bluuebunny/crossref_metadata_2025_split huggingface dataset:
Efficacy and Safety of Sofosbuvir-Based Direct-Acting Antiviral Agents Treatment for Patients with Genotype 3/6 Hepatitis C Virus Infection
Authors: Mei Yong-yu , Chen You-ming , Wu Yuan-kai , Zhang Xiao-hong , Xu Wen-xiong 
Published: November 2020

Aims. The aim is to evaluate the efficacy and safety of Sofosbuvir- (SOF-) based direct-acting antiviral agents (DAAs) treatment for patients with genotype (GT) 3/6 hepatitis C virus (HCV) infection. Methods. Patients infected with GT 3/6 HCV and treated with SOF-based DAAs were enrolled in this prospective, open, single-center, and real-world study. Drugs included Sofosbuvir (SOF), Velpatasvir (VEL), Daclatasvir (DCV), and Ribavirin (RBV). The treatment regimens included SOF + RBV for 24 weeks, SOF + DCV ± RBV for 12/24 weeks, and SOF/VEL ± RBV for 12 weeks. Results. A total of 54 patients were included. Age was 42.5 ± 10.4 years. Baseline HCV RNA was 6.29 ± 0.89log10 IU/mL. The numbers of GT 3a, 3b, and 6a patients were 10, 12, and 32, respectively. The numbers of chronic hepatitis, compensated cirrhosis, and decompensated cirrhosis patients were 39, 9, and 6, respectively. In patients with chronic hepatitis C and liver cirrhosis, sustained virological response 12 weeks after the end of treatment (SVR12) was 97.4% and 96.7%, respectively, and rapid virological response (RVR) was 75.0% and 57.1%, respectively. SVR12 of GT3a, GT3b, and GT6a was 100%, 83.3%, and 97%, respectively. ALT normality rate in chronic hepatitis group is higher than that in cirrhosis group at 4 weeks of treatment (89.7% versus 60.0%,

p

= 0.033) and at 12 weeks after EOT (94.9% versus 66.7%,

p

= 0.021). The overall incidence rate of adverse events was 44.4%, with fatigue being the most common (13.0%). Conclusion. SOF-based DAAs regimen can achieve ideal SVR12 for Chinese patients with both GT3a and GT6a HCV infection. The tolerance and safety of SOF-based DAAs regimen are good.
An Autochthonous Mouse Model ofMyd88- andBCL2-Driven Diffuse Large B-cell Lymphoma Reveals Actionable Molecular Vulnerabilities
Authors: Flümann Ruth , Rehkämper Tim , Nieper Pascal , Pfeiffer Pauline , Holzem Alessandra , Klein Sebastian , Bhatia Sanil , Kochanek Moritz , Kisis Ilmars , Pelzer Benedikt W. , Ahlert Heinz , Hauer Julia , da Palma Guerreiro Alexandra , Ryan Jeremy A. , Reimann Maurice , Riabinska Arina , Wiederstein Janica , Krüger Marcus , Deckert Martina , Altmüller Janine , Klatt Andreas R. , Frenzel Lukas P. , Pasqualucci Laura , Béguelin Wendy , Melnick Ari M. , Sander Sandrine , Montesinos-Rongen Manuel , Brunn Anna , Lohneis Philipp , Büttner Reinhard , Kashkar Hamid , Borkhardt Arndt , Letai Anthony , Persigehl Thorsten , Peifer Martin , Schmitt Clemens A. , Reinhardt Hans Christian , Knittel Gero 
Published: November 2020

AbstractBased on gene expression profiles, diffuse large B-cell lymphoma (DLBCL) is subdivided into germinal center B-cell–like (GCB) and activated B-cell–like (ABC) DLBCL. Two of the most common genomic aberrations in ABC-DLBCL are mutations in MYD88 as well as BCL2 copy-number gains. Here, we employ immune phenotyping, RNA sequencing, and whole-exome sequencing to characterize a Myd88- and BCL2-driven mouse model of ABC-DLBCL. We show that this model resembles features of human ABC-DLBCL. We further demonstrate an actionable dependence of our murine ABC-DLBCL model on BCL2. This BCL2 dependence was also detectable in human ABC-DLBCL cell lines. Moreover, human ABC-DLBCLs displayed increased PD-L1 expression compared with GCB-DLBCL. In vivo experiments in our ABC-DLBCL model showed that combined venetoclax and PD-1 blockade significantly increased the overall survival of lymphoma-bearing animals, indicating that this combination may be a viable option for selected human ABC-DLBCL cases harboring MYD88 and BCL2 aberrations.Significance:Oncogenic Myd88 and BCL2 cooperate in murine DLBCL lymphomagenesis. The resulting lymphomas display morphologic and transcriptomic features reminiscent of human ABC-DLBCL. Data derived from our Myd88/BCL2-driven autochthonous model demonstrate that combined BCL2 and PD-1 blockade displays substantial preclinical antilymphoma activity, providing preclinical proof-of-concept data, which pave the way for clinical translation.This article is highlighted in the In This Issue feature, p. 1
Interannual Relationship between the West Asian and East Asian Jet Meridional Displacements in Summer
Authors: Hong Xiaowei , Lu Riyu , Li Shuanglin 
Published: November 2020

AbstractThe meridional displacements of the upper-tropospheric westerly jet streams over both West Asia and East Asia (WJMD and EJMD, respectively) in summer manifest as the leading pattern of the zonal wind anomalies over their local domains on the interannual time scale. This study identifies a significant interannual relationship between these two leading patterns, tending to displace in the same meridional direction, either northward or southward. It is shown that the Silk Road pattern, which is a zonal teleconnection pattern along the Asian jet, is an important modulator for the WJMD–EJMD relationship. Another factor is the precipitation anomalies over a broad tropical region, including the Indian subcontinent, the northern Indian Ocean, and the western North Pacific Ocean. Enhanced or suppressed tropical precipitation respectively induces a northward or southward displacement of the primary body of the jet stream from West Asia to East Asia, which contributes to the in-phase WJMD–EJMD relationship, as suggested by both the observations and simple model results. The SST anomalies associated with the tropical precipitation and in-phase WJMD–EJMD relationship are also discussed. The WJMD–EJMD relationship may have an important implication for identifying and explaining the teleconnections of rainfall and temperature over the broad area from West Asia to East Asia, and from the tropics to the extratropics.
National Defence Under Alternative Trade Policy Regimes: Theory and Evidence from Developing Countries
Authors: Chatterjee Tonmoy , Chatterjee Nilendu 
Published: November 2020

Defence mechanism for any nation is the way through which internal as well as external geo-political condition can be stabilised. Moreover, defence sector can also be treated as one of the most potential sectors regarding financial transactions and the relevance of it is valid both in autarky and in the regime of international trade. Using Granger Causality for a panel of 27 developing countries across Asian and South American continents, we have found that different trade measures are playing major role in the way of functioning of national defence. For further analytical purpose and also to select the most effective trade policy regime among the alternatives, we have adopted a trade theoretic framework. In this regard, we have used a four-sector general equilibrium trade model with special emphasis on defence as well as R&D to defence to illustrate the impact of trade liberalisation on defence system. From such setup and by using bootstrap policy simulation we have found that trade liberalisation in the form foreign direct investment (specific to the R&D to defence) as the most effective trade regime to claim gains from trade in the presence of defence dualism for any small open developing economy. Such comparative statics is critical from the policy perspective. Policymakers should be cautious before defence industry liberalisation. JEL Codes: H56, C33, F11, F14, F21, D58
Spirituality, religiosity and the mental health consequences of social isolation during Covid-19 pandemic
Authors: Lucchetti Giancarlo , Góes Leonardo Garcia , Amaral Stefani Garbulio , Ganadjian Gabriela Terzian , Andrade Isabelle , Almeida Paulo Othávio de Araújo , do Carmo Victor Mendes , Manso Maria Elisa Gonzalez 
Published: November 2020

Background: Evidence shows that religiosity and spirituality (R/S) are highly used in critical moments of life and that these beliefs are associated with clinical outcomes. However, further studies are needed to assess these beliefs during the COVID-19 pandemic. Aims: To evaluate the use of R/S during the COVID-19 pandemic in Brazil and to investigate the association between R/S and the mental health consequences of social isolation. Methods: Cross-sectional study conducted in May 2020. Online surveys were carried out assessing sociodemographics, R/S measures, and social isolation characteristics and mental health consequences (hopefulness, fear, worrying and sadness). Adjusted regression models were used. Results: A total of 485 participants were included from all regions of Brazil. There was a high use of religious and spiritual beliefs during the pandemic and this use was associated with better mental health outcomes. Lower levels of worrying were associated with greater private religious activities (OR = 0.466, CI 95%: 0.307–0.706), religious attendance (OR = 0.587, CI 95%: 0.395–0.871), spiritual growth (OR = 0.667, CI 95%: 0.448–0.993) and with an increase in religious activities (OR = 0.660, CI 95%: 0.442–0.986); lower levels of fear were associated with greater private religious activities (OR = 0.632, CI 95%: 0.422–0.949) and spiritual growth (OR = 0.588, CI 95%: 0.392–0.882) and, lower levels of sadness (OR = 0.646, CI 95%: 0.418–0.997) were associated with spiritual growth. Finally, hope was associated with all R/S variables in different degrees (ranging from OR = 1.706 to 3.615). Conclusions: R/S seem to have an important role on the relief of suffering, having an influence on health outcomes and minimizing the consequences of social isolation. These results highlight the importance of public health measures that ensure the continuity of R/S activities during the pandemic and the training of healthcare professionals to address these issues.
Green Tax Reform and Employment Double Dividend in Australia Should Australia Follow Europe’s Footsteps? A CGE Analysis
Authors: Maxim Maruf Rahman , Zander Kerstin 
Published: November 2020

Australia has one of the highest per capita carbon emissions, and its energy sector contributes significantly to the country’s carbon emissions. Renewable energy and climate change call for a shift from fossil fuels to low-carbon technologies for energy production. Policies aiming to reduce carbon emissions are perceived by many people as leading to higher living costs, but changes in energy policies can also lead to economic gains in the presence of revenue recycling. This article applies a computable general equilibrium approach to study the effect of energy tax in the Australian economy. Four different scenarios of green tax reform (GTR) are simulated to test the employment double dividend (EDD) potential. All four scenarios simulate changes in energy tax and one of four tax revenue recycling policies including (a) value added tax reduction, (b) payroll tax reduction, (c) goods and services tax (GST) reduction and (d) a mixture of all three recycling policies. The results show strong EDD potential of GST and payroll tax reduction when used along with energy tax in a revenue-neutral GTR approach. The study also presents a comparison of an optimal EDD inducive policy design between the European and Australian GTR approaches. JEL classifications: H23, C68, H21, Q48
Outcomes of sequential intracorneal ring segment and phakic intraocular lens insertion for visual rehabilitation in keratoconus
Authors: McLintock Cameron A , McKelvie James , Miraflores Gomez Sara , Gatzioufas Zisis , Elalfy Mohamed , Hamada Samer 
Published: November 2020

Purpose: To report the visual and refractive outcomes of sequential intracorneal ring segment (ICRS) and toric phakic intraocular lens (IOL) insertion for visual rehabilitation in keratoconus. Methods: A retrospective interventional cohort study was performed through the Corneoplastics unit and Eye Bank, Queen Victoria Hospital, East Grinstead, United Kingdom. Results: 14 eyes of 12 patients had sequential ICRS and phakic IOL implantation for visual rehabilitation of keratoconus between June 2014 and February 2018. After at least 6 months follow-up, the number of eyes with an uncorrected distance visual acuity (UDVA) of 20/40 UDVA or better increased from zero (0%) to 10 (71%). 12 (85.7%) eyes achieved a post-operative UDVA equal to or better than the pre-operative corrected distance visual acuity (CDVA). The number percentage of eyes with a CDVA of 20/40 or better increased from 3 (31%) to 14 (100%). The mean final spherical equivalent improved from −4.07 to −0.17 ( p ⩽ 0.001). The mean refractive astigmatism magnitude improved from 4.76D to 1.23D ( p = 0.002). Seven (50%) eyes had 1.0D or less of refractive astigmatism post-operatively. Conclusion: In this cohort of eyes with keratoconus, sequential ICRS and phakic IOL implantation resulted in excellent visual and refractive outcomes after at least 6 months.
Pediatric Granulomatosis With Polyangiitis Mimicking IgA Vasculitis: A Case Report
Authors: Javadi Parvaneh Vadood , Shirzani Arezoo , Rahmani Khosro , Shiari Reza 
Published: November 2020

Background: Granulomatosis with polyangiitis (GPA) is a systemic vasculitis of the upper and lower respiratory tract along with glomerulonephritis and is very rare in childhood. Its renal manifestations similarity with IgA vasculitis can be misleading. Case presentation: Herein, we report a 12-years-old girl with the clinical picture of IgA vasculitis and renal involvement at the time of presentation, over time, elevated cytoplasmic Anti-neutrophil Cytoplasmic Antibody (C-ANCA) and tissue biopsy confirmed GPA. Conclusion: In the case of a patient with an unusual presentation of IgA vasculitis, to some degree of suspicion, the GPA should be considered. Also, in approach to non-thrombocytopenic palpable petechia and purpura a wide range of differential diagnosis such as infections, ANCA associated vasculitis, and secondary vasculitis should be considered. Therefore, 2 effective method of GPA diagnosis, the high titer of C-ANCA test and tissue biopsy, should be considered simultaneously.
Postoperative Management After Tracheostomy and Laryngectomy: Improving Nursing Knowledge With Bedside Posters
Authors: DeVictor Sam , Ong Adrian A. , Kelly Andrew P. , Burke Mark S. 
Published: November 2020

This study sought to improve nursing staff understanding regarding the differences in postoperative management between patients who have undergone tracheostomy and laryngectomy. The intervention involved a brief didactic session followed by the placement of an informative poster and anatomic diagram above the bed of tracheostomy and laryngectomy patients over a 6‐month period. Data were collected before and after the didactic session and poster implementation. Of the 50 nurses surveyed, 32% believed oral ventilation is appropriate for laryngectomy patients compared to 0% of nurses after the intervention. The percentage of nursing staff reporting self‐assessed clear understanding of the patient care differences between laryngectomy and tracheostomy improved after the intervention. The use of informational posters and didactic sessions significantly improves nursing staff understanding of the differences between tracheostomy and laryngectomy patients.Level of Evidence: IV
The impact of body mass index, central obesity and physical activity on lung function: results of the EpiHealth study
Authors: Svartengren Magnus , Cai Gui-Hong , Malinovschi Andrei , Theorell-Haglöw Jenny , Janson Christer , Elmståhl Sölve , Lind Lars , Lampa Erik , Lindberg Eva 
Published: November 2020

Study objectivesObesity is often associated with lower lung function; however, the interaction of lung function with central obesity and physical inactivity is less clear. As such, we investigated the effect on lung function of body size (body mass index (BMI)), central obesity (waist circumference (WC)) and self-reported physical activity.MethodsLung function, height, weight and WC were measured in 22 743 participants (12 791 women), aged 45–75 years, from the EpiHealth cohort study. Physical activity, gender and educational level were assessed using a questionnaire.ResultsObesity, central obesity and physical inactivity were all associated with lower forced expiratory volume in 1 s (FEV1) and forced vital capacity (FVC). However, in participants without central obesity there was an increase in both FEV1and FVC by BMI (% predicted FVC increasing from median 98%, interquartile range (IQR) 89–110% in underweight participants (BMI <20) to 103%, IQR 94–113% in obese participants (BMI ≥30)). In contrast, there was a decrease in % predicted FVC in participants with central obesity (from 98%, IQR 89–109% in the normal weight group to 95%, IQR 85–105% in the obese weight group). We further found a negative association between physical activity and lung function among those with low and high levels of physical activity (% predicted FEV197%, IQR 86–107%versus103%, IQR 94–113%, respectively and % predicted FVC 96%, IQR 85–106%versus103%, IQR 94–113%, respectively). All results remained when calculated by z-scores.ConclusionsThe association between BMI and lung function is dependent on the presence of central obesity. Independent of obesity, there is an association between physical activity and lung function.
First analysis of the Severe Paediatric Asthma Collaborative in Europe registry
Authors: Liu Norrice M. , Carlsen Karin C.L. , Cunningham Steve , Fenu Grazia , Fleming Louise J. , Gappa Monika , Karadag Bülent , Midulla Fabio , Petrarca Laura , Pijnenburg Marielle W.H. , Reier-Nilsen Tonje , Rutjes Niels W. , Rusconi Franca , Grigg Jonathan 
Published: November 2020

New biologics are being continually developed for paediatric asthma, but it is unclear whether there are sufficient numbers of children in Europe with severe asthma and poor control to recruit to trials needed for registration. To address these questions, the European Respiratory Society funded the Severe Paediatric Asthma Collaborative in Europe (SPACE), a severe asthma registry. We report the first analysis of the SPACE registry, which includes data from 10 paediatric respiratory centres across Europe.Data from 80 children with a clinical diagnosis of severe asthma who were receiving both high-dose inhaled corticosteroid and long-acting β2-agonist were entered into the registry between January 2019 and January 2020. Suboptimal control was defined by either asthma control test, or Global Initiative for Asthma criteria, or ≥2 severe exacerbations in the previous 12 months, or a combination.Overall, 62 out of 80 (77%) children had suboptimal asthma control, of whom 29 were not prescribed a biologic. However, in 24 there was an option for starting a licensed biologic. 33 children with suboptimal control were prescribed a biologic (omalizumab (n=24), or mepolizumab (n=7), or dupilumab (n=2)), and for 29 there was an option to switch to a different biologic.We conclude that the SPACE registry provides data that will support the planning of studies of asthma biologics. Not all children on biologics achieve good asthma control, and there is need for new trial designs addressing biologic switching.
Functional analysis of bovine interleukin-10 receptor alpha in response to Mycobacterium avium subsp. paratuberculosis lysate using CRISPR/Cas9
Authors: Mallikarjunappa Sanjay , Shandilya Umesh K. , Sharma Ankita , Lamers Kristen , Bissonnette Nathalie , Karrow Niel A. , Meade Kieran G. 
Published: November 2020

Abstract

Background
The interleukin-10 receptor alpha (IL10RA) gene codes for the alpha chain of the IL-10 receptor which binds the cytokine IL-10. IL-10 is an anti-inflammatory cytokine with immunoregulatory function during the pathogenesis of many inflammatory disorders in livestock, including Johne’s disease (JD). JD is a chronic enteritis in cattle caused by Mycobacterium avium subsp. paratuberculosis (MAP) and is responsible for significant economic losses to the dairy industry. Several candidate genes including IL10RA have been found to be associated with JD. The aim of this study was to better understand the functional significance of IL10RA in the context of immune stimulation with MAP cell wall lysate.

Results
An IL10RA knock out (KO) bovine mammary epithelial cell (MAC-T) line was generated using the CRISPR/cas9 (Clustered Regularly Interspaced Short Palindromic Repeats/CRISPR-associated protein 9) gene editing system. These IL10RA KO cells were stimulated with the immune stimulant MAP lysate +/− IL-10, or with LPS as a positive control. In comparison to unedited cells, relative quantification of immune-related genes after stimulation revealed that knocking out IL10RA resulted in upregulation of pro-inflammatory cytokine gene expression (TNFA, IL1A, IL1B and IL6) and downregulation of suppressor of cytokine signaling 3 (SOCS3), a negative regulator of pro-inflammatory cytokine signaling. At the protein level knocking out IL10RA also resulted in upregulation of inflammatory cytokines - TNF-α and IL-6 and chemokines - IL-8, CCL2 and CCL4, relative to unedited cells.

Conclusions
The findings of this study illustrate the broad and significant effects of knocking out the IL10RA gene in enhancing pro-inflammatory cytokine expression and further support the immunoregulatory role of IL10RA in eliciting an anti-inflammatory response as well as its potential functional involvement during the immune response associated with JD.
Label-free quantitative proteomic analysis of alfalfa in response to microRNA156 under high temperature
Authors: Arshad Muhammad , Puri Alpa , Simkovich Aaron J. , Renaud Justin , Gruber Margaret Y. , Marsolais Frédéric , Hannoufa Abdelali 
Published: November 2020

Abstract

Background
Abiotic stress, including heat, is one of the major factors that affect alfalfa growth and forage yield. The small RNA, microRNA156 (miR156), regulates multiple traits in alfalfa during abiotic stress. The aim of this study was to explore the role of miR156 in regulating heat response in alfalfa at the protein level.

Results
In this study, we compared an empty vector control and miR156 overexpressing (miR156OE) alfalfa plants after exposing them to heat stress (40 °C) for 24 h. We measured physiological parameters of control and miR156OE plants under heat stress, and collected leaf samples for protein analysis. A higher proline and antioxidant contents were detected in miR156OE plants than in controls under heat stress. Protein samples were analyzed by label-free quantification proteomics. Across all samples, a total of 1878 protein groups were detected. Under heat stress, 45 protein groups in the empty vector plants were significantly altered (P < 0.05; |log2FC| > 2). Conversely, 105 protein groups were significantly altered when miR156OE alfalfa was subjected to heat stress, of which 91 were unique to miR156OE plants. The identified protein groups unique to miR156OE plants were related to diverse functions including metabolism, photosynthesis, stress-response and plant defenses. Furthermore, we identified transcription factors in miR156OE plants, which belonged to squamosa promoter binding-like protein, MYB, ethylene responsive factors, AP2 domain, ABA response element binding factor and bZIP families of transcription factors.

Conclusions
These results suggest a positive role for miR156 in heat stress response in alfalfa. They reveal a miR156-regulated network of mechanisms at the protein level to modulate heat responses in alfalfa.