bluuebunny/crossref_metadata_2025 huggingface dataset:
Biofriendly micro/nanomotors operating on biocatalysis: from natural to biological environments
Authors: Guo Ziyi , Liu Jian , Wang Da-Wei , Xu Jiangtao , Liang Kang
Published: October 2020

Micro/nanomotors (MNMs) are tiny motorized objects that can autonomously navigate in complex fluidic environments under the influence of an appropriate source of energy. Internal energy-driven MNMs are composed of certain reactive materials that are capable of converting chemical energy from the surroundings into kinetic energy. Recent advances in smart nanomaterials design and processing have endowed the internal energy-driven MNMs with different geometrical designs and various mechanisms of locomotion, with remarkable traveling speed in diverse environments ranging from environmental water to complex body fluids. Among the different design principals, MNM systems that operate from biocatalysis possess biofriendly components, efficient energy conversion, and mild working condition, exhibiting a potential of stepping out of the proof-of-concept phase for addressing many real-life environmental and biotechnological challenges. The biofriendliness of MNMs should not only be considered for in vivo drug delivery but also for environmental remediation and chemical sensing that only environmentally friendly intermediates and degraded products are generated. This review aims to provide an overview of the recent advances in biofriendly MNM design using biocatalysis as the predominant driving force, towards practical applications in biotechnology and environmental technology.
Developing entrepreneurial education in national school curricula: lessons from North Macedonia and Wales
Authors: Penaluna Andrew , Penaluna Kathryn , Polenakovikj Radmil
Published: October 2020

In 2016, Eurydice reported that no country in Europe had fully integrated entrepreneurial education in schools and that teacher training was fragmented. However, supported by the World Bank, North Macedonia introduced a compulsory and progressively evaluated Entrepreneurship and Innovation curriculum in 2016, following policy decisions made in 2014. Teacher training initiatives from Wales informed progress. The Welsh Government decided to integrate an entrepreneurial culture within curriculum and assessment arrangements in schools which built upon prior work including education within Initial Teacher Training. This included funding to pilot training for teachers at all levels, from schools to universities and across all subject specialisms—to develop entrepreneurial education. Welsh Government’s Youth Entrepreneurship Strategy (YES) commenced in 2004 within the Ministry for Business and Transport (now Business Economy and Innovation), and since 2015, has been supported by the Ministry of Education and Skills. The sector now has 10 years of experience in entrepreneurial teacher training and has developed Doctoral-level study for educational leaders. In February 2020, the theme of ‘creative enterprising contributors’ was formally positioned as one of the four overarching ‘purposes’ of school education in Wales. This article provides reflective insights of knowledge exchange through the lens of the International Institute for Creative Entrepreneurial Development, in both a Macedonian and Welsh context, and will be of interest to those who wish to advance national policies and entrepreneurial educator development.
Brain Functional Biomarkers Distinguishing Premature Ejaculation From Anejaculation by ALFF: A Resting-State fMRI Study
Authors: Chen Jianhuai , Yang Jie , Huang Xinfei , Wang Qing , Lu Chao , Liu Shaowei , Chen Yun , Ni Liangyu
Published: October 2020

Introduction

Premature ejaculation (PE) and anejaculation (AJ) are 2 opposite disorders of male ejaculatory dysfunction. Recent studies have demonstrated that the process of ejaculation is mediated by certain neural circuits in the brain. However, different mechanisms between PE and AJ are still unclear.

Aim

Therefore, we used resting-state functional magnetic resonance imaging (fMRI) to explore the underlying neural mechanisms in patients with PE and AJ by measuring the amplitude of low-frequency fluctuations (ALFF).

Methods

Resting-state fMRI data were acquired in 17 PE, 20 AJ patients and 23 matched healthy controls (HC).

Main Outcome Measure

Differences of ALFF values among the 3 groups were compared. We also explored the correlations between brain regions showing altered ALFF values and scores of Premature Ejaculation Diagnostic Tool (PEDT) in the PE group.

Results

There were widespread differences of ALFF values among the 3 groups, which included left anterior cingulate gyrus, precentral and postcentral gyrus, paracentral lobule, superior temporal gyrus, calcarine fissure, putamen; right postcentral gyrus, paracentral lobule, middle temporal gyrus, putamen. Compared with HC, PE patients had greater ALFF in the right inferior frontal gyrus (opercular part), AJ patients had greater ALFF in the left postcentral gyrus. In addition, PE patients exhibited greater ALFF in the left Rolandic operculum, anterior cingulate gyrus, inferior frontal gyrus (orbital part), putamen, and right putamen when compared with AJ patients, as well as decreased ALFF in the right postcentral gyrus. Moreover, positive correlations were found between ALFF of left postcentral gyrus, inferior frontal gyrus (orbital part), right inferior frontal gyrus (opercular part), and PEDT scores.

Clinical Implications

The differences in central pathophysiological mechanisms between PE and AJ might be useful for improving the clinical diagnosis of ejaculation dysfunction.

Strength & Limitations

Our results showed that the method of fMRI could identify the differences of ALFF between PE and AJ and that these alterations in ALFF were related to clinical function. However, this was a relatively small sample study, and further multimodal neuroimaging studies with large samples were needed.

Conclusion

The findings demonstrated that altered ALFF of frontal, parietal cortex, and putamen might help distinguish premature ejaculation from anejaculation. Abnormal function of these brain regions might play a critical role in the physiopathology of ejaculatory dysfunction of patients.
Shakespeare and Senecan Tragedy
Authors: Perry Curtis
Published: October 2020

Shakespeare's tragic characters have often been seen as forerunners of modern personhood. It has been assumed that Shakespeare was able to invent such lifelike figures in part because of his freedom from the restrictions of classical form. Curtis Perry instead argues that characters such as Hamlet and King Lear have seemed modern to us in part because they are so robustly connected to the tradition of Senecan tragedy. Resituating Shakespearean tragedy in this way - as backward looking as well as forward looking - makes it possible to recover a crucial political dimension. Shakespeare saw Seneca as a representative voice from post-republican Rome: in plays such as Coriolanus and Othello he uses Senecan modes of characterization to explore questions of identity in relation to failures of republican community. This study has important implications for the way we understand character, community, and alterity in early modern drama.
NATURALISM AND MATERIALISM
Authors: Atkins Peter
Published: October 2020

This article explores the nature and intellectual argument for naturalism and its dependent attitude, materialism. It touches on some of the alternatives but argues that they are inferior approaches to the manner in which knowledge and understanding are obtained. It extends the argument by touching on two subsidiary questions: the role of mathematics in describing the world and the origin of the laws of Nature.
The last guardian of the throne: the regional army in the late Qing dynasty
Authors: Peng Linan
Published: October 2020

This paper investigates the organizational structure of the Xiang Army, one of the best-known regional armies in the late Qing dynasty. The army developed an organizational form to overcome problems that plagued the imperial army of the central government, namely, the poor recruitment and training of soldiers, the lack of incentives to fight in battles, and the coordination failure. This organizational structure, I argue, played a central role in the rise of the Xiang Army in the Qing dynasty.
Characteristics of Ionospheric Irregularities Using GNSS Scintillation Indices Measured at Jang Bogo Station, Antarctica (74.62°S, 164.22°E)
Authors: Hong Junseok , Chung Jong‐Kyun , Kim Yong Ha , Park Jaeheung , Kwon Hyuck‐Jin , Kim Jeong‐Han , Choi Jong‐Min , Kwak Young‐Sil
Published: October 2020

Global Navigation Satellite System (GNSS) signals strongly depend on the ionospheric conditions, which are composed of electrons and ions generated by solar radiation and particle precipitation. Ionospheric plasma irregularities may cause the scintillation of the GNSS signals or even the loss of signal lock, resulting in the reduction of positioning accuracy and timing precision. Phase scintillation phenomenon is known to occur frequently at high latitudes and primarily related to a significant plasma density gradient, which is due to fast plasma flows in the polar region, energetic particle precipitation in the auroral region, polar cap patches, or several instability mechanisms. Statistical studies are required to understand the characteristics of ionospheric (both phase and amplitude) scintillations at high latitudes. Here, we report the results of ionospheric scintillation measurements at Jang Bogo Station (JBS; 74.62°S, 164.22°E), located inside the polar cap region in Antarctica. The occurrence rates of ionospheric scintillations over the JBS are recorded for 2 years (2017–2018) during solar minimum conditions. The occurrence rates of amplitude scintillations increase only at lower elevation angles (below 30°), which are hard to determine whether the source is ionospheric irregularity or ambient noise such as multipath. In contrast, the occurrence rates of phase scintillations depend on the azimuth angle, season, magnetic activity, magnetic local time, and signal frequency. The results of our analysis suggest that users of the GNSS should consider these parameters to prepare for the degradation of the GNSS performance at high latitudes in the Southern Hemisphere.
Microtechnology-based methods for organoid models
Authors: Velasco Vanessa , Shariati S. Ali , Esfandyarpour Rahim
Published: October 2020

Innovations in biomaterials and stem cell technology have allowed for the emergence of novel three-dimensional (3D) tissue-like structures known as organoids and spheroids. As a result, compared to conventional 2D cell culture and animal models, these complex 3D structures have improved the accuracy and facilitated in vitro investigations of human diseases, human development, and personalized medical treatment. Due to the rapid progress of this field, numerous spheroid and organoid production methodologies have been published. However, many of the current spheroid and organoid production techniques are limited by complexity, throughput, and reproducibility. Microfabricated and microscale platforms (e.g., microfluidics and microprinting) have shown promise to address some of the current limitations in both organoid and spheroid generation. Microfabricated and microfluidic devices have been shown to improve nutrient delivery and exchange and have allowed for the arrayed production of size-controlled culture areas that yield more uniform organoids and spheroids for a higher throughput at a lower cost. In this review, we discuss the most recent production methods, challenges currently faced in organoid and spheroid production, and microfabricated and microfluidic applications for improving spheroid and organoid generation. Specifically, we focus on how microfabrication methods and devices such as lithography, microcontact printing, and microfluidic delivery systems can advance organoid and spheroid applications in medicine.
Single-electron detection utilizing coupled nonlinear microresonators
Authors: Wang Xuefeng , Wei Xueyong , Pu Dong , Huan Ronghua
Published: October 2020

Since the discovery of the electron, the accurate detection of electrical charges has been a dream of the scientific community. Owing to some remarkable advantages, micro/nanoelectromechanical system-based resonators have been used to design electrometers with excellent sensitivity and resolution. Here, we demonstrate a novel ultrasensitive charge detection method utilizing nonlinear coupling in two micromechanical resonators. We achieve single-electron charge detection with a high resolution up to 0.197 ± 0.056 $${\mathrm{e}}/\sqrt {{\mathrm{Hz}}}$$

e
/

Hz

at room temperature. Our findings provide a simple strategy for measuring electron charges with extreme accuracy.
Flexible and reconfigurable radio frequency electronics realized by high-throughput screen printing of vanadium dioxide switches
Authors: Li Weiwei , Vaseem Mohammad , Yang Shuai , Shamim Atif
Published: October 2020

Smart materials that can change their properties based on an applied stimulus are in high demand due to their suitability for reconfigurable electronics, such as tunable filters or antennas. In particular, materials that undergo a metal–insulator transition (MIT), for example, vanadium dioxide (VO2) (M), are highly attractive due to their tunable electrical and optical properties at a low transition temperature of 68 °C. Although deposition of this material on a limited scale has been demonstrated through vacuum-based fabrication methods, its scalable application for large-area and high-volume processes is still challenging. Screen printing can be a viable option because of its high-throughput fabrication process on flexible substrates. In this work, we synthesize high-purity VO2 (M) microparticles and develop a screen-printable VO2 ink, enabling the large-area and high-resolution printing of VO2 switches on various substrates. The electrical properties of screen-printed VO2 switches at the microscale are thoroughly investigated under both thermal and electrical stimuli, and the switches exhibit a low ON resistance of 1.8 ohms and an ON/OFF ratio of more than 300. The electrical performance of the printed switches does not degrade even after multiple bending cycles and for bending radii as small as 1 mm. As a proof of concept, a fully printed and mechanically flexible band-pass filter is demonstrated that utilizes these printed switches as reconfigurable elements. Based on the ON and OFF conditions of the VO2 switches, the filter can reconfigure its operating frequency from 3.95 to 3.77 GHz without any degradation in performance during bending.
Species-specific differences in synaptic transmission and plasticity
Authors: Beed Prateep , Ray Saikat , Velasquez Laura Moreno , Stumpf Alexander , Parthier Daniel , Swaminathan Aarti , Nitzan Noam , Breustedt Jörg , Las Liora , Brecht Michael , Schmitz Dietmar
Published: October 2020

Synaptic transmission and plasticity in the hippocampus are integral factors in learning and memory. While there has been intense investigation of these critical mechanisms in the brain of rodents, we lack a broader understanding of the generality of these processes across species. We investigated one of the smallest animals with conserved hippocampal macroanatomy—the Etruscan shrew, and found that while synaptic properties and plasticity in CA1 Schaffer collateral synapses were similar to mice, CA3 mossy fiber synapses showed striking differences in synaptic plasticity between shrews and mice. Shrew mossy fibers have lower long term plasticity compared to mice. Short term plasticity and the expression of a key protein involved in it, synaptotagmin 7 were also markedly lower at the mossy fibers in shrews than in mice. We also observed similar lower expression of synaptotagmin 7 in the mossy fibers of bats that are evolutionarily closer to shrews than mice. Species specific differences in synaptic plasticity and the key molecules regulating it, highlight the evolutionary divergence of neuronal circuit functions.
Area under the expiratory flow-volume curve: predicted values by artificial neural networks
Authors: Ioachimescu Octavian C. , Stoller James K. , Garcia-Rio Francisco
Published: October 2020

Area under expiratory flow-volume curve (AEX) has been proposed recently to be a useful spirometric tool for assessing ventilatory patterns and impairment severity. We derive here normative reference values for AEX, based on age, gender, race, height and weight, and by using artificial neural network (ANN) algorithms. We analyzed 3567 normal spirometry tests with available AEX values, performed on subjects from two countries (United States and Spain). Regular linear or optimized regression and ANN models were built using traditional predictors of lung function. The ANN-based models outperformed the de novo regression-based equations for AEXpredicted and AEX z scores using race, gender, age, height and weight as predictor factors. We compared these reference values with previously developed equations for AEX (by gender and race), and found that the ANN models led to the most accurate predictions. When we compared the performance of ANN-based models in derivation/training, internal validation/testing, and external validation random groups, we found that the models based on pooling samples from various geographic areas outperformed the other models (in both central tendency and dispersion of the residuals, ameliorating any cohort effects). In a geographically diverse cohort of subjects with normal spirometry, we computed by both regression and ANN models several predicted equations and z scores for AEX, an alternative measurement of respiratory function. We found that the dynamic nature of the ANN allows for continuous improvement of the predictive models’ performance, thus promising that the AEX could become an essential tool in assessing respiratory impairment.
Silk-sericin Nano-drug Delivery Systems
Authors: Orlandi Giulia , Bari Elia
Published: October 2020

The excellent biocompatibility, controllable biodegradability, non-immunogenicity and intrinsic biological activity, make silk sericin an ideal candidate for the formulation of drug delivery systems. Unfortunately, nanoparticles, nanocapsules or nanofibers based on silk sericin “alone” cannot be produced due to its physicochemical instability, influenced by the high water solubility. For this reason, cross-linking, blending, or combination with other polymers/compounds is required. This chapter provides an overview of the main preparation methods of sericin-based nanoparticles and nanofibers, as reported in the literature. Their applications, both in vitro and in vivo, are also described.
Physico-chemical Characterisation of Silk-based Materials
Authors: Catenacci Laura , Sorrenti Milena
Published: October 2020

Physico-chemical characterisation is essential to define and to assure quality, safety and efficacy of silk-based materials when intended for pharmaceutical and biomedical use. In fact, the possible interconversion and interactions between the various conformations of the fibroin and sericin, and the transitions from the most stable crystalline forms to the metastable amorphous ones, can modify (i) the release properties of the drugs from the silk-based delivery systems, (ii) the silk-based carrier's superficial properties, determining the targeting mechanisms to the site of action. Thermal analysis and spectrophotometric methods, supported by X-ray diffraction analysis and microscopic techniques, are useful to characterise the main crystal structures and the three conformations, Silk I, Silk II and unstable Silk III, of proteins. This chapter reports some applicative examples of the analyses performed with these techniques concerning the characterisation of silk proteins and silk-based micro/nano-drug delivery systems.
The equilibrium potentials of Ni–Ln alloys over the whole composition range in the phase diagram: experiment and prediction
Authors: Xu Hengbin , Zhang Milin , Yan Yongde , Sun Xin , Qiu Min , Chen Jiaming
Published: October 2020

The phase diagrams and equilibrium potentials of complex systems are of great importance for the material development and processing optimization.
Hierarchical-metal–organic framework-templated Cu0.5Zn0.5In2S4-rGO-g-C3N4: flexible synthesis and enhanced photocatalytic activity
Authors: Xu Mei-Ling , Liu Ling-Wang , Wang Kai , Dou Yi-Chuan , Li Kui , Cheng Xin , Zhang Feng-Ming
Published: October 2020

The g-C3N4-rGO nanosheets are uniformly inserted into hollow Cu0.5Zn0.5In2S4 quaternary sulfide derived from ZnCu-MIM@In-PTA hierarchical-MOFs, which illustrates excellent photocatalytic hydrogen evolution rate even in pure water.
Gate-tunable two-dimensional superconductivity revealed in flexible wafer-scale hybrid structures
Authors: Han Xiaowen , Gao Min , Wu Yufeng , Mu Gang , Zhang Miao , Mei Yongfeng , Chu Paul K. , Xie Xiaoming , Hu Tao , Di Zengfeng
Published: October 2020

Wafer-scale flexible superconducting devices are constructed on a two-dimensional (2D) superconducting system consisting of superconducting discrete Pb nano-islands and single-crystalline graphene on a stretchable parylene C substrate.
Theoretical investigation of oscillator strengths and lifetimes in Ti II
Authors: Li W. , Hartman H. , Wang K. , Jönsson P.
Published: October 2020

Aims. Accurate atomic data for Ti II are essential for abundance analyses in astronomical objects. The aim of this work is to provide accurate and extensive results of oscillator strengths and lifetimes for Ti II.

Methods. The multiconfiguration Dirac–Hartree–Fock and relativistic configuration interaction (RCI) methods, which are implemented in the general-purpose relativistic atomic structure package GRASP2018, were used in the present work. In the final RCI calculations, the transverse-photon (Breit) interaction, the vacuum polarisation, and the self-energy corrections were included.

Results. Energy levels and transition data were calculated for the 99 lowest states in Ti II. Calculated excitation energies are found to be in good agreement with experimental data from the Atomic Spectra Database of the National Institute of Standards and Technology based on the study by Huldt et al. Lifetimes and transition data, for example, line strengths, weighted oscillator strengths, and transition probabilities for radiative electric dipole (E1), magnetic dipole (M1), and electric quadrupole (E2) transitions, are given and extensively compared with the results from previous calculations and measurements, when available. The present theoretical results of the oscillator strengths are, overall, in better agreement with values from the experiments than the other theoretical predictions. The computed lifetimes of the odd states are in excellent agreement with the measured lifetimes. Finally, we suggest a relabelling of the 3d2(12D)4p y2 D3/2o and z2 P3/2o levels.
Cloud Image Classification Method Based on Deep Convolutional Neural Network
Authors: Zhang Fei , Yan Jie
Published: October 2020

Compared with satellite remote sensing images, ground-based invisible images have limited swath, but featured in higher resolution, more distinct cloud features, and the cost is greatly reduced, conductive to continuous meteorological observation of local areas. For the first time, this paper proposed a high-resolution cloud image classification method based on deep learning and transfer learning technology for ground-based invisible images. Due to the limited amount of samples, traditional classifiers such as support vector machine can't effectively extract the unique features of different types of clouds, and directly training deep convolutional neural networks leads to over-fitting. In order to prevent the network from over-fitting, this paper proposed applying transfer learning method to fine-tune the pre-training model. The proposed network achieved as high as 85.19% test accuracy on 6-type cloud images classification task. The networks proposed in this paper can be applied to classify digital photos captured by cameras directly, which will reduce the cost of system greatly.
The Analysis for Source Aerosol Optical Properties and Long Range Transportation of Dust Storm in Winter
Authors: Wang Lifang , Qin Fuqiang , Shao Shiyong
Published: October 2020

By the combination of ground detection and satellite, the source and development process of strong dust storm in the northwest provinces, including Xinjiang, Gansu, Neimenggu, Ningxia, etc., occurred in November 17 to 18, 2016, is discussed by using the optical properties of aerosols. The ground detection equipments were used to measure the extinction coefficient and optical depth of dust aerosol near the source. The evolution path, formation process and cause of dissipation of dust storm were analyzed by satellite data. The reason why dust storm is not easy to spread to the eastern part of China is preliminarily given.
Rationale Therapieentscheidungen bei Intensivpatienten
Authors: Riessen Reimer , Haap Michael , Marckmann Georg , Mahling Moritz
Published: October 2020

Was ist neu?

Zeitlich begrenzter Therapieversuch (Time-limited Trial, TLT) Kann die Entscheidung für oder gegen eine Intensivtherapie nicht unmittelbar getroffen werden, ist die zeitlich begrenzte Behandlung auf einer Intensivstation eine gute Strategie, um im Verlauf die erforderlichen prognostischen Informationen für die Entscheidung zu gewinnen.

Prognosefaktoren im Rahmen einer Intensivbehandlung Die Kenntnis von Prognosefaktoren ist für ein informiertes Patientengespräch relevant. Während das kurzfristige Überleben maßgeblich vom Schweregrad der akuten Erkrankung bestimmt wird, haben Alter und Komorbiditäten einen großen Einfluss auf das langfristige Überleben. Die aus diesen Faktoren resultierende Gebrechlichkeit (Frailty) beeinflusst ebenfalls wesentlich die langfristige Prognose.

Konzept für die Entscheidungshilfe bei knappen Ressourcen Stehen nicht ausreichend Ressourcen zur Versorgung aller Patienten zur Verfügung, muss unter dem ärztlichen Handlungsprinzip der Gerechtigkeit eine Priorisierung der Patienten erfolgen. Die aktuellen Leitlinien schlagen in solchen Situationen (z. B. im Rahmen der COVID-19-Pandemie) vor, sich hierbei primär am Kriterium der klinischen Erfolgsaussicht zu orientieren.
The Role of Alpha Defensins in Patients with Ankylosing Spondylitis
Authors: Oktayoglu Pelin , Mete Nuriye , Caglayan Mehmet
Published: October 2020

Objectives Defensins are a family of antimicrobial peptides. Elevated levels of human neutrophil peptides (HNP 1–3) are seen in blood samples of patients with inflammatory bowel disease (IBD) and in many rheumatic diseases. It has been suggested that they may play a significant role in the progression and pathogenesis of these diseases. Therefore, we aimed to investigate the levels of HNP 1–3 in sera of patients with ankylosing spondylitis (AS) and its association with disease activity and other clinical features of AS.

Methods A total of 36 patients, who met the Modified New York Criteria for AS, and 50 healthy controls (HCs) were included in this study. The Bath AS Disease Activity Index (BASDAI) and the Ankylosing Spondylitis Disease Activity Score (ASDAS) were used to assess disease activity. The Bath AS Radiology Index (BASRI) was used to assess radiological damage. Spinal and hip measurements were determined by the Bath AS Metrology Index (BASMI). An AS Quality of Life (ASQoL) questionnaire was administered to assess the disease-related quality of life. Serum HNP 1–3 levels were determined using the ELISA kit.

Results Mean serum HNP 1–3 levels were significantly higher in patients with AS (287.01±201.307 vs. 152.09±43.75 pg/ml) compared with HCs (p=0.001). HNP 1–3 levels did not correlate with BASDAI (p=0.519), ASDAS-CRP (p=0.424), BASRI (p=0.280), BASMI (p=0.168), ASQoL (p=0.307), ESR (p=0.706) and CRP (p=0.157) values.

Conclusion Elevated serum levels of HNP 1–3 may play an important role in the pathogenetic mechanisms of AS. This result may give us an opportunity to develop new treatment strategies considering the role of these peptides in the pathogenetic mechanisms of AS.
Summer irrigation of pasture enhances the transfer and short-term storage of soil organic carbon in the particulate and mineral-associated organic matter fractions
Authors: Carmona Carmen R. , Clough Timothy J. , Beare Michael H. , McNally Samuel R.
Published: October 2020

Soil organic carbon (SOC) is both a source and sink of atmospheric carbon dioxide (CO2), with important implications for global climate change. Irrigation of grazed pastures has reportedly increased, reduced or made no difference to SOC stocks relative to dryland management. This study examined, over an annual plant growth cycle, the persistence of photosynthate-derived carbon (C) previously allocated to the plant–soil system during summer, under irrigated or dryland conditions. A continuous 13CO2 pulse labelling method was used to label ryegrass (Lolium perenne L.) and white clover (Trifolium repens L.) mesocosms under simulated dryland or irrigated conditions. Plant and soil 13C was traced over 349 days using destructive sampling on days 1, 12, 125, 237 and 349 (T1–T5 respectively). After the cessation of labelling and summer irrigation, the mesocosms were maintained under the same seasonal soil moisture conditions. The persistence of 13C in the aboveground plant C pools was lower than in the root C pool. Approximately 50% of the initial mass of 13C recovered in roots at T1 remained by T5. There was no difference between the summer irrigated and dryland treatments in terms of the 13C recovered from the soil over the subsequent annual growing season. There was also no significant change in the 13C recovered in the soil between T1 and T5. However, summer irrigation did affect the spatial and temporal distribution of the photosynthate-derived C within the soil size fractions relative to summer dryland conditions. Summer irrigation promoted the transfer and storage of 13C in the fine particulate organic matter and clay size fractions.
Posttranscriptional regulation of human endogenous retroviruses by RNA-binding motif protein 4, RBM4
Authors: Foroushani Amir K. , Chim Bryan , Wong Madeline , Rastegar Andre , Smith Patrick T. , Wang Saifeng , Barbian Kent , Martens Craig , Hafner Markus , Muljo Stefan A.
Published: October 2020

Significance

The expression of endogenous retroviruses (ERVs) appears to have broad impact on human biology. Nevertheless, only a handful of transcriptional or posttranscriptional regulators of ERV expression are known. We implemented a computational pipeline that allowed us to identify RNA-binding proteins (RBPs) that modulate ERV expression levels. Experimental validation of one of the prime candidates we identified, RNA-binding motif protein 4 (RBM4), showed that it indeed bound RNAs made from ERVs and negatively regulated the levels of those RNAs. We hereby identify a layer of ERV regulation by RBPs. We suspect that this work on RBM4 is only the beginning in recognizing a broader set among the >1,500 human RBPs that act on transcripts derived from endogenous and exogenous viruses.
Myeloid/Lymphoid Neoplasms Associated With Eosinophilia and Rearrangements of PDGFRA, PDGFRB, or FGFR1 or With PCM1-JAK2
Authors: Pozdnyakova Olga , Orazi Attilio , Kelemen Katalin , King Rebecca , Reichard Kaaren K , Craig Fiona E , Quintanilla-Martinez Leticia , Rimsza Lisa , George Tracy I , Horny Hans-Peter , Wang Sa A
Published: October 2020

Objectives

To summarize cases submitted to the 2019 Society for Hematopathology/European Association for Haematopathology Workshop under the category of myeloid/lymphoid neoplasms with eosinophilia and PDGFRA, PDGFRB, or FGFR1 or with PCM1-JAK2 rearrangements, focusing on recent updates and relevant practice findings.

Methods

The cases were summarized according to their respective gene rearrangement to illustrate the spectrum of clinical, laboratory, and histopathology manifestations and to explore the appropriate molecular genetic tests.

Results

Disease presentations were heterogeneous, including myeloproliferative neoplasms (MPNs), myelodysplastic syndromes (MDSs), MDS/MPN, acute myeloid leukemia, acute B- or T-lymphoblastic lymphoma/acute lymphoblastic lymphoma (ALL/LBL), or mixed-lineage neoplasms. Frequent extramedullary involvement occurred. Eosinophilia was common but not invariably present. With the advancement of RNA sequencing, cryptic rearrangements were recognized in genes other than PDGFRA. Additional somatic mutations were more frequent in the FGFR1-rearranged cases. Cases with B-ALL presentations differed from Philadelphia-like B-ALL by the presence of an underlying MPN. Cases with FLT3 and ABL1 rearrangements could be potential candidates for future inclusion in this category.

Conclusions

Accurate diagnosis and classification of this category of myeloid/lymphoid neoplasms has important therapeutic implications. With the large number of submitted cases, we expand our understanding of these rare neoplasms and improve our ability to diagnose these genetically defined disorders.
Serum ACE2, Angiotensin II, and Aldosterone Levels Are Unchanged in Patients With COVID-19
Authors: Rieder Marina , Wirth Luisa , Pollmeier Luisa , Jeserich Maren , Goller Isabella , Baldus Niklas , Schmid Bonaventura , Busch Hans-Joerg , Hofmann Maike , Kern Winfried , Bode Christoph , Duerschmied Daniel , Lother Achim
Published: October 2020

Background

The role of the renin–angiotensin–aldosterone system (RAAS) in coronavirus disease 2019 (COVID-19) is controversially discussed. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) enters host cells by binding to angiotensin-converting enzyme 2 (ACE2) and activity of the RAAS may affect susceptibility to SARS-CoV-2 infection and outcome of patients with COVID-19.

Methods

In this prospective single-center study, we determined the serum levels of ACE2, angiotensin II, and aldosterone in patients with COVID-19 compared with control patients presenting with similar symptoms in the emergency unit.

Results

We analyzed serum samples from 24 SARS-CoV-2 positive and 61 SARS-CoV-2 negative patients. SARS-CoV-2 positive and control patients did not differ in baseline patients characteristics, symptoms, and clinical presentation. Mean serum concentrations of ACE2, angiotensin II, and aldosterone did not differ between the SARS-CoV-2 positive and the control group. In line with this, serum potassium as surrogate parameter for RAAS activity and blood pressure were similar in both groups.

Conclusions

In summary, we did not find evidence for altered RAAS activity including angiotensin II, aldosterone, or potassium levels, and blood pressure in patients with COVID-19.

Clinical trials registration

Trial Number DRKS00021206.
A review on drug repurposing applicable to COVID-19
Authors: Dotolo Serena , Marabotti Anna , Facchiano Angelo , Tagliaferri Roberto
Published: October 2020

Drug repurposing involves the identification of new applications for existing drugs at a lower cost and in a shorter time. There are different computational drug-repurposing strategies and some of these approaches have been applied to the coronavirus disease 2019 (COVID-19) pandemic. Computational drug-repositioning approaches applied to COVID-19 can be broadly categorized into (i) network-based models, (ii) structure-based approaches and (iii) artificial intelligence (AI) approaches. Network-based approaches are divided into two categories: network-based clustering approaches and network-based propagation approaches. Both of them allowed to annotate some important patterns, to identify proteins that are functionally associated with COVID-19 and to discover novel drug–disease or drug–target relationships useful for new therapies. Structure-based approaches allowed to identify small chemical compounds able to bind macromolecular targets to evaluate how a chemical compound can interact with the biological counterpart, trying to find new applications for existing drugs. AI-based networks appear, at the moment, less relevant since they need more data for their application.
A parsimonious personalized dose-finding model via dimension reduction
Authors: Zhou Wenzhuo , Zhu Ruoqing , Zeng Donglin
Published: October 2020

Learning an individualized dose rule in personalized medicine is a challenging statistical problem. Existing methods often suffer from the curse of dimensionality, especially when the decision function is estimated nonparametrically. To tackle this problem, we propose a dimension reduction framework that effectively reduces the estimation to an optimization on a lower-dimensional subspace of the covariates. We exploit the fact that the individualized dose rule can be defined in a subspace spanned by a few linear combinations of the covariates to obtain a more parsimonious model. Owing to direct maximization of the value function, the proposed framework does not require the inverse probability of the propensity score under observational studies. This distinguishes our approach from the outcome-weighted learning framework, which also solves decision rules directly. Within the same framework, we further propose a pseudo-direct learning approach that focuses more on estimating the dimensionality-reduced subspace of the treatment outcome. Parameters in both approaches can be estimated efficiently using an orthogonality-constrained optimization algorithm on the Stiefel manifold. Under mild regularity assumptions, results on the asymptotic normality of the proposed estimators are established. We also derive the consistency and convergence rate of the value function under the estimated optimal dose rule. We evaluate the performance of the proposed approaches through extensive simulation studies and analysis of a pharmacogenetic dataset.
Dietary carbohydrates restriction inhibits the development of cardiac hypertrophy and heart failure
Authors: Nakamura Michinari , Odanovic Natalija , Nakada Yasuki , Dohi Satomi , Zhai Peiyong , Ivessa Andreas , Yang Zhi , Abdellatif Maha , Sadoshima Junichi
Published: October 2020

Aims

A diet with modified components, such as a ketogenic low-carbohydrate (LC) diet, potentially extends longevity and healthspan. However, how an LC diet impacts on cardiac pathology during haemodynamic stress remains elusive. This study evaluated the effects of an LC diet high in either fat (Fat-LC) or protein (Pro-LC) in a mouse model of chronic hypertensive cardiac remodelling.

Methods and results

Wild-type mice were subjected to transverse aortic constriction, followed by feeding with the Fat-LC, the Pro-LC, or a high-carbohydrate control diet. After 4 weeks, echocardiographic, haemodynamic, histological, and biochemical analyses were performed. LC diet consumption after pressure overload inhibited the development of pathological hypertrophy and systolic dysfunction compared to the control diet. An anti-hypertrophic serine/threonine kinase, GSK-3β, was re-activated by both LC diets; however, the Fat-LC, but not the Pro-LC, diet exerted cardioprotection in GSK-3β cardiac-specific knockout mice. β-hydroxybutyrate, a major ketone body in mammals, was increased in the hearts of mice fed the Fat-LC, but not the Pro-LC, diet. In cardiomyocytes, ketone body supplementation inhibited phenylephrine-induced hypertrophy, in part by suppressing mTOR signalling.

Conclusion

Strict carbohydrate restriction suppresses pathological cardiac growth and heart failure after pressure overload through distinct anti-hypertrophic mechanisms elicited by supplemented macronutrients.
Haploinsufficiency ofTmem43in cardiac myocytes activates the DNA damage response pathway leading to a late-onset senescence-associated pro-fibrotic cardiomyopathy
Authors: Rouhi Leila , Cheedipudi Sirisha M , Chen Suet Nee , Fan Siyang , Lombardi Raffaella , Chen Xiaofan , Coarfa Cristian , Robertson Matthew J , Gurha Priyatansh , Marian Ali J
Published: October 2020

Aims

Arrhythmogenic cardiomyopathy (ACM) encompasses a genetically heterogeneous group of myocardial diseases whose manifestations are sudden cardiac death, cardiac arrhythmias, heart failure, and in a subset fibro-adipogenic infiltration of the myocardium. Mutations in the TMEM43 gene, encoding transmembrane protein 43 (TMEM43) are known to cause ACM. The purpose of the study was to gain insights into the molecular pathogenesis of ACM caused by TMEM43 haploinsufficiency.

Methods and results

The Tmem43 gene was specifically deleted in cardiac myocytes by crossing the Myh6-Cre and floxed Tmem43 mice. Myh6-Cre:Tmem43W/F mice showed an age-dependent phenotype characterized by an increased mortality, cardiac dilatation and dysfunction, myocardial fibrosis, adipogenesis, and apoptosis. Sequencing of cardiac myocyte transcripts prior to and after the onset of cardiac phenotype predicted early activation of the TP53 pathway. Increased TP53 activity was associated with increased levels of markers of DNA damage response (DDR), and a subset of senescence-associated secretary phenotype (SASP). Activation of DDR, TP53, SASP, and their selected downstream effectors, including phospho-SMAD2 and phospho-SMAD3 were validated by alternative methods, including immunoblotting. Expression of SASP was associated with epithelial–mesenchymal transition and age-dependent expression of myocardial fibrosis and apoptosis in the Myh6-Cre:Tmem43W/F mice.

Conclusion

TMEM43 haploinsufficiency is associated with activation of the DDR and the TP53 pathways, which lead to increased expression of SASP and an age-dependent expression of a pro-fibrotic cardiomyopathy. Given that TMEM43 is a nuclear envelope protein and our previous data showing deficiency of another nuclear envelope protein, namely lamin A/C, activates the DDR/TP53 pathway, we surmise that DNA damage is a shared mechanism in the pathogenesis of cardiomyopathies caused by mutations involving nuclear envelope proteins.
A different type of acute myocarditis: a case report of acute autoimmune myocarditis mediated by anti-PD-1 T lymphocyte receptor (pembrolizumab)
Authors: Salido Iniesta Mario , López López Laura , Carreras Costa Francesc , Sionis Alessandro
Published: October 2020

Background 

Pembrolizumab is an immune check-point inhibitor (ICI), which acts by blocking the T lymphocyte PD-1 inhibitor receptor. It has been increasingly used in advanced or non-responsive tumours with promising results. However, acute myocarditis is an infrequent but potentially life-threatening autoimmune adverse effect related to ICIs.

Case summary 

This case deals with a 69-year-old gentleman on second-line therapy with pembrolizumab for advanced non-small cell lung cancer. Three weeks after first dose, the patient was diagnosed with an autoimmune hepatitis, treated with decreasing corticoid dosage, followed by acute heart failure. On admission, his electrocardiogram (ECG) showed diffuse repolarization changes and a transthoracic echocardiography revealed severe left ventricle impairment (left ventricular ejection fraction 32%). High-sensitivity cardiac troponin was elevated and a coronary angiogram was performed showing non-significant obstructive disease. An autoimmune myocarditis was suspected, and high-dose intravenous corticoid, intravenous vasodilators, and loop diuretics were started with favourable response. Cardiac magnetic resonance (CMR) imaging, performed 2 weeks after clinical onset, revealed extracellular oedema in the anteroseptal-apical left ventricle segments. A new transthoracic echocardiography, performed after 3 months, showed preserved left ventricle ejection fraction. Finally, the patient was readmitted due to an autoimmune myasthenia-like syndrome.

Discussion 

Acute autoimmune myocarditis related to ICIs is a challenging diagnosis and its incidence has been underestimated in early studies. Endomyocardial biopsy (EMB) is the gold standard test for its diagnosis. Nevertheless, a definite myocarditis diagnosis is possible without EMB when characteristic clinical syndrome, elevated myonecrosis markers, and electrocardiographic, echocardiographic, and CMR changes are present together.
Mitochondrial Genome Evolution of Placozoans: Gene Rearrangements and Repeat Expansions
Authors: Miyazawa Hideyuki , Osigus Hans-Jürgen , Rolfes Sarah , Kamm Kai , Schierwater Bernd , Nakano Hiroaki
Published: October 2020

Placozoans, nonbilaterian animals with the simplest known metazoan bauplan, are currently classified into 20 haplotypes belonging to three genera, Polyplacotoma, Trichoplax, and Hoilungia. The latter two comprise two and five clades, respectively. In Trichoplax and Hoilungia, previous studies on six haplotypes belonging to four different clades have shown that their mtDNAs are circular chromosomes of 32–43 kb in size, which encode 12 protein-coding genes, 24 tRNAs, and two rRNAs. These mitochondrial genomes (mitogenomes) also show unique features rarely seen in other metazoans, including open reading frames (ORFs) of unknown function, and group I and II introns. Here, we report seven new mitogenomes, covering the five previously described haplotypes H2, H17, H19, H9, and H11, as well as two new haplotypes, H23 (clade III) and H24 (clade VII). The overall gene content is shared between all placozoan mitochondrial genomes, but genome sizes, gene orders, and several exon–intron boundaries vary among clades. Phylogenomic analyses strongly support a tree topology different from previous 16S rRNA analyses, with clade VI as the sister group to all other Hoilungia clades. We found small inverted repeats in all 13 mitochondrial genomes of the Trichoplax and Hoilungia genera and evaluated their distribution patterns among haplotypes. Because Polyplacotoma mediterranea (H0), the sister to the remaining haplotypes, has a small mitochondrial genome with few small inverted repeats and ORFs, we hypothesized that the proliferation of inverted repeats and ORFs substantially contributed to the observed increase in the size and GC content of the Trichoplax and Hoilungia mitochondrial genomes.
When I Learn the News is False: How Fact-Checking Information Stems the Spread of Fake News Via Third-Person Perception
Authors: Chung Myojung , Kim Nuri
Published: October 2020

While fact-checking has received much attention as a potential tool to combat fake news, whether and how fact-checking information lessens intentions to share fake news on social media remains underexplored. Two experiments uncovered a theoretical mechanism underlying the effect of fact-checking on sharing intentions, and identified an important contextual cue (i.e., social media metrics) that interacts with fact-checking effects. Exposure to fake news with fact-checking information (vs. fake news without fact-checking information) yielded more negative evaluations of the news and a greater belief that others are more influenced by the news than oneself (third-person perception [TPP]). Increased TPP, in turn, led to weaker intentions to share fake news on social media. Fact-checking information also nullified the effect of social media metrics on sharing intentions; without fact-checking information, higher (vs. lower) social media metrics induced greater intentions to share the news. However, when fact-checking debunked the news, such an effect disappeared.