bluuebunny/crossref_metadata_2025 huggingface dataset:
Directions in Music: Stakeholder Perspectives on Blockchain Innovations in Music Streaming
Authors: Lovett Matthew
Published: December 2020

In its various guises, blockchain technology has generated friction across a range of sectors; most notably as an enabler of anonymous trading, but perhaps more significantly in terms of longer-term adoption, via its application in supply-chain monitoring, and rights management. This article draws on stakeholder theory to examine the deployment of blockchain technology in the music streaming sector, in order to assess how these blockchain-based innovations - via interactions with users, market environments, and overarching economic and political frameworks - are contributing to evolving conceptions of ownership, inclusion and involvement. Initially, the article examines three approaches to theorizing and designing inclusive governance structures that acknowledge the distributed, and at times collaborative, nature of interaction between members of a group; be that a society, a company or other form of organized grouping. Here I draw on three discourses to underpin the evolving role that stakeholders - in the guise of networks, companies, societies and platforms – can play in digital commerce: (i) John Rawls’ concept of Distributive Justice, (ii) a set of principles known as the ‘Scandinavian approach to Participatory Design’; and (iii) the emergent concept of ‘New Economics,’ a term particularly associated with current and emergent left-wing political perspectives in the United Kingdom. Taking three use cases in Resonate, Musicoin and Choon, the article engages with how blockchain-based music start-ups are interacting with an evolving marketplace; identifying the benefits and beneficiaries of blockchain uptake, along with a wider set of structural changes that are taking place within music commerce. The article focuses on music streaming in particular to explore how blockchain is transforming the way that things are owned, and how it is contributing to an evolving conception of ownership, and reflects on how blockchain is finding increased used within the physical world of private and public property, and political governance. In response to this integrative analysis of blockchain in relation to critical perspectives on ownership and governance, the article concludes by considering how stakeholders with the music streaming sector are indicative of wider changes, challenges and tensions within the digital marketplace, and the role that innovations in blockchain can play in this transition.
Alkaline Phosphatases Account for Low Plasma Levels of Inorganic Pyrophosphate in Chronic Kidney Disease
Authors: Laurain Audrey , Rubera Isabelle , Duranton Christophe , Rutsch Frank , Nitschke Yvonne , Ray Elodie , Vido Sandor , Sicard Antoine , Lefthériotis Georges , Favre Guillaume
Published: December 2020

Introduction

Patients on dialysis and kidney transplant recipients (KTR) present the syndrome of mineral and bone disorders (MBD), which share common traits with monogenic calcifying diseases related to disturbances of the purinergic system. Low plasma levels of inorganic pyrophosphate (PPi) and ectopic vascular calcifications belong to these two conditions. This suggests that the purinergic system may be altered in chronic kidney disease with MBD. Therefore, we perform a transversal pilot study in order to compare the determinants of PPi homeostasis and the plasma levels of PPi in patients on dialysis, in KTR and in healthy people.

Patients and Methods

We included 10 controls, 10 patients on maintenance dialysis, 10 early KTR 3 ± 1 months after transplantation and nine late KTR 24 ± 3 months after transplantation. We measured aortic calcifications, plasma and urine levels of PPi, the renal fractional excretion of PPi (FePPi), nucleoside triphosphate hydrolase (NPP) and ALP activities in plasma. Correlations and comparisons were assessed with non-parametric tests.

Results

Low PPi was found in patients on dialysis [1.11 (0.88–1.35), p = 0.004], in early KTR [0.91 (0.66–0.98), p = 0.0003] and in late KTR [1.16 (1.07–1.45), p = 0.02] compared to controls [1.66 (1.31–1.72) μmol/L]. Arterial calcifications were higher in patients on dialysis than in controls [9 (1–75) vs. 399 (25–526) calcium score/cm2, p < 0.05]. ALP activity was augmented in patients on dialysis [113 (74–160), p = 0.01] and in early KTR [120 (84–142), p = 0.002] compared to controls [64 (56–70) UI/L]. The activity of NPP and FePPi were not different between groups. ALP activity was negatively correlated with PPi (r = −0.49, p = 0.001).

Discussion

Patients on dialysis and KTR have low plasma levels of PPi, which are partly related to high ALP activity, but neither to low NPP activity, nor to increased renal excretion of PPi. Further work is necessary to explore comprehensively the purinergic system in chronic kidney disease.
MicroRNA-20a-5p Ameliorates Non-alcoholic Fatty Liver Disease via Inhibiting the Expression of CD36
Authors: Wang Xin , Ma Yan , Yang Long-Yan , Zhao Dong
Published: December 2020

Fatty acid translocase CD36 (CD36) plays an important role in the initiation and pathogenesis of chronic liver disease and non-alcoholic fatty liver disease (NAFLD). The purpose of this study is to investigate the regulation of microRNA-20a-5p (miR-20a-5p) on CD36 in the pathogenesis of NAFLD. Human plasma samples were obtained from NAFLD patients and healthy controls. Mice were fed with high-fat diet to induce an in vivo NAFLD model. Histology staining was performed to examine the morphology and lipid deposition of mouse liver tissue. Real-time PCR, dual-luciferase assay, and western blotting were employed to detect the relationship between miR-20a-5p and CD36. The expression level of miR-20a-5p was decreased in NAFLD patients, HFD mice, and free fatty acid (FFA)-treated HepG2 cells or primary mouse hepatocytes, accompanied by increased lipid production in hepatocytes. MiR-20a-5p suppressed the expression of CD36 to reduce lipid accumulation via binding to its 3’-untranslated region (UTR). However, under the condition of interference with CD36, further inhibition of miR-20a-5p would not cause lipid over-accumulation. In this study, we found that miR-20a-5p played a protective role in lipid metabolic disorders of NAFLD by targeting CD36, which indicated the prospect of miR-20a-5p as a biomarker and treatment target for NAFLD.
The Extracellular Matrix in the Evolution of Cortical Development and Folding
Authors: Amin Salma , Borrell Víctor
Published: December 2020

The evolution of the mammalian cerebral cortex leading to humans involved a remarkable sophistication of developmental mechanisms. Specific adaptations of progenitor cell proliferation and neuronal migration mechanisms have been proposed to play major roles in this evolution of neocortical development. One of the central elements influencing neocortex development is the extracellular matrix (ECM). The ECM provides both a structural framework during tissue formation and to present signaling molecules to cells, which directly influences cell behavior and movement. Here we review recent advances in the understanding of the role of ECM molecules on progenitor cell proliferation and neuronal migration, and how these contribute to cerebral cortex expansion and folding. We discuss how transcriptomic studies in human, ferret and mouse identify components of ECM as being candidate key players in cortex expansion during development and evolution. Then we focus on recent functional studies showing that ECM components regulate cortical progenitor cell proliferation, neuron migration and the mechanical properties of the developing cortex. Finally, we discuss how these features differ between lissencephalic and gyrencephalic species, and how the molecular evolution of ECM components and their expression profiles may have been fundamental in the emergence and evolution of cortex folding across mammalian phylogeny.
Tunable Non-linear Refraction Properties and Ultrafast Excited State Dynamics of Dicyanomethylene Dihydrofuran Derivative
Authors: Yang Linpo , Li Zhongguo , Wei Taihui , Zhou Liming , Li Feng , Fang Shaoming , Song Yinglin
Published: December 2020

The third order non-linear optical response of a dicyanomethylene dihydrofuran compound (DCDHF-2V) was investigated using a Z-scan technique in picosecond and nanosecond time regimes. The results show that DCDHF-2V has excellent excited state non-linear refraction properties on both time regimes, and the non-linear refraction index is also solvent-dependent in the nanosecond regime. The excited state relaxation dynamics of DCDHF-2V were demystified via femtosecond transient absorption spectroscopy. The TA spectra reveal that the solvent viscosities have a substantial impact on the excited state relaxation of DCDHF-2V. The exotic photophysical phenomena in DCDHF-2V reported herein can shed new light on future development of small organic non-linear optical materials with large non-linear coefficients and fast response.
Alkyl Chain Grafted-Reduced Graphene Oxide Membrane for Effective Separation of Water/Alcohol Miscible Mixtures
Authors: Zhang Hailong , Yang Jianbo , Li Ting , Ji Xingxiang , Xu Zhen , Zhu Yaling , Liu Libin
Published: December 2020

Separation of water/alcohol miscible mixtures via direct filtration only under gravity is a great challenge. Here, different alkyl chain grafted-reduced graphene oxide (alkyl-RGO) is synthesized and characterized. The hydrophobic alkyl chains can considerably modify the oil-wettability of the membranes and avoid water permeation. The alkyl-RGO membrane obtained by vacuum filtration can separate water/oil immiscible mixtures. Importantly, water/alcohol miscible mixtures could also be separated solely under gravity, where alcohols efficiently permeate the alkyl-RGO membrane while water is prevented through the membrane. The separation efficiency of C12H-RGO membrane reaches up to about 0.04 vol% of water content for the case of separating an n-propanol/water (90:10 v/v) mixture with high n-propanol permeability of approx. 685 mL m−2 h−1. Molecular simulations indicate that the selective absorption ability and diffusion rate also affect water/alcohol separation. The alkyl-RGO membranes via gravity driven filtration can extend the applications of separation of water/alcohol miscible mixtures.
Impact and Correction of Analytical Positioning on Accuracy of Zircon U-Pb Dating by SIMS
Authors: Liu Yu , Li Qiu-Li , Ling Xiao-Xiao , Tang Guo-Qiang , Li Jiao , Li Xian-Hua
Published: December 2020

Secondary ion mass spectrometry (SIMS) is one of the most important analytical tools for geochronology, especially for zircon U-Pb dating. Due to its advantages in spatial resolution and analytical precision, SIMS is the preferred option for multi-spot analyses on single zircon grain with complex structures. However, whether or how much the relative positions of multiple analytical spots on one zircon grain affect the U-Pb age accuracy is an important issue that has been neglected by most researchers. In this study, we carried out a series of investigation on the influence of relative analytical position during zircon U-Pb age analyses, using Cameca IMS 1280-HR instrument. The results demonstrated a significant influence on the second spot, with apparent U-Pb age deviation as high as around 10% especially on the left and right side with overlap in the raster area. Nevertheless, a linear correlation between a secondary ion centering parameter (DTCA-X) and age deviation in percentage terms was found, and a calibration method was established to correct this position effect. Four zircon standards (91500, M257, TEMORA-2, and Plešovice) were measured to prove the reliability of the established procedure. The original U-Pb apparent data show inconsistent deviation on four directions relative to the datum, while the final U-Pb age results is calibrated to be consistent with their recommended values, within uncertainties of ~1%. This work calls for re-examination for the previous SIMS U-Pb dating results on core-rim dating strategy, and provides a calibration protocol to correct the relative position effect.
Spies and the Virus: The COVID-19 Pandemic and Intelligence Communication in the United States
Authors: Lankford Ana Maria , Storzieri Derrick , Fitsanakis Joseph
Published: December 2020

This paper introduces a crucial parameter to the novel coronavirus response in the United States, by shedding light on the early-warning role of intelligence agencies. It argues that the intelligence components of the federal government's Biological Defense Program offered actionable forewarning about an impending pandemic in the years leading to the COVID-19 outbreak. Yet, almost from the opening stages of the pandemic, senior US government officials, including President Donald Trump, have repeatedly claimed that the virus “came out of nowhere” and that “nobody saw it coming.” We show that these assertions contradict more than 15 years of pandemic preparedness warnings by intelligence professionals, and disregard the existence of intelligence-led federal pandemic response strategies of every US administration in our time. However, rather than simply placing blame on the White House for discounting these warnings, we advance a conceptual analysis of what many in the US Intelligence Community view as a critical breakdown in strategic communication between intelligence professionals and key government decision-makers. This study agrees with those who suggest that the White House disregarded its own pandemic experts. However, it also posits that the means of strategic communication employed by intelligence experts to alert the White House to the threat were unproductive. These alerts were communicated largely through the President's Daily Brief, an archaic, and ineffectual method of communication that is not designed to facilitate the kind of laser-focused, unequivocal exchange of information needed when potentially catastrophic threats confront the world. This study suggests that the Intelligence Community must implement more direct, immediate and conclusive methods of communicating intelligence to decision-makers, and should seriously consider creating a new line of products that addresses existential challenges to national security. Lastly, we contend it is time to re-evaluate existing rules that prevent intelligence analysts from offering advice on policy. Although we agree that intelligence professionals should refrain from providing policy advice on routine matters, we question the value of preventing these highly knowledgeable experts from communicating strategic policy advice to decision-makers when it comes to threats of a catastrophic nature, which may prove potentially existential for the US, its allies, and the world.
Multimodality Imaging for Discordant Low-Gradient Aortic Stenosis: Assessing the Valve and the Myocardium
Authors: Guzzetti Ezequiel , Annabi Mohamed-Salah , Pibarot Philippe , Clavel Marie-Annick
Published: December 2020

Aortic stenosis (AS) is a disease of the valve and the myocardium. A correct assessment of the valve disease severity is key to define the need for aortic valve replacement (AVR), but a better understanding of the myocardial consequences of the increased afterload is paramount to optimize the timing of the intervention. Transthoracic echocardiography remains the cornerstone of AS assessment, as it is universally available, and it allows a comprehensive structural and hemodynamic evaluation of both the aortic valve and the rest of the heart. However, it may not be sufficient as a significant proportion of patients with severe AS presents with discordant grading (i.e., an AVA ≤ 1 cm2 and a mean gradient <40 mmHg) which raises uncertainty about the true severity of AS and the need for AVR. Several imaging modalities (transesophageal or stress echocardiography, computed tomography, cardiovascular magnetic resonance, positron emission tomography) exist that allow a detailed assessment of the stenotic aortic valve and the myocardial remodeling response. This review aims to provide an updated overview of these multimodality imaging techniques and seeks to highlight a practical approach to help clinical decision making in the challenging group of patients with discordant low-gradient AS.
Systematic Pharmacology and GEO Database Mining Revealed the Therapeutic Mechanism of Xuefu Zhuyu Decoration for Atherosclerosis Cardiovascular Disease
Authors: Liang Bin , Xiang Yang , Zhang Xiaokang , Wang Chen , Jin Bingyu , Zhao Yue , Zheng Fang
Published: December 2020

Background: Xuefu Zhuyu decoration (XFZYD), as a traditional Chinese compound recipe, has been used to treat atherosclerosis cardiovascular disease (ASCVD) for thousands of years in China, but its effective compounds and underlying treatment molecular mechanism remains promiscuous, which severely limits its clinical application.

Methods: The effective components and their targets of XFZYD were predicted and screened based on the Traditional Chinese Medicine System Pharmacology (TCMSP) database. The candidate therapeutic targets of ASCVD were screened by Pharmacogenomics Knowledgebase (PharmGKB) and Comparative Toxicogenomics Database (CTD). Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses for target proteins were performed using the Database for Annotation, Visualization and Integrated Discovery (DAVID) database. Differentially expressed genes were identified using the GEO2R online tool. Molecular docking was performed by Schrodinger software. To assess the efficacy of the prediction, human umbilical vein endothelial cells (HUVECs) treated with the effective compound of XFZYD were used as the in vitro model.

Results: A total of 108 effective compounds (including quercetin) and 137 candidate therapeutic targets were identified. Analyzing the relationships among effective compounds, candidate therapeutic targets, and signaling pathways, the therapy mechanisms of XFZYD were mainly reflected in the protection of vascular endothelium, anti-inflammatory, antioxidant stress, etc. Accordingly, we found the effective compound of XFZYD (quercetin) decreased intracellular adhesion molecule 1 (ICAM-1) and vascular cell adhesion molecule 1 (VCAM-1) expressions and pro-inflammatory cytokines in HUVECs treated with lipopolysaccharide (LPS), and reduced the adhesion function of HUVECs with monocytes. The inhibitor of the predicted target protein (PTGS2) could further reduce the expressions of VCAM-1, ICAM-1, and TNF-α induced by LPS, and inhibit the adhesion function of HUVECs with monocytes, while PTGS2 agonists partially counteracted the protective effect of quercetin.

Conclusions: In this study, the effective components and potential therapeutic targets of XFZYD for ASCVD treatment were explored from the perspective of systemic pharmacology. The effective component quercetin was verified to protect endothelial cells by reducing endothelial inflammatory response and impeding the attachment of monocytes against the predicted therapeutic target PTGS2.
Creative Problem Solving as Overcoming a Misunderstanding
Authors: Bagassi Maria , Macchi Laura
Published: December 2020

Solving or attempting to solve problems is the typical and, hence, general function of thought. A theory of problem solving must first explain how the problem is constituted, and then how the solution happens, but also how it happens that it is not solved; it must explain the correct answer and with the same means the failure. The identification of the way in which the problem isformattedshould help to understand how the solution of the problems happens, but even before that, the source of the difficulty. Sometimes the difficulty lies in the calculation, the number of operations to be performed, and the quantity of data to be processed and remembered. There are, however, other problems – the insight problems – in which the difficulty does not lie so much in the complexity of the calculations, but in one or more critical points that are susceptible tomisinterpretation, incompatible with the solution. In our view, the way of thinking involved in insight problem solving is very close to the process involved in the understanding of an utterance, when a misunderstanding occurs. In this case, a more appropriate meaning has to be selected to resolve the misunderstanding (the “impasse”), the default interpretation (the “fixation”) has to be dropped in order to “restructure.” to grasp another meaning which appears more relevant to the context and the speaker’s intention (the “aim of the task”). In this article we support our view with experimental evidence, focusing on how a misunderstanding is formed. We have studied a paradigmatic insight problem, an apparent trivial arithmetical task, the Ties problem. We also reviewed other classical insight problems, reconsidering in particular one of the most intriguing one, which at first sight appears impossible to solve, the Study Window problem. By identifying the problem knots that alter the aim of the task, the reformulation technique has made it possible to eliminate misunderstanding, without changing the mathematical nature of the problem. With the experimental versions of the problems exposed we have obtained a significant increase in correct answers. Studying how an insight problem is formed, and not just how it is solved, may well become an important topic in education. We focus on undergraduate students’ strategies and their errors while solving problems, and the specific cognitive processes involved in misunderstanding, which are crucial to better exploit what could be beneficial to reach the solution and to teach how to improve the ability to solve problems.
Virtual Teaching in the Time of COVID-19: Rethinking Our WEIRD Pedagogical Commitments to Teacher Education
Authors: Thomas M'Balia
Published: December 2020

Teacher Educators confront a professional future in which online instruction will play an increased role in student learning. As instructional activities are delivered online, a critical challenge for teacher educators will be to continue supporting those ideals key to the missions of many Schools and Colleges of Education—the creation of an instructional environment that is culturally responsive, committed to equity and inclusion, and able to support a diverse and “well” student body.
Genetics of Hypercholesterolemia: Comparison Between Familial Hypercholesterolemia and Hypercholesterolemia Nonrelated to LDL Receptor
Authors: Jarauta Estíbaliz , Bea-Sanz Ana Ma , Marco-Benedi Victoria , Lamiquiz-Moneo Itziar
Published: December 2020

Severe hypercholesterolemia (HC) is defined as an elevation of total cholesterol (TC) due to the increase in LDL cholesterol (LDL-C) >95th percentile or 190 mg/dl. The high values of LDL-C, especially when it is maintained over time, is considered a risk factor for the development of atherosclerotic cardiovascular disease (ASCVD), mostly expressed as ischemic heart disease (IHD). One of the best characterized forms of severe HC, familial hypercholesterolemia (FH), is caused by the presence of a major variant in one gene (LDLR, APOB, PCSK9, orApoE), with an autosomal codominant pattern of inheritance, causing an extreme elevation of LDL-C and early IHD. Nevertheless, an important proportion of serious HC cases, denominated polygenic hypercholesterolemia (PH), may be attributed to the small additive effect of a number of single nucleotide variants (SNVs), located along the whole genome. The diagnosis, prevalence, and cardiovascular risk associated with PH has not been fully established at the moment. Cascade screening to detect a specific genetic defect is advised in all first- and second-degree relatives of subjects with FH. Conversely, in the rest of cases of HC, it is only advised to screen high values of LDL-C in first-degree relatives since there is not a consensus for the genetic diagnosis of PH. FH is associated with the highest cardiovascular risk, followed by PH and other forms of HC. Early detection and initiation of high-intensity lipid-lowering treatment is proposed in all subjects with severe HC for the primary prevention of ASCVD, with an objective of LDL-C <100 mg/dl or a decrease of at least 50%. A more aggressive reduction in LDL-C is necessary in HC subjects who associate personal history of ASCVD or other cardiovascular risk factors.
Gene Expression Dynamics in Rice Peduncles at the Heading Stage
Authors: Kandpal Manu , Vishwakarma Chandrapal , Krishnan Kushagra , Chinnusamy Viswanathan , Pareek Ashwani , Sharma Manoj K. , Sharma Rita
Published: December 2020

Improving grain yield in the staple food crop rice has been long sought goal of plant biotechnology. One of the traits with significant impact on rice breeding programs is peduncle elongation at the time of heading failing which leads to significant reduction in grain yield due to incomplete panicle exsertion. To decipher transcriptional dynamics and molecular players underlying peduncle elongation, we performed RNA sequencing analysis of elongating and non-elongating peduncles in two Indian cultivars, Swarna and Pokkali, at the time of heading. Along with genes associated with cell division and cell wall biosynthesis, we observed significant enrichment of genes associated with auxins, gibberellins, and brassinosteroid biosynthesis/signaling in the elongating peduncles before heading in both the genotypes. Similarly, genes associated with carbohydrate metabolism and mobilization, abiotic stress response along with cytokinin, abscisic acid, jasmonic acid, and ethylene biosynthesis/signaling were enriched in non-elongating peduncles post heading. Significant enrichment of genes belonging to key transcription factor families highlights their specialized roles in peduncle elongation and grain filling before and after heading, respectively. A comparison with anther/pollen development-related genes provided 76 candidates with overlapping roles in anther/pollen development and peduncle elongation. Some of these are important for carbohydrate remobilization to the developing grains. These can be engineered to combat with incomplete panicle exsertion in male sterile lines and manipulate carbohydrate dynamics in grasses. Overall, this study provides baseline information about potential target genes for engineering peduncle elongation with implications on plant height, biomass composition and grain yields in rice.
Evidence of B Cell Clonality and Investigation Into Properties of the IgM in Patients With Schnitzler Syndrome
Authors: Pathak Shelly , Rowczenio Dorota , Lara-Reyna Samuel , Kacar Mark , Owen Roger , Doody Gina , Krause Karoline , Lachmann Helen , Doffinger Rainer , Newton Darren , Savic Sinisa
Published: December 2020

The Schnitzler Syndrome (SchS) is an acquired, autoinflammatory condition successfully treated with IL-1 inhibition. The two main defining features of this late-onset condition are neutrophilic urticarial dermatoses (NUD) and the presence of an IgM monoclonal component. While the former aspect has been extensively studied in this disease setting, the enigmatic paraproteinaemia and its potential consequential effects within SchS, has not previously been thoroughly addressed. Previous studies analyzing clonal B cell repertoires have largely focused on autoimmune disorders such as Systemic Lupus Erythematous (SLE) and hematological malignancies such as Chronic Lymphocytic Leukaemia (CLL), where B-cell clonality is central to disease pathology. The present study uses next-generation sequencing to provide detailed insight into aspects of B cell VDJ recombination and properties of the resulting immunoglobulin chains. An overview of IgH regional dynamics in 10 SchS patients, with a particular focus on CDR3 sequences and VDJ gene usage is reported, highlighting the presence of specific B cell expansions. Protein microarray detected a substantial proportion of autoreactive IgM to nuclear target proteins, though a single universal target was not identified. Together, these genetic and functional findings impart new understanding into this rare disorder.
Multifunctionality of an Urbanized Coastal Marine Ecosystem
Authors: Archana Anand , Baker David Michael
Published: December 2020

Coastal marine ecosystems provide numerous invaluable services and benefits to humankind. However, urbanization of coastal areas has homogenized and reduced the biodiversity of the surrounding marine environment and the sustainability of the multiple ecosystem services it provides. Studies have focused on single ecosystem functions despite human populations relying on several functions being delivered at once (known as multifunctionality). This study investigates five ecosystem functions (primary productivity, herbivory, predation, organic matter decomposition and carbon sequestration) and overall multifunctionality in four sites along a gradient of 16 environmental parameters. Ecosystem function varied significantly between sites that were farthest apart. In determining factors that drove ecosystem functioning, we found a positive relationship between coral cover and primary productivity but negative relationships between coral cover and levels of herbivory and predation intensity. Higher temperatures and greater concentrations of chlorophyll-a had a positive impact on predation and herbivory, respectively. Notably, we found a significant negative impact of total inorganic nitrogen and significant positive impact of total Kjeldahl nitrogen on carbon sequestration. Further, individual functions were compared with fish abundance (obtained from seawater eDNA), and benthic community composition (obtained from plate % coverage of autonomous reef monitoring structures). Increasing herbivorous fish abundance had a positive impact on Ulva mass loss. Overall, relative abundance of predatory, omnivorous and planktivorous fish exerted overriding influences on primary productivity and predation intensity, implying that fishing pressure and marine protected area status are important factors. Importantly, we found significant effects from environmental parameters indicating that reliably predicting the effects of future anthropogenic impacts will not be straightforward as multiple drivers are likely to have complex effects. Taken together, urbanized coastal ecosystems exhibit varying levels of multifunctionality depending on the extent of human impact, and the functional diversity of the benthic community present.
Does Warming Enhance the Effects of Eutrophication in the Seagrass Posidonia oceanica?
Authors: Pazzaglia Jessica , Santillán-Sarmiento Alex , Helber Stephanie B. , Ruocco Miriam , Terlizzi Antonio , Marín-Guirao Lázaro , Procaccini Gabriele
Published: December 2020

Seagrass meadows are disappearing at rates comparable to those reported for mangroves, coral reefs, and tropical rainforests. One of the main causes of their decline is the so-called cultural eutrophication, i.e., the input of abnormal amounts of nutrients derived from human activities. Besides the impact of eutrophication at a local scale, the occurrence of additional stress factors such as global sea warming may create synergisms in detriment of seagrass meadows’ health. In the present study, we aimed to evaluate if plants undergoing chronic cultural eutrophication and plants growing in relatively pristine waters are more (or less) sensitive to heat stress, nutrient load and the combination of both stressors. To address this question, a mesocosm experiment was conducted using Posidonia oceanica collected from two environments with different nutrients load history. Plants were exposed in controlled conditions to high nutrient concentrations, increased temperature and their combination for 5 weeks, to assess the effect of the single stressors and their interaction. Our results revealed that plants experiencing chronic cultural eutrophication (EU) are more sensitive to further exposure to multiple stressors than plants growing in oligotrophic habitats (OL). OL and EU plants showed different morphological traits and physiological performances, which corroborates the role of local pressures in activating different strategies in response to global environmental changes. EU-plants appeared to be weaker during the treatments, showing the greatest percentage of mortality, particularly under increased temperature. Temperature and nutrient treatments showed opposite effects when tested individually and an offset response when combined. The activation of physiological strategies with high energetic expenses to cope with excess of nutrients and other stressors, could affect plants present and future persistence, particularly under eutrophic conditions. Our results represent a step forward in understanding the complex interactions that occur in natural environments. Moreover, unraveling intraspecific strategies and the role of local acclimation/adaptation in response to multiple stressors could be crucial for seagrass conservation strategies under a climate change scenario.
Indicators of Coastal Wetlands Restoration Success: A Systematic Review
Authors: Cadier Charles , Bayraktarov Elisa , Piccolo Renee , Adame Maria Fernanda
Published: December 2020

Coastal wetlands restoration is an emerging field which aims to recover the ecological characteristics of degraded ecosystems to natural ones. The recent UN declaration of 2021–2030 as the “Decade on Ecosystem Restoration” will hopefully encourage global implementation of these projects. However, a lack of common indicators of restoration success hinders our knowledge on the ecological outcomes of restoration projects. We conducted a literature review to determine trends in monitoring indicators. We classified indicators following the Society for Ecological Restoration template, adapting it to coastal wetlands. We found that indicators on structural diversity (e.g., tree height, fish size) were the mostly commonly used. Indicators on ecosystem function were the second most investigated, with half of the assessed studies including them, especially those focusing on carbon, nutrient and sediment dynamics. We propose a recovery wheel framework adapted to coastal wetlands. Structural diversity indicators are generally easier to measure and often the traits that recover the fastest. However, ecosystem function indicators could be more important to assess the recovery of ecosystem services, which is a primary objective of restoration. Restoration objectives and goals are variable for each project, and we encourage future restoration projects on coastal wetlands to select the most appropriate indicators on the basis of the recovery wheel proposed in this study to plan a monitoring framework. Future studies assessing coastal wetlands restoration ecological outcomes should include ecosystem function indicators and monitor the sites over periods adequate to their recovery.
Phenylalanine Hydroxylase RNAi Knockdown Negatively Affects Larval Development, Molting and Swimming Performance of Salmon Lice
Authors: Guragain Prashanna , Sporsheim Bjørnar , Skjesol Astrid , Båtnes Anna Solvang , Olsen Yngvar , Bones Atle M. , Winge Per
Published: December 2020

Phenylalanine hydroxylase (PAH) is a crucial enzyme involved in tyrosine biosynthesis, having roles in neurological and physiological processes. The purpose of PAH has received little attention in crustaceans despite extensive investigations in other arthropods. Here, we characterize the PAH gene for the first time in the parasite Lepeophtheirus salmonis, a copepod that is responsible for huge economic losses in salmonid fish farming. Phylogenetic and sequence analyses confirmed that LsPAH is closely related to the metazoan PAH with conserved ACT regulatory and catalytic domains. Temporal expression patterns revealed that LsPAH is expressed throughout all developmental stages peaking during the copepodite stages, suggesting an essential role in developmental physiology. We used RNAi to knockdown LsPAH expression in the nauplius I stage to study developmental function during the larval stages. PAH knockdown impaired larval development, molting and swimming ability with severe morphological defects. This study provides insight into the role of PAH in copepods and demonstrates the importance of this metabolic gene in salmon louse growth and development.
Efficacy and Safety of Glecaprevir/Pibrentasvir in HCV Patients With Previous Direct-Acting Antiviral Therapy Failures: A Meta-Analysis
Authors: Shen Chao , Fan Haozhi , Ge Zhijun , Cai Weihua , Shao Jianguo , Dong Chen , Xue Hong , Fu Zuqiang , Li Jun , Zhang Yun , Yue Ming
Published: December 2020

Background: Since a greater number of hepatitis C virus (HCV) patients have access to direct-acting antiviral (DAA) based therapies, the number of patients not properly responding to prior DAA regimens is increasing. The objective of this comprehensive analysis was to assess the efficacy and safety of glecaprevir/pibrentasvir (GLE/PIB) in HCV patients who experienced previous DAA therapy failures.

Methods: Bibliographic databases were systematically searched for relevant articles published by November 2020. The main endpoints were sustained viral response after 12 weeks (SVR12), adverse events (AEs; any grade) and severe adverse events (SAEs). Publication bias assessment was performed using funnel plots and the Egger's test.

Results: Fourteen studies consisting of a total of 1,294 subjects were included in this study and the pooled estimate of SVR12, AEs and SAEs rates were 96.8% (95%CI: 95.1–98.2), 47.1% (95%CI: 26.0–69.3), and 1.8% (95%CI: 0.7–3.4), respectively. Subgroup analysis showed that pooled SVR12 rates were 97.9% (95%CI: 96.7–98.9) for Japan and 91.1% (95%CI: 87.3–94.3) for the United States; 95.8% (95%CI: 93.9–97.4) for genotype (GT)1 and 100.0% (95%CI: 99.6–100.0) for GT2; 95.3% (95%CI: 92.4–97.2) for cirrhosis and 96.3% (95%CI: 94.2–97.7) for non-cirrhosis cases. There was no publication bias included this study.

Conclusion: This comprehensive analysis revealed that GLE/PIB is an effective and secure retreatment option for patients who did not optimally respond to DAA treatment, especially the Asian population with GT1-2.
Secondary Membranous Nephropathy. A Narrative Review
Authors: Moroni Gabriella , Ponticelli Claudio
Published: December 2020

Membranous nephropathy (MN) is a common cause of proteinuria and nephrotic syndrome all over the world. It can be subdivided into primary and secondary forms. Primary form is an autoimmune disease clinically characterized by nephrotic syndrome and slow progression. It accounts for ~70% cases of MN. In the remaining cases MN may be secondary to well-defined causes, including infections, drugs, cancer, or autoimmune diseases, such as systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), urticarial vasculitis, sarcoidosis, thyroiditis, Sjogren syndrome, systemic sclerosis, or ankylosing spondylitis. The clinical presentation is similar in primary and secondary MN. However, the outcome may be different, being often related to that of the original disease in secondary MN. Also, the treatment may be different, being targeted to the etiologic cause in secondary MN. Thus, the differential diagnosis between primary and secondary MN is critical and should be based not only on history and clinical features of the patient but also on immunofluorescence and electron microscopy analysis of renal biopsy as well as on the research of circulating antibodies. The identification of the pathologic events underlying a secondary MN is of paramount importance, since the eradication of the etiologic factors may be followed by remission or definitive cure of MN. In this review we report the main diseases and drugs responsible of secondary MN, the outcome and the pathogenesis of renal disease in different settings and the possible treatments.
Characterization of the Mycobacterial MSMEG-3762/63 Efflux Pump in Mycobacterium smegmatis Drug Efflux
Authors: De Siena Barbara , Campolattano Nicoletta , D’Abrosca Gianluca , Russo Luigi , Cantillon Daire , Marasco Rosangela , Muscariello Lidia , Waddell Simon J. , Sacco Margherita
Published: December 2020

Multi-drug resistant tuberculosis (MDR-TB) represents a major health problem worldwide. Drug efflux and the activity of efflux transporters likely play important roles in the development of drug-tolerant and drug-resistant mycobacterial phenotypes. This study is focused on the action of a mycobacterial efflux pump as a mechanism of drug resistance. Previous studies demonstrated up-regulation of the TetR-like transcriptional regulator MSMEG_3765 in Mycobacterium smegmatis and its ortholog Rv1685c in Mycobacterium tuberculosis (Mtb) in acid-nitrosative stress conditions. MSMEG-3765 regulates the expression of the MSMEG_3762/63/65 operon, and of the orthologous region in Mtb (Rv1687c/86c/85c). MSMEG-3762 and Rv1687c are annotated as ATP-binding proteins, while MSMEG-3763 and Rv1686c are annotated as trans-membrane polypeptides, defining an ABC efflux pump in both M. smegmatis and Mtb. The two putative efflux systems share a high percentage of identity. To examine the role of the putative efflux system MSMEG-3762/63, we constructed and characterized a MSMEG-3763 deletion mutant in M. smegmatis (∆MSMEG_3763). By comparative analysis of wild type, knockout, and complemented strains, together with structural modeling and molecular docking bioinformatics analyses of the MSMEG-3763 trans-membrane protein, we define the protein complex MSMEG-3762/63 as an efflux pump. Moreover, we demonstrate involvement of this pump in biofilm development and in the extrusion of rifampicin and ciprofloxacin (CIP), antimicrobial drugs used in first- and second-line anti-TB therapies.
A Biological Inventory of Prophages in A. baumannii Genomes Reveal Distinct Distributions in Classes, Length, and Genomic Positions
Authors: Loh Belinda , Chen Jiayuan , Manohar Prasanth , Yu Yunsong , Hua Xiaoting , Leptihn Sebastian
Published: December 2020

Acinetobacter baumannii is of major clinical importance as the bacterial pathogen often causes hospital acquired infections, further complicated by the high prevalence of antibiotic resistant strains. Aside from natural tolerance to certain antibiotic classes, resistance is often acquired by the exchange of genetic information via conjugation but also by the high natural competence exhibited by A. baumannii. In addition, bacteriophages are able to introduce resistance genes but also toxins and virulence factors via phage mediated transduction. In this work, we analyzed the complete genomes of 177 A. baumannii strains for the occurrence of prophages, and analyzed their taxonomy, size and positions of insertion. Among all the prophages that were detected, Siphoviridae and Myoviridae were the two most commonly found families, while the average genome size was determined to be approximately 4 Mbp. Our data shows the wide variation in the number of prophages in A. baumannii genomes and the prevalence of certain prophages within strains that are most “successful” or potentially beneficial to the host. Our study also revealed that only two specific sites of insertion within the genome of the host bacterium are being used, with few exceptions only. Lastly, we analyzed the existence of genes that are encoded in the prophages, which may confer antimicrobial resistance (AMR). Several phages carry AMR genes, including OXA-23 and NDM-1, illustrating the importance of lysogenic phages in the acquisition of resistance genes.
Stable Expression of a Hepatitis E Virus (HEV) RNA Replicon in Two Mammalian Cell Lines to Assess Mechanism of Innate Immunity and Antiviral Response
Authors: Xu Ling-Dong , Zhang Fei , Peng Lei , Luo Wen-Ting , Chen Chu , Xu Pinglong , Huang Yao-Wei
Published: December 2020

Hepatitis E virus (HEV) is one of the major etiological agents responsible for acute hepatitis. Hepatitis E virus does not replicate efficiently in mammalian cell cultures, thus a useful model that mimics persistent HEV replication is needed to dissect the molecular mechanism of pathogenesis. Here we report a genotype-3 HEV RNA replicon expressing an EGFP-Zeocin (EZ) resistant gene (p6-EZ) that persistently self-replicated in cell lines of human (Huh-7-S10-3) or hamster (BHK-21) origin after transfection with in vitro RNA transcripts and subsequent drug screening. Two cell lines, S10-3-EZ and BHK-21-EZ, stably expressed EGFP in the presence of Zeocin during continuous passages. Both genomic and subgenomic HEV RNAs and viral replicase proteins were stably expressed in persistent HEV replicon cells. The values of the cell models in antiviral testing, innate immune RNA sensing and type I IFN in host defense were further demonstrated. We revealed a role of RIG-I like receptor-interferon regulatory factor 3 in host antiviral innate immune sensing during HEV replication. We further demonstrated that treatment with interferon (IFN-α) or ribavirin significantly reduced expression of replicon RNA in a dose-dependent manner. The availability of the models will greatly facilitate HEV-specific antiviral development, and delineate mechanisms of HEV replication.
Development of a Dairy-Free Fermented Oat-Based Beverage With Enhanced Probiotic and Bioactive Properties
Authors: Chen Liwei , Wu Daoyan , Schlundt Joergen , Conway Patricia L.
Published: December 2020

Lactobacillus fermentum PC1 with proven probiotic properties was used to ferment oats with added honey to develop a probiotic beverage with enhanced bioactive ingredients. The viable Lactobacilli were enumerated during the fermentation and storage at 4°C, as well as after exposure to simulated gastrointestinal tract conditions. Good survival was noted both during storage as well as when exposed to the in vitro digestive tract conditions. Comparative analysis of the antioxidant activity, total phenolic content, and phenolic composition indicated fermentation improved the total antioxidant capacity and phenolic acid concentration. An increase of more than 50% of gallic acid, catechin, vanillic acid, caffeic acid, p-coumaric acid, and ferulic acid was observed in the methanol extracts. Moreover, no significant decrease in the β-glucan content was noted during fermentation and storage. In conclusion, this fermented product has a great potential as a functional food with enhanced probiotic survival and increased bioactive ingredients.
A 5-min Cognitive Task With Deep Learning Accurately Detects Early Alzheimer's Disease
Authors: Almubark Ibrahim , Chang Lin-Ching , Shattuck Kyle F. , Nguyen Thanh , Turner Raymond Scott , Jiang Xiong
Published: December 2020

Introduction: The goal of this study was to investigate and compare the classification performance of machine learning with behavioral data from standard neuropsychological tests, a cognitive task, or both.

Methods: A neuropsychological battery and a simple 5-min cognitive task were administered to eight individuals with mild cognitive impairment (MCI), eight individuals with mild Alzheimer's disease (AD), and 41 demographically match controls (CN). A fully connected multilayer perceptron (MLP) network and four supervised traditional machine learning algorithms were used.

Results: Traditional machine learning algorithms achieved similar classification performances with neuropsychological or cognitive data. MLP outperformed traditional algorithms with the cognitive data (either alone or together with neuropsychological data), but not neuropsychological data. In particularly, MLP with a combination of summarized scores from neuropsychological tests and the cognitive task achieved ~90% sensitivity and ~90% specificity. Applying the models to an independent dataset, in which the participants were demographically different from the ones in the main dataset, a high specificity was maintained (100%), but the sensitivity was dropped to 66.67%.

Discussion: Deep learning with data from specific cognitive task(s) holds promise for assisting in the early diagnosis of Alzheimer's disease, but future work with a large and diverse sample is necessary to validate and to improve this approach.