bluuebunny/crossref_metadata_2025 huggingface dataset:
CD58 Immunobiology at a Glance
Authors: Zhang Yalu , Liu Qiaofei , Yang Sen , Liao Quan
Published: June 2021

The glycoprotein CD58, also known as lymphocyte-function antigen 3 (LFA-3), is a costimulatory receptor distributed on a broad range of human tissue cells. Its natural ligand CD2 is primarily expressed on the surface of T/NK cells. The CD2-CD58 interaction is an important component of the immunological synapse (IS) that induces activation and proliferation of T/NK cells and triggers a series of intracellular signaling in T/NK cells and target cells, respectively, in addition to promoting cell adhesion and recognition. Furthermore, a soluble form of CD58 (sCD58) is also present in cellular supernatantin vitroand in local tissuesin vivo. The sCD58 is involved in T/NK cell-mediated immune responses as an immunosuppressive factor by affecting CD2-CD58 interaction. Altered accumulation of sCD58 may lead to immunosuppression of T/NK cells in the tumor microenvironment, allowing sCD58 as a novel immunotherapeutic target. Recently, the crucial roles of costimulatory molecule CD58 in immunomodulation seem to be reattracting the interests of investigators. In particular, the CD2-CD58 interaction is involved in the regulation of antiviral responses, inflammatory responses in autoimmune diseases, immune rejection of transplantation, and immune evasion of tumor cells. In this review, we provide a comprehensive summary of CD58 immunobiology.
Serum Bilirubin Is Correlated With the Progression of IgA Vasculitis With Nephritis
Authors: Tan Jiaxing , Pei Gaiqin , Xu Yicong , Hu Tengyue , Tan Li , Zhong Zhengxia , Tarun Padamata , Tang Yi , Qin Wei
Published: June 2021

Background: Bilirubin has been identified as an endogenous antioxidant and cellular protectant. The present study was performed to clarify the potential influence of serum bilirubin on IgA vasculitis with nephritis (IgAV-N).

Methods: One hundred and eighty-nine IgAV-N patients over 14 years old were enrolled. The patients were divided into two groups by the optimum cut-off value calculated by ROC curve. The composite endpoints were defined as a 60% decline in estimate glomerular filtration rate (e-GFR), end-stage renal disease (ESRD) and/or death. Kaplan-Meier (K-M) analysis and multivariate Cox analysis were carried out to determine the predictors for renal outcomes. In order to eliminate the influence of different baseline data, a 1:2 propensity score (PS) match was performed to make the results comparable and convictive.

Results: The baseline data suggested that patients in low serum bilirubin group had significantly higher levels of systolic blood pressure, proteinuria, serum creatinine and crescent formation ratio and lower levels of serum albumin and hemoglobin. Renal survival analysis indicated that lower serum bilirubin levels were significantly correlated with a poorer prognosis. Multivariate Cox analysis demonstrated that the higher level of serum bilirubin was an independent protective factor for renal survival (HR, 0.172; 95% CI, 0.030–0.991; P = 0.049). After PS matching, the baseline characters of two groups had no statistical differences. Similar outcomes were demonstrated in K-M curve and the multivariate Cox analysis.

Conclusion: Elevated bilirubin levels might be related to the favorable renal outcomes.
Diet–Microbiota Interactions Alter Mosquito Development
Authors: Martinson Vincent G. , Strand Michael R.
Published: June 2021

Gut microbes and diet can both strongly affect the biology of multicellular animals, but it is often difficult to disentangle microbiota–diet interactions due to the complex microbial communities many animals harbor and the nutritionally variable diets they consume. While theoretical and empirical studies indicate that greater microbiota diversity is beneficial for many animal hosts, there have been few tests performed in aquatic invertebrates. Most mosquito species are aquatic detritivores during their juvenile stages that harbor variable microbiotas and consume diets that range from nutrient rich to nutrient poor. In this study, we produced a gnotobiotic model that allowed us to examine how interactions between specific gut microbes and diets affect the fitness of Aedes aegypti, the yellow fever mosquito. Using a simplified seven-member community of bacteria (ALL7) and various laboratory and natural mosquito diets, we allowed larval mosquitoes to develop under different microbial and dietary conditions and measured the resulting time to adulthood and adult size. Larvae inoculated with the ALL7 or a more complex community developed similarly when fed nutrient-rich rat chow or fish food laboratory diets, whereas larvae inoculated with individual bacterial members of the ALL7 community exhibited few differences in development when fed a rat chow diet but exhibited large differences in performance when fed a fish food diet. In contrast, the ALL7 community largely failed to support the growth of larvae fed field-collected detritus diets unless supplemented with additional protein or yeast. Collectively, our results indicate that mosquito development and fitness are strongly contingent on both diet and microbial community composition.
Implications of Climate Change: How Does Increased Water Temperature Influence Biofilm and Water Quality of Chlorinated Drinking Water Distribution Systems?
Authors: Calero Preciado Carolina , Boxall Joby , Soria-Carrasco Víctor , Martínez Soledad , Douterelo Isabel
Published: June 2021

Temperature variation can promote physico-chemical and microbial changes in the water transported through distribution systems and influence the dynamics of biofilms attached to pipes, thus contributing to the release of pathogens into the bulk drinking water. An experimental real-scale chlorinated DWDS was used to study the effect of increasing temperature from 16 to 24°C on specific pathogens, bacterial-fungal communities (biofilm and water samples) and determine the risk of material accumulation and mobilisation from the pipes into the bulk water. Biofilm was developed for 30 days at both temperatures in the pipe walls, and after this growth phase, a flushing was performed applying 4 gradual steps by increasing the shear stress. The fungal-bacterial community characterised by Illumina MiSeq sequencing, and specific pathogens were studied using qPCR: Mycobacterium spp., Mycobacterium avium complex, Acanthamoeba spp., Pseudomonas aeruginosa, Legionella pneumophilia, and Stenotrophomonas maltophilia. Sequencing data showed that temperature variation significantly modified the structure of biofilm microbial communities from the early stages of biofilm development. Regarding bacteria, Pseudomonas increased its relative abundance in biofilms developed at 24°C, while fungal communities showed loss of diversity and richness, and the increase in dominance of Fusarium genus. After the mobilisation phase, Pseudomonas continued being the most abundant genus at 24°C, followed by Sphingobium and Sphingomonas. For biofilm fungal communities after the mobilisation phase, Helotiales incertae sedis and Fusarium were the most abundant taxa. Results from qPCR showed a higher relative abundance of Mycobacterium spp. on day 30 and M. avium complex throughout the growth phase within the biofilms at higher temperatures. The temperature impacts were not only microbial, with physical mobilisation showing higher discolouration response and metals release due to the increased temperature. While material accumulation was accelerated by temperature, it was not preferentially to either stronger or weaker biofilm layers, as turbidity results during the flushing steps showed. This research yields new understanding on microbial challenges that chlorinated DWDS will undergo as global temperature rises, this information is needed in order to protect drinking water quality and safety while travelling through distribution systems.
Comparative Growth Inhibition of Bread Spoilage Fungi by Different Preservative Concentrations Using a Rapid Turbidimetric Assay System
Authors: Garcia Marcelo Valle , Garcia-Cela Esther , Magan Naresh , Copetti Marina Venturini , Medina Angel
Published: June 2021

Bread and intermediate moisture bakery products are mainly spoiled by yeasts and filamentous fungi. The inoculum load and preservation system used determines their shelf life. To extend the shelf life of such commodities, the use of chemical preservatives is the most common way to try and control the initiation of mold spoilage of bread. This study has utilized a rapid turbidimetric assay system (Bioscreen C) to examine the temporal efficacy of calcium propionate (CP) and potassium sorbate (PS) for controlling the growth of important bread spoilage fungi. The objectives were to compare the temporal growth of strains of three important spoilage fungi Hyphopichia burtonii (HB17), Paecilomyces variotii (PV11), and Penicillium roqueforti (PR06) isolated from visibly molded bread to (a) different concentrations of CP and PS (0–128 mM), (b) temperatures (25°C, 30°C), (c) water activity (aw; 0.95, 0.97), and (d) pH (5.0, 5.5). All three abiotic factors, pH, aw, and temperature, and preservative concentrations influenced the relative growth of the species examined. In general, PS was more effective than CP in inhibiting the growth of the strains of these three species. In addition, the Time to Detection (TTD) for the efficacy of the preservatives under the interacting abiotic factors was compared. The strain of Paecilomyces variotii (PV10) was the most tolerant to the preservatives, with the shortest TTD values for both preservatives. P. roqueforti was the most sensitive with the longest TTD values under all conditions examined. These results are discussed in the context of the evolution of resistance to food-grade preservatives by such spoilage fungi in bakery products.
Evaluation of the Relationships Between Microbiota and Metabolites in Soft-Type Ripened Cheese Using an Integrated Omics Approach
Authors: Unno Ryosuke , Suzuki Toshihiro , Matsutani Minenosuke , Ishikawa Morio
Published: June 2021

Cheese ripening is effected by various microorganisms and results in the characteristic flavors of cheese. Owing to the complexity of the microbiota involved, the relationship between microorganisms and components during ripening remains unclear. In this study, metagenomics and metabolomics were integrated to reveal these relationships in three kinds of surface mold-ripened cheeses and two kinds of bacterial smear-ripened cheeses. The microbiota is broadly divided into two groups to correspond with different cheese types. Furthermore, surface mold-ripened cheese showed similar microbiota regardless of the cheese variety, whereas bacterial smear-ripened cheese showed specific microbiota characterized by marine bacteria (MB) and halophilic and alkaliphilic lactic acid bacteria for each cheese variety. In the metabolite analysis, volatile compounds suggested differences in cheese types, although organic acids and free amino acids could not determine the cheese characteristics. On the other hand, Spearman correlation analysis revealed that the abundance of specific bacteria was related to the formation of specific organic acids, free amino acids, and volatile compounds. In particular, MB was positively correlated with esters and pyrazines, indicating their contribution to cheese quality. These methodologies and results further our understanding of microorganisms and allow us to select useful strains for cheese ripening.
Complete Nucleotide Sequence, Genome Organization, and Comparative Genomic Analyses of Citrus Yellow-Vein Associated Virus (CYVaV)
Authors: Kwon Sun-Jung , Bodaghi Sohrab , Dang Tyler , Gadhave Kiran R. , Ho Thien , Osman Fatima , Al Rwahnih Maher , Tzanetakis Ioannis E. , Simon Anne E. , Vidalakis Georgios
Published: June 2021

Citrus yellow-vein disease (CYVD) was first reported in California in 1957. We now report that CYVD is associated with a virus-like agent, provisionally named citrus yellow-vein associated virus (CYVaV). The CYVaV RNA genome has 2,692 nucleotides and codes for two discernable open reading frames (ORFs). ORF1 encodes a protein of 190 amino acid (aa) whereas ORF2 is presumably generated by a −1 ribosomal frameshifting event just upstream of the ORF1 termination signal. The frameshift product (717 aa) encodes the RNA-dependent RNA polymerase (RdRp). Phylogenetic analyses suggest that CYVaV is closely related to unclassified virus-like RNAs in the familyTombusviridae. Bio-indexing and RNA-seq experiments indicate that CYVaV can induce yellow vein symptoms independently of known citrus viruses or viroids.
A Novel Identified Long Non-coding RNA, lncRNA MEF2C-AS1, Inhibits Cervical Cancer via Regulation of miR-592/RSPO1
Authors: Wang Xiaoping , Zhang Changhong , Gong Meixuan , Jiang Chen
Published: June 2021

Purpose: Our purpose was to investigate the effect of lncRNA MEF2C antisense RNA 1 (MEF2C-AS1) on cervical cancer and further explore its underlying molecular mechanisms.

Methods: The proliferation, migration and invasion of CC cells were determined by counting Kit-8 (CCK-8), colony formation assay, and transwell assays, respectively. qRT-PCR and western blot were conducted to quantitatively detect the expression of lncRNA MEF2C-AS1, miR-592 and R-spondin1 (RSPO1). Kaplan-Meier survival curve from the Cancer Genome Atlas (TCGA) database and the Gene Expression Profiling Interactive Analysis (GEPIA) website was used to describe the overall survival. Bioinformatics analysis was performed to search the downstream target of lncRNA MEF2C-AS1 and miR-592. Luciferase reporter assay was conducted to detect the interaction between lncRNA MEF2C-AS1 and miR-592 or miR-592 and RSPO1.

Results: The data from GEPIA website showed that lncRNA MEF2C-AS1 expression was down-regulated in CC tissues and also associated with survival rate of CC patients. Moreover, the results of qRT-PCR also showed lncRNA MEF2C-AS1 was lowly expressed in CC cells. Subsequently, we confirmed that overexpression of lncRNA MEF2C-AS1 inhibited the proliferation, migration and invasion of CC cells. Further research illustrated that lncRNA MEF2C-AS1 was the target of miR-592, and RSPO1 was the downstream target gene of miR-592. Importantly, functional research findings indicated that lncRNA MEF2C-AS1 inhibited CC via suppressing miR-592 by targeting RSPO1.

Conclusion: In our study, we demonstrated the functional role of the lncRNA MEF2C-AS1-miR-592-RSPO1 axis in the progression of CC, which provides a latent target for CC treatment.
High-Fat Diet Alleviates Neuroinflammation and Metabolic Disorders of APP/PS1 Mice and the Intervention With Chinese Medicine
Authors: Fan Xiaorui , Liu Bin , Zhou Junyi , Gu Xinru , Zhou Yanyan , Yang Yifei , Guo Feifei , Wei Xiaolu , Wang Hongjie , Si Nan , Yang Jian , Bian Baolin , Zhao Haiyu
Published: June 2021

Alzheimer's disease (AD) is a progressive neurodegenerative disease caused by the complex interaction of multiple mechanisms. Recent studies examining the effect of high-fat diet (HFD) on the AD phenotype have demonstrated a significant influence on both inflammation and cognition. However, different studies on the effect of high-fat diet on AD pathology have reported conflicting conclusions. To explore the involvement of HFD in AD, we investigated phenotypic and metabolic changes in an AD mouse model in response to HFD. The results indicated there was no significant effect on Aβ levels or contextual memory due to HFD treatment. Of note, HFD did moderate neuroinflammation, despite spurring inflammation and increasing cholesterol levels in the periphery. In addition, diet affected gut microbiota symbiosis, altering the production of bacterial metabolites. HFD created a favorable microenvironment for bile acid alteration and arachidonic acid metabolism in APP/PS1 mice, which may be related to the observed improvement in LXR/PPAR expression. Our previous research demonstrated that Huanglian Jiedu decoction (HLJDD) significantly ameliorated impaired learning and memory. Furthermore, HLJDD may globally suppress inflammation and lipid accumulation to relieve cognitive impairment after HFD intervention. It was difficult to define the effect of HFD on AD progression because the results were influenced by confounding factors and biases. Although there was still obvious damage in AD mice treated with HFD, there was no deterioration and there was even a slight remission of neuroinflammation. Moreover, HLJDD represents a potential AD drug based on its anti-inflammatory and lipid-lowering effects.
Mitophagy in Cerebral Ischemia and Ischemia/Reperfusion Injury
Authors: Shen Luoan , Gan Qinyi , Yang Youcheng , Reis Cesar , Zhang Zheng , Xu Shanshan , Zhang Tongyu , Sun Chengmei
Published: June 2021

Ischemic stroke is a severe cerebrovascular disease with high mortality and morbidity. In recent years, reperfusion treatments based on thrombolytic and thrombectomy are major managements for ischemic stroke patients, and the recanalization time window has been extended to over 24 h. However, with the extension of the time window, the risk of ischemia/reperfusion (I/R) injury following reperfusion therapy becomes a big challenge for patient outcomes. I/R injury leads to neuronal death due to the imbalance in metabolic supply and demand, which is usually related to mitochondrial dysfunction. Mitophagy is a type of selective autophagy referring to the process of specific autophagic elimination of damaged or dysfunctional mitochondria to prevent the generation of excessive reactive oxygen species (ROS) and the subsequent cell death. Recent advances have implicated the protective role of mitophagy in cerebral ischemia is mainly associated with its neuroprotective effects in I/R injury. This review discusses the involvement of mitochondria dynamics and mitophagy in the pathophysiology of ischemic stroke and I/R injury in particular, focusing on the therapeutic potential of mitophagy regulation and the possibility of using mitophagy-related interventions as an adjunctive approach for neuroprotective time window extension after ischemic stroke.
Exploiting hiPSCs in Leber's Hereditary Optic Neuropathy (LHON): Present Achievements and Future Perspectives
Authors: Peron Camille , Maresca Alessandra , Cavaliere Andrea , Iannielli Angelo , Broccoli Vania , Carelli Valerio , Di Meo Ivano , Tiranti Valeria
Published: June 2021

More than 30 years after discovering Leber's hereditary optic neuropathy (LHON) as the first maternally inherited disease associated with homoplasmic mtDNA mutations, we still struggle to achieve effective therapies. LHON is characterized by selective degeneration of retinal ganglion cells (RGCs) and is the most frequent mitochondrial disease, which leads young people to blindness, in particular males. Despite that causative mutations are present in all tissues, only a specific cell type is affected. Our deep understanding of the pathogenic mechanisms in LHON is hampered by the lack of appropriate models since investigations have been traditionally performed in non-neuronal cells. Effective in-vitro models of LHON are now emerging, casting promise to speed our understanding of pathophysiology and test therapeutic strategies to accelerate translation into clinic. We here review the potentials of these new models and their impact on the future of LHON patients.
Assessment Methods of Post-stroke Gait: A Scoping Review of Technology-Driven Approaches to Gait Characterization and Analysis
Authors: Mohan Dhanya Menoth , Khandoker Ahsan Habib , Wasti Sabahat Asim , Ismail Ibrahim Ismail Alali Sarah , Jelinek Herbert F. , Khalaf Kinda
Published: June 2021

Background: Gait dysfunction or impairment is considered one of the most common and devastating physiological consequences of stroke, and achieving optimal gait is a key goal for stroke victims with gait disability along with their clinical teams. Many researchers have explored post stroke gait, including assessment tools and techniques, key gait parameters and significance on functional recovery, as well as data mining, modeling and analyses methods.

Research Question: This study aimed to review and summarize research efforts applicable to quantification and analyses of post-stroke gait with focus on recent technology-driven gait characterization and analysis approaches, including the integration of smart low cost wearables and Artificial Intelligence (AI), as well as feasibility and potential value in clinical settings.

Methods: A comprehensive literature search was conducted within Google Scholar, PubMed, and ScienceDirect using a set of keywords, including lower extremity, walking, post-stroke, and kinematics. Original articles that met the selection criteria were included.

Results and Significance: This scoping review aimed to shed light on tools and technologies employed in post stroke gait assessment toward bridging the existing gap between the research and clinical communities. Conventional qualitative gait analysis, typically used in clinics is mainly based on observational gait and is hence subjective and largely impacted by the observer's experience. Quantitative gait analysis, however, provides measured parameters, with good accuracy and repeatability for the diagnosis and comparative assessment throughout rehabilitation. Rapidly emerging smart wearable technology and AI, including Machine Learning, Support Vector Machine, and Neural Network approaches, are increasingly commanding greater attention in gait research. Although their use in clinical settings are not yet well leveraged, these tools promise a paradigm shift in stroke gait quantification, as they provide means for acquiring, storing and analyzing multifactorial complex gait data, while capturing its non-linear dynamic variability and offering the invaluable benefits of predictive analytics.
Energy Balance-Related Behavior Risk Pattern and Its Correlates During COVID-19 Related Home Confinement
Authors: Bhutani Surabhi , vanDellen Michelle R. , Haskins LeeAnn B. , Cooper Jamie A.
Published: June 2021

Self-reported weight gain during the COVID-19 shelter-at-home has raised concerns for weight increases as the pandemic continues. We aimed to investigate the relationship of psychological and health markers with energy balance-related behaviors during the pandemic-related extended home confinement. Ratings for stress, boredom, cravings, sleep, self-control, and beliefs about weight control were collected from 1,609 adults using a questionnaire between April 24th–May 4th, 2020, while COVID-19 associated shelter-in-place guidelines were instituted across the US. We calculated four energy balance behavior scores (physical activity risk index, unhealthy eating risk index, healthy eating risk index, sedentary behavior index), and conducted a latent profile analysis of the risk factors. We examined psychological and health correlates of these risk patterns. Boredom, cravings for sweet/savory foods, and high sleepiness ratings related to high risk of increasing unhealthy eating and sedentary behavior and decreasing physical activity and healthy eating. Having greater self-control, control over cravings, or positive mood was related to lowering all aspects of energy intake and energy expenditure risks. Although individuals in risk pattern classes showed similarity in physical activity and healthy/unhealthy eating habits, they exhibited different patterns of positive mood, craving control, food cravings, boredom, and self-control. Psychological and health variables may have a significant role to play in risk behaviors associated with weight gain during the COVID-19 related home confinement. Emerging behavioral patterns may be meaningful in developing targeted weight management interventions during the current pandemic.
Genetic Alterations in Gliomas Remodel the Tumor Immune Microenvironment and Impact Immune-Mediated Therapies
Authors: Garcia-Fabiani Maria B. , Haase Santiago , Comba Andrea , Carney Stephen , McClellan Brandon , Banerjee Kaushik , Alghamri Mahmoud S. , Syed Faisal , Kadiyala Padma , Nunez Felipe J. , Candolfi Marianela , Asad Antonela , Gonzalez Nazareno , Aikins Marisa E. , Schwendeman Anna , Moon James J. , Lowenstein Pedro R. , Castro Maria G.
Published: June 2021

High grade gliomas are malignant brain tumors that arise in the central nervous system, in patients of all ages. Currently, the standard of care, entailing surgery and chemo radiation, exhibits a survival rate of 14-17 months. Thus, there is an urgent need to develop new therapeutic strategies for these malignant brain tumors. Currently, immunotherapies represent an appealing approach to treat malignant gliomas, as the pre-clinical data has been encouraging. However, the translation of the discoveries from the bench to the bedside has not been as successful as with other types of cancer, and no long-lasting clinical benefits have been observed for glioma patients treated with immune-mediated therapies so far. This review aims to discuss our current knowledge about gliomas, their molecular particularities and the impact on the tumor immune microenvironment. Also, we discuss several murine models used to study these therapies pre-clinically and how the model selection can impact the outcomes of the approaches to be tested. Finally, we present different immunotherapy strategies being employed in clinical trials for glioma and the newest developments intended to harness the immune system against these incurable brain tumors.
Identification of Novel Alternative Splicing Events Associated With Tumorigenesis, Protein Modification, and Immune Microenvironment in Early-Onset Gastric Cancer
Authors: Zhang Jian , Goel Ajay , Zhu Lin
Published: June 2021

Background

Alternative splicing (AS), e.g. the tandem alternative polyadenylation (TAPA), has emerged as major post-transcriptional modification events in human disease. However, the roles of the AS and TAPA in early-onset gastric cancer (EOGC) have not been revealed.

Methods

The global AS profiles of 80 EOGC patients were analyzed. The EOGC-specific AS events (ESASs) were identified in both the EOGC and adjacent non-tumor tissues. The functional enrichment analysis, Splicing network, Alternative Polyadenylation (APA) core factor network, and cell abundancy analysis were performed. Furthermore, the landscapes of the AS events in the varied subtypes of the EOGC patients were evaluated.

Results

Overall, 66,075 AS events and 267 ESASs were identified in the EOGC. Furthermore, 4809 genes and 6152 gene isoforms were found to be aberrantly expressed in the EOGC. The Gene Ontology (GO) and Kyoto Encyclopedia of Gene and Genome (KEGG) pathway analyses showed that the significant pathway alterations might exist in these AS events, genes, and gene isoforms. Moreover, the Protein-protein interaction (PPI) network analysis revealed that the UBC, NEK2, EPHB2, and DCTN1 genes were the hub genes in the AS events in the EOGC. The immune cell infiltration analysis indicated a correlation between the AS events and the cancer immune microenvironment. The distribution of the AS events in varied EOGC subtypes, protein phosphorylation and glycosylation was uneven.

Conclusion

The study highlighted the vital roles of the AS in the EOGC, including modulating the specific protein modification and reshaping the cancer immune microenvironment, and yielded new insights into the diagnosis of the EOGC as well as cancer treatment.
Bromodomain Inhibition Attenuates the Progression and Sensitizes the Chemosensitivity of Osteosarcoma by Repressing GP130/STAT3 Signaling
Authors: Jiang Yafei , Wang Gangyang , Mu Haoran , Ma Xiaojun , Wang Zhuoying , Lv Yu , Zhang Tao , Xu Jing , Wang Jinzeng , Li Yunqi , Han Jing , Yang Mengkai , Wang Zongyi , Zeng Ke , Jin Xinmeng , Xue Song , Yin Mingzhu , Sun Wei , Hua Yingqi , Cai Zhengdong
Published: June 2021

Osteosarcoma is the most common primary malignant bone tumor, and there are few ideal clinically available drugs. The bromodomain and extraterminal domain (BET) protein is an emerging target for aggressive cancer, but therapies targeting the BET in osteosarcoma have been unsuccessful in clinical trials to date, and further exploration of specific BET inhibitors is of great significance. In our study, we demonstrated that NHWD-870, a potent BET inhibitor in a phase I clinical trial, significantly inhibited tumor proliferation and promoted cell apoptosis by reversing the oncogenic signature in osteosarcoma. More importantly, we identified NHWD-870 impeded binding of BRD4 to the promoter of GP130 leading to diminished activation of JAK/STAT3 signaling pathway. Furthermore, GP130 knockdown significantly sensitizes the chemosensitivity in vitro. In OS cell-derived xenografts, NHWD-870 effectively inhibited the growth of osteosarcoma. Beyond that, NHWD-870 effectively inhibited the differentiation and maturation of precursor osteoclasts in vitro and attenuated osteoclast-mediated bone loss in vivo. Finally, we confirmed the efficacy of synthetic lethal effects of NHWD-870 and cisplatin in antagonizing osteosarcoma in a preclinical PDX model. Taken together, these findings demonstrate that NHWD-870, as an effective BET inhibitor, may be a potential candidate for osteosarcoma intervention linked to its STAT3 signaling inhibitory activity. In addition, NHWD-870 appears to be a promising therapeutic strategy for bone-associated tumors, as it interferes with the vicious cycle of tumor progression and bone destruction.
DIVIS: Integrated and Customizable Pipeline for Cancer Genome Sequencing Analysis and Interpretation
Authors: He Xiaoyu , Zhang Yu , Yuan Danyang , Han Xinyin , He Jiayin , Duan Xiaohong , Liu Siyao , Wang Xintong , Niu Beifang
Published: June 2021

Next-generation sequencing (NGS) has drastically enhanced human cancer research, but diverse sequencing strategies, complicated open-source software, and the identification of massive numbers of mutations have limited the clinical application of NGS. Here, we first presented GPyFlow, a lightweight tool that flexibly customizes, executes, and shares workflows. We then introduced DIVIS, a customizable pipeline based on GPyFlow that integrates read preprocessing, alignment, variant detection, and annotation of whole-genome sequencing, whole-exome sequencing, and gene-panel sequencing. By default, DIVIS screens variants from multiple callers and generates a standard variant-detection format list containing caller evidence for each sample, which is compatible with advanced analyses. Lastly, DIVIS generates a statistical report, including command lines, parameters, quality-control indicators, and mutation summary. DIVIS substantially facilitates complex cancer genome sequencing analyses by means of a single powerful and easy-to-use command. The DIVIS code is freely available at https://github.com/niu-lab/DIVIS, and the docker image can be downloaded from https://hub.docker.com/repository/docker/sunshinerain/divis.
Mean Platelet Volume/Platelet Count Ratio and Risk of Progression in Glioblastoma
Authors: Wach Johannes , Apallas Stefanos , Schneider Matthias , Weller Johannes , Schuss Patrick , Vatter Hartmut , Herrlinger Ulrich , Güresir Erdem
Published: June 2021

Objective

The mean platelet volume/platelet count (MPV/PC) ratio is an emerging biomarker in selected types of cancer. The objective of this study is to analyze the association of MPV/PC ratio with progression and survival in glioblastoma (GB) patients, with consideration of patient demographics, tumor morphology, extent of resection, molecular pathology, and oncological therapy.

Methods

One hundred ninety-one patients with newly diagnosed GB were analyzed retrospectively. MPV/PC ratio groups (≤ or >0.0575) were dichotomized into low-MPV/PC ratio (≤0.0575) and high-MPV/PC ratio (>0.0575) groups according to the most significant split in the log-rank test.

Results

A two-sided Fisher’s exact test showed no significant differences in the confounders between the low- and high-MPV/PC ratio groups. The median progression-free survival (PFS) was 9.0 months (95% CI=8.0–10.0) in the low-MPV/PC ratio group (n=164) and 6.0 months (95% CI=3.0–8.9) in the high-MPV/PC group (n=28) (p=0.013). Multivariate Cox regression analysis including the O-6-methylguanine-DNA methyltransferase (MGMT) status, age (≤/>65 years), baseline Karnofsky Performance Status (KPS), and MPV/PC ratio showed high-MPV/PC ratio as a predictor of progression (p =0.04, HR=1.61, 95% CI=1.01–2.57). In the subgroup of IDH1 wild-type GBs, high MPV/PC ratio was still a significant predictor for shortened PFS (p=0.042, HR=1.60, 95% CI=1.02–2.52). MPV/PC ratio showed no significant effect in the overall survival (OS) analysis. Median OS was 15.0 months in the high-MPV/PC ratio group and 21.0 months in the low-MPV/PC ratio group (p=0.22).

Conclusion

MPV/PC ratio may independently predict the progression-free survival rates of patients with glioblastoma multiforme.
Test–Retest Reliability and Responsiveness of PROMIS Sleep Short Forms Within an RCT in Women With Fibromyalgia
Authors: Chimenti Ruth L. , Rakel Barbara A. , Dailey Dana L. , Vance Carol G. T. , Zimmerman Miriam B. , Geasland Katharine M. , Williams Jon M. , Crofford Leslie J. , Sluka Kathleen A.
Published: June 2021

Background: Nonrestorative sleep is commonly reported by individuals with fibromyalgia, but there is limited information on the reliability and responsiveness of self-reported sleep measures in this population.

Objectives: (1) Examine the reliability and validity of the Patient-Reported Outcomes Measurement Information System (PROMIS) sleep measures in women with fibromyalgia, and (2) Determine the responsiveness of the PROMIS sleep measures to a daily transcutaneous electrical nerve stimulation (TENS) intervention in women with fibromyalgia over 4 weeks compared with other measures of restorative sleep.

Methods: In a double-blinded, dual-site clinical trial, 301 women with fibromyalgia were randomly assigned to utilize either Active-TENS, Placebo-TENS, or No-TENS at home. Measures were collected at baseline and after 4 weeks of treatment. To assess self-reported sleep, the participants completed three PROMIS short forms: Sleep Disturbance, Sleep-Related Impairment, Fatigue, and the Pittsburgh Sleep Quality Index (PSQI). To assess device-measured sleep, actigraphy was used to quantify total sleep time, wake after sleep onset, and sleep efficiency. Linear mixed models were used to examine the effects of treatment, time, and treatment*time interactions.

Results: The PROMIS short forms had moderate test–retest reliability (ICC 0.62 to 0.71) and high internal consistency (Cronbach's alpha 0.89 to 0.92). The PROMIS sleep measures [mean change over 4 weeks, 95% confidence interval (CI)], Sleep Disturbance: −1.9 (−3.6 to −0.3), Sleep-Related Impairment: −3 (−4.6 to −1.4), and Fatigue: −2.4 (−3.9 to −0.9) were responsive to improvement in restorative sleep and specific to the Active-TENS group but not in the Placebo-TENS [Sleep Disturbance: −1.3 (−3 to 0.3), Sleep-Related Impairment: −1.2 (−2.8 to 0.4), Fatigue: −1.1 (−2.7 to 0.9)] or No-TENS [Sleep Disturbance: −0.1 (−1.6 to 1.5), Sleep-Related Impairment: −0.2 (−1.7 to 1.4), Fatigue: –.3 (−1.8 to 1.2)] groups. The PSQI was responsive but not specific with improvement detected in both the Active-TENS: −0.9 (−1.7 to −0.1) and Placebo-TENS: −0.9 (−1.7 to 0) groups but not in the No-TENS group: −0.3 (−1.1 to 0.5). Actigraphy was not sensitive to any changes in restorative sleep with Active-TENS [Sleep Efficiency: −1 (−2.8 to 0.9), Total Sleep Time: 3.3 (−19.8 to 26.4)].

Conclusion: The PROMIS sleep measures are reliable, valid, and responsive to improvement in restorative sleep in women with fibromyalgia.

Clinical Trial Registration:www.ClinicalTrials.gov, identifier: NCT01888640.
T Lymphocytes, Multi-Omic Interactions and Bronchopulmonary Dysplasia
Authors: Toldi Gergely , Hummler Helmut , Pillay Thillagavathie
Published: June 2021

Bronchopulmonary dysplasia (BPD) remains a significant clinical challenge in neonatal medicine. BPD is clearly a multifactorial disease with numerous antenatal and postnatal components influencing lung development. Extremely immature infants are born in the late canalicular or early saccular stage and usually receive intensive care until the early alveolar stage of lung development, resulting in varying magnitudes of impairment of alveolar septation, lung fibrosis, and abnormal vascular development. The interactions between T lymphocytes, the genome and the epigenome, the microbiome and the metabolome, as well as nutrition and therapeutic interventions such as the exposure to oxygen, volutrauma, antibiotics, corticosteroids, caffeine and omeprazole, play an important role in pathogenesis and disease progression. While our general understanding of these interactions thanks to basic research is improving, this knowledge is yet to be translated into comprehensive prevention and clinical management strategies for the benefit of preterm infants developing BPD and later during infancy and childhood suffering from the disease itself and its sequelae. In this review, we summarise existing evidence on the interplay between T lymphocytes, lung multi-omics and currently used therapeutic interventions in BPD, and highlight avenues for potential future immunology related research in the field.
Rikkunshito as a Therapeautic Agent for Functional Dyspepsia and its Prokinetic and Non-Prokinetic Effects
Authors: Inokuchi Kazumi , Masaoka Tatsuhiro , Kanai Takanori
Published: June 2021

Prokinetics is one of the therapeutic agents for functional and motility disorders of the stomach. However, its efficacy is limited. Kampo medicine is a unique medical system that was developed in Japan. In Kampo medicine, herbal medicine is prescribed based on the patient’s condition. Therefore, even for functional and motility disorders of the stomach, some herbal medicines are considered as a therapeutic option. Recently, there has been an increase in evidence for the efficacy or the mechanism of herbal medicine for functional and motility disorders of the stomach. Among these, rikkunshito is a well-studied herbal medicine that could be used as an alternative to prokinetics. In this review, we discuss the possibilities of rikkunshito for functional dyspepsia with its prokinetic and non-prokinetic effects and provide an overview of their current use with a focus on their therapeutic mechanism.
Functional and Predictive Structural Characterization of WRINKLED2, A Unique Oil Biosynthesis Regulator in Avocado
Authors: Behera Jyoti R. , Rahman Md. Mahbubur , Bhatia Shina , Shockey Jay , Kilaru Aruna
Published: June 2021

WRINKLED1 (WRI1), a member of the APETALA2 (AP2) class of transcription factors regulates fatty acid biosynthesis and triacylglycerol (TAG) accumulation in plants. Among the four known Arabidopsis WRI1 paralogs, only WRI2 was unable to complement and restore fatty acid content in wri1-1 mutant seeds. Avocado (Persea americana) mesocarp, which accumulates 60-70% dry weight oil content, showed high expression levels for orthologs of WRI2, along with WRI1 and WRI3, during fruit development. While the role of WRI1 as a master regulator of oil biosynthesis is well-established, the function of WRI1 paralogs is poorly understood. Comprehensive and comparative in silico analyses of WRI1 paralogs from avocado (a basal angiosperm) with higher angiosperms Arabidopsis (dicot), maize (monocot) revealed distinct features. Predictive structural analyses of the WRI orthologs from these three species revealed the presence of AP2 domains and other highly conserved features, such as intrinsically disordered regions associated with predicted PEST motifs and phosphorylation sites. Additionally, avocado WRI proteins also contained distinct features that were absent in the nonfunctional Arabidopsis ortholog AtWRI2. Through transient expression assays, we demonstrated that both avocado WRI1 and WRI2 are functional and drive TAG accumulation in Nicotiana benthamiana leaves. We predict that the unique features and activities of ancestral PaWRI2 were likely lost in orthologous genes such as AtWRI2 during evolution and speciation, leading to at least partial loss of function in some higher eudicots. This study provides us with new targets to enhance oil biosynthesis in plants.
The HADES Yield Prediction System – A Case Study on the Turkish Hazelnut Sector
Authors: Bregaglio Simone , Fischer Kim , Ginaldi Fabrizio , Valeriano Taynara , Giustarini Laura
Published: June 2021

Crop yield forecasting activities are essential to support decision making of farmers, private companies and public entities. While standard systems use georeferenced agro-climatic data as input to process-based simulation models, new trends entail the application of machine learning for yield prediction. In this paper we present HADES (HAzelnut yielD forEcaSt), a hazelnut yield prediction system, in which process-based modeling and machine learning techniques are hybridized and applied in Turkey. Official yields in the top hazelnut producing municipalities in 2004–2019 are used as reference data, whereas ground observations of phenology and weather data represent the main HADES inputs. A statistical analysis allows inferring the occurrence and magnitude of biennial bearing in official yields and is used to aid the calibration of a process-based hazelnut simulation model. Then, a Random Forest algorithm is deployed in regression mode using the outputs of the process-based model as predictors, together with information on hazelnut varieties, the presence of alternate bearing in the yield series, and agro-meteorological indicators. HADES predictive ability in calibration and validation was balanced, with relative root mean square error below 20%, and R2 and Nash-Sutcliffe modeling efficiency above 0.7 considering all municipalities together. HADES paves the way for a next-generation yield prediction system, to deliver timely and robust information and enhance the sustainability of the hazelnut sector across the globe.
Management of the Wheat Curl Mite and Wheat Streak Mosaic Virus With Insecticides on Spring and Winter Wheat
Authors: Murphy Carmen Y. , Burrows Mary E.
Published: June 2021

The wheat curl mite (WCM, Aceria tosichella, Keifer) is an eriophyid mite species complex that causes damage to cereal crops in the Northern Great Plains by feeding damage and through the transmission of plant viruses, such as wheat streak mosaic virus. Insecticide treatments were evaluated in the greenhouse and field for efficacy at managing the WCM complex on wheat. Treatments tested were carbamates, organophosphates, pyrethroids, a neonicotinoid seed treatment, mite growth inhibitors, and Organic Materials Review Institute–approved biocontrols, soaps, and oils. Treatment with carbamates, organophosphates, and pyrethroids decreased WCM in greenhouse trials compared with untreated controls 14 days after infestation. The seed treatment, mite growth inhibitors, and organic pesticides did not reduce WCM populations effectively and consistently. The timing of application was tested using a sulfur solution as the experimental treatment. Treating plants with sulfur seven days after mite infestation reduced mites compared with the untreated control. In contrast, prophylactically applied sulfur and sulfur applied 14 days after mite infestation were not effective. When tested under field conditions with plots infested with viruliferous mites, there was no yield difference detected between untreated control plots and plots sprayed with insecticides. Select carbamates, organophosphates, and pyrethroids have a potential for use in greenhouse mite management when appropriate.
Social Media, Cognitive Reflection, and Conspiracy Beliefs
Authors: Stecula Dominik A. , Pickup Mark
Published: June 2021

A growing number of Americans stay informed about current events through social media. But using social media as a source of news is associated with increased likelihood of being misinformed about important topics, such as COVID-19. The two most popular platforms—Facebook and YouTube—remain relatively understudied in comparison to Twitter, which tends to be used by elites, but less than a quarter of the American public. In this brief research report, we investigate how cognitive reflection can mitigate the potential effects of using Facebook, YouTube and Twitter for news on subsequent conspiracy theory endorsement. To do that, we rely on an original dataset of 1,009 survey responses collected during the first wave of the coronavirus pandemic in the United States, on March 31, 2020. We find that using Facebook and YouTube for news increases conspiracy belief (both general and COVID-19 specific), controlling for cognitive reflection, traditional news media use, use of web-based news media, partisanship, education, age, and income. We also find that the impact of Facebook use on conspiracy belief is moderated by cognitive reflection. Facebook use increases conspiracy belief among those with low cognitive reflection but has no effect among those with moderate levels of cognitive reflection. It might even decrease conspiracy belief among those with the highest levels of cognitive reflection.
What’s the Link Between Theory of Mind and Other Cognitive Abilities – A Co-twin Control Design of Neurodevelopmental Disorders
Authors: Isaksson Johan , Neufeld Janina , Bölte Sven
Published: June 2021

Theory of mind (ToM), or the ability to attribute mental states to oneself and others, is a core element of social cognition (SC). Even though its importance for social functioning in general, and neurodevelopmental disorders (NDDs), in particular, is well established, the links between ToM and other cognitive functions are not. Especially the familial underpinnings of such links remain unclear. Using a co-twin control design, we examined N = 311 twins (mean age M = 17.19 years, 47% females) diagnosed with autism spectrum disorder (ASD), attention-deficit/hyperactivity disorder (ADHD), other NDDs, or typically developing individuals. We used the Reading the Mind in the Eyes Test to operationalize ToM, the Fragmented Pictures Test for central coherence (CC), the Tower Test for executive functioning (EF), and the general ability index in the Wechsler Intelligence Scales for IQ. In the linear regressions, weak CC and a lower IQ were associated with a reduced ToM ability across pairs. Female sex and higher age were robustly associated with increased ToM ability, whereas EF was not associated with ToM. In the within-pair analyses, where unmeasured familial confounders are implicitly adjusted, the associations between ToM and other cognitive functions, were attenuated and the association with CC was non-significant. The result suggests that familial factors shared by the twins, such as genetic and shared environment, influence the association between CC, IQ, and ToM. Future studies need to include a larger sample of monozygotic twins, who are genetically identical, in order to draw more firm conclusions regarding the influence of familial factors, and to differentiate between shared environmental and genetic effects on the associations between cognitive functions.
Emotional Tension as a Frame for Argumentation and Decision-Making: Vegetarian vs. Omnivorous Diets
Authors: Jiménez-Aleixandre María Pilar , Brocos Pablo
Published: June 2021

Argumentative discourse has a complexity that is not entirely captured by purely structural analyses. In arguments about socio-scientific issues (SSI), a range of dimensions, besides scientific knowledge, including values, ethical concerns, cultural habits, or emotions, are mobilized. The relationship between argumentation and emotions is now drawing attention of researchers. Our focus is on the dynamic interactions among emotions and scientific evidence. We draw from Plantin, who proposed that emotions are mobilized as argumentative resources alongside knowledge. The goal of our study is to examine in which ways emotional tension frames the construction of arguments about vegetarian vs. omnivorous diets (ODs) with a group of four preservice teachers. The results suggest that the interactions between the group emotional tension and the evaluation of evidence drive a change toward a decision that would be emotionally acceptable for all participants. Participants attended to the epistemic dimension, weighing evidence, and values about the choices, but the emotional framing took priority. We suggest that the analysis of this emotive framing may be a fruitful approach for sophisticated studies of argumentation beyond structural issues.