bluuebunny/crossref_metadata_2025 huggingface dataset:
Associations Between CAMKK1 Polymorphism rs7214723 and the Prognosis of Patients With Lung Cancer
Authors: Zhang Haorui , Chen Bocen , Zou Zixiu , Feng Jian , Li Yutao , Wang Yi , He Xing , Xu Chang , Wang Haijian , Guo Shicheng , Jin Li , Li Qiang , Wang Jiucun , Xiao Man , Li Feng , Wu Junjie
Published: November 2021

Background

The 5-year survival rate of patients with lung cancer in China is less than 20% and predicting their prognosis is challenging. We investigated the association between a common non-synonymous single nucleotide polymorphism (SNP), rs7214723, in the Ca2+/calmodulin-dependent protein kinase kinase 1 (CAMKK1) gene and the prognosis of patients with lung cancer.

Methods

Genomic DNA was extracted from the blood samples of 839 patients with lung cancer, recruited from Changhai Hospital (n = 536) and Taizhou Institute of Health Sciences (n = 352), and genotyped using the SNPscan technique. The association between patient prognosis and the genotypic data for CAMKK1 was analyzed using a multivariate Cox proportional hazards model adjusted for multiple potential confounders. The CRISPR/Cas9 gene-editing system was used to introduce point mutations in the CAMKK1 rs7214723 of A549 and NCI-H358 cells. Subsequently, Cell proliferation and migration ability were assessed with the Cell Counting Kit-8 and scratch assay. The Annexin V-FITC apoptosis detection kit was used to detect cell apoptosis.

Results

The CAMKK1 rs7214723 recessive CC genotype conferred significantly better overall survival (CC vs. TT + TC: adjusted hazard ratio = 0.78, 95% confidence interval [CI], 0.61-1.00, P = 0.049) than the TT + TC genotypes. Stratified analysis showed that the CAMKK1 rs7214723 CC genotype and recessive CC genotype conferred a significantly decreased risk of death in patients who were male, had a smoking history, or had stage III + IV cancer, compared with the TT and TT + TC genotypes. Relative to the TT + TC genotypes, the rs7214723 recessive CC genotype was also associated with a decreased risk of death in patients aged < 60 years (CC vs. TT + TC: adjusted hazard ratio = 0.59, 95% CI, 0.37-0.93, P = 0.024) and patients with squamous cell carcinoma (CC vs. TT + TC: adjusted hazard ratio = 0.65, 95% CI, 0.44-0.98, P = 0.038). Remarkably, CRISPR/Cas9-guided single nucleotide editing demonstrated that CAMKK1 rs7214723 T > C mutation significantly inhibits cell proliferation and migration and promotes cell apoptosis.

Conclusions

CAMKK1 SNP rs7214723 may be a significant prognostic factor for the risk of death among patients with lung cancer.
Biogeography of the Respiratory Tract Microbiome in Patients With Malignant Tracheal Tumors
Authors: Liu Kai-Xiong , Liu Hai-Xia , Zhang Jing , Zhang Nan , Zhou Yun-Zhi , Tao Mei-Mei , Wang Hong-Wu , Qu Jie-Ming
Published: November 2021

Background

This study aimed to characterize the bacterial microbiota in the oral cavity (OC), throat, trachea, and distal alveoli of patients with primary malignant tracheal tumors (PMTT), including squamous cell carcinoma (SCC) and salivary gland carcinoma patients (SGC), for comparison with a matched non-malignant tracheal tumor (NMTT) group.

Methods

Patients with pathological diagnosis of PMTT and NMTT were included in this study. Saliva, throat swab (TS), trachea protected specimen brush (PSB), and bronchoalveolar lavage fluid (BALF) samples were collected for 16S rRNA gene sequencing. The composition, diversity, and distribution of the microbiota were compared among biogeographic sampling sites and patient groups. The relationship between the genera-level taxon abundance and tracheal tumor types was also investigated to screen for candidate biomarkers.

Findings

The most represented phyla in the four sites were Bacteroidetes, Firmicutes, Proteobacteria, and Fusobacteria. In SCC patients, the relative abundance of Bacteroidetes and Firmicutes gradually decreased with increasing depth into the respiratory tract, while the relative abundance of Proteobacteria gradually increased. Bacterial communities at the four biogeographic sites formed two distinct clusters, with OC and TS samples comprising one cluster and PSB and BALF samples comprising the other group. Principal coordinate analysis showed that trachea microbiota in SCC patients were distinct from that of SGC or NMTT patients. In the trachea, AUCs generated by Prevotella and Alloprevotella showed that the abundance of these genera could distinguish SCC patients from both NMTT and SGC patients.

Interpretation

The structure of respiratory tract microbiota in PMTT patients is related to tumor type. Certain bacteria could potentially serve as markers of SCC, although verification with large-sample studies is necessary.
Neutrophil Extracellular Traps in Digestive Cancers: Warrior or Accomplice
Authors: Chen Yuxin , Han Lulu , Qiu Xiaoyan , Wang Gang , Zheng Junnian
Published: November 2021

Characterized as a complex of extracellular DNA fibers and granule proteins, neutrophil extracellular traps (NETs) are generated specifically by neutrophils which play a critical role in host defense and immune regulation. NETs have been initially found crucial for neutrophil anti-microbial function. Recent studies suggest that NETs are involved in tumorigenesis and cancer progression. However, the function of NETs in cancer remains unclear, which might be due to the variation of research models and the heterogeneity of cancers. Although most of malignant tumors have similar biological behaviors, significant differences indeed exist in various systems. Malignant tumors of the digestive system cause the most incidence and mortality of cancer worldwide. In this review, we would focus on research developments on NETs in digestive cancers to provide insights on their role in digestive cancer progression and future research directions.
Cancer-Immunity Cycle and Therapeutic Interventions- Opportunities for Including Pet Dogs With Cancer
Authors: Von Rueden Samantha K. , Fan Timothy M.
Published: November 2021

The tumor-immune interplay represents a dynamic series of events executed by cellular and soluble participants that either promote or inhibit successful tumor formation and growth. Throughout a tumor’s development and progression, the host organism’s immune system reacts by generating anti-cancer defenses through various incremental and combinatorial mechanisms, and this reactive orchestration is termed the cancer-immunity cycle. Success or failure of the cancer-immunity cycle dictates the fate of both host and tumor as winner or loser. Insights into how the tumor and host immune system continuously adapt to each other throughout the lifecycle of the tumor is necessary to rationally develop new effective immunotherapies. Additionally, the evolving nature of the cancer-immunity cycle necessitates therapeutic agility, requiring real-time serial assessment of immunobiologic markers that permits tailoring of therapies to the everchanging tumor immune microenvironment. In order to accelerate advances in the field of immuno-oncology, this review summarizes the steps comprising the cancer-immunity cycle, and underscores key breakpoints in the cycle that either favor cancer regression or progression, as well as shaping of the tumor microenvironment and associated immune phenotypes. Furthermore, specific large animal models of spontaneous cancers that are deemed immunogenic will be reviewed and proposed as unique resources for validating investigational immunotherapeutic protocols that are informed by the cancer-immunity cycle. Collectively, this review will provide a progressive look into the dynamic interplay between tumor and host immune responses and raise awareness for how large animal models can be included for developing combinatorial and sequenced immunotherapies to maximizing favorable treatment outcomes.
Development of Siglec-9 Blocking Antibody to Enhance Anti-Tumor Immunity
Authors: Choi Hyeree , Ho Michelle , Adeniji Opeyemi S. , Giron Leila , Bordoloi Devivasha , Kulkarni Abhijeet J. , Puchalt Alfredo Perales , Abdel-Mohsen Mohamed , Muthumani Kar
Published: November 2021

Sialic acid-binding Immunoglobulin-like lectin-9 (Siglec-9) is a glyco-immune negative checkpoint expressed on several immune cells. Siglec-9 exerts its inhibitory effects by binding to sialoglycan ligands expressed on cancer cells, enabling them to evade immunosurveillance. We developed a panel of human anti-Siglec-9 hybridoma clones by immunizing mice with Siglec-9-encoding DNA and Siglec-9 protein. The lead antibodies, with high specificity and functionality against Siglec-9, were identified through screening of clones. The in vitro cytotoxicity assays showed that our lead antibody enhances anti-tumor immune activity. Further, in vivo testing utilizing ovarian cancer humanized mouse model showed a drastic reduction in tumor volume. Together, we developed novel antibodies that augment anti-tumor immunity through interference with Siglec-9-mediated immunosuppression.
Incidence, Prognostic Factors, and Survival Trend in Pineal Gland Tumors: A Population-Based Analysis
Authors: Vuong Huy Gia , Ngo Tam N. M. , Dunn Ian F.
Published: November 2021

Introduction

Pineal gland tumors are exceedingly rare and account for 0.4-1.0% of brain neoplasms. Their rarity has confounded a clear understanding of the prognostic factors and standards of care for these neoplasms. In this study, we aimed to investigate the incidence, prognostic indicators, and survival trend of tumors emanating from the pineal gland.

Methods

We accessed the Surveillance, Epidemiology, End Results (SEER) Program for pineal gland tumors from 1975-2016. A multivariate Cox regression model was used to investigate the impact of clinicopathological parameters on all-cause mortality. For survival trend analysis, we employed the Kaplan Meier curve and pairwise comparisons to examine the trend.

Results

We found 1,792 and 310,003 pineal gland and brain neoplasms during 1975-2016 resulting in an incidence of 0.6%. In the multivariate Cox proportional hazards model, older age, male gender, non-germ cell tumor, and receipt of chemotherapy were significantly associated with poor survival (p < 0.001). The extent of resection and radiotherapy administration did not produce survival advantages. Our result also highlighted an increased survival of pineal gland tumors over the years.

Conclusion

Our study investigated the prognostic factors that influenced survival in patients with pineal gland tumors. Chemotherapy use adversely affected patient outcomes and should be considered carefully in specific circumstances to avoid its harmful effects. These findings provide important evidence to improve current standards of care for this rare group of tumors. The survival of pineal tumors has improved over time reflecting improvements in current practice.
The Association of Positive or Negative Religious Coping Methods With Psychological Distress and Quality of Life Among Parents of Infants With Congenital Heart Disease
Authors: Liu Jian-Feng , Xie Wen-Peng , Lin Wen-Hao , Cao Hua , Chen Qiang
Published: November 2021

Objective: The purpose of this study was to evaluate whether positive and negative religious coping methods were associated with psychological distress and quality of life in parents of infants with congenital heart disease (CHD).

Methods: This descriptive, cross-sectional study was conducted at a provincial hospital in Fujian, China. Clinical data from 115 parents of infants with CHD were collected. Chinese Sociodemographic Forms, Brief RCOPE, Beck Depression Interview (BDI), and the Short Form Health Survey (SF-36) were used in this study.

Results: The sex of caregivers in infants with CHD was an independent predictor of BDI scores. The positive religious coping score and the negative religious coping score were both independent predictors of the BDI score (β = −5.365, P = 0.006 and β = 4.812, p = 0.017). The correlation between the quality-of-life scores and positive or negative religious coping scores indicated that positive religious coping scores were significantly positively correlated with Vitality, Social Functioning, and Mental Health scores. There was a significant negative correlation between negative religious coping scores and mental health scores.

Conclusions: Positive or negative religious coping methods may be associated with psychological distress and quality of life among parents of infants with CHD. It is suggested that more attention should be devoted to the influence of religious coping methods on parents of infants with CHD, and the use of religious resources should be encouraged.
Lactobacillus fermentum ZS40 Ameliorates Inflammation in Mice With Ulcerative Colitis Induced by Dextran Sulfate Sodium
Authors: Chen Zixia , Yi Long , Pan Yanni , Long Xingyao , Mu Jianfei , Yi Ruokun , Zhao Xin
Published: November 2021

Ulcerative colitis is an inflammatory disease of the intestine caused by many reasons, and it may even develop into colon cancer. Probiotics are normal bacteria that exist in the human body and have been proven to regulate the balance of intestinal flora and alleviate inflammation. The current study aimed to study the effect of Lactobacillus fermentum ZS40 (ZS40) on dextran sulfate sodium (DSS)-induced ulcerative colitis mice. The length and weight of the colon were measured, and the histopathological morphological changes of colon tissue were observed to evaluate the effects of ZS40 on colitis. Biochemical kits, ELISA kits, real-time quantitative PCR (RT-qPCR), and western blot were also used to detect the effects of ZS40 on serum and colon tissue related oxidative indicators and pro-inflammatory and anti-inflammatory cytokines. We found that ZS40 could reduce colonic inflammatory cell infiltration and goblet cell necrosis, increase total superoxide dismutase and catalase in mouse serum, and reduce myeloperoxidase and malondialdehyde levels. ZS40 could down-regulate the level of proinflammatory cytokines and up-regulate the level of anti-inflammatory cytokines. More importantly, ZS40 down-regulated the relative expression of nuclear factor-κB p65 (NF-κBp65), IL-6, and TNF-α mRNA and protein, up-regulated the relative expression of inhibitor kapa B alpha (IκB-α). By regulating the NF-κB and MAPK pathways to down-regulated the relative expression of p38 and JNK1/2 mRNA and p38, p-p38, JNK1/2, and p-JNK1/2 proteins. Our study suggested that ZS40 may serve as a potential therapeutical strategy for ulcerative colitis.
In Vitro and In Vivo Anti-infective Potential of Thymol Against Early Childhood Caries Causing Dual Species Candida albicans and Streptococcus mutans
Authors: Priya Arumugam , Selvaraj Anthonymuthu , Divya Dass , Karthik Raja Ramalingam , Pandian Shunmugiah Karutha
Published: November 2021

Early childhood caries (ECC), a severe form of caries due to cross-kingdom interaction of Candida albicans and Streptococcus mutans, is a serious childhood dental disease that affects majority of the children with poor background. The present study investigated the anti-infective potential of thymol against C. albicans and S. mutans dual species for the management of ECC. Thymol, a plant derivative of the monoterpene group, has been well known for its numerous biological activities. Thymol at 300 μg/ml concentration completely arrested growth and proliferation of dual species of C. albicans and S. mutans. Rapid killing efficacy of pathogens, within a span of 2 min, was observed in the time kill assay. In addition, at sub-inhibitory concentrations, thymol effectively diminished the biofilm formation and virulence of both C. albicans and S. mutans such as yeast-to-hyphal transition, hyphal-to-yeast transition, filamentation, and acidogenicity and acidurity, respectively, in single and dual species state. qPCR analysis was consistent with virulence assays. Also, through the invertebrate model system Galleria mellonella, in vivo toxicity and efficacy of the phytocompound was assessed, and it was found that no significant toxic effect was observed. Moreover, thymol was found to be proficient in diminishing the infection under single and dual state in in vivo condition. Overall, the results from the present study illustrate the anti-infective potential of thymol against the ECC-causing dual species, C. albicans and S. mutans, and the applicability of thymol in medicated dentifrice formulation.
Molecular Pathology of Sodium Channel Beta-Subunit Variants
Authors: Angsutararux Paweorn , Zhu Wandi , Voelker Taylor L. , Silva Jonathan R.
Published: November 2021

The voltage-gated Na+ channel regulates the initiation and propagation of the action potential in excitable cells. The major cardiac isoform NaV1.5, encoded by SCN5A, comprises a monomer with four homologous repeats (I-IV) that each contain a voltage sensing domain (VSD) and pore domain. In native myocytes, NaV1.5 forms a macromolecular complex with NaVβ subunits and other regulatory proteins within the myocyte membrane to maintain normal cardiac function. Disturbance of the NaV complex may manifest as deadly cardiac arrhythmias. Although SCN5A has long been identified as a gene associated with familial atrial fibrillation (AF) and Brugada Syndrome (BrS), other genetic contributors remain poorly understood. Emerging evidence suggests that mutations in the non-covalently interacting NaVβ1 and NaVβ3 are linked to both AF and BrS. Here, we investigated the molecular pathologies of 8 variants in NaVβ1 and NaVβ3. Our results reveal that NaVβ1 and NaVβ3 variants contribute to AF and BrS disease phenotypes by modulating both NaV1.5 expression and gating properties. Most AF-linked variants in the NaVβ1 subunit do not alter the gating kinetics of the sodium channel, but rather modify the channel expression. In contrast, AF-related NaVβ3 variants directly affect channel gating, altering voltage-dependent activation and the time course of recovery from inactivation via the modulation of VSD activation.
JAZ8 Interacts With VirE3 Attenuating Agrobacterium Mediated Root Tumorigenesis
Authors: Li Shijuan , Xu Bingliang , Niu Xiaolei , Lu Xiang , Cheng Jianping , Zhou Meiliang , Hooykaas Paul J. J.
Published: November 2021

Agrobacterium tumefaciens can cause crown gall tumors by transferring both an oncogenic piece of DNA (T-DNA) and several effector proteins into a wide range of host plants. For the translocated effector VirE3 multiple functions have been reported. It acts as a transcription factor in the nucleus binding to the Arabidopsis thaliana pBrp TFIIB-like protein to activate the expression of VBF, an F-box protein involved in degradation of the VirE2 and VIP1 proteins, facilitating Agrobacterium-mediated transformation. Also VirE3 has been found at the plasma membrane, where it could interact with VirE2. Here, we identified AtJAZ8 in a yeast two-hybrid screening with VirE3 as a bait and confirmed the interaction by pull-down and bimolecular fluorescence complementation assays. We also found that the deletion of virE3 reduced Agrobacterium virulence in a root tumor assay. Overexpression of virE3 in Arabidopsis enhanced tumorigenesis, whereas overexpression of AtJAZ8 in Arabidopsis significantly decreased the numbers of tumors formed. Further experiments demonstrated that AtJAZ8 inhibited the activity of VirE3 as a plant transcriptional regulator, and overexpression of AtJAZ8 in Arabidopsis activated AtPR1 gene expression while it repressed the expression of AtPDF1.2. Conversely, overexpression of virE3 in Arabidopsis suppressed the expression of AtPR1 whereas activated the expression of AtPDF1.2. Our results proposed a novel mechanism of counter defense signaling pathways used by Agrobacterium, suggesting that VirE3 and JAZ8 may antagonistically modulate the salicylic acid/jasmonic acid (SA/JA)-mediated plant defense signaling response during Agrobacterium infection.
Research on the Influence of Emotional Intelligence and Emotional Labor on the Service Recovery Effect of Online Travel Agency
Authors: Wei Jiahua , Hou Zhiping , Zhou Xiaorui
Published: November 2021

At present, online travel agency (OTA) service failure events emerge continually, which makes the OTA service operation mode face new challenges. This study uses the situational experiment method to explore the effects of OTA employees’ emotional intelligence and emotional labor (surface behavior and deep behavior) on the effect of service recovery. The results show that the emotional intelligence of OTA employees has a positive impact on the surface behavior and deep behavior; the emotional intelligence and deep behavior of employees have a significant positive impact on service recovery satisfaction, but the positive impact of employees’ surface behavior on service recovery satisfaction is not statistically significant; finally, service recovery satisfaction has a positive impact on customer loyalty. This study helps to better explain the mechanism of OTA service recovery effect and provides a theoretical reference for improving the service recovery effect of OTA.
Application of Deep Learning-Based Integrated Trial-Error + Science, Technology, Reading/Writing, Engineer, Arts, Mathematics Teaching Mode in College Entrepreneurship Education
Authors: Qu Guangfu , Hu Wenbo , Jiao Wenxiu , Jin Jiangbo
Published: November 2021

The purpose is to achieve a high-quality teaching effect in quality education using the new teaching concept. Firstly, the Deep Learning (DL) theory is introduced to improve the trial-error teaching method, then the trial-error teaching is combined with STREAM education. Afterward, the conical section hyperbola teaching in college entrepreneurship education is specifically studied under experimental analysis using the proposed DL-based integrated trail-error + STREAM teaching methods. The experimental results read: student’s average veracity on the multiple-choice question is 93.4% and 90.1% for the experimental group and control group, respectively; student’s average veracity on short-answer questions is 92.3% and 90.3% for the experimental group and control group, respectively. The results show that the application of DL to the trial-error teaching method can cultivate students’ in-depth analysis and logical thinking ability for mathematical problems. Meanwhile, the DL-based integrated trial-error + STREAM teaching methods stimulate students’ initiative to learn more difficult knowledge, establish integral knowledge systems, and more comprehensively and deeply understand the teaching content. As a result, students’ scientific literacy and humanistic literacy are both improved. Therefore, the proposed DL-based integrated trial-error + STREAM teaching method in college entrepreneurship education has a guiding significance for other disciplines and provides ideas for the expansion and development of STREAM teaching in the future.
Trends in Research on Art Therapy Indexed in the Web of Science: A Bibliometric Analysis
Authors: Rodriguez Novo Natalia , Novo Muñoz Maria Mercedes , Cuellar-Pompa Leticia , Rodriguez Gomez Jose Angel
Published: November 2021

Aim: Despite the increase in international research in art therapy, few studies have been developed with a bibliometric approach which describe the situation regarding this area of knowledge. Thus, the aim of this study is to describe and contextualize international scientific production in the visual arts modality in the context of artistic therapies, to offer a broader and more in-depth vision of the structure of this area of knowledge through of a bibliometric analysis of the publications indexed in the core collection of the Web of Science.

Methods: This is a retrospective, exploratory and descriptive, cross-sectional study to analyze the bibliographic data retrieved from the databases of the core collection. The analysis parameters included the data corresponding to the production according to type of document, country, journal, and institution. In addition, the main lines of research were located and classified and the subject matter of the most cited articles in each of them was summarized. Four periods were selected, between 1994 and 2020, to facilitate the thematic analysis and offer an evolutionary perspective of art therapy research.

Results: A total of 563 works were published, in 250 journals, in the 63 years between 1958, when the first document was published, and April 2021. The annual growth rate was 7.3% with a mean average of 8.7 publications per year, and 83.13% of the published works were articles. A total of 1,269 authors from 56 countries were counted. The mean number of citations per document was 5.6 and the mean number of citations per document and year was 0.6. The main research domains were psychology and/or rehabilitation and the highest production on this topic was concentrated in only three journals. In general, a high degree of variability was observed in the study topics and numerous theoretical and methodological articles. The most used visual arts modalities were in the main drawing, painting and photography.

Conclusion: This work did not find previous existence of any bibliometric analysis on the international scientific production in art therapy. In general terms, there has been a substantial growth in the number of publications on the subject over the last decade. However, this research area does not appear to have peaked, but, on the contrary, is still growing and progressing despite its long history in clinical practice.
The Independent and Joint Effects of Different Childhood Abuse Types on Subjective Prospective and Retrospective Memory Impairment During Pregnancy
Authors: Zhang Xuan , Wu Liuliu , Wang Juan , Mao Fangxiang , Sun Jiwei , Cao Danfeng , Cao Fenglin
Published: November 2021

Background and Objective: Childhood abuse is considered a risk factor in various health outcomes during pregnancy. However, no study has explored the relationship between childhood abuse and memory impairment during pregnancy. This study is the first to explore the relationship between childhood abuse and subjective memory impairment.

Participants, Setting, and Methods: A total of 1,825 pregnant women were recruited from a comprehensive hospital in Shandong province, China, and completed a questionnaire survey. Multivariable linear regression analysis was used to explore the relationship between childhood abuse and subjective prospective and retrospective memory.

Results: Pregnant women with high total childhood abuse scores had high prospective and retrospective memory impairment. Among pregnant women reporting only emotional abuse, only physical abuse, or only sexual abuse, women reporting only emotional abuse were found to have high prospective and retrospective memory impairment. Women with all three childhood abuse types also had high prospective and retrospective memory impairment.

Conclusion: Women who experienced childhood abuse, especially childhood emotional abuse, had high subjective memory impairment during pregnancy. It is important to ask pregnant women about their experiences of childhood abuse, especially emotional abuse, during early prenatal care, as such abuse is likely to have negative effects on memory during pregnancy.
Are There Heterogeneous Impacts of Air Pollution on Mental Health?
Authors: Hu Qingqing , Feng Yanhong , Xu Mark
Published: November 2021

Many studies reveal that air pollution is related to mental health. However, the level of impact and the regulatory mechanism of air pollution on different types of mental health are unknown. This paper examines the heterogeneous impact and mediating mechanisms of air pollution on mental health based on data of 51 countries from 2010 to 2017 by using panel Tobit random effect model, mediating effect model, and bootstrap test. The findings show that, firstly, there is heterogeneous impact of air pollution on different types of mental health. Specifically, air pollution has a significant positive impact on depression; and the impacts on happiness and anxiety are closely related to income level. Secondly, the heterogeneous impact of air pollution on mental health is contingent on income levels. Thirdly, the heterogeneous impacts under different income levels are exacerbated by different levels of education and population density. Lastly, the mediating effect of physical health on different types of mental health is also heterogeneous. To be specific, the effects of air pollution on depression and anxiety are partly mediated by physical health; whereas the effect on happiness is not. These findings contribute to the understanding of air pollution on public health, and have significant implication for social and public health policy makers.
Theorizing Community for Sport Management Research and Practice
Authors: Rich Kyle A. , Spaaij Ramón , Misener Laura
Published: November 2021

Community is a context for much research in sport, sport management, and sport policy, yet relatively few authors explicitly articulate the theoretical frameworks with which they interrogate the concept. In this paper, we draw from communitarian theory and politics in order to contribute to a robust discussion and conceptualization of community in and for sport management research and practice. We provide a synthesis of current sport management and related research in order to highlight contemporary theoretical and methodological approaches to studying community. We distinguish between community as a context, as an outcome, as a site for struggle or resistance, as well as a form of regulation or social control. We then advance a critical communitarian agenda and consider the practical implications and considerations for research and practice. This paper synthesizes current research and establishes a foundation upon which sport management scholars and practitioners might critically reflect on community and deliberatively articulate its implications in both future research and practice.
miRNAs Related to Different Processes of Fracture Healing: An Integrative Overview
Authors: Groven Rald V. M. , van Koll Johan , Poeze Martijn , Blokhuis Taco J. , van Griensven Martijn
Published: November 2021

Fracture healing is a complex, dynamic process that is directed by cellular communication and requires multiple cell types, such as osteoblasts, osteoclasts, and immune cells. Physiological fracture healing can be divided into several phases that consist of different processes, such as angiogenesis, osteogenesis, and bone resorption/remodelling. This is needed to guarantee proper bone regeneration after fracture. Communication and molecular regulation between different cell types and within cells is therefore key in successfully orchestrating these processes to ensure adequate bone healing. Among others, microRNAs (miRNAs) play an important role in cellular communication. microRNAs are small, non-coding RNA molecules of ~22 nucleotides long that can greatly influence gene expression by post-transcriptional regulation. Over the course of the past decade, more insights have been gained in the field of miRNAs and their role in cellular signalling in both inter- and intracellular pathways. The interplay between miRNAs and their mRNA targets, and the effect thereof on different processes and aspects within fracture healing, have shown to be interesting research topics with possible future diagnostic and therapeutic potential. Considering bone regeneration, research moreover focusses on specific microRNAs and their involvement in individual pathways. However, it is required to combine these data to gain more understanding on the effects of miRNAs in the dynamic process of fracture healing, and to enhance their translational application in research, as well as in the clinic. Therefore, this review aims to provide an integrative overview on miRNAs in fracture healing, related to several key aspects in the fracture healing cascade. A special focus will be put on hypoxia, angiogenesis, bone resorption, osteoclastogenesis, mineralization, osteogenesis, osteoblastogenesis, osteocytogenesis, and chondrogenesis.
An Interaction-Based Convolutional Neural Network (ICNN) Toward a Better Understanding of COVID-19 X-ray Images
Authors: Lo Shaw-Hwa , Yin Yiqiao
Published: November 2021

The field of explainable artificial intelligence (XAI) aims to build explainable and interpretable machine learning (or deep learning) methods without sacrificing prediction performance. Convolutional neural networks (CNNs) have been successful in making predictions, especially in image classification. These popular and well-documented successes use extremely deep CNNs such as VGG16, DenseNet121, and Xception. However, these well-known deep learning models use tens of millions of parameters based on a large number of pretrained filters that have been repurposed from previous data sets. Among these identified filters, a large portion contain no information yet remain as input features. Thus far, there is no effective method to omit these noisy features from a data set, and their existence negatively impacts prediction performance. In this paper, a novel interaction-based convolutional neural network (ICNN) is introduced that does not make assumptions about the relevance of local information. Instead, a model-free influence score (I-score) is proposed to directly extract the influential information from images to form important variable modules. This innovative technique replaces all pretrained filters found by trial-and-error with explainable, influential, and predictive variable sets (modules) determined by the I-score. In other words, future researchers need not rely on pretrained filters; the suggested algorithm identifies only the variables or pixels with high I-score values that are extremely predictive and important. The proposed method and algorithm were tested on real-world data set and a state-of-the-art prediction performance of 99.8% was achieved without sacrificing the explanatory power of the model. This proposed design can efficiently screen patients infected by COVID-19 before human diagnosis and can be a benchmark for addressing future XAI problems in large-scale data sets.
“As Long as There’s Me. As Long as There’s You”: Trauma and Migration in David Bowie’s Berlin Triptych
Authors: Junyk Ihor
Published: November 2021

This essay explores David Bowie’s so-called “Berlin Triptych”: Low, “Heroes”, and Lodger. The essay takes issue with previous interpretations that have claimed that the albums do not form a “triptych” of any meaningful kind, and that this pretentious term was only applied ex post facto as a marketing strategy. At the heart of my argument is the concept and experience of migration. In the mid-1970s David Bowie was living in Los Angeles at a highpoint of fame and acclaim. His life, however, was also an increasingly hellish nightmare of delusion, paranoia, and cocaine psychosis. In order to save his music, and his life, the singer decamped to Europe. For the next several years he lived an itinerant life with Berlin at its centre. The experience of displacement, and a series of encounters that this displacement facilitated (with the European new wave and a longer tradition of avant-garde modernism), led to both a reshuffling of the self and a radical new sound. The “triptych” tells the story of this progression, both narratively and sonically.
A Novel Proton Pencil Beam Scanning FLASH RT Delivery Method Enables Optimal OAR Sparing and Ultra-High Dose Rate Delivery: A Comprehensive Dosimetry Study for Lung Tumors
Authors: Wei Shouyi , Lin Haibo , Choi J. Isabelle , Simone Charles B. , Kang Minglei
Published: November 2021

Purpose: While transmission proton beams have been demonstrated to achieve ultra-high dose rate FLASH therapy delivery, they are unable to spare normal tissues distal to the target. This study aims to compare FLASH treatment planning using single energy Bragg peak proton beams versus transmission proton beams in lung tumors and to evaluate Bragg peak plan optimization, characterize plan quality, and quantify organ-at-risk (OAR) sparing. Materials and Methods: Both Bragg peak and transmission plans were optimized using an in-house platform for 10 consecutive lung patients previously treated with proton stereotactic body radiation therapy (SBRT). To bring the dose rate up to the FLASH-RT threshold, Bragg peak plans with a minimum MU/spot of 1200 and transmission plans with a minimum MU/spot of 400 were developed. Two common prescriptions, 34 Gy in 1 fraction and 54 Gy in 3 fractions, were studied with the same beam arrangement for both Bragg peak and transmission plans (n = 40 plans). RTOG 0915 dosimetry metrics and dose rate metrics based on different dose rate calculations, including average dose rate (ADR), dose-averaged dose rate (DADR), and dose threshold dose rate (DTDR), were investigated. We then evaluated the effect of beam angular optimization on the Bragg peak plans to explore the potential for superior OAR sparing. Results: Bragg peak plans significantly reduced doses to several OAR dose parameters, including lung V7.4Gy and V7Gy by 32.0% (p < 0.01) and 30.4% (p < 0.01) for 34Gy/fx plans, respectively; and by 40.8% (p < 0.01) and 41.2% (p < 0.01) for 18Gy/fx plans, respectively, compared with transmission plans. Bragg peak plans have ~3% less in DADR and ~10% differences in mean OARs in DTDR and DADR relative to transmission plans due to the larger portion of lower dose regions of Bragg peak plans. With angular optimization, optimized Bragg peak plans can further reduce the lung V7Gy by 20.7% (p < 0.01) and V7.4Gy by 19.7% (p < 0.01) compared with Bragg peak plans without angular optimization while achieving a similar 3D dose rate distribution. Conclusion: The single-energy Bragg peak plans achieve superior dosimetry performances in OARs to transmission plans with comparable dose rate performances for lung cancer FLASH therapy. Beam angle optimization can further improve the OAR dosimetry parameters with similar 3D FLASH dose rate coverage.
Oxidative Stress and Autophagy as Key Targets in Melanoma Cell Fate
Authors: Catalani Elisabetta , Giovarelli Matteo , Zecchini Silvia , Perrotta Cristiana , Cervia Davide
Published: November 2021

Melanoma originates from the malignant transformation of melanocytes and is one of the most aggressive forms of cancer. The recent approval of several drugs has increased the chance of survival although a significant subset of patients with metastatic melanoma do not show a long-lasting response to these treatments. The complex cross-talk between oxidative stress and the catabolic process autophagy seems to play a central role in all aspects of melanoma pathophysiology, from initiation to progression and metastasis, including drug resistance. However, determining the fine role of autophagy in cancer death and in response to redox disruption is still a fundamental challenge in order to advance both basic and translational aspects of this field. In order to summarize the interactions among reactive oxygen and nitrogen species, autophagy machinery and proliferation/growth/death/apoptosis/survival, we provide here a narrative review of the preclinical evidence for drugs/treatments that modulate oxidative stress and autophagy in melanoma cells. The significance and the potential for pharmacological targeting (also through multiple and combination approaches) of these two different events, which can contribute independently or simultaneously to the fate of melanoma, may help to define new processes and their interconnections underlying skin cancer biology and unravel new reliable approaches.
A Multiparametric MR-Based RadioFusionOmics Model with Robust Capabilities of Differentiating Glioblastoma Multiforme from Solitary Brain Metastasis
Authors: Wu Jialiang , Liang Fangrong , Wei Ruili , Lai Shengsheng , Lv Xiaofei , Luo Shiwei , Wu Zhe , Chen Huixian , Zhang Wanli , Zeng Xiangling , Ye Xianghua , Wu Yong , Wei Xinhua , Jiang Xinqing , Zhen Xin , Yang Ruimeng
Published: November 2021

This study aimed to evaluate the diagnostic potential of a novel RFO model in differentiating GBM and SBM with multiparametric MR sequences collected from 244 (131 GBM and 113 SBM) patients. Three basic volume of interests (VOIs) were delineated on the conventional axial MR images (T1WI, T2WI, T2_FLAIR, and CE_T1WI), including volumetric non-enhanced tumor (nET), enhanced tumor (ET), and peritumoral edema (pTE). Using the RFO model, radiomics features extracted from different multiparametric MRI sequence(s) and VOI(s) were fused and the best sequence and VOI, or possible combinations, were determined. A multi-disciplinary team (MDT)-like fusion was performed to integrate predictions from the high-performing models for the final discrimination of GBM vs. SBM. Image features extracted from the volumetric ET (VOIET) had dominant predictive performances over features from other VOI combinations. Fusion of VOIET features from the T1WI and T2_FLAIR sequences via the RFO model achieved a discrimination accuracy of AUC = 0.925, accuracy = 0.855, sensitivity = 0.856, and specificity = 0.853, on the independent testing cohort 1, and AUC = 0.859, accuracy = 0.836, sensitivity = 0.708, and specificity = 0.919 on the independent testing cohort 2, which significantly outperformed three experienced radiologists (p = 0.03, 0.01, 0.02, and 0.01, and p = 0.02, 0.01, 0.45, and 0.02, respectively) and the MDT-decision result of three experienced experts (p = 0.03, 0.02, 0.03, and 0.02, and p = 0.03, 0.02, 0.44, and 0.03, respectively).
The Hidden Link of Exosomes to Head and Neck Cancer
Authors: Teng Yong , Gao Lixia , Loveless Reid , Rodrigo Juan P. , Strojan Primož , Willems Stefan M. , Nathan Cherie-Ann , Mäkitie Antti A. , Saba Nabil F. , Ferlito Alfio
Published: November 2021

Head and neck squamous cell carcinoma (HNSCC) represents an aggressive and heterogenous group of cancers whose pathologies remain largely unresolved. Despite recent advances in HNSCC therapeutic strategies, the overall survival of HNSCC patients remains poor and continues to prompt efforts to develop more effective therapies. Exosomes are a subtype of extracellular vesicles secreted by a variety of cells that have begun to spark significant interest in their roles in cancer. As membranous vesicles, spanning from 30–150 nm in diameter, exosomes mediate the transport of various molecules, such as proteins, nucleic acids, and lipids, intercellularly throughout the body. In doing so, exosomes not only act to deliver materials to cancer cells but also as signals that can confer their progression. Accumulating evidence shows the direct correlation between exosomes and the aggressiveness of HNSCC. However, more research is warranted in this field to further our understanding. In this review, we attempt to highlight the tumor-supporting roles and therapeutic potential of exosomes in HNSCC. We introduce first the biogenesis and component features of exosomes, followed by their involvement in HNSCC proliferation and metastasis. We then move on to discuss HNSCC-derived exosomes’ influence on the tumor microenvironment and their function in tumor drug resistance. Finally, we explore the promising potential of exosomes as HNSCC biomarkers and therapeutic targets and drug carriers for HNSCC treatments.
Medial Inguino-Femoral Lymphadenectomy for Vulvar Cancer: An Approach to Decrease Lymphedema without Compromising Survival
Authors: Hacker Neville F. , Barlow Ellen , Morrell Stephen , Tang Katrina
Published: November 2021

Background: Lower limb lymphedema is a long-term complication of inguino-femoral lymphadenectomy and is related to the number of lymph nodes removed. Our hypothesis was that lymph nodes lateral to the femoral artery could be left in situ if the medial nodes were negative, thereby decreasing this risk. Methods: We included patients with vulvar cancer of any histological type, even if the cancer extended medially to involve the urethra, anus, or vagina. We excluded patients whose tumor extended (i) laterally onto the thigh, (ii) posteriorly onto the buttocks, or (iii) anteriorly onto the mons pubis. After resection, the inguinal nodes were divided into a medial and a lateral group, based on the lateral border of the femoral artery. Results: Between December 2010 and July 2018, 76 patients underwent some form of groin node dissection, and data were obtained from 112 groins. Approximately one-third of nodes were located lateral to the femoral artery. Positive groin nodes were found in 29 patients (38.2%). All patients with positive nodes had positive nodes medial to the femoral artery. Five patients (6.6%) had positive lateral inguinal nodes. The probability of having a positive lateral node given a negative medial node was estimated to be 0.00002. Conclusion: Provided the medial nodes are negative, medial inguino-femoral lymphadenectomy may suffice and should reduce lower limb lymphedema without compromising survival.
Comprehensive Draft Genome Analyses of Three Rockfishes (Scorpaeniformes, Sebastiscus) via Genome Survey Sequencing
Authors: Jia Chenghao , Yang Tianyan , Yanagimoto Takashi , Gao Tianxiang
Published: November 2021

Sebastiscus species, marine rockfishes, are of essential economic value. However, the genomic data of this genus is lacking and incomplete. Here, whole genome sequencing of all species of Sebastiscus was conducted to provide fundamental genomic information. The genome sizes were estimated to be 802.49 Mb (S. albofasciatus), 786.79 Mb (S. tertius), and 776.00 Mb (S. marmoratus) by using k-mer analyses. The draft genome sequences were initially assembled, and genome-wide microsatellite motifs were identified. The heterozygosity, repeat ratios, and numbers of microsatellite motifs all suggested possibly that S. tertius is more closely related to S. albofasciatus than S. marmoratus at the genetic level. Moreover, the complete mitochondrial genome sequences were assembled from the whole genome data and the phylogenetic analyses genetically supported the validation of Sebastiscus species. This study provides an important genome resource for further studies of Sebastiscus species.
Two New Species of the Genus Longipedia Claus, 1863 (Copepoda: Harpacticoida: Longipediidae) from Korea, with an Update and a Key to Species
Authors: Bang Hyun Woo , Moon Heejin , Back Jinwook
Published: November 2021

Benthic harpacticoids were collected from Korean waters. Two species were identified as members of the genus Longipedia Claus, 1863, because they have an extremely elongated distal segment of the P2 endopod. Longipedia koreana sp. nov. is morphologically most closely related to L. nichollsi Wells, 1980 and L. scotti Sars, 1903, but it can clearly be distinguished from both species based on the following morphological characteristics: P1 coxa with strong spinules near the outer margin and the distal element being much bigger than the proximal elements, P2 coxa with a small inner seta on the anterior surface, P4 exopod first segment without an inner element, and the P5 with a rectangular exopod (more than 3.5 times as long as wide). L. ulleungensis sp. nov. is similar to L. brevispinosa Gurney, 1927, L. spinulosa Itô, 1981, and L. weberi Scott A., 1909. However, L. ulleungensis sp. nov. is characterized by the P2 coxa with a reduced inner seta, the P4 exopod second segment without an inner seta, and the anal operculum with a long median projection, a single spine, and a group of outer spines on each side. In a molecular analysis using the mitochondrial cytochrome c oxidase subunit I (COI) and 18S ribosomal RNA (18S rRNA) genes, the inter-specific variation was 22.525–23.102% and 1.325–1.382% of COI and 18S rRNA between the two new species, respectively. A key to the family Longipediidae is provided herein.