bluuebunny/crossref_metadata_2025 huggingface dataset:
Small RNA Regulation of Virulence in Pathogenic Escherichia coli
Authors: Sy Brandon M. , Tree Jai J.
Published: January 2021

Enteric and extraintestinal pathotypes of Escherichia coli utilize a wide range of virulence factors to colonize niches within the human body. During infection, virulence factors such as adhesins, secretions systems, or toxins require precise regulation and coordination to ensure appropriate expression. Additionally, the bacteria navigate rapidly changing environments with fluctuations in pH, temperature, and nutrient levels. Enteric pathogens utilize sophisticated, interleaved systems of transcriptional and post-transcriptional regulation to sense and respond to these changes and modulate virulence gene expression. Regulatory small RNAs and RNA-binding proteins play critical roles in the post-transcriptional regulation of virulence. In this review we discuss how the mosaic genomes of Escherichia coli pathotypes utilize small RNA regulation to adapt to their niche and become successful human pathogens.
Cardiomyocyte Na+/H+ Exchanger-1 Activity Is Reduced in Hypoxia
Authors: Kandilci Hilmi Burak , Richards Mark A. , Fournier Marjorie , Şimşek Gül , Chung Yu Jin , Lakhal-Littleton Samira , Swietach Pawel
Published: January 2021

Fully-activated Na+/H+ exchanger-1 (NHE1) generates the cardiomyocyte's largest trans-membrane extrusion of H+ ions for an equimolar influx of Na+ ions. This has the desirable effect of clearing excess intracellular acidity, but comes at a large energetic premium because the exchanged Na+ ions must ultimately be extruded by the sodium pump, a process that consumes the majority of the heart's non-contractile ATP. We hypothesize that the state of NHE1 activation depends on metabolic resources, which become limiting in periods of myocardial hypoxia. To test this functionally, NHE1 activity was measured in response to in vitro and in vivo hypoxic treatments. NHE1 flux was interrogated as a function of intracellular pH by fluorescence imaging of rodent ventricular myocytes loaded with pH-sensitive dyes BCECF or cSNARF1. Anoxic superfusates promptly inhibited NHE1, tracking the time-course of mitochondrial depolarization. Mass spectrometry of NHE1 immuno-precipitated from Langendorff-perfused anoxic hearts identified Tyr-581 dephosphorylation and Tyr-561 phosphorylation. The latter residue is part of the domain that interacts with phosphatidylinositol 4,5-bisphosphate (PIP2), a membrane lipid that becomes depleted under metabolic inhibition. Tyr-561 phosphorylation is expected to electrostatically weaken this activatory interaction. To test if a period of hypoxia produces a persistent inhibition of NHE1, measurements under normoxia were performed on myocytes that had been incubated in 2% O2 for 4 h. NHE1 activity remained inhibited, but the effect was ablated in the presence of Dasatinib, an inhibitor of Abl/Src-family tyrosine kinases. Chronic tissue hypoxia in vivo, attained in a mouse model of anemic hypoxia, also resulted in persistently slower NHE1. In summary, we show that NHE1 responds to oxygen, a physiologically-relevant metabolic regulator, ostensibly to divert ATP for contraction. We describe a novel mechanism of NHE1 inhibition that may be relevant in cardiac disorders featuring altered oxygen metabolism, such as myocardial ischemia and reperfusion injury.
The Main Nile Valley at the End of the Pleistocene (28–15 ka): Dispersal Corridor or Environmental Refugium?
Authors: Leplongeon Alice
Published: January 2021

Under present environmental conditions, the Nile Valley acts as a ‘natural’ route between Africa and Eurasia, and is often considered as a corridor for dispersals out of and back into Africa in the past. This review aims to address the role played by the Nile Valley at the end of the Pleistocene (28-15 ka) in the context of post-‘Out of Africa’ modern human dispersals. Genetic studies based on both modern and ancient DNA suggest pre-Holocene dispersals ‘back into Africa’ as well as genetic interactions between modern humans across Africa and the Levant. During the Last Glacial, the lowering, or even complete desiccation of major eastern African lakes, including Lake Victoria, reduced the White Nile to a highly seasonal river, depriving the main Nile from its most important tributary in the dry season. This had major consequences, the specifics of which are still debated, on the behavior of the main Nile and the landscape around the Nile Delta. Despite this shift to more arid conditions, there is abundant evidence for human occupation in the main Nile Valley. Combining available geological, palaeoenvironmental, anthropological, genetic and archaeological data, this article discusses problems encountered when trying to reconcile results from different fields, the current limitations of the available data and research perspectives to further address the role of the Nile Valley as a dispersal corridor or an environmental refugium at the end of the Pleistocene.
Carbon-Interlayer SnO2–Sb2O3 Composite Core–Shell Structure Anodes for Sodium-Ion Batteries
Authors: Zhang Guoju , Qu Yuanduo , Zhao Fanghui , Dang Rongxin , Yang Jie , Wang Liying , Zhang Yuanpeng , Duan Lianfeng
Published: January 2021

Although great efforts have been dedicated to improving electrochemical property of oxides anode material for sodium-ion batteries, the cycling life and rate capability of oxides anode materials are still far from its theoretical value. Herein, novel uniform SnO2@C@Sb2O3 submicrospheres with multilayer core–shell hollow structure have been synthesized as anode of sodium-ion batteries. The multilayer core–shell structure SnO2@C@Sb2O3 composite delivers a reversible capacity of 269 mAh g−1 at higher current density (1,500 mA g−1) after 100 cycles and exhibited excellent rate performance. The conductivity of the anode composite is promoted by the uniformly carbon dispersion through the whole submicrospheres. The dramatic volume change of electrode material could be mitigated by the porous core–shell structure of Sb2O3 and SnO2 during charge–discharge process. The enhanced specific capacity and rate performance are mainly ascribed to the integrity of structure and synergy effect between different metal oxides.
Citizen Science and Biological Invasions: A Review
Authors: Encarnação João , Teodósio Maria Alexandra , Morais Pedro
Published: January 2021

Biological invasions are among the most challenging ecological and conservation riddles of our times. Fortunately, citizen science projects became a valuable tool to detect non-indigenous species (NIS), document their spread, prevent dispersion, and eradicate localized populations. We evaluated the most undisputed definitions of citizen science and proposed that a combination of two of them is a better reflection of what citizen science has become. Thus, citizen science is any environmental and/or biological data collection and analysis, including data quality control, undertaken by members of the general public, as individuals or as organized groups of citizens, with the guidance and/or assistance of scientists toward solving environmental and/or community questions. With this review, we also assessed how citizen science has been advancing biological invasions research and its focus, by analyzing 126 peer-reviewed articles that used citizen science methods or data concerning NIS. Most of the articles studied terrestrial species (68%) and terrestrial plants were the most studied group (22.7%). Surprisingly, most first detection reports were of non-indigenous marine fish probably due to the constraints in accessing aquatic ecosystems which delays the detection of new NIS. Citizen science projects running over broad geographical areas are very cost-effective for the early detection of NIS, regardless of the studied environment. We also discuss the applicability and need to adapt the methods and approaches toward the studied ecosystem and species, but also the profile of the participating citizens, their motivations, level of engagement, or social status. We recommend authors to better acknowledge the work done by contributing citizens, and the putative limitations of data generated by citizen science projects. The outreach planning of citizen science projects is also evaluated, including the use of dedicated web platforms vs. pre-existent and disseminated web platforms, while discussing how such outreach actions can be maximized. Lastly, we present a framework that contextualizes the contributions of citizen science, scientific research, and regional and national stakeholders toward the integrated management of biological invasions.
ANKLE1 as New Hotspot Mutation for Breast Cancer in Indian Population and Has a Role in DNA Damage and Repair in Mammalian Cells
Authors: Bakshi Divya , Katoch Archana , Chakraborty Souneek , Shah Ruchi , Sharma Bhanu , Bhat Amrita , Verma Sonali , Bhat Gh. Rasool , Nagpal Ashna , Vaishnavi Samantha , Goswami Anindya , Kumar Rakesh
Published: January 2021

Breast cancer has replaced cervical cancer as being the most common and having the highest mortality among women in India. ANKLE gene is conserved among organisms during evolutionary succession and is a member of LEM family proteins in lower metazoans and is involved in critical functions in the nuclear architecture, gene expression and cell signaling. ANKLE1 is the human orthologous of LEM-3 and is involved in DNA damage response and DNA repair. Whole Exome Sequencing (WES) of paired breast cancer samples was performed and ANKLE1 was found to be a new possible hotspot for predisposition of breast cancer. The mass array genotyping for breast cancer variant rs2363956 further confirmed the ANKLE1 association with the studied population of breast cancer. To elucidate the role of ANKLE1 in DNA damage, it was knocked down in MCF-7 breast cancer cell line and the expression of γH2AX was assessed. ANKLE1 knockdown cells displayed elevated levels of γ-H2AX foci in response to the cisplatin induced replication stress. The localization pattern of ANKLE1 further emphasized the role of ANKLE1 in DNA repair process. We observed that ANKLE1 is required for maintaining genomic stability and plays a role in DNA damage and repair process. These findings provided a molecular basis for the suspected role of ANKLE1 in human breast cancer and suggested an important role of this gene in controlling breast cancer development among women in India.
Integrin Alpha E (CD103) Limits Virus-Induced IFN-I Production in Conventional Dendritic Cells
Authors: Duhan Vikas , Khairnar Vishal , Kitanovski Simo , Hamdan Thamer A. , Klein Andrés D. , Lang Judith , Ali Murtaza , Adomati Tom , Bhat Hilal , Friedrich Sarah-Kim , Li Fanghui , Krebs Philippe , Futerman Anthony H. , Addo Marylyn M. , Hardt Cornelia , Hoffmann Daniel , Lang Philipp A. , Lang Karl S.
Published: January 2021

Early and strong production of IFN-I by dendritic cells is important to control vesicular stomatitis virus (VSV), however mechanisms which explain this cell-type specific innate immune activation remain to be defined. Here, using a genome wide association study (GWAS), we identified Integrin alpha-E (Itgae, CD103) as a new regulator of antiviral IFN-I production in a mouse model of vesicular stomatitis virus (VSV) infection. CD103 was specifically expressed by splenic conventional dendritic cells (cDCs) and limited IFN-I production in these cells during VSV infection. Mechanistically, CD103 suppressed AKT phosphorylation and mTOR activation in DCs. Deficiency in CD103 accelerated early IFN-I in cDCs and prevented death in VSV infected animals. In conclusion, CD103 participates in regulation of cDC specific IFN-I induction and thereby influences immune activation after VSV infection.
An AIREless Breath: Pneumonitis Caused by Impaired Central Immune Tolerance
Authors: Ferré Elise M. N. , Lionakis Michail S.
Published: January 2021

Autoimmune-polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED), a monogenic disorder caused by biallelic mutations in the AIRE gene, has historically been defined by the development of chronic mucocutaneous candidiasis together with autoimmune endocrinopathies, primarily hypoparathyroidism and adrenal insufficiency. Recent work has drawn attention to the development of life-threatening non-endocrine manifestations such as autoimmune pneumonitis, which has previously been poorly recognized and under-reported. In this review, we present the clinical, radiographic, autoantibody, and pulmonary function abnormalities associated with APECED pneumonitis, we highlight the cellular and molecular basis of the autoimmune attack in the AIRE-deficient lung, and we provide a diagnostic and a therapeutic roadmap for patients with APECED pneumonitis. Beyond APECED, we discuss the relevance and potential broader applicability of these findings to other interstitial lung diseases seen in secondary AIRE deficiency states such as thymoma and RAG deficiency or in common polygenic autoimmune disorders such as idiopathic Sjögren’s syndrome.
Spatial Connectivity and Drivers of Shark Habitat Use Within a Large Marine Protected Area in the Caribbean, The Bahamas Shark Sanctuary
Authors: Gallagher Austin J. , Shipley Oliver N. , van Zinnicq Bergmann Maurits P. M. , Brownscombe Jacob W. , Dahlgren Craig P. , Frisk Michael G. , Griffin Lucas P. , Hammerschlag Neil , Kattan Sami , Papastamatiou Yannis P. , Shea Brendan D. , Kessel Steven T. , Duarte Carlos M.
Published: January 2021

Marine protected areas (MPAs) have emerged as potentially important conservation tools for the conservation of biodiversity and mitigation of climate impacts. Among MPAs, a large percentage has been created with the implicit goal of protecting shark populations, including 17 shark sanctuaries which fully protect sharks throughout their jurisdiction. The Commonwealth of the Bahamas represents a long-term MPA for sharks, following the banning of commercial longlining in 1993 and subsequent designation as a shark sanctuary in 2011. Little is known, however, about the long-term behavior and space use of sharks within this protected area, particularly among reef-associated sharks for which the sanctuary presumably offers the most benefit. We used acoustic telemetry to advance our understanding of the ecology of such sharks, namely Caribbean reef sharks (Carcharhinus perezi) and tiger sharks (Galeocerdo cuvier), over two discrete islands (New Providence and Great Exuma) varying in human activity level, over 2 years. We evaluated which factors influenced the likelihood of detection of individuals, analyzed patterns of movement and occurrence, and identified variability in habitat selection among species and regions, using a dataset of 23 Caribbean reef sharks and 15 tiger sharks which were passively monitored in two arrays with a combined total of 13 acoustic receivers. Caribbean reef sharks had lower detection probabilities than tiger sharks, and exhibited relatively low habitat connectivity and high residency, while tiger sharks demonstrated wider roaming behavior across much greater space. Tiger sharks were associated with shallow seagrass habitats where available, but frequently transited between and connected different habitat types. Our data support the notion that large MPAs afford greater degrees of protection for highly resident species such as Caribbean reef sharks, yet still may provide substantial benefits for more migratory species such as tiger sharks. We discuss these findings within the context of species-habitat linkages, ecosystem services, and the establishment of future MPAs.
Current Status of the Algae Production Industry in Europe: An Emerging Sector of the Blue Bioeconomy
Authors: Araújo Rita , Vázquez Calderón Fatima , Sánchez López Javier , Azevedo Isabel Costa , Bruhn Annette , Fluch Silvia , Garcia Tasende Manuel , Ghaderiardakani Fatemeh , Ilmjärv Tanel , Laurans Martial , Mac Monagail Micheal , Mangini Silvio , Peteiro César , Rebours Céline , Stefansson Tryggvi , Ullmann Jörg
Published: January 2021

The EU Bioeconomy Strategy aims to support the sustainable growth and development of the EU bio-based sectors while creating jobs, innovation and services. Despite the recognized potential of the algae biomass value chain, significant knowledge gaps still exist regarding the dimension, capability, organization and structure of the algae production in Europe. This study presents and analyses the results of a comprehensive mapping and detailed characterization of the algae production at the European scale, encompassing macroalgae, microalgae, and the cyanobacteria Spirulina. This work mapped 447 algae and Spirulina production units spread between 23 countries, which represents an important addition to the reported number of algae producing countries. More than 50% of these companies produce microalgae and/or Spirulina. Macroalgae production is still depending on harvesting from wild stocks (68% of the macroalgae producing units) but macroalgae aquaculture (land-based and at sea) is developing in several countries in Europe currently representing 32% of the macroalgae production units. France, Ireland, and Spain are the top 3 countries in number of macroalgae production units while Germany, Spain, and Italy stand for the top 3 for microalgae. Spirulina producers are predominantly located in France, Italy, Germany, and Spain. Algae and Spirulina biomass is directed primarily for food and food-related applications including the extraction of high-value products for food supplements and nutraceuticals. Algae production in Europe remains limited by a series of technological, regulatory and market-related barriers. Yet, the results of this study emphasize that the European algae sector has a considerable potential for sustainable development as long as the acknowledged economic, social and environmental challenges are addressed.
Biopassivation Method for the Preservation of Copper and Bronze Artefacts
Authors: Joseph Edith
Published: January 2021

A biopassivation method has been proposed as a new ecological and sustainable solution for preserving copper-based artefacts using selected microorganisms. This technology is based on the natural capacity of some fungi to form copper oxalates on the corroded surface of copper alloys. Existing unstable and pulverulent corrosion products are converted into an insoluble and chemically stable biopatina that provides the treated surfaces with a stabilization of the corrosion process and an aesthetically attractive green color. This treatment allows to stabilize the active corrosion induced for example by copper chlorides and to prevent green staining of surrounding materials (stone pedestal, wall…) due the leaching and loss of pulverulent and water-soluble corrosion products (i.e. copper sulfates). The behavior and performance of the proposed treatment have been followed during natural aging procedures, which have shown that this method stabilizes the corrosion process while having less chromatic variation compared to more traditional protective systems. The application protocol was then validated on real cases such as outdoor sculptures and archaeological objects. Based on these results, a ready-to-use kit is now proposed to conservators.
CRISPR-Cas9-Based Toolkit for Clostridium botulinum Group II Spore and Sporulation Research
Authors: Mertaoja Anna , Nowakowska Maria B. , Mascher Gerald , Heljanko Viivi , Groothuis Daphne , Minton Nigel P. , Lindström Miia
Published: January 2021

The spores of Clostridium botulinum Group II strains pose a significant threat to the safety of modern packaged foods due to the risk of their survival in pasteurization and their ability to germinate into neurotoxigenic cultures at refrigeration temperatures. Moreover, spores are the infectious agents in wound botulism, infant botulism, and intestinal toxemia in adults. The identification of factors that contribute to spore formation is, therefore, essential to the development of strategies to control related health risks. Accordingly, development of a straightforward and versatile gene manipulation tool and an efficient sporulation-promoting medium is pivotal. Our strategy was to employ CRISPR-Cas9 and homology-directed repair (HDR) to replace targeted genes with mutant alleles incorporating a unique 24-nt “bookmark” sequence that could act as a single guide RNA (sgRNA) target for Cas9. Following the generation of the sporulation mutant, the presence of the bookmark allowed rapid generation of a complemented strain, in which the mutant allele was replaced with a functional copy of the deleted gene using CRISPR-Cas9 and the requisite sgRNA. Then, we selected the most appropriate medium for sporulation studies in C. botulinum Group II strains by measuring the efficiency of spore formation in seven different media. The most effective medium was exploited to confirm the involvement of a candidate gene in the sporulation process. Using the devised sporulation medium, subsequent comparisons of the sporulation efficiency of the wild type (WT), mutant and “bookmark”-complemented strain allowed the assignment of any defective sporulation phenotype to the mutation made. As a strain generated by complementation with the WT gene in the original locus would be indistinguishable from the parental strain, the gene utilized in complementation studies was altered to contain a unique “watermark” through the introduction of silent nucleotide changes. The mutagenesis system and the devised sporulation medium provide a solid basis for gaining a deeper understanding of spore formation in C. botulinum, a prerequisite for the development of novel strategies for spore control and related food safety and public health risk management.
Structure of the Complete Dimeric Human GDAP1 Core Domain Provides Insights into Ligand Binding and Clustering of Disease Mutations
Authors: Nguyen Giang Thi Tuyet , Sutinen Aleksi , Raasakka Arne , Muruganandam Gopinath , Loris Remy , Kursula Petri
Published: January 2021

Charcot-Marie-Tooth disease (CMT) is one of the most common inherited neurological disorders. Despite the common involvement of ganglioside-induced differentiation-associated protein 1 (GDAP1) in CMT, the protein structure and function, as well as the pathogenic mechanisms, remain unclear. We determined the crystal structure of the complete human GDAP1 core domain, which shows a novel mode of dimerization within the glutathione S-transferase (GST) family. The long GDAP1-specific insertion forms an extended helix and a flexible loop. GDAP1 is catalytically inactive toward classical GST substrates. Through metabolite screening, we identified a ligand for GDAP1, the fatty acid hexadecanedioic acid, which is relevant for mitochondrial membrane permeability and Ca2+ homeostasis. The fatty acid binds to a pocket next to a CMT-linked residue cluster, increases protein stability, and induces changes in protein conformation and oligomerization. The closest homologue of GDAP1, GDAP1L1, is monomeric in its full-length form. Our results highlight the uniqueness of GDAP1 within the GST family and point toward allosteric mechanisms in regulating GDAP1 oligomeric state and function.
C-Terminal-Pro-Endothelin-1 Adds Incremental Prognostic Value for Risk Stratification After Ischemic Stroke
Authors: Westphal Laura P. , Schweizer Juliane , Fluri Felix , De Marchis Gian Marco , Christ-Crain Mirjam , Luft Andreas R. , Katan Mira
Published: January 2021

Background and Aims: Endothelins have shown to play a role in the pathophysiology of ischemic stroke. We aimed at evaluating the incremental prognostic value of C-terminal-pro-endothelin-1 (CT-pro-ET-1) in a well-described cohort of acute stroke patients.

Methods: We performed serial measurements of CT-pro-ET-1 in 361 consecutively enrolled ischemic stroke patients and assessed functional outcome and mortality after 90 days. As we found peak levels of CT-pro-ET-1 and the most prominent association with mortality on day 1 after admission (n = 312), we focused on this time point for further outcome analyses. We calculated logistic regression and cox proportional hazards models to estimate the association of CT-pro-ET-1 with our outcome measures after adjusting for demographic and clinical risk factors. To evaluate the incremental value of CT-pro-ET-1, we calculated the area under the receiver operating characteristics (AUC) curve and the continuous net reclassification index (cNRI) comparing the model with and without the biomarker CT-pro-ET-1.

Results: In the univariate analysis CT-pro-ET-1 with a peak on day 1 after admission was associated with unfavorable outcome with an OR of 1.32 (95% CI, 1.16–1.51, p < 0.001) and with mortality with a HR of 1.45 (95% CI, 1.29–1.63, p < 0.001). After adjusting, CT-pro-ET-1 remained an independent predictor of mortality with an adjusted HR of 1.50 (95% CI, 1.29–1.74, p < 0.001), but not for functional outcome. Adding CT-pro-ET-1 to the cox-regression model for mortality, the discriminatory accuracy improved from 0.89 (95% CI, 0.84–0.94) to 0.92 (95% CI, 0.88–0.96) p < 0.001, and the cNRI was 0.72 (95% CI, 0.17–1.13).

Conclusion: CT-pro-ET-1 with a peak level on day 1 was an independent predictor of mortality adding incremental prognostic value beyond traditional risk factors.
Disturbance of the Glutamate-Glutamine Cycle, Secondary to Hepatic Damage, Compromises Memory Function
Authors: Limón Ilhuicamina Daniel , Angulo-Cruz Isael , Sánchez-Abdon Lesli , Patricio-Martínez Aleidy
Published: January 2021

Glutamate fulfils many vital functions both at a peripheral level and in the central nervous system (CNS). However, hyperammonemia and hepatic failure induce alterations in glutamatergic neurotransmission, which may be the main cause of hepatic encephalopathy (HE), an imbalance which may explain damage to both learning and memory. Cognitive and motor alterations in hyperammonemia may be caused by a deregulation of the glutamate-glutamine cycle, particularly in astrocytes, due to the blocking of the glutamate excitatory amino-acid transporters 1 and 2 (EAAT1, EAAT2). Excess extracellular glutamate triggers mechanisms involving astrocyte-mediated inflammation, including the release of Ca2+-dependent glutamate from astrocytes, the appearance of excitotoxicity, the formation of reactive oxygen species (ROS), and cell damage. Glutamate re-uptake not only prevents excitotoxicity, but also acts as a vital component in synaptic plasticity and function. The present review outlines the evidence of the relationship between hepatic damage, such as that occurring in HE and hyperammonemia, and changes in glutamine synthetase function, which increase glutamate concentrations in the CNS. These conditions produce dysfunction in neuronal communication. The present review also includes data indicating that hyperammonemia is related to the release of a high level of pro-inflammatory factors, such as interleukin-6, by astrocytes. This neuroinflammatory condition alters the function of the membrane receptors, such as N-methyl-D-aspartate (NMDA), (α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid) AMPA, and γ-aminobutyric acid (GABA), thus affecting learning and spatial memory. Data indicates that learning and spatial memory, as well as discriminatory or other information acquisition processes in the CNS, are damaged by the appearance of hyperammonemia and, moreover, are associated with a reduction in the production of cyclic guanosine monophosphate (cGMP). Therefore, increased levels of pharmacologically controlled cGMP may be used as a therapeutic tool for improving learning and memory in patients with HE, hyperammonemia, cerebral oedema, or reduced intellectual capacity.
The Effect of Plasma Treated Water Unit Processes on the Food Quality Characteristics of Fresh-Cut Endive
Authors: Schnabel Uta , Handorf Oliver , Winter Hauke , Weihe Thomas , Weit Christoph , Schäfer Jan , Stachowiak Jörg , Boehm Daniela , Below Harald , Bourke Paula , Ehlbeck Jörg
Published: January 2021

This study evaluated the impact of a defined plasma treated water (PTW) when applied to various stages within fresh-cut endive processing. The quality characteristic responses were investigated to establish the impact of the PTW unit processes and where PTW may be optimally applied in a model process line to retain or improve produce quality. Different stages of application of PTW within the washing process were investigated and compared to tap water and chlorine dioxide. Fresh-cut endive (Cichorium endiviaL.) samples were analyzed for retention of food quality characteristics. Measurements included color, texture, and nitrate quantification. Effects on tissue surface and cell organelles were observed through scanning electron and atomic force microscopy. Overall, the endive quality characteristics were retained by incorporating PTW in the washing process. Furthermore, promising results for color and texture characteristics were observed, which were supported by the microscopic assays of the vegetal tissue. While ion chromatography detected high concentrations of nitrite and nitrate in PTW, these did not affect the nitrate concentration of the lettuce tissue post-processing and were below the concentrations within EU regulations. These results provide a pathway to scale up the industrial application of PTW to improve and retain quality characteristic retention of fresh leafy products, whilst also harnessing the plasma functionalized water as a process intervention for reducing microbial load at multiple points, whether on the food surface, within the process water or on food-processing surfaces.
Computed Tomography Radiomics for Predicting Pathological Grade of Renal Cell Carcinoma
Authors: Yi Xiaoping , Xiao Qiao , Zeng Feiyue , Yin Hongling , Li Zan , Qian Cheng , Wang Cikui , Lei Guangwu , Xu Qingsong , Li Chuanquan , Li Minghao , Gong Guanghui , Zee Chishing , Guan Xiao , Liu Longfei , Chen Bihong T.
Published: January 2021

Background

Clear cell renal cell carcinoma (ccRCC) is the most common renal cancer and it has the worst prognosis among all renal cancers. However, traditional radiological characteristics on computed tomography (CT) scans of ccRCC have been insufficient to predict the pathological grade of ccRCC before surgery.

Methods

Patients with ccRCC were retrospectively enrolled into this study and were separated into two groups according to the World Health Organization (WHO)/International Society of Urological Pathology (ISUP) grading system, i.e., low-grade (Grade I and II) group and high-grade (Grade III and IV) group. Traditional CT radiological characteristics such as tumor size, pre- and post-enhancing CT densities were assessed. In addition, radiomic texture analysis based on the CT imaging of the ccRCC were also performed. A CT-based machine learning method combining the traditional radiological characteristics and radiomic features was used in the predictive modeling for differentiating the low-grade from the high-grade ccRCC. Model performance was evaluated with the receiver operating characteristic curve (ROC) analysis.

Results

A total of 264 patients with pathologically confirmed ccRCC were included in this study. In this cohort, 206 patients had the low-grade tumors and 58 had the high-grade tumors. The model built with traditional radiological characteristics achieved an area under the curve (AUC) of 0.9175 (95% CI: 0.8765–0.9585) and 0.8088 (95% CI: 0.7064–0.9113) in differentiating the low-grade from the high-grade ccRCC for the training cohort and the validation cohort respectively. The model built with the radiomic textural features yielded an AUC value of 0.8170 (95% CI: 0.7353–0.8987) and 0.8017 (95% CI: 0.6878–0.9157) for the training cohort and the validation cohort, respectively. The combined model integrating both the traditional radiological characteristics and the radiomic textural features achieved the highest efficacy, with an AUC of 0.9235 (95% CI: 0.8646–0.9824) and an AUC of 0.9099 (95% CI: 0.8324–0.9873) for the training cohort and validation cohort, respectively.

Conclusion

We developed a machine learning radiomic model achieving a satisfying performance in differentiating the low-grade from the high-grade ccRCC. Our study presented a potentially useful non-invasive imaging-focused method to predict the pathological grade of renal cancers prior to surgery.
Combination Therapy of PTH and Antiresorptive Drugs on Osteoporosis: A Review of Treatment Alternatives
Authors: Zhang Chenggui , Song Chunli
Published: January 2021

Antiresorptive drugs have been widely used for osteoporosis. Intermittent parathyroid hormone (PTH), an anabolic agent, increases osteoblast production rate and inhibits apoptosis of osteoblasts, thus increasing skeletal mass besides improving bone microarchitecture and strength. Combination therapy for osteoporosis produced great interests and controversies. Therefore, we performed a systematic literature search from PubMed, EMBASE, Scopus, Web of Science, CINDHL, and the Cochrane Database of Systematic Reviews using the search terms PTH or teriparatide combined with bisphosphonate, alendronate, ibandronate, risedronate, raloxifene, denosumab, and zoledronic acid with the limit osteoporosis. At last, 36 related articles were included for further analysis. Findings from previous studies revealed that combination therapy in different conditions of naive or previous bisphosphonate treatment might have different outcomes. The use of combination therapy, however, may be an alternative option among osteoporotic patients with a history of bisphosphonate use. Combined teriparatide with denosumab appear to show the most substantial and clinically relevant skeletal benefits to osteoporotic patients. Additional research is necessary to define optimal methods of developing sequential and/or cyclical combinations of PTH and antiresorptive agents.
DRD4 Mitigates Myocardial Ischemia/Reperfusion Injury in Association With PI3K/AKT Mediated Glucose Metabolism
Authors: Liu Xue-song , Zeng Jing , Yang Yu-xue , Qi Chun-lei , Xiong Ting , Wu Geng-ze , Zeng Chun-yu , Wang Da-xin
Published: January 2021

Ischemia-reperfusion (I/R) could cause heart irreversible damage, which is tightly combined with glucose metabolism disorder. It is demonstrated that GLUT4 (glucose transporter 4) translocation is critical for glucose metabolism in the cardiomyocytes under I/R injury. Moreover, DRD4 (dopamine receptor D4) modulate glucose metabolism, and protect neurocytes from anoxia/reoxygenation (A/R) injury. Thus, DRD4 might regulate myocardial I/R injury in association with GLUT4-mediated glucose metabolism. However, the effects and mechanisms are largely unknown. In the present study, the effect of DRD4 in heart I/R injury were studied ex vivo and in vitro. For I/R injury ex vivo, DRD4 agonist (PD168077) was perfused by Langendorff system in the isolated rat heart. DRD4 activated by PD168077 improved cardiac function in the I/R-injured heart as determined by the left ventricular developed pressure (LVDP), +dp/dt, and left ventricular end diastolic pressure (LVEDP), and reduced heart damage evidenced by infarct size, the release of troponin T (TNT) and lactate dehydrogenase (LDH). DRD4 activation diminished I/R injury induced apoptosis and enhanced cell viability impaired by I/R injury in cardiomyocyte, showed by TUNEL staining, flow cytometer and CCK8 assay. Furthermore, DRD4 activation did not change total GULT4 protein expression level but increased the membrane GULT4 localization determined by western blot. In terms of mechanism, DRD4 activation increased pPI3K/p-AKT but not the total PI3K/AKT during anoxia/reoxygenation (A/R) injury in vitro. Interestingly, PI3K inhibitor, Wortmannin, blocked PI3K/AKT pathway and depleted the membrane GULT4, and further promoted apoptosis showed by TUNEL staining, flow cytometer, western blot of cleaved caspase 3, BAX and BCL2 expression. Thus, DRD4 activation exerted a protective effect against I/R injury by promoting GLUT4 translocation depended on PI3K/AKT pathway, which enhanced the ability of glucose uptake, and ultimately reduced the apoptosis in cardiomyocytes.
Detection of Interfractional Morphological Changes in Proton Therapy: A Simulation and In Vivo Study With the INSIDE In-Beam PET
Authors: Fiorina Elisa , Ferrero Veronica , Baroni Guido , Battistoni Giuseppe , Belcari Nicola , Camarlinghi Niccolo , Cerello Piergiorgio , Ciocca Mario , De Simoni Micol , Donetti Marco , Dong Yunsheng , Embriaco Alessia , Fischetti Marta , Franciosini Gaia , Giraudo Giuseppe , Kraan Aafke , Laruina Francesco , Luongo Carmela , Maestri Davide , Magi Marco , Magro Giuseppe , Malekzadeh Etesam , Mancini Terracciano Carlo , Marafini Michela , Mattei Ilaria , Mazzoni Enrico , Mereu Paolo , Mirabelli Riccardo , Mirandola Alfredo , Morrocchi Matteo , Muraro Silvia , Patera Alessandra , Patera Vincenzo , Pennazio Francesco , Retico Alessandra , Rivetti Angelo , Da Rocha Rolo Manuel Dionisio , Rosso Valeria , Sarti Alessio , Schiavi Angelo , Sciubba Adalberto , Solfaroli Camillocci Elena , Sportelli Giancarlo , Tampellini Sara , Toppi Marco , Traini Giacomo , Valle Serena Marta , Valvo Francesca , Vischioni Barbara , Vitolo Viviana , Wheadon Richard , Bisogni Maria Giuseppina
Published: January 2021

In particle therapy, the uncertainty of the delivered particle range during the patient irradiation limits the optimization of the treatment planning. Therefore, an in vivo treatment verification device is required, not only to improve the plan robustness, but also to detect significant interfractional morphological changes during the treatment itself. In this article, an effective and robust analysis to detect regions with a significant range discrepancy is proposed. This study relies on an in vivo treatment verification by means of in-beam Positron Emission Tomography (PET) and was carried out with the INSIDE system installed at the National Center of Oncological Hadrontherapy (CNAO) in Pavia, which is under clinical testing since July 2019. Patients affected by head-and-neck tumors treated with protons have been considered. First, in order to tune the analysis parameters, a Monte Carlo (MC) simulation was carried out to reproduce a patient who required a replanning because of significant morphological changes found during the treatment. Then, the developed approach was validated on the experimental measurements of three patients recruited for the INSIDE clinical trial (ClinicalTrials.govID: NCT03662373), showing the capability to estimate the treatment compliance with the prescription both when no morphological changes occurred and when a morphological change did occur, thus proving to be a promising tool for clinicians to detect variations in the patients treatments.
Aerobic Metabolic Adaptations in Endurance Eccentric Exercise and Training: From Whole Body to Mitochondria
Authors: Touron Julianne , Costes Frédéric , Coudeyre Emmanuel , Perrault Hélène , Richard Ruddy
Published: January 2021

A characteristic feature of eccentric as compared with concentric exercise is the ability to generate greater mechanical loads for lower cardiopulmonary demands. Current evidence concurs to show that eccentric training translates into considerable gains in muscle mass and strength. Less is known, however, regarding its impact on oxygen transport and on factors to be considered for optimizing its prescription and monitoring. This article reviews the existing evidence for endurance eccentric exercise effects on the components of the oxygen transport system from systemic to mitochondria in both humans and animals. In the studies reviewed, specially designed cycle-ergometers or downhill treadmill running were used to generate eccentric contractions. Observations to date indicate that overall, the aerobic demand associated with the eccentric training load was too low to significantly increase peak maximal oxygen consumption. By extension, it can be inferred that the very high eccentric power output that would have been required to solicit a metabolic demand sufficient to enhance peak aerobic power could not be tolerated or sustained by participants. The impact of endurance eccentric training on peripheral flow distribution remains largely undocumented. Given the high damage susceptibility of eccentric exercise, the extent to which skeletal muscle oxygen utilization adaptations would be seen depends on the balance of adverse and positive signals on mitochondrial integrity. The article examines the protection provided by repeated bouts of acute eccentric exercise and reports on the impact of eccentric cycling and downhill running training programs on markers of mitochondrial function and of mitochondrial biogenesis using mostly from animal studies. The summary of findings does not reveal an impact of training on skeletal muscle mitochondrial respiration nor on selected mitochondrial messenger RNA transcripts. The implications of observations to date are discussed within future perspectives for advancing research on endurance eccentric exercise physiological impacts and using a combined eccentric and concentric exercise approach to optimize functional capacity.
Cardiopulmonary Exercise Testing in the Assessment of Dysfunctional Breathing
Authors: Ionescu Maria F. , Mani-Babu Sethu , Degani-Costa Luiza H. , Johnson Martin , Paramasivan Chelliah , Sylvester Karl , Fuld Jonathan
Published: January 2021

Dysfunctional breathing (DB) is a disabling condition which affects the biomechanical breathing pattern and is challenging to diagnose. It affects individuals in many circumstances, including those without underlying disease who may even be athletic in nature. DB can also aggravate the symptoms of those with established heart or lung conditions. However, it is treatable and individuals have much to gain if it is recognized appropriately. Here we consider the role of cardiopulmonary exercise testing (CPET) in the identification and management of DB. Specifically, we have described the diagnostic criteria and presenting symptoms. We explored the physiology and pathophysiology of DB and physiological consequences in the context of exercise. We have provided examples of its interplay with co-morbidity in other chronic diseases such as asthma, pulmonary hypertension and left heart disease. We have discussed the problems with the current methods of diagnosis and proposed how CPET could improve this. We have provided guidance on how CPET can be used for diagnosis, including consideration of pattern recognition and use of specific data panels. We have considered categorization, e.g., predominant breathing pattern disorder or acute or chronic hyperventilation. We have explored the distinction from gas exchange or ventilation/perfusion abnormalities and described other potential pitfalls, such as false positives and periodic breathing. We have also illustrated an example of a clinical pathway utilizing CPET in the diagnosis and treatment of individuals with suspected DB.
RNA-Seq Highlights Molecular Events Associated With Impaired Pollen-Pistil Interactions Following Short-Term Heat Stress in Brassica napus
Authors: Lohani Neeta , Singh Mohan B. , Bhalla Prem L.
Published: January 2021

The global climate change is leading to increased frequency of heatwaves with crops getting exposed to extreme temperature events. Such temperature spikes during the reproductive stage of plant development can harm crop fertility and productivity. Here we report the response of short-term heat stress events on the pollen and pistil tissues in a commercially grown cultivar ofBrassica napus. Our data reveals that short-term temperature spikes not only affect pollen fitness but also impair the ability of the pistil to support pollen germination and pollen tube growth and that the heat stress sensitivity of pistil can have severe consequences for seed set and yield. Comparative transcriptome profiling of non-stressed and heat-stressed (40°C for 30 min) pollen and pistil (stigma + style) highlighted the underlying cellular mechanisms involved in heat stress response in these reproductive tissues. In pollen, cell wall organization and cellular transport-related genes possibly regulate pollen fitness under heat stress while the heat stress-induced repression of transcription factor encoding transcripts is a feature of the pistil response. Overall, high temperature altered the expression of genes involved in protein processing, regulation of transcription, pollen-pistil interactions, and misregulation of cellular organization, transport, and metabolism. Our results show that short episodes of high-temperature exposure inB. napusmodulate key regulatory pathways disrupted reproductive processes, ultimately translating to yield loss. Further investigations on the genes and networks identified in the present study pave a way toward genetic improvement of the thermotolerance and reproductive performance ofB. napusvarieties.
Mental Health Consequences for Healthcare Workers During the COVID-19 Pandemic: A Scoping Review to Draw Lessons for LMICs
Authors: Moitra Modhurima , Rahman Muhammad , Collins Pamela Y. , Gohar Fatima , Weaver Marcia , Kinuthia John , Rössler Wulf , Petersen Stefan , Unutzer Jurgen , Saxena Shekhar , Huang Keng Yen , Lai Joanna , Kumar Manasi
Published: January 2021

Background: The COVID-19 pandemic has had a significant impact on the mental health of healthcare workers (HCWs) particularly in low and middle-income countries (LMICs). This scoping review provides a summary of current evidence on the mental health consequences of COVID on HCWs.

Methods: A scoping review was conducted searching PubMed and Embase for articles relevant to mental health conditions among HCWs during COVID-19. Relevant articles were screened and extracted to summarize key outcomes and findings.

Results: A total of fifty-one studies were included in this review. Depressive symptoms, anxiety symptoms, psychological trauma, insomnia and sleep quality, workplace burnout and fatigue, and distress were the main outcomes reviewed. Most studies found a high number of symptoms endorsed for depression, anxiety, and other conditions. We found differences in symptoms by sex, age, and HCW role, with female, younger-aged, frontline workers, and non-physician workers being affected more than other subgroups.

Conclusion: This review highlights the existing burden of mental health conditions reported by HCWs during COVID-19. It also demonstrates emerging disparities among affected HCW subgroups. This scoping review emphasizes the importance of generating high quality evidence and developing informed interventions for HCW mental health with a focus on LMICs.
Health Information Seeking Among University Students Before and During the Corona Crisis—Findings From Germany
Authors: Schäfer Markus , Stark Birgit , Werner Antonia M. , Tibubos Ana Nanette , Reichel Jennifer L. , Pfirrmann Daniel , Edelmann Dennis , Heller Sebastian , Mülder Lina Marie , Rigotti Thomas , Letzel Stephan , Dietz Pavel
Published: January 2021

Health information-seeking behavior is the process of gathering information about health and disease and can be influential for health-related perception and behavior. University students are an important target group for prevention and health promotion and largely belong to an age group that is considered to play a leading role in propagating the SARS-CoV-2 epidemic in Germany. The paper deals with students' health information-seeking behavior before and during the corona crisis, aiming to give insights into its determinants and implications. Using the example of a large German comprehensive university and based on two cross-sectional surveys in the summer of 2019 (n = 4,351) and 2020 (n = 3,066), we investigate which information channels students use for health information, how information seeking changes during the course of the pandemic, and to what extent information seeking is associated with risk perception and risk behavior. For a subsample of participants that participated in both surveys (n = 443), we also trace developments at the individual level through a longitudinal analysis. The results show that students' health information seeking takes place primarily online and changed markedly during the corona crisis. The comparatively high relevance of sources that are largely based on unchecked user-generated content raises the concern whether students' health information-seeking behavior guarantees the necessary quality and reliability of health information. Significant correlations between the intensity of corona-related information seeking, risk perception, and actual risk behavior were found.