National Panel Survey (TZ-NPS), which covered 1,228 poultry-keeping households. Disease was the most frequently reported cause of bird losses and, in the majority of households, accounted for more than half of reported bird losses. However, given that poultry rarely contributed more than 10% to total annual household income, for 95% of households the value of birds lost to disease represented <10% of annual income. The value placed on poultry within households may vary by gender and the overall figure may mask differential intra-household impacts. The break-even cost for various levels of reduction of disease losses is estimated using a partial budget analysis. Even if achieved at no cost, a 75% reduction in disease-associated mortality would only result in a one percent increase of annual household income. Thus, to the “average” village poultry-keeping household, investments in poultry may not be of high priority, even when cost-effective. Where risks of disease spread impact on the wider community and generate significant externalities, poultry keepers must be supported by wider societal actions rather than being expected to invest in biosecurity for purely personal gain.
Hemolysin Co-regulated Family Proteins Hcp1 and Hcp2 Contribute to Edwardsiella ictaluri Pathogenesis
Authors: Kalindamar Safak , Abdelhamed Hossam , Kordon Adef O. , Pinchuk Lesya M. , Karsi Attila
Published: June 2021

Edwardsiella ictaluri is a Gram-negative facultative intracellular pathogen causing enteric septicemia of catfish (ESC), a devastating disease resulting in significant economic losses in the U.S. catfish industry. Bacterial secretion systems are involved in many bacteria's virulence, and Type VI Secretion System (T6SS) is a critical apparatus utilized by several pathogenic Gram-negative bacteria. E. ictaluri strain 93–146 genome has a complete T6SS operon with 16 genes, but the roles of these genes are still not explored. In this research, we aimed to understand the roles of two hemolysin co-regulated family proteins, Hcp1 (EvpC) and Hcp2. To achieve this goal, single and double E. ictaluri mutants (EiΔevpC, EiΔhcp2, and EiΔevpCΔhcp2) were generated and characterized. Catfish peritoneal macrophages were able to kill EiΔhcp2 better than EiΔevpC, EiΔevpCΔhcp2, and E. ictaluri wild-type (EiWT). The attachment of EiΔhcp2 and EiΔevpCΔhcp2 to ovary cells significantly decreased compared to EiWT whereas the cell invasion rates of these mutants were the same as that of EiWT. Mutants exposed to normal catfish serum in vitro showed serum resistance. The fish challenges demonstrated that EiΔevpC and EiΔevpCΔhcp2 were attenuated completely and provided excellent protection against EiWT infection in catfish fingerlings. Interestingly, EiΔhcp2 caused higher mortality than that of EiWT in catfish fingerlings, and severe clinical signs were observed. Although fry were more susceptible to vaccination with EiΔevpC and EiΔevpCΔhcp2, their attenuation and protection were significantly higher compared to EiWT and sham groups, respectively. Taken together, our data indicated that evpC (hcp1) is involved in E. ictaluri virulence in catfish while hcp2 is involved in adhesion to epithelial cells and survival inside catfish macrophages.
Key Assumptions Underlying a Competency-Based Approach to Medical Sciences Education, and Their Applicability to Veterinary Medical Education
Authors: Danielson Jared A.
Published: June 2021

This perspective explores six key assumptions of a competency-based approach to medical-sciences education, as they relate to veterinary medical education. Those assumptions, derived from characteristics of competency based medical education (CBME) identified by CBME proponents are: (1) There are sufficient shortcomings in the medical competence of graduate veterinarians that solutions are necessary, and changes in the way we teach veterinarians will address those problems. (2) It is feasible to identify generally accepted core competencies in veterinary medical practice. (3) Teaching to defined learning outcomes will produce greater achievement for learners than approaches that do not emphasize clearly defined outcomes. (4) In veterinary medical education, it is possible to articulate the development of competence sequentially in a manner that is relatively consistent across learners, and carefully planning and sequencing learning activities will produce better learning outcomes. (5) Competency-focused instruction, which tailors the pace and progression of instruction to learners, is feasible in veterinary medical education, and will produce better outcomes than instruction that moves all students through an equivalent process in a set time frame. (6) Programmatic Assessment, including numerous direct observations with feedback, will improve learning outcomes, and is feasible in veterinary medical education. While available research does not unequivocally support all six assumptions, overall the potential benefits of adopting a competency-based approach seem promising for veterinary medical education.
Serum 5-Hydroxyindoleacetic Acid and Ratio of 5-Hydroxyindoleacetic Acid to Serotonin as Metabolomics Indicators for Acute Oxidative Stress and Inflammation in Vancomycin-Associated Acute Kidney Injury
Authors: Lee Hyun-Seung , Kim Sang-Mi , Jang Ja-Hyun , Park Hyung-Doo , Lee Soo-Youn
Published: June 2021

The incidence of vancomycin-associated acute kidney injury (VAKI) varies from 5–43%, and early detection of VAKI is important in deciding whether to discontinue nephrotoxic agents. Oxidative stress is the main mechanism of VAKI, and serotonin (5-HT) and its metabolite 5-hydroxyindoleacetic acid (5-HIAA) have been examined with respect to their involvement in ischemia/reperfusion damage in experimental animal models. In the current study, we assessed 5-HT and 5-HIAA as novel biomarkers for detecting VAKI in patients who have infections or compromised renal function, using a mass spectrometry–based metabolomics approach. We conducted amino acid profiling analysis and measurements of 5-HT and 5-HIAA using serum from subjects with VAKI (n = 28) and non-VAKI control subjects (n = 69), consisting of the infection subgroup (n = 23), CKD subgroup (n = 23), and healthy controls (HCs, n = 23). 5-HT was significantly lower in the VAKI group than in the non-VAKI groups, and the concentration of 5-HIAA and the ratio of 5-HIAA to 5-HT (5-HIAA/5-HT) showed higher values in the VAKI group. The infection subgroup presented a significantly greater 5-HIAA/5-HT ratio compared with the HC subgroup. Our study revealed that increased 5-HIAA/5-HT ratio has the potential to act as a VAKI surrogate marker, reflecting acute oxidative stress and inflammation.
A Tissue-Engineered Tracheobronchial In Vitro Co-Culture Model for Determining Epithelial Toxicological and Inflammatory Responses
Authors: Soriano Luis , Khalid Tehreem , O’Brien Fergal J. , O’Leary Cian , Cryan Sally-Ann
Published: June 2021

Translation of novel inhalable therapies for respiratory diseases is hampered due to the lack of in vitro cell models that reflect the complexity of native tissue, resulting in many novel drugs and formulations failing to progress beyond preclinical assessments. The development of physiologically-representative tracheobronchial tissue analogues has the potential to improve the translation of new treatments by more accurately reflecting in vivo respiratory pharmacological and toxicological responses. Herein, advanced tissue-engineered collagen hyaluronic acid bilayered scaffolds (CHyA-B) previously developed within our group were used to evaluate bacterial and drug-induced toxicity and inflammation for the first time. Calu-3 bronchial epithelial cells and Wi38 lung fibroblasts were grown on either CHyA-B scaffolds (3D) or Transwell® inserts (2D) under air liquid interface (ALI) conditions. Toxicological and inflammatory responses from epithelial monocultures and co-cultures grown in 2D or 3D were compared, using lipopolysaccharide (LPS) and bleomycin challenges to induce bacterial and drug responses in vitro. The 3D in vitro model exhibited significant epithelial barrier formation that was maintained upon introduction of co-culture conditions. Barrier integrity showed differential recovery in CHyA-B and Transwell® epithelial cultures. Basolateral secretion of pro-inflammatory cytokines to bacterial challenge was found to be higher from cells grown in 3D compared to 2D. In addition, higher cytotoxicity and increased basolateral levels of cytokines were detected when epithelial cultures grown in 3D were challenged with bleomycin. CHyA-B scaffolds support the growth and differentiation of bronchial epithelial cells in a 3D co-culture model with different transepithelial resistance in comparison to the same co-cultures grown on Transwell® inserts. Epithelial cultures in an extracellular matrix like environment show distinct responses in cytokine release and metabolic activity compared to 2D polarised models, which better mimic in vivo response to toxic and inflammatory stimuli offering an innovative in vitro platform for respiratory drug development.
Current Perspective on the Natural Compounds and Drug Delivery Techniques in Glioblastoma Multiforme
Authors: Behl Tapan , Sharma Aditi , Sharma Lalit , Sehgal Aayush , Singh Sukhbir , Sharma Neelam , Zengin Gokhan , Bungau Simona , Toma Mirela Marioara , Gitea Daniela , Babes Elena Emilia , Judea Pusta Claudia Teodora , Bumbu Adrian Gheorghe
Published: June 2021

Glioblastoma multiforme (GBM) is one of the debilitating brain tumors, being associated with extremely poor prognosis and short median patient survival. GBM is associated with complex pathogenesis with alterations in various cellular signaling events, that participate in cell proliferation and survival. The impairment in cellular redox pathways leads to tumorigenesis. The current standard pharmacological regimen available for glioblastomas, such as radiotherapy and surgical resection following treatment with chemotherapeutic drug temozolomide, remains fatal, due to drug resistance, metastasis and tumor recurrence. Thus, the demand for an effective therapeutic strategy for GBM remains elusive. Hopefully, novel products from natural compounds are suggested as possible solutions. They protect glial cells by reducing oxidative stress and neuroinflammation, inhibiting proliferation, inducing apoptosis, inhibiting pro-oncogene events and intensifying the potent anti-tumor therapies. Targeting aberrant cellular pathways in the amelioration of GBM could promote the development of new therapeutic options that improve patient quality of life and extend survival. Consequently, our review emphasizes several natural compounds in GBM treatment. We also assessed the potential of drug delivery techniques such as nanoparticles, Gliadel wafers and drug delivery using cellular carriers which could lead to a novel path for the obliteration of GBM.
Automated Detection and Classification of Oral Lesions Using Deep Learning to Detect Oral Potentially Malignant Disorders
Authors: Tanriver Gizem , Soluk Tekkesin Merva , Ergen Onur
Published: June 2021

Oral cancer is the most common type of head and neck cancer worldwide, leading to approximately 177,757 deaths every year. When identified at early stages, oral cancers can achieve survival rates of up to 75–90%. However, the majority of the cases are diagnosed at an advanced stage mainly due to the lack of public awareness about oral cancer signs and the delays in referrals to oral cancer specialists. As early detection and treatment remain to be the most effective measures in improving oral cancer outcomes, the development of vision-based adjunctive technologies that can detect oral potentially malignant disorders (OPMDs), which carry a risk of cancer development, present significant opportunities for the oral cancer screening process. In this study, we explored the potential applications of computer vision techniques in the oral cancer domain within the scope of photographic images and investigated the prospects of an automated system for detecting OPMD. Exploiting the advancements in deep learning, a two-stage model was proposed to detect oral lesions with a detector network and classify the detected region into three categories (benign, OPMD, carcinoma) with a second-stage classifier network. Our preliminary results demonstrate the feasibility of deep learning-based approaches for the automated detection and classification of oral lesions in real time. The proposed model offers great potential as a low-cost and non-invasive tool that can support screening processes and improve detection of OPMD.
Population Pharmacokinetics of Oxycodone and Metabolites in Patients with Cancer-Related Pain
Authors: Agema Bram C. , Oosten Astrid W. , Sassen Sebastiaan D.T. , Rietdijk Wim J.R. , van der Rijt Carin C.D. , Koch Birgit C.P. , Mathijssen Ron H.J. , Koolen Stijn L.W.
Published: June 2021

Oxycodone is frequently used for treating cancer-related pain, while not much is known about the factors that influence treatment outcomes in these patients. We aim to unravel these factors by developing a population-pharmacokinetic model to assess the pharmacokinetics of oxycodone and its metabolites in cancer patients, and to associate this with pain scores, and adverse events. Hospitalized patients with cancer-related pain, who were treated with oral oxycodone, could participate. Pharmacokinetic samples and patient-reported pain scores and occurrence and severity of nine adverse events were taken every 12 h. In 28 patients, 302 pharmacokinetic samples were collected. A one-compartment model for oxycodone and each metabolite best described oxycodone, nor-oxycodone, and nor-oxymorphone pharmacokinetics. Furthermore, oxycodone exposure was not associated with average and maximal pain scores, and oxycodone, nor-oxycodone, and nor-oxymorphone exposure were not associated with adverse events (all p > 0.05). This is the first model to describe the pharmacokinetics of oxycodone including the metabolites nor-oxycodone and nor-oxymorphone in hospitalized patients with cancer pain. Additional research, including more patients and a more timely collection of pharmacodynamic data, is needed to further elucidate oxycodone (metabolite) pharmacokinetic/pharmacodynamic relationships. This model is an important starting point for further studies to optimize oxycodone dosing regiments in patients with cancer-related pain.
Clinicopathological-Associated Regulatory Network of Deregulated circRNAs in Hepatocellular Carcinoma
Authors: Han Jian , Thurnherr Thomas , Chung Alexander Y. F. , Goh Brian K. P. , Chow Pierce K. H. , Chan Chung Yip , Cheow Peng Chung , Lee Ser Yee , Lim Tony K. H. , Chong Samuel S. , Ooi London L. P. J. , Lee Caroline G.
Published: June 2021

Hepatocellular carcinoma (HCC) is one of the most common and lethal cancers worldwide. Here, we present a novel strategy to identify key circRNA signatures of clinically relevant co-expressed circRNA-mRNA networks in pertinent cancer-pathways that modulate prognosis of HCC patients, by integrating clinic-pathological features, circRNA and mRNA expression profiles. Through further integration with miRNA expression profiles, clinically relevant competing-endogenous-RNA (ceRNA) networks of circRNA-miRNA-mRNAs were constructed. At least five clinically relevant nodal-circRNAs, co-expressed with numerous genes, were identified from the circRNA-mRNA networks. These nodal circRNAs upregulated proliferation (except circRaly) and transformation in cells. The most upregulated nodal-circRNA, circGPC3, associated with higher-grade tumors and co-expressed with 33 genes, competes with 11 mRNAs for two shared miRNAs. circGPC3 was experimentally demonstrated to upregulate cell-cycle and migration/invasion in both transformed and non-transformed liver cell-lines. circGPC3 was further shown to act as a sponge of miR-378a-3p to regulate APSM (Abnormal spindle-like microcephaly associated) expression and modulate cell transformation. This study identifies 5 key nodal master circRNAs in a clinically relevant circRNA-centric network that are significantly associated with poorer prognosis of HCC patients and promotes tumorigenesis in cell-lines. The identification and characterization of these key circRNAs in clinically relevant circRNA-mRNA and ceRNA networks may facilitate the design of novel strategies targeting these important regulators for better HCC prognosis.