bluuebunny/crossref_metadata_2025_split huggingface dataset:
Screening cardiovascular patients for aortic aneurysms (SCAN) – high prevalence of abdominal aortic aneurysms in coronary heart disease patients requiring intervention
Authors: Reutersberg Benedikt , Salvermoser Michael , Haller Bernhard , Schäffer Christoph , Knipfer Eva , Laugwitz Karl-Ludwig , Eckstein Hans-Henning 
Published: July 2020

Summary: Background: Since the prevalence of abdominal aortic aneurysms (AAA) in Europe has declined to about 2.5%, general screening programs of elderly men are being called into question. On the other hand, other vascular diseases (e.g. coronary heart disease, CHD) are associated with a higher prevalence of AAA. This might have an impact on future targeted AAA screening programs. This study aimed to reevaluate the current prevalence of AAA in male patients with CHD, in order to assess whether CHD patients should be offered a targeted AAA ultrasound screening program. Patients and methods: The SCAN (Screening Cardiovascular Patients for Aortic Aneurysms) study prospectively evaluated the AAA prevalence in 1000 consecutive male CHD patients (70.1 ± 11.2 years) requiring any coronary intervention at an university hospital. All patients received transverse and longitudinal ultrasound scans of the abdominal aorta. Aortic diameter was assessed using the outer-to-outer measurement-technique. Primary endpoint was the prevalence of AAA. Secondary outcomes included stratification in 1-, 2-, or 3-vessel CHD. Results: AAA was detected in 85 patients (median diameter 38 mm, range 30–80 mm), corresponding to an overall prevalence of 8.5%. AAA prevalence was significantly associated with CHD severity: 5.6% in 1-vessel, 7.1% in 2-vessel, and 10.8% in 3-vessel CHD (P = 0.037). The multivariable analysis showed, that age per 10 years increase (OR 1.5, 95% CI 1.2–1.9, P = 0.001) and hyperlipidemia (OR 2.2, 95% CI 1.3–3.8, P = 0.003) were significantly associated with an AAA. The likelihood to be diagnosed with an AAA was significantly lower in non-smokers (OR 0.24, 95% CI, P < 0.001). Conclusions: This study confirms that CHD requiring any type of coronary intervention is strongly associated with AAA in male patients. AAA prevalence increases with CHD severity. Since the AAA prevalence is still significantly higher than in the general population, targeted ultrasound screening should be considered for all CHD patients.
Personality and Dementia Risk in England and Australia
Authors: Aschwanden Damaris , Sutin Angelina R. , Luchetti Martina , Stephan Yannick , Terracciano Antonio 
Published: July 2020

Abstract. Evidence for the relationship between personality and dementia risk comes mainly from American samples. We tested whether personality-dementia links extend to populations from England and Australia. Data from the English Longitudinal Study of Ageing (ELSA; N = 6,887; Follow-up mean: 5.64 years) and the Household, Income and Labour Dynamics in Australia (HILDA; N = 2,778; Follow-up mean: 10.96 years) were analyzed using Cox PH models. In both samples, higher Neuroticism was associated with increased dementia risk. In ELSA, lower Conscientiousness was related to increased risk. In HILDA, Conscientiousness had a similar effect but did not reach statistical significance. The present work found a consistent association for Neuroticism and suggests similar personality-dementia links across demographic groups and high-income countries.
The Mosquito, the Virus, the Climate: An Unforeseen Réunion in 2018
Authors: DiSera Laurel , Sjödin Henrik , Rocklöv Joacim , Tozan Yesim , Súdre Bertrand , Zeller Herve , Muñoz Ángel G. 
Published: July 2020

AbstractThe 2018 outbreak of dengue in the French overseas department of Réunion was unprecedented in size and spread across the island. This research focuses on the cause of the outbreak, asserting that climate played a large role in the proliferation of the Aedes albopictus mosquitoes, which transmitted the disease, and led to the dengue outbreak in early 2018. A stage‐structured model was run using observed temperature and rainfall data to simulate the life cycle and abundance of the Ae. albopictus mosquito. Further, the model was forced with bias‐corrected subseasonal forecasts to determine if the event could have been forecast up to 4 weeks in advance. With unseasonably warm temperatures remaining above 25°C, along with large tropical‐cyclone‐related rainfall events accumulating 10–15 mm per event, the modeled Ae. albopictus mosquito abundance did not decrease during the second half of 2017, contrary to the normal behavior, likely contributing to the large dengue outbreak in early 2018. Although subseasonal forecasts of rainfall for the December–January period in Réunion are skillful up to 4 weeks in advance, the outbreak could only have been forecast 2 weeks in advance, which along with seasonal forecast information could have provided enough time to enhance preparedness measures. Our research demonstrates the potential of using state‐of‐the‐art subseasonal climate forecasts to produce actionable subseasonal dengue predictions. To the best of the authors' knowledge, this is the first time subseasonal forecasts have been used this way.
Historical Evaluation and Future Projections of 100‐m Wind Energy Potentials Over CORDEX‐East Asia
Authors: Li Delei , Feng Jianlong , Dosio Alessandro , Qi Jifeng , Xu Zhenhua , Yin Baoshu 
Published: July 2020

AbstractCountries in East Asia have set ambitious goals for the development of wind energy to meet the increasing energy demand and to mitigate anthropogenic climate change. However, few studies have investigated changes in wind energy over East Asia under future climatic conditions. In this study, we investigate future changes of 100‐m wind speed and wind energy potential over the CORDEX‐East Asia region under the Representative Concentration Pathway (RCP) 8.5 scenario, by using ensemble simulations from the regional climate model Consortium for small‐scale modeling in CLimate Mode (CCLM). A multivariate bias adjustment method based on the N‐dimensional probability density function transform is used to correct raw simulated horizontal wind components. The comparison between future climate (2021–2050 and 2070–2099) and the present climate (1971–2000) shows decreases in wind speed, wind power density, and wind energy output over most of the CORDEX‐East Asia region, especially in the tropics. Projected increases are pronounced over the Himalayan regions, the Indo‐China Peninsula, the South China Sea, and the western Pacific Ocean in summer and over northeastern China, parts of Western China and the Indo‐China Peninsula in winter. Interannual and intra‐annual variability of wind power density are projected to intensify significantly for most of the CORDEX‐East Asia region. The occurrence of weak wind speeds (<3 m/s) is projected to increase, while strong wind speeds (>11 m/s) are projected to decrease over most of the ocean.
What Controls the Water Vapor Isotopic Composition Near the Surface of Tropical Oceans? Results From an Analytical Model Constrained by Large‐Eddy Simulations
Authors: Risi Camille , Muller Caroline , Blossey Peter 
Published: July 2020

AbstractThe goal of this study is to understand the mechanisms controlling the isotopic composition of the water vapor near the surface of tropical oceans, at the scale of about a hundred kilometers and a month. In the tropics, it has long been observed that the isotopic compositions of rain and vapor near the surface are more depleted when the precipitation rate is high. This is called the “amount effect.” Previous studies, based on observations or models with parameterized convection, have highlighted the roles of deep convective and mesoscale downdrafts and rain evaporation. But the relative importance of these processes has never been quantified. We hypothesize that it can be quantified using an analytical model constrained by large‐eddy simulations. Results from large‐eddy simulations confirm that the classical amount effect can be simulated only if precipitation rate changes result from changes in the large‐scale circulation. We find that the main process depleting the water vapor compared to the equilibrium with the ocean is the fact that updrafts stem from areas where the water vapor is more enriched. The main process responsible for the amount effect is the fact that when the large‐scale ascent increases, isotopic vertical gradients are steeper, so that updrafts and downdrafts deplete the subcloud layer more efficiently.
COVID-19 PICU guidelines: for high- and limited-resource settings
Authors: Kache Saraswati , Chisti Mohammod Jobayer , Gumbo Felicity , Mupere Ezekiel , Zhi Xia , Nallasamy Karthi , Nakagawa Satoshi , Lee Jan Hau , Di Nardo Matteo , de la Oliva Pedro , Katyal Chhavi , Anand Kanwaljeet J. S. , de Souza Daniela Carla , Lanziotti Vanessa Soares , Carcillo Joseph 
Published: July 2020

Abstract
Background
Fewer children than adults have been affected by the COVID-19 pandemic, and the clinical manifestations are distinct from those of adults. Some children particularly those with acute or chronic co-morbidities are likely to develop critical illness. Recently, a multisystem inflammatory syndrome (MIS-C) has been described in children with some of these patients requiring care in the pediatric ICU.

Methods
An international collaboration was formed to review the available evidence and develop evidence-based guidelines for the care of critically ill children with SARS-CoV-2 infection. Where the evidence was lacking, those gaps were replaced with consensus-based guidelines.

Results
This process has generated 44 recommendations related to pediatric COVID-19 patients presenting with respiratory distress or failure, sepsis or septic shock, cardiopulmonary arrest, MIS-C, those requiring adjuvant therapies, or ECMO. Evidence to explain the milder disease patterns in children and the potential to use repurposed anti-viral drugs, anti-inflammatory or anti-thrombotic therapies are also described.

Conclusion
Brief summaries of pediatric SARS-CoV-2 infection in different regions of the world are included since few registries are capturing this data globally. These guidelines seek to harmonize the standards and strategies for intensive care that critically ill children with COVID-19 receive across the world.

Impact

At the time of publication, this is the latest evidence for managing critically ill children infected with SARS-CoV-2.

Referring to these guidelines can decrease the morbidity and potentially the mortality of children effected by COVID-19 and its sequalae.

These guidelines can be adapted to both high- and limited-resource settings.
ISG15 induces ESRP1 to inhibit lung adenocarcinoma progression
Authors: Qu Tongyuan , Zhang Wenshuai , Qi Lisha , Cao Lu , Liu Changxu , Huang Qiujuan , Li Guangning , Li Lingmei , Wang Yalei , Guo Qianru , Guo Yuhong , Ren Danyang , Gao Yanan , Wang Jinpeng , Meng Bin , Zhang Bin , Cao Wenfeng 
Published: July 2020

AbstractOur previous work demonstrated that Epithelial Splicing Regulatory Protein 1 (ESRP1) could inhibit the progression of lung adenocarcinoma (ADC). When ESRP1 was upregulated, the interferon (IFN) pathway was activated and Interferon-stimulated gene 15 (ISG15) expression increased exponentially in our microarray result. In this study, we aim to explore the function of ISG15 and its interactions with ESRP1 and to provide new insights for ADC treatment. ISG15 expression in lung ADC tissues was determined by immunohistochemistry (IHC) staining. The effect of ISG15 on lung ADC progression was examined by in vitro and in vivo assays. The mechanism of action on ESRP1 regulating ISG15 was investigated using Western blotting, RT-qPCR, immunofluorescence staining, chromatin immunoprecipitation, and a dual luciferase reporter system. The ISGylation between ISG15 and ESRP1 was detected by co-immunoprecipitation. Patients with high ISG15 expression were associated with higher survival rates, especially those with ISG15 expression in the nucleus. In vitro and in vivo experiments showed that upregulation of ISG15 inhibited EMT in lung ADC. ESRP1 upregulated the expression of ISG15 through CREB with enriched ISG15 in the nucleus. Importantly, ISG15 promoted ISGylation of ESRP1 and slowed the degradation of ESRP1, which demonstrated that ESRP1 and ISG15 formed a positive feedback loop and jointly suppressed EMT of lung ADC. In conclusion, ISG15 serves as an independent prognostic marker for long-term survival in lung ADC patients. We have revealed the protective effect of ISG15 against lung ADC progression and the combinatorial benefit of ISG15 and ESRP1 on inhibiting EMT. These findings suggest that reconstituting ISG15 and ESRP1 may have the potential for treating lung ADC.
Insulators for 2D nanoelectronics: the gap to bridge
Authors: Illarionov Yury Yu. , Knobloch Theresia , Jech Markus , Lanza Mario , Akinwande Deji , Vexler Mikhail I. , Mueller Thomas , Lemme Max C. , Fiori Gianluca , Schwierz Frank , Grasser Tibor 
Published: July 2020

AbstractNanoelectronic devices based on 2D materials are far from delivering their full theoretical performance potential due to the lack of scalable insulators. Amorphous oxides that work well in silicon technology have ill-defined interfaces with 2D materials and numerous defects, while 2D hexagonal boron nitride does not meet required dielectric specifications. The list of suitable alternative insulators is currently very limited. Thus, a radically different mindset with respect to suitable insulators for 2D technologies may be required. We review possible solution scenarios like the creation of clean interfaces, production of native oxides from 2D semiconductors and more intensive studies on crystalline insulators.
Pathogenic ARH3 mutations result in ADP-ribose chromatin scars during DNA strand break repair
Authors: Hanzlikova Hana , Prokhorova Evgeniia , Krejcikova Katerina , Cihlarova Zuzana , Kalasova Ilona , Kubovciak Jan , Sachova Jana , Hailstone Richard , Brazina Jan , Ghosh Shereen , Cirak Sebahattin , Gleeson Joseph G. , Ahel Ivan , Caldecott Keith W. 
Published: July 2020

AbstractNeurodegeneration is a common hallmark of individuals with hereditary defects in DNA single-strand break repair; a process regulated by poly(ADP-ribose) metabolism. Recently, mutations in the ARH3 (ADPRHL2) hydrolase that removes ADP-ribose from proteins have been associated with neurodegenerative disease. Here, we show that ARH3-mutated patient cells accumulate mono(ADP-ribose) scars on core histones that are a molecular memory of recently repaired DNA single-strand breaks. We demonstrate that the ADP-ribose chromatin scars result in reduced endogenous levels of important chromatin modifications such as H3K9 acetylation, and that ARH3 patient cells exhibit measurable levels of deregulated transcription. Moreover, we show that the mono(ADP-ribose) scars are lost from the chromatin of ARH3-defective cells in the prolonged presence of PARP inhibition, and concomitantly that chromatin acetylation is restored to normal. Collectively, these data indicate that ARH3 can act as an eraser of ADP-ribose chromatin scars at sites of PARP activity during DNA single-strand break repair.
Highly reversible oxygen redox in layered compounds enabled by surface polyanions
Authors: Chen Qing , Pei Yi , Chen Houwen , Song Yan , Zhen Liang , Xu Cheng-Yan , Xiao Penghao , Henkelman Graeme 
Published: July 2020

AbstractOxygen-anion redox in lithium-rich layered oxides can boost the capacity of lithium-ion battery cathodes. However, the over-oxidation of oxygen at highly charged states aggravates irreversible structure changes and deteriorates cycle performance. Here, we investigate the mechanism of surface degradation caused by oxygen oxidation and the kinetics of surface reconstruction. Considering Li2MnO3, we show through density functional theory calculations that a high energy orbital (lO2p’) at under-coordinated surface oxygen prefers over-oxidation over bulk oxygen, and that surface oxygen release is then kinetically favored during charging. We use a simple strategy of turning under-coordinated surface oxygen into polyanionic (SO4)2−, and show that these groups stabilize the surface of Li2MnO3 by depressing gas release and side reactions with the electrolyte. Experimental validation on Li1.2Ni0.2Mn0.6O2 shows that sulfur deposition enhances stability of the cathode with 99.0% capacity remaining (194 mA h g−1) after 100 cycles at 1 C. Our work reveals a promising surface treatment to address the instability of highly charged layered cathode materials.
R-loop induced G-quadruplex in non-template promotes transcription by successive R-loop formation
Authors: Lee Chun-Ying , McNerney Christina , Ma Kevin , Zhao Walter , Wang Ashley , Myong Sua 
Published: July 2020

AbstractG-quadruplex (G4) is a noncanonical secondary structure of DNA or RNA which can enhance or repress gene expression, yet the underlying molecular mechanism remains uncertain. Here we show that when positioned downstream of transcription start site, the orientation of potential G4 forming sequence (PQS), but not the sequence alters transcriptional output. Ensemble in vitro transcription assays indicate that PQS in the non-template increases mRNA production rate and yield. Using sequential single molecule detection stages, we demonstrate that while binding and initiation of T7 RNA polymerase is unchanged, the efficiency of elongation and the final mRNA output is higher when PQS is in the non-template. Strikingly, the enhanced elongation arises from the transcription-induced R-loop formation, which in turn generates G4 structure in the non-template. The G4 stabilized R-loop leads to increased transcription by a mechanism involving successive rounds of R-loop formation.
Cryo-EM structure of arabinosyltransferase EmbB from Mycobacterium smegmatis
Authors: Tan Yong Zi , Rodrigues José , Keener James E. , Zheng Ruixiang Blake , Brunton Richard , Kloss Brian , Giacometti Sabrina I. , Rosário Ana L. , Zhang Lei , Niederweis Michael , Clarke Oliver B. , Lowary Todd L. , Marty Michael T. , Archer Margarida , Potter Clinton S. , Carragher Bridget , Mancia Filippo 
Published: July 2020

AbstractArabinosyltransferase B (EmbB) belongs to a family of membrane-bound glycosyltransferases that build the lipidated polysaccharides of the mycobacterial cell envelope, and are targets of anti-tuberculosis drug ethambutol. We present the 3.3 Å resolution single-particle cryo-electron microscopy structure of Mycobacterium smegmatis EmbB, providing insights on substrate binding and reaction mechanism. Mutations that confer ethambutol resistance map mostly around the putative active site, suggesting this to be the location of drug binding.
In silico modelling of cancer nanomedicine, across scales and transport barriers
Authors: Stillman Namid R. , Kovacevic Marina , Balaz Igor , Hauert Sabine 
Published: July 2020

AbstractNanoparticles promise to improve the treatment of cancer through their increasingly sophisticated functionalisations and ability to accumulate in certain tumours. Yet recent work has shown that many nanomedicines fail during clinical trial. One issue is the lack of understanding of how nanoparticle designs impact their ability to overcome transport barriers in the body, including their circulation in the blood stream, extravasation into tumours, transport through tumour tissue, internalisation in the targeted cells, and release of their active cargo. Increased computational power, as well as improved multi-scale simulations of tumours, nanoparticles, and the biological transport barriers that affect them, now allow us to investigate the influence of a range of designs in biologically relevant scenarios. This presents a new opportunity for high-throughput, systematic, and integrated design pipelines powered by data and machine learning. With this paper, we review latest results in multi-scale simulations of nanoparticle transport barriers, as well as available software packages, with the aim of focussing the wider research community in building a common computational framework that can overcome some of the current obstacles facing efficient nanoparticle design.
Single-cell RNA sequencing reveals that lung mesenchymal progenitor cells in IPF exhibit pathological features early in their differentiation trajectory
Authors: Beisang Daniel J. , Smith Karen , Yang Libang , Benyumov Alexey , Gilbertsen Adam , Herrera Jeremy , Lock Eric , Racila Emilian , Forster Colleen , Sandri Brian J. , Henke Craig A. , Bitterman Peter B. 
Published: July 2020

AbstractIn Idiopathic Pulmonary Fibrosis (IPF), there is unrelenting scarring of the lung mediated by pathological mesenchymal progenitor cells (MPCs) that manifest autonomous fibrogenicity in xenograft models. To determine where along their differentiation trajectory IPF MPCs acquire fibrogenic properties, we analyzed the transcriptome of 335 MPCs isolated from the lungs of 3 control and 3 IPF patients at the single-cell level. Using transcriptional entropy as a metric for differentiated state, we found that the least differentiated IPF MPCs displayed the largest differences in their transcriptional profile compared to control MPCs. To validate entropy as a surrogate for differentiated state functionally, we identified increased CD44 as a characteristic of the most entropic IPF MPCs. Using FACS to stratify IPF MPCs based on CD44 expression, we determined that CD44hi IPF MPCs manifested an increased capacity for anchorage-independent colony formation compared to CD44lo IPF MPCs. To validate our analysis morphologically, we used two differentially expressed genes distinguishing IPF MPCs from control (CD44, cell surface; and MARCKS, intracellular). In IPF lung tissue, pathological MPCs resided in the highly cellular perimeter region of the fibroblastic focus. Our data support the concept that IPF fibroblasts acquire a cell-autonomous pathological phenotype early in their differentiation trajectory.
A novel humanized mouse model to study the function of human cutaneous memory T cells in vivo in human skin
Authors: Klicznik Maria M. , Benedetti Ariane , Gail Laura M. , Varkhande Suraj R. , Holly Raimund , Laimer Martin , Stoecklinger Angelika , Sir Andreas , Reitsamer Roland , Neuper Theresa , Horejs-Hoeck Jutta , Rosenblum Michael D. , Campbell Daniel J. , Murauer Eva M. , Gratz Iris K. 
Published: July 2020

AbstractHuman skin contains a population of memory T cells that supports tissue homeostasis and provides protective immunity. The study of human memory T cells is often restricted to in vitro studies and to human PBMC serving as primary cell source. Because the tissue environment impacts the phenotype and function of memory T cells, it is crucial to study these cells within their tissue. Here we utilized immunodeficient NOD-scid IL2rγnull (NSG) mice that carried in vivo-generated engineered human skin (ES). ES was generated from human keratinocytes and fibroblasts and was initially devoid of skin-resident immune cells. Upon adoptive transfer of human PBMC, this reductionist system allowed us to study human T cell recruitment from a circulating pool of T cells into non-inflamed human skin in vivo. Circulating human memory T cells preferentially infiltrated ES and showed diverse functional profiles of T cells found in fresh human skin. The chemokine and cytokine microenvironment of ES closely resembled that of non-inflamed human skin. Upon entering the ES T cells assumed a resident memory T cell-like phenotype in the absence of infection, and a proportion of these cutaneous T cells can be locally activated upon injection of monocyte derived dendritic cells (moDCs) that presented Candida albicans. Interestingly, we found that CD69+ memory T cells produced higher levels of effector cytokines in response to Candida albicans, compared to CD69- T cells. Overall, this model has broad utility in many areas of human skin immunology research, including the study of immune-mediated skin diseases.