bluuebunny/crossref_metadata_2025 huggingface dataset:
Antitumor Activity of Curcumin in Glioblastoma
Authors: Walker Blake C. , Mittal Sandeep
Published: December 2020

Current standard-of-care treatment for glioblastoma, the most common malignant primary central nervous system (CNS) tumor, consists of surgical resection followed by adjuvant chemotherapy and radiation (Stupp protocol), providing an overall median survival of 15 months. With additional treatment using tumor-treating fields (Optune® therapy, Novocure Ltd., Haifa, Israel), survival can be extended up to 20 months. In spite of significant progress in our understanding of the molecular pathogenesis, the prognosis for patients with malignant gliomas remains poor and additional treatment modalities are critically needed. Curcumin is a bright yellow pigment found in the rhizome of the widely utilized spice, turmeric (Curcuma longa). It has long been used in South Asian traditional medicines and has been demonstrated to have in vitro antioxidant, anti-inflammatory, and antiproliferative effects. Curcumin has been demonstrated to induce multiple cytotoxic effects in tumor cells including cell cycle arrest, apoptosis, autophagy, changes in gene expression, and disruption of molecular signaling. Additionally, curcumin has been shown to potentiate the effect of radiation on cancer cells, while exhibiting a protective effect on normal tissue. Curcumin’s positive safety profile and widespread availability make it a promising compound for future clinical trials for high-grade gliomas.
Putative Role of Protein Palmitoylation in Cardiac Lipid-Induced Insulin Resistance
Authors: Schianchi Francesco , Glatz Jan F. C. , Navarro Gascon Artur , Nabben Miranda , Neumann Dietbert , Luiken Joost J. F. P.
Published: December 2020

In the heart, inhibition of the insulin cascade following lipid overload is strongly associated with contractile dysfunction. The translocation of fatty acid transporter CD36 (SR-B2) from intracellular stores to the cell surface is a hallmark event in the lipid-overloaded heart, feeding forward to intracellular lipid accumulation. Yet, the molecular mechanisms by which intracellularly arrived lipids induce insulin resistance is ill-understood. Bioactive lipid metabolites (diacyl-glycerols, ceramides) are contributing factors but fail to correlate with the degree of cardiac insulin resistance in diabetic humans. This leaves room for other lipid-induced mechanisms involved in lipid-induced insulin resistance, including protein palmitoylation. Protein palmitoylation encompasses the reversible covalent attachment of palmitate moieties to cysteine residues and is governed by protein acyl-transferases and thioesterases. The function of palmitoylation is to provide proteins with proper spatiotemporal localization, thereby securing the correct unwinding of signaling pathways. In this review, we provide examples of palmitoylations of individual signaling proteins to discuss the emerging role of protein palmitoylation as a modulator of the insulin signaling cascade. Second, we speculate how protein hyper-palmitoylations (including that of CD36), as they occur during lipid oversupply, may lead to insulin resistance. Finally, we conclude that the protein palmitoylation machinery may offer novel targets to fight lipid-induced cardiomyopathy.
Space-Dependent Glia–Neuron Interplay in the Hippocampus of Transgenic Models of β-Amyloid Deposition
Authors: Lana Daniele , Ugolini Filippo , Giovannini Maria Grazia
Published: December 2020

This review is focused on the description and discussion of the alterations of astrocytes and microglia interplay in models of Alzheimer’s disease (AD). AD is an age-related neurodegenerative pathology with a slowly progressive and irreversible decline of cognitive functions. One of AD’s histopathological hallmarks is the deposition of amyloid beta (Aβ) plaques in the brain. Long regarded as a non-specific, mere consequence of AD pathology, activation of microglia and astrocytes is now considered a key factor in both initiation and progression of the disease, and suppression of astrogliosis exacerbates neuropathology. Reactive astrocytes and microglia overexpress many cytokines, chemokines, and signaling molecules that activate or damage neighboring cells and their mutual interplay can result in virtuous/vicious cycles which differ in different brain regions. Heterogeneity of glia, either between or within a particular brain region, is likely to be relevant in healthy conditions and disease processes. Differential crosstalk between astrocytes and microglia in CA1 and CA3 areas of the hippocampus can be responsible for the differential sensitivity of the two areas to insults. Understanding the spatial differences and roles of glia will allow us to assess how these interactions can influence the state and progression of the disease, and will be critical for identifying therapeutic strategies.
MiR-96-5p Induced by Palmitic Acid Suppresses the Myogenic Differentiation of C2C12 Myoblasts by Targeting FHL1
Authors: Nguyen Mai Thi , Min Kyung-Ho , Lee Wan
Published: December 2020

Skeletal myogenesis is a multi-stage process that includes the cell cycle exit, myogenic transcriptional activation, and morphological changes to form multinucleated myofibers. Recent studies have shown that saturated fatty acids (SFA) and miRNAs play crucial roles in myogenesis and muscle homeostasis. Nevertheless, the target molecules and myogenic regulatory mechanisms of miRNAs are largely unknown, particularly when myogenesis is dysregulated by SFA deposition. This study investigated the critical role played by miR-96-5p on the myogenic differentiation in C2C12 myoblasts. Long-chain SFA palmitic acid (PA) significantly reduced FHL1 expression and inhibited the myogenic differentiation of C2C12 myoblasts but induced miR-96-5p expression. The knockdown of FHL1 by siRNA stimulated cell proliferation and inhibited myogenic differentiation of myoblasts. Interestingly, miR-96-5p suppressed FHL1 expression by directly targeting the 3’UTR of FHL1 mRNA. The transfection of an miR-96-5p mimic upregulated the expressions of cell cycle-related genes, such as PCNA, CCNB1, and CCND1, and increased myoblast proliferation. Moreover, the miR-96-5p mimic inhibited the expressions of myogenic factors, such as myoblast determination protein (MyoD), myogenin (MyoG), myocyte enhancer factor 2C (MEF2C), and myosin heavy chain (MyHC), and dramatically impeded differentiation and fusion of myoblasts. Overall, this study highlights the role of miR-96-5p in myogenesis via FHL1 suppression and suggests a novel regulatory mechanism for myogenesis mediated by miRNA in a background of obesity.
The Role of Epigenomics in Osteoporosis and Osteoporotic Vertebral Fracture
Authors: Kim Kyoung-Tae , Lee Young-Seok , Han Inbo
Published: December 2020

Osteoporosis is a complex multifactorial condition of the musculoskeletal system. Osteoporosis and osteoporotic vertebral fracture (OVF) are associated with high medical costs and can lead to poor quality of life. Genetic factors are important in determining bone mass and structure, as well as any predisposition for bone degradation and OVF. However, genetic factors are not enough to explain osteoporosis development and OVF occurrence. Epigenetics describes a mechanism for controlling gene expression and cellular processes without altering DNA sequences. The main mechanisms in epigenetics are DNA methylation, histone modifications, and non-coding RNAs (ncRNAs). Recently, alterations in epigenetic mechanisms and their activity have been associated with osteoporosis and OVF. Here, we review emerging evidence that epigenetics contributes to the machinery that can alter DNA structure, gene expression, and cellular differentiation during physiological and pathological bone remodeling. A progressive understanding of normal bone metabolism and the role of epigenetic mechanisms in multifactorial osteopathy can help us better understand the etiology of the disease and convert this information into clinical practice. A deep understanding of these mechanisms will help in properly coordinating future individual treatments of osteoporosis and OVF.
Current Status of Circulating Tumor Cells, Circulating Tumor DNA, and Exosomes in Breast Cancer Liquid Biopsies
Authors: Tellez-Gabriel Marta , Knutsen Erik , Perander Maria
Published: December 2020

Breast cancer is the most common cancer among women worldwide. Although the five-, ten- and fifteen-year survival rates are good for breast cancer patients diagnosed with early-stage disease, some cancers recur many years after completion of primary therapy. Tumor heterogeneity and clonal evolution may lead to distant metastasis and therapy resistance, which are the main causes of breast cancer-associated deaths. In the clinic today, imaging techniques like mammography and tissue biopsies are used to diagnose breast cancer. Even though these methods are important in primary diagnosis, they have limitations when it comes to longitudinal monitoring of residual disease after treatment, disease progression, therapy responses, and disease recurrence. Over the last few years, there has been an increasing interest in the diagnostic, prognostic, and predictive potential of circulating cancer-derived material acquired through liquid biopsies in breast cancer. Thanks to the development of sensitive devices and platforms, a variety of tumor-derived material, including circulating cancer cells (CTCs), circulating DNA (ctDNA), and biomolecules encapsulated in extracellular vesicles, can now be extracted and analyzed from body fluids. Here we will review the most recent studies on breast cancer, demonstrating the clinical potential and utility of CTCs and ctDNA. We will also review literature illustrating the potential of circulating exosomal RNA and proteins as future biomarkers in breast cancer. Finally, we will discuss some of the advantages and limitations of liquid biopsies and the future perspectives of this field in breast cancer management.
Molecular Characterization of Constipation Disease as Novel Phenotypes in CRISPR-Cas9-Generated Leptin Knockout Mice with Obesity
Authors: Kim Ji Eun , Choi Yun Ju , Lee Su Jin , Gong Jeong Eun , Lim Yong , Hong Jin Tae , Hwang Dae Youn
Published: December 2020

(1) Background: We characterized a novel animal model with obesity-induced constipation because constipation is rarely known in genetically engineered mice (GEM); (2) Methods: The changes in the constipation parameters and mechanisms were analyzed in CRISPR-Cas9-mediated leptin (Lep) knockout (KO) mice from eight to 24 weeks; (3) Results: Significant constipation phenotypes were observed in the Lep KO mice since 16 weeks old. These mice showed a significant decrease in the gastrointestinal motility, mucosal layer thickness and ability for mucin secretion as well as the abnormal ultrastructure of Lieberkühn crypts in the transverse colon. The density or function of the enteric neurons, intestinal Cajal cells (ICC), smooth muscle cells, and the concentration of gastrointestinal (GI) hormones for the GI motility were remarkably changed in Lep KO mice. The downstream signaling pathway of muscarinic acetylcholine receptors (mAChRs) were activated in Lep KO mice, while the expression of adipogenesis-regulating genes were alternatively reduced in the transverse colon of the same mice; (4) Conclusions: These results provide the first strong evidence that Lep KO mice can represent constipation successfully through dysregulation of the GI motility mediated by myenteric neurons, ICC, and smooth muscle cells in the transverse colon during an abnormal function of the lipid metabolism.
Temporal Changes in In Vivo Glutamate Signal during Demyelination and Remyelination in the Corpus Callosum: A Glutamate-Weighted Chemical Exchange Saturation Transfer Imaging Study
Authors: Lee Do-Wan , Heo Hwon , Woo Chul-Woong , Woo Dong-Cheol , Kim Jeong-Kon , Kim Kyung-Won , Lee Dong-Hoon
Published: December 2020

Background: Glutamate-weighted chemical exchange saturation transfer (GluCEST) is a useful imaging tool that can be used to detect changes in glutamate levels in vivo and could also be helpful in the diagnosis of brain myelin changes. We investigated glutamate level changes in the cerebral white matter of a rat model of cuprizone-administered demyelination and remyelination using GluCEST. Method: We used a 7 T pre-clinical magnetic resonance imaging (MRI) system. The rats were divided into the normal control (CTRL), cuprizone-administered demyelination (CPZDM), and remyelination (CPZRM) groups. GluCEST data were analyzed using the conventional magnetization transfer ratio asymmetry in the corpus callosum. Immunohistochemistry and transmission electron microscopy analyses were also performed to investigate the myelinated axon changes in each group. Results: The quantified GluCEST signals differed significantly between the CPZDM and CTRL groups (−7.25 ± 1.42% vs. −2.84 ± 1.30%; p = 0.001). The increased GluCEST signals in the CPZDM group decreased after remyelination (−6.52 ± 1.95% in CPZRM) to levels that did not differ significantly from those in the CTRL group (p = 0.734). Conclusion: The apparent temporal signal changes in GluCEST imaging during demyelination and remyelination demonstrated the potential usefulness of GluCEST imaging as a tool to monitor the myelination process.
Interferon Beta Activity Is Modulated via Binding of Specific S100 Proteins
Authors: Kazakov Alexey S. , Sofin Alexander D. , Avkhacheva Nadezhda V. , Denesyuk Alexander I. , Deryusheva Evgenia I. , Rastrygina Victoria A. , Sokolov Andrey S. , Permyakova Maria E. , Litus Ekaterina A. , Uversky Vladimir N. , Permyakov Eugene A. , Permyakov Sergei E.
Published: December 2020

Interferon-β (IFN-β) is a pleiotropic cytokine used for therapy of multiple sclerosis, which is also effective in suppression of viral and bacterial infections and cancer. Recently, we reported a highly specific interaction between IFN-β and S100P lowering IFN-β cytotoxicity to cancer cells (Int J Biol Macromol. 2020; 143: 633–639). S100P is a member of large family of multifunctional Ca2+-binding proteins with cytokine-like activities. To probe selectivity of IFN-β—S100 interaction with respect to S100 proteins, we used surface plasmon resonance spectroscopy, chemical crosslinking, and crystal violet assay. Among the thirteen S100 proteins studied S100A1, S100A4, and S100A6 proteins exhibit strictly Ca2+-dependent binding to IFN-β with equilibrium dissociation constants, Kd, of 0.04–1.5 µM for their Ca2+-bound homodimeric forms. Calcium depletion abolishes the S100—IFN-β interactions. Monomerization of S100A1/A4/A6 decreases Kd values down to 0.11–1.0 nM. Interferon-α is unable of binding to the S100 proteins studied. S100A1/A4 proteins inhibit IFN-β-induced suppression of MCF-7 cells viability. The revealed direct influence of specific S100 proteins on IFN-β activity uncovers a novel regulatory role of particular S100 proteins, and opens up novel approaches to enhancement of therapeutic efficacy of IFN-β.
The Role of Nucleoporin Elys in Nuclear Pore Complex Assembly and Regulation of Genome Architecture
Authors: Shevelyov Yuri Y.
Published: December 2020

For a long time, the nuclear lamina was thought to be the sole scaffold for the attachment of chromosomes to the nuclear envelope (NE) in metazoans. However, accumulating evidence indicates that nuclear pore complexes (NPCs) comprised of nucleoporins (Nups) participate in this process as well. One of the Nups, Elys, initiates NPC reassembly at the end of mitosis. Elys directly binds the decondensing chromatin and interacts with the Nup107–160 subcomplex of NPCs, thus serving as a seeding point for the subsequent recruitment of other NPC subcomplexes and connecting chromatin with the re-forming NE. Recent studies also uncovered the important functions of Elys during interphase where it interacts with chromatin and affects its compactness. Therefore, Elys seems to be one of the key Nups regulating chromatin organization. This review summarizes the current state of our knowledge about the participation of Elys in the post-mitotic NPC reassembly as well as the role that Elys and other Nups play in the maintenance of genome architecture.
Monoclonal Antibodies and Airway Diseases
Authors: Lyly Annina , Laulajainen-Hongisto Anu , Gevaert Philippe , Kauppi Paula , Toppila-Salmi Sanna
Published: December 2020

Monoclonal antibodies, biologics, are a relatively new treatment option for severe chronic airway diseases, asthma, allergic rhinitis, and chronic rhinosinusitis (CRS). In this review, we focus on the physiological and pathomechanisms of monoclonal antibodies, and we present recent study results regarding their use as a therapeutic option against severe airway diseases. Airway mucosa acts as a relative barrier, modulating antigenic stimulation and responding to environmental pathogen exposure with a specific, self-limited response. In severe asthma and/or CRS, genome–environmental interactions lead to dysbiosis, aggravated inflammation, and disease. In healthy conditions, single or combined type 1, 2, and 3 immunological response pathways are invoked, generating cytokine, chemokine, innate cellular and T helper (Th) responses to eliminate viruses, helminths, and extracellular bacteria/fungi, correspondingly. Although the pathomechanisms are not fully known, the majority of severe airway diseases are related to type 2 high inflammation. Type 2 cytokines interleukins (IL) 4, 5, and 13, are orchestrated by innate lymphoid cell (ILC) and Th subsets leading to eosinophilia, immunoglobulin E (IgE) responses, and permanently impaired airway damage. Monoclonal antibodies can bind or block key parts of these inflammatory pathways, resulting in less inflammation and improved disease control.
CTLA-4Ig Improves Hyperalgesia in a Mouse Model of Osteoporosis
Authors: Nagao Nobuto , Wakabayashi Hiroki , Miyamura Gaku , Kato Sho , Naito Yohei , Sudo Akihiro
Published: December 2020

This study aimed to evaluate skeletal pain associated with osteoporosis and to examine the inhibitory effects of cytotoxic T lymphocyte-associated antigen-4Ig (CTLA-4Ig) administration in ovariectomized (OVX) mice. Eight-week-old female ddY mice were assigned to three groups: sham-operated mice (SHAM) treated with vehicle, OVX mice treated with vehicle (OVX), and OVX mice treated with CTLA-4Ig (CTLA-4Ig). Vehicle or CTLA-4Ig was injected intraperitoneally, starting immediately after surgery. After 4 weeks of treatment, mechanical sensitivity was examined, and the bilateral hind limbs were removed and evaluated by micro-computed tomography, immunohistochemical analyses, and messenger RNA expression analysis. Ovariectomy induced bone loss and mechanical hyperalgesia in the hindlimbs. CTLA-4Ig treatment prevented bone loss in the hindlimbs compared to vehicle administration in the OVX group. Moreover, mechanical hyperalgesia was significantly decreased in the CTLA-4Ig treatment group in comparison to the OVX group. The expression levels of tumor necrosis factor-α (TNF-α) and sclerostin (SOST), as well as the number of osteoclasts, were increased, and the expression level of Wnt-10b was decreased in the OVX group compared with the SHAM group, whereas these parameters were improved in the CTLA-4Ig group compared with the OVX group. The novelty of this research is that CTLA-4Ig administration prevented bone loss and mechanical hyperalgesia induced by ovariectomy in the hindlimbs.
Possible Role of Crystal-Bearing Cells in Tomato Fertility and Formation of Seedless Fruits
Authors: Baranova Ekaterina N. , Chaban Inna A. , Kurenina Ludmila V. , Konovalova Ludmila N. , Varlamova Natalia V. , Khaliluev Marat R. , Gulevich Alexander A.
Published: December 2020

Crystal-bearing cells or idioblasts, which deposit calcium oxalate, are located in various tissues and organs of many plant species. The functional significance of their formation is currently unclear. Idioblasts in the leaf parenchyma and the development of crystal-bearing cells in the anther tissues of transgenic tomato plants (Solanum lycopersicon L.), expressing the heterologous FeSOD gene and which showed a decrease in fertility, were studied by transmission and scanning electron microscopy. The amount of calcium oxalate crystals was found to increase significantly in the transgenic plants compared to the wild type (WT) ones in idioblasts and crystal-bearing cells of the upper part of the anther. At the same time, changes in the size and shape of the crystals and their location in anther organs were noted. It seems that the interruption in the break of the anther stomium in transgenic plants was associated with the formation and cell death regulation of a specialized group of crystal-bearing cells. This disturbance caused an increase in the pool of these cells and their localization in the upper part of the anther, where rupture is initiated. Perturbations were also noted in the lower part of the anther in transgenic plants, where the amount of calcium oxalate crystals in crystal-bearing cells was reduced that was accompanied by disturbances in the morphology of pollen grains. Thus, the induction of the formation of crystal-bearing cells and calcium oxalate crystals can have multidirectional effects, contributing to the regulation of oxalate metabolism in the generative and vegetative organs and preventing fertility when the ROS balance changes, in particular, during oxidative stresses accompanying most abiotic and biotic environmental factors.
The Molecular ‘Myc-anisms’ behind Myc-Driven Tumorigenesis and the Relevant Myc-Directed Therapeutics
Authors: McAnulty Jessica , DiFeo Analisa
Published: December 2020

MYC, a well-studied proto-oncogene that is overexpressed in >20% of tumors across all cancers, is classically known as “undruggable” due to its crucial roles in cell processes and its lack of a drug binding pocket. Four decades of research and creativity led to the discovery of a myriad of indirect (and now some direct!) therapeutic strategies targeting Myc. This review explores the various mechanisms in which Myc promotes cancer and highlights five key therapeutic approaches to disrupt Myc, including transcription, Myc-Max dimerization, protein stability, cell cycle regulation, and metabolism, in order to develop more specific Myc-directed therapies.
Genome-Wide Survey and Expression Analysis of the KT/HAK/KUP Family in Brassica napus and Its Potential Roles in the Response to K+ Deficiency
Authors: Zhou Jie , Zhou Hong-Jun , Chen Ping , Zhang Lan-Lan , Zhu Jia-Tian , Li Peng-Feng , Yang Jin , Ke Yun-Zhuo , Zhou Yong-Hong , Li Jia-Na , Du Hai
Published: December 2020

The KT/HAK/KUP (HAK) family is the largest potassium (K+) transporter family in plants, which plays key roles in K+ uptake and homeostasis, stress resistance, and root and embryo development. However, the HAK family has not yet been characterized in Brassica napus. In this study, 40 putative B. napus HAK genes (BnaHAKs) are identified and divided into four groups (Groups I–III and V) on the basis of phylogenetic analysis. Gene structure analysis revealed 10 conserved intron insertion sites across different groups. Collinearity analysis demonstrated that both allopolyploidization and small-scale duplication events contributed to the large expansion of BnaHAKs. Transcription factor (TF)-binding network construction, cis-element analysis, and microRNA prediction revealed that the expression of BnaHAKs is regulated by multiple factors. Analysis of RNA-sequencing data further revealed extensive expression profiles of the BnaHAKs in groups II, III, and V, with limited expression in group I. Compared with group I, most of the BnaHAKs in groups II, III, and V were more upregulated by hormone induction based on RNA-sequencing data. Reverse transcription-quantitative polymerase reaction analysis revealed that the expression of eight BnaHAKs of groups I and V was markedly upregulated under K+-deficiency treatment. Collectively, our results provide valuable information and key candidate genes for further functional studies of BnaHAKs.
Coffee Berry Borer (Hypothenemus hampei), a Global Pest of Coffee: Perspectives from Historical and Recent Invasions, and Future Priorities
Authors: Johnson Melissa A. , Ruiz-Diaz Claudia Patricia , Manoukis Nicholas C. , Verle Rodrigues Jose Carlos
Published: December 2020

Coffee berry borer (Hypothenemus hampei (Ferrari), CBB) has invaded nearly every coffee-producing country in the world, and it is commonly recognized as the most damaging insect pest of coffee. While research has been conducted on this pest in individual coffee-growing regions, new insights may be gained by comparing and contrasting patterns of invasion and response across its global distribution. In this review, we explore the existing literature and focus on common themes in the invasion biology of CBB by examining (1) how it was introduced into each particular region and the response to its invasion, (2) flight activity and infestation patterns, (3) economic impacts, and (4) management strategies. We highlight research conducted over the last ten years in Hawaii as a case study for the development and implementation of an effective integrated pest management (IPM) program for CBB, and also discuss biosecurity issues contributing to incursion and establishment. Potential areas for future research in each of the five major components of CBB IPM (monitoring and sampling, cultural, biological, chemical, and physical controls) are also presented. Finally, we emphasize that outreach efforts are crucial to the successful implementation of CBB IPM programs. Future research programs should strive to include coffee growers as much as possible to ensure that management options are feasible and cost-effective.
Portable Oxygen Therapy: Is the 6-Minute Walking Test Overestimating the Actual Oxygen Needs?
Authors: Sanchez-Morillo Daniel , Lara-Doña Alejandro , Priego-Torres Blanca , Morales-Gonzalez Maria , Montoro-Ballesteros Francisca , Leon-Jimenez Antonio
Published: December 2020

The appropriate titration for the personalized oxygen needs of patients with chronic obstructive pulmonary disease (COPD) and severe hypoxemia is a determining factor in the success of long-term oxygen therapy. There are no standardized procedures to assist in determining the patient’s needs during the physical activities of daily life. Despite that effort tests are a wide broad approach, further research concerning the development of protocols to titrate O2 therapy is needed. The main objective of this study was to assess whether the level of oxygen titrated through the 6-minute walking test (6MWT) for patients with COPD and exertional hypoxemia is adequate to meet the patients’ demand during their activities of daily living. Physiological and subjective variables were estimated for a study population during two walking tests: a 6MWT and a 20-minute walking circuit (20MWC), designed ad-hoc to reproduce daily physical activities more truthfully. The results indicate that in a significant proportion of patients, the 6MWT might not accurately predict their oxygen needs at a domiciliary environment. Therefore, the titration of the portable O2 therapy could not be optimal in these cases, with the detrimental impact on the patient’s health (hyperoxia episodes), the autonomy of the oxygen device, and the decrease of time out of the home.
The Inflammatory Cytokine Profile of Patients with Malignant Pleural Effusion Treated with Pleurodesis
Authors: Hsu Li-Han , Soong Thomas C. , Chu Nei-Min , Huang Chung-Yu , Kao Shu-Huei , Lin Yung-Feng
Published: December 2020

Patients with malignant pleural effusion (MPE) who underwent successful pleurodesis survive longer than those for whom it fails. We hypothesize that the therapy-induced inflammatory responses inhibit the cancer progression, and thereby lead to a longer survival. Thirty-three consecutive patients with MPE that were eligible for bleomycin pleurodesis between September 2015 and December 2017 were recruited prospectively. Nineteen patients (57.6%) achieved fully or partially successful pleurodesis, while 14 patients either failed or survived less than 30 days after pleurodesis. Two patients without successful pleurodesis were excluded because of missing data. Interleukin (IL)-1 beta, IL-6, IL-10, transforming growth factor beta, tumor necrosis factor alpha (TNF-α), and vascular endothelial growth factor in the pleural fluid were measured before, and after 3 and 24 h of pleurodesis. Their pleurodesis outcome and survival were monitored and analyzed. Patients who underwent successful pleurodesis had a longer survival rate. Patients without successful pleurodesis had significantly higher TNF-α and IL-10 levels in their pleural fluid than in the successful patients before pleurodesis. Following pleurodesis, there was a significant increment of IL-10 in the first three hours in the successful patients. In contrast, significant increments of TNF-α and IL-10 were found in the unsuccessful patients between 3 and 24 h after pleurodesis. The ability to produce specific cytokines in the pleural space following pleurodesis may be decisive for the patient’s outcome and survival. Serial measurement of cytokines can help allocate the patients to adequate treatment strategies. Further study of the underlying mechanism may shed light on cytokine therapies as novel approaches.
CDKN2A-Inactivated Pancreatic Ductal Adenocarcinoma Exhibits Therapeutic Sensitivity to Paclitaxel: A Bioinformatics Study
Authors: Lin Jiunn-Chang , Liu Tsang-Pai , Yang Pei-Ming
Published: December 2020

The mutation of cyclin dependent kinase inhibitor 2A (CDKN2A) is frequently found in pancreatic ductal adenocarcinoma (PDAC). However, its prognostic and therapeutic roles in PDAC have not been extensively investigated yet. In this study, we mined and integrated the cancer genomics and chemogenomics data to investigate the roles of CDKN2A genetic alterations in PDAC patients’ prognosis and treatment. We found that functional CDKN2A inactivation caused by mutations and deep deletions predicted poor prognosis in PDAC patients. CDKN2A inactivation was associated with the upregulation of genes related to estrogen response, which can be overcome by CDKN2A restoration. Chemosensitivity profiling of PDAC cell lines and patient-derived organoids found that CDKN2A inactivation was associated with the increased sensitivity to paclitaxel and SN-38 (the active metabolite of irinotecan). However, only paclitaxel can mimic the effect of CDKN2A restoration, and its drug sensitivity was correlated with genes related to estrogen response. Therefore, our study suggested that CDKN2A-inactivated PDAC patients could benefit from the precision treatment with paclitaxel, whose albumin-stabilized nanoparticle formulation (nab-paclitaxel) has been approved for treating PDAC.
Gender Phenotyping of Patients with Obstructive Sleep Apnea Syndrome Using a Network Science Approach
Authors: Topîrceanu Alexandru , Udrescu Lucreția , Udrescu Mihai , Mihaicuta Stefan
Published: December 2020

We defined gender-specific phenotypes for men and women diagnosed with obstructive sleep apnea syndrome (OSAS) based on easy-to-measure anthropometric parameters, using a network science approach. We collected data from 2796 consecutive patients since 2005, from 4 sleep laboratories in Western Romania, recording sleep, breathing, and anthropometric measurements. For both genders, we created specific apnea patient networks defined by patient compatibility relationships in terms of age, body mass index (BMI), neck circumference (NC), blood pressure (BP), and Epworth sleepiness score (ESS). We classified the patients with clustering algorithms, then statistically analyzed the groups/clusters. Our study uncovered eight phenotypes for each gender. We found that all males with OSAS have a large NC, followed by daytime sleepiness and high BP or obesity. Furthermore, all unique female phenotypes have high BP, followed by obesity and sleepiness. We uncovered gender-related differences in terms of associated OSAS parameters. In males, we defined the pattern large NC–sleepiness–high BP as an OSAS predictor, while in women, we found the pattern of high BP–obesity–sleepiness. These insights are useful for increasing awareness, improving diagnosis, and treatment response.
Discordance between Primary Breast Cancer and Ipsilateral Breast Cancer Tumor Recurrence as a Function of Distance
Authors: Jud Sebastian M. , Hatko Reinhard , Emons Julius , Lauterbach Bianca , Hack Carolin C. , Preuß Caroline , Adler Werner , Beckmann Matthias W. , Heindl Felix
Published: December 2020

Background: Risk factors for ipsilateral breast cancer tumor recurrence (IBTR) are well established and include grading, nodal status, and receptor status. Little is known about the influence of the local distance between the primary tumor and recurrences on changes in tumor characteristics and prognosis. Methods: In a retrospective setting, we analyzed primary breast cancers and their recurrences. Localizations of primary and recurrent breast cancer were recorded to calculate the relative distance in pixels. Analysis was performed regarding tumor characteristics, relative distance between both, and their impact on breast cancer prognosis. Results: In a cohort of 142 patients with ipsilateral recurrence, no statistically significant difference could be shown in the change in tumor characteristics depending on distance. Progesterone receptor (PR) and estrogene receptor (ER) status changed in 22.7% and 14.9% of cases, respectively. human epidermal growth factor receptor 2 (ERBB2, HER2) status changed in 18.3% of cases. Survival was in accordance with the literature, with luminal-A-like tumors as best and triple negative breast cancers (TNBC) as worst prognosis. With a threshold of 162 pixels, the survival was significantly better in the group with shorter distance. Conclusion: Change in tumor characteristics from primary breast cancer to recurrence occurs more often in PR than ER. In contrast to other work, in this dataset, recurrences with a larger distance to the primary tumor had a worse prognosis in univariate analysis. A Cox model might indicate the possibility that this influence is independent of other risk factors.
4D Bragg Edge Tomography of Directional Ice Templated Graphite Electrodes
Authors: Ziesche Ralf F. , Tremsin Anton S. , Huang Chun , Tan Chun , Grant Patrick S. , Storm Malte , Brett Dan J. L. , Shearing Paul R. , Kockelmann Winfried
Published: December 2020

Bragg edge tomography was carried out on novel, ultra-thick, directional ice templated graphite electrodes for Li-ion battery cells to visualise the distribution of graphite and stable lithiation phases, namely LiC12 and LiC6. The four-dimensional Bragg edge, wavelength-resolved neutron tomography technique allowed the investigation of the crystallographic lithiation states and comparison with the electrode state of charge. The tomographic imaging technique provided insight into the crystallographic changes during de-/lithiation over the electrode thickness by mapping the attenuation curves and Bragg edge parameters with a spatial resolution of approximately 300 µm. This feasibility study was performed on the IMAT beamline at the ISIS pulsed neutron spallation source, UK, and was the first time the 4D Bragg edge tomography method was applied to Li-ion battery electrodes. The utility of the technique was further enhanced by correlation with corresponding X-ray tomography data obtained at the Diamond Light Source, UK.
Use of Very High Spatial Resolution Commercial Satellite Imagery and Deep Learning to Automatically Map Ice-Wedge Polygons across Tundra Vegetation Types
Authors: Bhuiyan Md Abul Ehsan , Witharana Chandi , Liljedahl Anna K.
Published: December 2020

We developed a high-throughput mapping workflow, which centers on deep learning (DL) convolutional neural network (CNN) algorithms on high-performance distributed computing resources, to automatically characterize ice-wedge polygons (IWPs) from sub-meter resolution commercial satellite imagery. We applied a region-based CNN object instance segmentation algorithm, namely the Mask R-CNN, to automatically detect and classify IWPs in North Slope of Alaska. The central goal of our study was to systematically expound the DLCNN model interoperability across varying tundra types (sedge, tussock sedge, and non-tussock sedge) and image scene complexities to refine the understanding of opportunities and challenges for regional-scale mapping applications. We corroborated quantitative error statistics along with detailed visual inspections to gauge the IWP detection accuracies. We found promising model performances (detection accuracies: 89% to 96% and classification accuracies: 94% to 97%) for all candidate image scenes with varying tundra types. The mapping workflow discerned the IWPs by exhibiting low absolute mean relative error (AMRE) values (0.17–0.23). Results further suggest the importance of increasing the variability of training samples when practicing transfer-learning strategy to map IWPs across heterogeneous tundra cover types. Overall, our findings demonstrate the robust performances of IWPs mapping workflow in multiple tundra landscapes.
Emulation of X-ray Light-Field Cameras
Authors: Viganò Nicola , Lucka Felix , de La Rochefoucauld Ombeline , Coban Sophia Bethany , van Liere Robert , Fajardo Marta , Zeitoun Philippe , Batenburg Kees Joost
Published: December 2020

X-ray plenoptic cameras acquire multi-view X-ray transmission images in a single exposure (light-field). Their development is challenging: designs have appeared only recently, and they are still affected by important limitations. Concurrently, the lack of available real X-ray light-field data hinders dedicated algorithmic development. Here, we present a physical emulation setup for rapidly exploring the parameter space of both existing and conceptual camera designs. This will assist and accelerate the design of X-ray plenoptic imaging solutions, and provide a tool for generating unlimited real X-ray plenoptic data. We also demonstrate that X-ray light-fields allow for reconstructing sharp spatial structures in three-dimensions (3D) from single-shot data.
Underwater Pipeline Oil Spill Detection Based on Structure of Root and Branch Cells
Authors: Song Huajun , Song Jie , Ren Peng
Published: December 2020

The existing oil spill detection methods mainly rely on physical sensors or numerical models cannot locate the spill position accurately and in time. To solve this problem, combining with underwater image processing technology, an unsupervised detection algorithm for oil spill in underwater pipelines is proposed for the first time. First, the oil spill region to be detected is regarded as the moving target, and the foreground detection algorithm is applied to the processed images. Then, the HSV (Hue, Saturation, Value) color space of the image is used to screen the oil spill region meeting the threshold requirements. Next, the bitwise of foreground mask and HSV mask into cells are divided. Finally, according to the characteristics of the oil spill image, false detection is eliminated by classifying cells three times. After qualitative and quantitative analysis, it is proved that the proposed algorithm can detect oil spill region accurately.
Experimental Observation on Beach Evolution Process with Presence of Artificial Submerged Sand Bar and Reef
Authors: Kuang Cuiping , Ma Yue , Han Xuejian , Pan Shunqi , Zhu Lei
Published: December 2020

For observation on the influence mechanism of environmentally and aesthetically friendly artificial submerged sand bars and reefs in a process-based way, a set of experiments was conducted in a 50 m-long flume to reproduce the cross-shore beach morphodynamic process under four irregular wave conditions. The beach behavior is characterized by the scarp (indicating erosion) and the breaker bar (indicating deposition), respectively, and the scarp location can be formulated as a linear equation regarding the natural exponential of the duration time. Overall, main conclusions are: (1) the cross-shore structure of significant wave height and set-up is mainly determined by the artificial reef (AR); (2) the cross-shore distribution of wave skewness, asymmetry, and undertow (indicating shoaling and breaking) is more affected by the artificial submerged sand bar (ASB); (3) the ASB deforms and loses its sand as it attenuates incident waves, which leads to a complex sediment transport pattern; (4) the scarp retreat is related to the beach state, which can be changed by the AR and the ASB; (5) the AR, the ASB, and their combination decrease wave attack on the beach. In conclusion, this study proves positive effects of the AR and the ASB in beach protection through their process-based influences on beach behaviors and beach states for erosive waves.
Management of Dredging Activities in a Highly Vulnerable Site: Simulation Modelling and Monitoring Activity
Authors: De Padova Diana , Ben Meftah Mouldi , De Serio Francesca , Mossa Michele
Published: December 2020

Unfortunately, more and more contaminants, such as heavy metals and other organic micro-pollutants, degrade the good ecological status of marine systems. The removal of contaminated sediments from harbours through dredging activities may cause harmful changes in the environment. This present work shows how monitoring the activity and validated numerical models can be of great help to dredging activities that can cause environmental impacts due to the increase of the suspended solid concentration (SSC) and their dispersion and deposition far from the dredging point. This study is applied to a hypothetical dredging project in a very vulnerable coastal site in Southern Italy, the Mar Piccolo Basin. A statistical analysis of the simulated parameter SSC was carried out to numerically estimate its spatial (vertical and horizontal) variability, thereby allowing an evaluation of the potential environmental effects on the coastal area.
Advances against Aspergillosis and Mucormycosis
Authors: Stevens David A.
Published: December 2020

The 9th meeting of Advances Against Aspergillosis in beautiful Lugano, Switzerland clearly had the most drama of any of the previous meetings, exceeding even the 1st one, in San Francisco, when we, the Co-Organizers, weren’t sure that although we had a great educational idea, and had put together a great list of speakers and topics, we might have few attendees, and go bankrupt! (The story of the birth efforts in initiating these meetings is described, for the historical record [...]
Dissemination of Isaria fumosorosea Spores by Steinernema feltiae and Heterorhabditis bacteriophora
Authors: Nermuť Jiří , Konopická Jana , Zemek Rostislav , Kopačka Michal , Bohatá Andrea , Půža Vladimír
Published: December 2020

Entomopathogenic nematodes and fungi are globally distributed soil organisms that are frequently used as bioagents in biological control and integrated pest management. Many studies have demonstrated that the combination of biocontrol agents can increase their efficacy against target hosts. In our study, we focused on another potential benefit of the synergy of two species of nematodes, Steinernema feltiae and Heterorhabditis bacteriophora, and the fungus Isaria fumosorosea. According to our hypothesis, these nematodes may be able to disseminate this fungus into the environment. To test this hypothesis, we studied fungal dispersal by the nematodes in different arenas, including potato dextrose agar (PDA) plates, sand heaps, sand barriers, and glass tubes filled with soil. The results of our study showed, for the first time, that the spreading of both conidia and blastospores of I. fumosorosea is significantly enhanced by the presence of entomopathogenic nematodes, but the efficacy of dissemination is negatively influenced by the heterogeneity of the testing arena. We also found that H. bacteriophora spread fungi more effectively than S. feltiae. This phenomenon could be explained by the differences in the presence and persistence of second-stage cuticles or by different foraging behavior. Finally, we observed that blastospores are disseminated more effectively than conidia, which might be due to the different adherence of these spores (conidia are hydrophobic, while blastospores are hydrophilic). The obtained results showed that entomopathogenic nematodes (EPNs) can enhance the efficiency of fungal dispersal.
On the Fly: Tritrophic Associations of Bats, Bat Flies, and Fungi
Authors: de Groot Michiel D. , Dumolein Iris , Hiller Thomas , Sándor Attila D. , Szentiványi Tamara , Schilthuizen Menno , Aime M. Catherine , Verbeken Annemieke , Haelewaters Danny
Published: December 2020

Parasitism is one of the most diverse and abundant modes of life, and of great ecological and evolutionary importance. Notwithstanding, large groups of parasites remain relatively understudied. One particularly unique form of parasitism is hyperparasitism, where a parasite is parasitized itself. Bats (Chiroptera) may be parasitized by bat flies (Diptera: Hippoboscoidea), obligate blood-sucking parasites, which in turn may be parasitized by hyperparasitic fungi, Laboulbeniales (Ascomycota: Laboulbeniomycetes). In this study, we present the global tritrophic associations among species within these groups and analyze their host specificity patterns. Bats, bat flies, and Laboulbeniales fungi are shown to form complex networks, and sixteen new associations are revealed. Bat flies are highly host-specific compared to Laboulbeniales. We discuss possible future avenues of study with regard to the dispersal of the fungi, abiotic factors influencing the parasite prevalence, and ecomorphology of the bat fly parasites.
Fungal Dysbiosis Correlates with the Development of Tumor-Induced Cachexia in Mice
Authors: Jabes Daniela L. , de Maria Yara N. L. F. , Aciole Barbosa David , Santos Kaltinaitis B. N. H. , Carvalho Lucas M. , Humberto Ana Carolina , Alencar Valquíria C. , Costa de Oliveira Regina , Batista Miguel L. , Menegidio Fabiano B. , Nunes Luiz R.
Published: December 2020

Cachexia (CC) is a devastating metabolic syndrome associated with a series of underlying diseases that greatly affects life quality and expectancy among cancer patients. Studies involving mouse models, in which CC was induced through inoculation with tumor cells, originally suggested the existence of a direct correlation between the development of this syndrome and changes in the relative proportions of several bacterial groups present in the digestive tract. However, these analyses have focus solely on the characterization of bacterial dysbiosis, ignoring the possible existence of changes in the relative populations of fungi, during the development of CC. Thus, the present study sought to expand such analyses, by characterizing changes that occur in the gut fungal population (mycobiota) of mice, during the development of cancer-induced cachexia. Our results confirm that cachectic animals, submitted to Lewis lung carcinoma (LLC) transplantation, display significant differences in their gut mycobiota, when compared to healthy controls. Moreover, identification of dysbiotic fungi showed remarkable consistency across successive levels of taxonomic hierarchy. Many of these fungi have also been associated with dysbioses observed in a series of gut inflammatory diseases, such as obesity, colorectal cancer (CRC), myalgic encephalomyelitis (ME) and inflammatory bowel disease (IBD). Nonetheless, the dysbiosis verified in the LLC model of cancer cachexia seems to be unique, presenting features observed in both obesity (reduced proportion of Mucoromycota) and CRC/ME/IBD (increased proportions of Sordariomycetes, Saccharomycetaceae and Malassezia). One species of Mucoromycota (Rhyzopus oryzae) stands out as a promising probiotic candidate in adjuvant therapies, aimed at treating and/or preventing the development of CC.