bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effects of hot extrusion deformation on microstructure and mechanical properties of the spray-deposition 17 vol.% SiCp/7055Al composite
Authors: Tang Binbin , Jiang Xianquan , Jin Peipeng , Wang Haitao , Peng He 
Published: July 2021

Abstract
In this study, the microstructure evolution and mechanical properties under hot extrusion of 17 vol.% SiCp/7055Al composite fabricated through the spray-deposition was investigated by employing the Microscope (SEM), the x-ray diffraction (XRD) and the electron back scattering diffraction (EBSD) under a range of deformation conditions. The extrusion temperature reached 400 °C, 450 °C, 500 °C, and the extrusion ratio was at 9, 13, 20 respectively. As revealed from the results the microstructure evolution and mechanical properties of the composite were affected by the extrusion and the precipitated phase. As indicated from the Optical microscope (OM) and the EBSD analysis, the structure variation of the hot extrusion deformation at 450 °C was mainly the dynamic recovery (DRV). However, the dynamic recrystallization (DRX) was dominating at the extrusion temperature of 500 °C and a ratio of 20. In the DRX process, the dislocation substructures appeared within the grains, to reduce low angle grain boundaries (LAGBs) progressively. The textures with {110} 〈111〉 paralleling to TD and the recrystallization textures {001} 〈100〉 and {124} 〈211〉 were characterized. As indicated from the tensile tests, the extrusion eliminated the preparation defects and accommodated the thermal expansion (CTE) mismatch between the matrix and the SiC particles, thereby improving the performance of the composite.
MiR-200c-based metabolic modulation in glioblastoma cells as a strategy to overcome tumor chemoresistance
Authors: Cardoso Ana M , Morais Catarina M , Sousa Madalena , Rebelo Olinda , Tão Hermínio , Barbosa Marcos , Pedroso de Lima Maria C , Jurado Amália S 
Published: July 2021

Abstract
Glioblastoma (GB) is the most aggressive and common form of primary brain tumor characterized by fast proliferation, high invasion and resistance to current standard treatment. The average survival rate post-diagnosis is 14.6 months, despite the aggressive standard post-surgery radiotherapy concomitant with chemotherapy with temozolomide (TMZ). Currently, efforts are being endowed to develop new and more efficient therapeutic approaches capable to overcome chemoresistance, inhibit tumor progression and improve overall patient survival rate. Abnormal microRNA (miRNA) expression has been correlated with chemoresistance, proliferation and resistance to apoptosis, which result from their master regulatory role of gene expression. Altered cell metabolism, favoring glycolysis, was identified as an emerging cancer hallmark and has been described in GB, thus offering a new target for innovative GB therapies. In this work, we hypothesized that a gene therapy-based strategy consisting of the overexpression of a miRNA downregulated in GB and predicted to target crucial metabolic enzymes might promote a shift of GB cell metabolism, decreasing the glycolytic dependence of tumor cells and contributing to their sensitization to chemotherapy with TMZ. The increase of miR-200c levels in DBTRG cells resulted in downregulation of messenger RNA of enzymes involved in bioenergetics pathways and impaired cell metabolism and mobility. In addition, miR-200c overexpression prior to DBTRG cell exposure to TMZ resulted in cell cycle arrest. Overall, our results show that miR-200c overexpression could offer a way to overcome chemoresistance developed by GB cells in response to current standard chemotherapy, providing an improvement to current GB standard treatment, with benefit for patient outcome.
Secondary Market Transparency and Corporate Bond Issuing Costs
Authors: Brugler James , Comerton-Forde Carole , Martin J Spencer 
Published: July 2021

Abstract
Mandated post-trade transparency in secondary markets lowers the cost of issuing corporate bonds. We show that costs are lower due to the mitigation of information asymmetry in the issuing process. Three pieces of evidence support this finding. First, new issues with higher information asymmetry experience relatively larger reductions in issuing costs. These bonds also experience lower reductions in trading activity than lower information asymmetry bonds, so liquidity cannot explain these results. Second, when a larger fraction of trades in comparable bonds are made post-trade transparent, new issue pricing improves. This holds when conditioning on expected bond liquidity. Third, transparency raises prices in the secondary market, but not by as much as it does for newly issued bonds.
Using host genetics to infer the global spread and evolutionary history of HCV subtype 3a
Authors: Lin Shang-Kuan , De Maio Nicola , Pedergnana Vincent , Wu Chieh-Hsi , Thézé Julien , Wilson Daniel J , Barnes Eleanor , Ansari M Azim 
Published: July 2021

Abstract
Studies have shown that hepatitis C virus subtype 3a (HCV-3a) is likely to have been circulating in South Asia before its global spread. However, the time and route of this dissemination remain unclear. For the first time, we generated host and virus genome-wide data for more than 500 patients infected with HCV-3a from the UK, North America, Australia, and New Zealand. We used the host genomic data to infer the ancestry of the patients and used this information to investigate the epidemic history of HCV-3a. We observed that viruses from hosts of South Asian ancestry clustered together near the root of the tree, irrespective of the sampling country, and that they were more diverse than viruses from other host ancestries. We hypothesized that South Asian hosts are more likely to have been infected in South Asia and used the inferred host ancestries to distinguish between the location where the infection was acquired and where the sample was taken. Next, we inferred that three independent transmission events resulted in the spread of the virus from South Asia to the UK, North America, and Oceania. This initial spread happened during or soon after the end of World War II. This was subsequently followed by many independent transmissions between the UK, North America, and Oceania. Using both host and virus genomic information can be highly informative in studying the virus epidemic history, especially in the context of chronic infections where migration histories need to be accounted for.
Racial Disparities in the Risk of Complications After Nonobstetric Surgery in Pregnancy
Authors: McKiever Monique , Lynch Courtney D. , Nafiu Olubukola O. , Mpody Christian , O'Malley David M. , Landon Mark B. , Costantine Maged M. , Pawlik Timothy M. , Venkatesh Kartik K. 
Published: July 2021

OBJECTIVE:
To examine whether there are racial and ethnic differences in postoperative complications after nonobstetric surgery during pregnancy in the United States.

METHODS:
We conducted a secondary analysis of the prospective ACS NSQIP (American College of Surgeons National Surgical Quality Improvement) program from 2005 to 2012. We assessed pregnant women 18–50 years without prior surgery in the preceding 30 days who underwent a nonobstetric surgery. Race and ethnicity were categorized as non-Hispanic Black, Hispanic, and non-Hispanic White (reference). The primary outcome was a composite of 30-day major postoperative complications inclusive of cardiovascular, pulmonary, and infectious complications, reoperation, unplanned readmission, blood transfusion, and death. We used modified Poisson regression to estimate the relative risk of complications.

RESULTS:
Among 3,093 pregnant women, 18% were non-Hispanic Black, 20% Hispanic, and 62% non-Hispanic White. The most common surgeries were appendectomy (36%) and cholecystectomy (19%). Black women (18%) were more likely to be assigned American Society of Anesthesiologists (ASA) physical status class III or higher than their White (12%) or Hispanic (9%) peers. Non-Hispanic Black pregnant women had a higher risk of 30-day major postoperative complications compared with their White peers (9% vs 6%; adjusted relative risk [aRR] 1.41, 95% CI 1.11–1.99). This difference persisted when limiting the analysis to apparently healthy women (ASA class I or II) (7% vs 4%; aRR 1.64, 95% CI 1.08–2.50), those who underwent appendectomy (10% vs 3%; aRR 2.36, 95% CI 1.13–4.96), and when appendectomy and cholecystectomy were performed by laparoscopy (7% vs 3%; aRR 2.62, 95% CI 1.22–5.58). Hispanic pregnant women were not at an increased risk of complications compared with non-Hispanic pregnant White women.

CONCLUSIONS:
Pregnant non-Hispanic Black women were at higher risk of major postoperative complications after nonobstetric surgery compared with their White counterparts.
RNA sequencing of whole blood defines the signature of high intensity exercise at altitude in elite speed skaters
Authors: Glotov Andrey S. , Zelenkova Irina E. , Vashukova Elena S. , Shuvalova Anna R. , Zolotareva Alexandra D. , Polev Dmitrii E. , Barbitoff Yury A. , Glotov Oleg S. , Sarana Andrey M. , Scherbak Sergey G. , Rozina Mariya A. , Gogotova Victoria L. , Predeus Alexander V. 
Published: July 2021

AbstractObjectivesAlthough high altitude training has been increasingly popular in endurance athletes, the molecular and cellular bases of this adaptation remain poorly understood. We aimed to define the underlying physiological changes and screen for potential biomarkers of adaptation using transcriptional profiling of whole blood. More generally, we aimed to evaluate the utility of blood RNA sequencing as a modern and sensitive method of athlete’s health monitoring.MethodsSeven elite female speed skaters were profiled before and after 1h intense exercise, on the 18th day of Live High, Train High (LHTH) training programme. Whole blood RNA sequencing (RNA-seq) with globin depletion was used to measure gene expression changes associated with high intensity exercise at high altitude. Eight public microarray datasets were used to identify genes uniquely regulated at high altitude. Gene markers derived from single cell RNA-seq data were used to evaluate the changes of individual cell types in the whole blood.ResultsUsing individual cell type signatures, we were able to deconvolute the changes of finely defined cell populations from the whole blood RNA-seq. We have detected the increase in neutrophils, platelets, erythrocytes, and CD14 monocytes, and the decrease in natural killers, CD8 T cells, memory CD4 T cells, B cells, and plasmacytoid dendritic cells. The levels of naive CD4 T cells, CD16 monocytes, and myeloid dendritic cells were unchanged. Leveraging the previously published transcriptomic data allowed us to define the expression signature unique to high-altitude adaptation. Among the identified genes we highlight PHOSPHO1, which has a known role in erythropoiesis, and MARC1 with a proposed role in endogenic NO metabolism. Finally, we find that platelets and, to a lesser extent, erythrocytes are the two major cell types that uniquely respond to altitude exercise, while neutrophils represent a more generic marker of intense exercise.ConclusionsUsing publicly available data from both single-cell RNA-seq atlases and exercise-related blood profiling dramatically increases the value of whole blood RNA-seq for dynamic evaluation of physiological changes in an athlete’s body. In addition to the measurement of individual gene expression changes, our approach allowed us to estimate changes of blood cell type counts from a small peripheral blood sample, without sorting or other expensive and unfeasible equipment. We also discuss a surprising parallel of hypoxia and increased thrombosis, and hypothesize about the role exercise can play in COVID-19 outcomes.
Genome-wide pleiotropy analysis of coronary artery disease and pneumonia identifies shared immune pathways
Authors: Yu Zhi , Zekavat Seyedeh M. , Haidermota Sara , Bernardo Rachel , Libby Peter , Finucane Hilary , Natarajan Pradeep 
Published: July 2021

AbstractCoronary artery disease (CAD) remains the leading cause of death despite scientific advances. Elucidating shared CAD/pneumonia pathways may reveal novel insights regarding CAD pathways. We performed genome-wide pleiotropy analyses of CAD and pneumonia, examined the causal effects of the expression of genes near independently replicated SNPs and interacting genes with CAD and pneumonia, and tested interactions between disruptive coding mutations of each pleiotropic gene and smoking status on CAD and pneumonia risks. Identified pleiotropic SNPs were annotated toADAMTS7andIL6R. IncreasedADAMTS7expression across tissues consistently showed decreased risk for CAD and increased risk for pneumonia; increasedIL6Rexpression showed increased risk for CAD and decreased risk for pneumonia. We similarly observed opposing CAD/pneumonia effects forNLRP3. ReducedADAMTS7expression conferred a reduced CAD risk without increased pneumonia risk only among never-smokers. Genetic immune-inflammatory axes of CAD linked to respiratory infections implicateADAMTS7andIL6R, and related genes.
Development and Content Validation of the Symptoms Evolution of COVID-19: A Patient-Reported Electronic Daily Diary in Clinical and Real-World Studies
Authors: Rofail Diana , McGale Nadine , Im Joseph , Rams Alissa , Przydzial Krystian , Mastey Vera , Sivapalasingam Sumathi , Podolanczuk Anna J. 
Published: July 2021

AbstractImportanceAt the onset of the COVID-19 pandemic, there was limited understanding of symptom experience and disease progression.ObjectiveWe developed and validated a fit-for-purpose, disease-specific instrument to assess symptoms in patients with COVID-19 to inform endpoints in an interventional trial for non-hospitalized patients.DesignThe initial drafting of the 23-item Symptoms Evolution of COVID-19 (SE-C19) Instrument was developed based on the Centers for Disease Control and Prevention symptom list and available published literature specific to patients with COVID-19 as of Spring 2020. The measurement principles in the Food and Drug Administration patient-reported outcomes guidance and the four methodological Patient-Focused Drug Development Guidances were also considered.SettingInterviews were conducted virtually with patients recruited through a healthcare research firm.ParticipantsSemi-structured qualitative interviews were conducted with a purposive sample of 30 non-hospitalized patients with COVID-19InterventionInterviews involved two stages: (1) concept elicitation, to obtain information about the symptoms experienced as a result of COVID-19 in patients’ own words, and (2) cognitive debriefing, for patients to describe their understanding of the SE-C19 instructions, specific symptoms, response options, and recall period to ensure the content of the SE-C19 is relevant and comprehensive. Five clinicians treating COVID-19 outpatients were interviewed to obtain their insights on symptoms experienced by patients and provide input on the SE-C19.Main Outcome and MeasurePatients reported no issues regarding the relevance or appropriateness of the SE-C19 instructions, including the recall period. The comprehensiveness of the SE-C19 was confirmed against the conceptual model developed in the qualitative research. Minor conceptual gaps were revealed to capture nuances in the experience of nasal and gustatory symptoms, and systemic manifestations of sickness.Almost all items were endorsed by patients as being appropriate and well understood. The clinicians largely approved all items, response options, and recall period.Conclusions and RelevanceThe qualitative research provided supportive evidence of the content validity of the SE-C19 instrument to assess the symptoms of outpatients with COVID-19 and its use in clinical trials to evaluate the benefit of treatment. Minor changes may be considered to improve conceptual clarity and ease of responding.Trial RegistrationR10933-10987-COV-2067 (https://clinicaltrials.gov/ct2/show/NCT04425629)
Effectiveness of Ivermectin-Based Multidrug Therapy in Severe Hypoxic Ambulatory COVID-19 Patients
Authors: Hazan Sabine , Dave Sonya , Gunaratne Anoja W. , Dolai Sibasish , Clancy Robert L , McCullough Peter A. , Borody Thomas J. 
Published: July 2021

AbstractIvermectin is a safe, inexpensive and effective early COVID-19 treatment validated in 20+ RCTs. Having developed combination therapies for Helicobacter pylori, we tested various COVID-19 combinations and describe the most effective. In 24 consecutive COVID-19 subjects with high risk features, hypoxia and untreated moderate-severe symptoms averaging 9 days, we trialed this novel combination comprising ivermectin, doxycycline, zinc, and Vitamins D and C. It was highly effective. All subjects resolved symptoms in 11 days on average, and oxygen saturation improved in 24hrs (87.4% to 93.1%, p=0.001). Hospitalizations and deaths were significantly fewer (p<0.002 or 0.05, respectively) than in background-matched controls from the CDC database. Triple combination therapy is safe and effective even in moderate-severe patients with hypoxia treated in the outpatient setting.Trial RegistrationN/A, see methods.
Multivalent designed proteins protect against SARS-CoV-2 variants of concern
Authors: Hunt Andrew C. , Case James Brett , Park Young-Jun , Cao Longxing , Wu Kejia , Walls Alexandra C. , Liu Zhuoming , Bowen John E. , Yeh Hsien-Wei , Saini Shally , Helms Louisa , Zhao Yan Ting , Hsiang Tien-Ying , Starr Tyler N. , Goreshnik Inna , Kozodoy Lisa , Carter Lauren , Ravichandran Rashmi , Green Lydia B. , Matochko Wadim L. , Thomson Christy A. , Vögeli Bastain , Krüger-Gericke Antje , VanBlargan Laura A. , Chen Rita E. , Ying Baoling , Bailey Adam L. , Kafai Natasha M. , Boyken Scott , Ljubetič Ajasja , Edman Natasha , Ueda George , Chow Cameron , Addetia Amin , Panpradist Nuttada , Gale Michael , Freedman Benjamin S. , Lutz Barry R. , Bloom Jesse D. , Ruohola-Baker Hannele , Whelan Sean P. J. , Stewart Lance , Diamond Michael S. , Veesler David , Jewett Michael C. , Baker David 
Published: July 2021

AbstractEscape variants of SARS-CoV-2 are threatening to prolong the COVID-19 pandemic. To address this challenge, we developed multivalent protein-based minibinders as potential prophylactic and therapeutic agents. Homotrimers of single minibinders and fusions of three distinct minibinders were designed to geometrically match the SARS-CoV-2 spike (S) trimer architecture and were optimized by cell-free expression and found to exhibit virtually no measurable dissociation upon binding. Cryo-electron microscopy (cryoEM) showed that these trivalent minibinders engage all three receptor binding domains on a single S trimer. The top candidates neutralize SARS-CoV-2 variants of concern with IC50values in the low pM range, resist viral escape, and provide protection in highly vulnerable human ACE2-expressing transgenic mice, both prophylactically and therapeutically. Our integrated workflow promises to accelerate the design of mutationally resilient therapeutics for pandemic preparedness.One-Sentence SummaryWe designed, developed, and characterized potent, trivalent miniprotein binders that provide prophylactic and therapeutic protection against emerging SARS-CoV-2 variants of concern.
Hippocampal Astrocytes Encode Reward Location
Authors: Doron Adi , Rubin Alon , Benmelech-Chovav Aviya , Benaim Netai , Carmi Tom , Kreisel Tirzah , Ziv Yaniv , Goshen Inbal 
Published: July 2021

AbstractAstrocytic calcium dynamics have been implicated in the encoding of sensory information, and modulating them has been shown to impact behavior. However, real-time calcium activity of astrocytes in the hippocampus of awake mice has never been investigated. We used 2-photon microscopy to chronically image CA1 astrocytes as mice ran in familiar or novel virtual environments and obtained water rewards. We found that astrocytes exhibit persistent ramping activity towards the reward location in a familiar environment, but not in a novel one. Using linear decoders, we could precisely predict the location of the mouse in a familiar environment from astrocyte activity alone. We could not do the same in the novel environment, suggesting astrocyte spatial activity is experience dependent. This is the first indication that astrocytes can encode location in spatial contexts, thereby extending their known computational capabilities, and their role in cognitive functions.
Patch-seq of mouse DRG neurons reveals candidate genes for specific mechanosensory functions
Authors: Parpaite Thibaud , Brosse Lucie , Séjourné Nina , Laur Amandine , Mechioukhi Yasmine , Delmas Patrick , Coste Bertrand 
Published: July 2021

SUMMARYA variety of mechanosensory neurons are involved in touch, proprioception and pain. Many molecular components of the mechanotransduction machinery subserving these sensory modalities remain to be discovered. Here, we combined recordings of mechanosensitive (MS) currents in mechanosensory neurons with single cell RNA sequencing. In silico combined analysis with a large-scale dataset enables assigning each transcriptome to DRG genetic clusters. Correlation of current signatures with single-cell transcriptomes provides a one-to-one correspondence between mechanoelectric properties and transcriptomically-defined neuronal populations. Moreover, gene expression differential comparison provides a set of candidate genes for mechanotransduction complexes. Piezo2 was expectedly found to be enriched in rapidly adapting MS current-expressing neurons, whereas Tmem120a and Tmem150c, thought to mediate slow-type MS currents, were uniformly expressed in all neuron subtypes, irrespective of their mechano-phenotype. Further knock-down experiments disqualified them as mediating DRG MS currents. This dataset constitutes an open-resource to explore further the cell-type-specific determinants of mechanosensory properties.
Exploring digital sustainability of/through Estonia’s e-residency: Africa’s case and the importance of culture for sustainability
Authors: Abaku Tamunonengiyeofori , Calzati Stefano , Masso Anu 
Published: July 2021

Purpose
This paper aims to take the lead from the United Nations Sustainable Development Goals (SDGs) 9 and 10 – foster “resilient infrastructures and inclusive innovation” and “reduce disparities of opportunities, income and power” – as key for digital sustainability. Moving beyond existing research, here this paper conceptualise “digital sustainability” as a framework for analysing the sustainability of digital services.

Design/methodology/approach
Combining different works, this paper identifies five dimensions: social, economic, institutional, environmental and technical. The framework is then tested on Estonia’s e-residency program, of which, in this way, this paper explores the potential digital sustainability. By allowing anyone to run location-independent businesses as if virtually in Estonia, the e-residency program aligns to what SDGs 9 and 10 prescribe in terms of socio-economic inclusiveness and inclusive innovation. As such, the program is particularly valuable for citizens from developing countries in that it gives them access to European markets. Hence, to explore e-residency’s digital sustainability, this paper focuses on the experiences of African e-residents.

Findings
In-depth interviews highlight a series of criticalities involving one or more dimensions of the framework. This is because of the program having a global outreach by default but not accommodating contextual diversity by design.

Originality/value
Suggestions for improving the program are provided, alongside the recommendation to also include the cultural dimension into the conceptualisation of digital sustainability.