bluuebunny/crossref_metadata_2025_split huggingface dataset:
Sociodemographic determinants of intraurban variations in COVID-19 incidence: the case of Barcelona
Authors: López-Gay Antonio , Spijker Jeroen , Cole Helen V S , Marques Antonio G , Triguero-Mas Margarita , Anguelovski Isabelle , Marí-Dell'Olmo Marc , Módenes Juan A , Álamo-Junquera Dolores , López-Gallego Fernando , Borrell Carme 
Published: June 2021

BackgroundIntraurban sociodemographic risk factors for COVID-19 have yet to be fully understood. We investigated the relationship between COVID-19 incidence and sociodemographic factors in Barcelona at a fine-grained geography.MethodsThis cross-sectional ecological study is based on 10 550 confirmed cases of COVID-19 registered during the first wave in the municipality of Barcelona (population 1.64 million). We considered 16 variables on the demographic structure, urban density, household conditions, socioeconomic status, mobility and health characteristics for 76 geographical units of analysis (neighbourhoods), using a lasso analysis to identify the most relevant variables. We then fitted a multivariate Quasi-Poisson model that explained the COVID-19 incidence by neighbourhood in relation to these variables.ResultsNeighbourhoods with: (1) greater population density, (2) an aged population structure, (3) a high presence of nursing homes, (4) high proportions of individuals who left their residential area during lockdown and/or (5) working in health-related occupations were more likely to register a higher number of cases of COVID-19. Conversely, COVID-19 incidence was negatively associated with (6) percentage of residents with post-secondary education and (7) population born in countries with a high Human Development Index.ConclusionLike other historical pandemics, the incidence of COVID-19 is associated with neighbourhood sociodemographic factors with a greater burden faced by already deprived areas. Because urban social and health injustices already existed in those geographical units with higher COVID-19 incidence in Barcelona, the current pandemic is likely to reinforce both health and social inequalities, and urban environmental injustice all together.
Use of a screening questionnaire for systemic lupus erythematosus among pregnant women in a Mexican population
Authors: Lucero-Morales Luis , Romero-Diaz Juanita , Copado-Mendoza Diana Yazmin , Zamora-Medina María del Carmen , Acevedo-Gallegos Sandra , Gallardo-Gaona Juan Manuel , Velazquez-Torres Berenice , Ramirez-Calvo Jose Antonio , Camarena-Cabrera Dulce Maria , Rodriguez-Sibaja Maria Jose 
Published: June 2021

ObjectiveTo conduct a diagnostic assessment of pregnant women using a screening questionnaire for SLE.Materials and methodsThis was an analytical cross-sectional study carried out at the National Institute of Perinatology between 1 November 2019 and 28 February 2020, using a screening questionnaire for SLE. Antinuclear antibody and anti-double stranded DNA antibody tests and a clinical assessment by a rheumatologist were conducted for participants who obtained ≥4 positive responses on the questionnaire. The sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of the screening questionnaire for SLE were calculated.ResultsThe questionnaire survey was conducted with 540 pregnant patients, 22 of whom (4.1%) had ≥4 positive responses. An antinuclear antibody test was conducted in all aforementioned 22 patients; 17 (77.3%) showed titres of ≥1:80. Of the 22 patients, 19 (86.4%) underwent clinical assessment by a rheumatologist. The patients were classified according to the SLE classification criteria: 7/19 (36.9%) met the revised 1997 American College Rheumatology (ACR) criteria, 8/19 (42.1%) met the Systemic Lupus International Collaborating Clinics criteria and 7/19 (36.9%) met the 2019 ACR/EULAR criteria (sensitivity=0.86, specificity=0.97, PPV=0.77 and NPV=1 for antinuclear antibody titre of ≥1:80; sensitivity=0.88, specificity=0.98, PPV=0.37 and NPV=1 for SLE according to the 2019 ACR/EULAR criteria).ConclusionsThe questionnaire showed high sensitivity and specificity in the diagnosis of SLE. Given its usability and cost:benefit ratio, this strategy should be used for all patients coming in for their first visit to determine who requires antinuclear antibody testing and who needs to be referred to a rheumatologist.
Study on Agent Incentives for Resource Sharing on P2P Networks
Authors: Cheng Yukun , Deng Xiaotie , Li Yuhao 
Published: June 2021

There have recently been extensive studies on proportional response protocol, which is motivated by the successful BitTorrent system for file sharing over a P2P network. The proportional response protocol has been proved to be strategy-proof against weight cheating attacks and edge cheating attacks, in order to allocate a single type of resource on P2P networks. This strategy-proof property holds due to an elegant combinatorial structure: the bottleneck decomposition of the underlying network structure, and the utility function, defined as the total resources that one agent receives from its neighbors. However, Sybil attacks, under which an agent may form several fictitious players and split its resource among them, have been shown as a more difficult attack to defend against, and thus a strategic agent playing Sybil attacks may result in personal gain. Previous efforts have been made to show that an agent may generate a gain, but with limited gains by Sybil attacks on several special networks, including trees, cliques, and rings. This paper is the first to study the agent’s incentives by adopting a Sybil attack on general networks. The main contribution is to prove that any agent cannot obtain more than three times as much as the revenue when it plays honestly.
High-pressure new phase of AgN3
Authors: Niu Shifeng , Liu Ran , Shi Xuhan , Yao Zhen , Liu Bingbing , Lu Shuangchen 
Published: June 2021

The structural evolutionary behaviors of AgN3 have been studied by using the particle swarm optimization structure search method combined with the density functional theory. One stable high-pressure metal polymeric phase with the [Formula: see text] space group is suggested. The enthalpy difference analysis indicates that the Ibam-AgN3 phase will transfer to the I4/mcm-AgN3 phase at 4.7 GPa and then to the [Formula: see text]-AgN3 phase at 24 GPa. The [Formula: see text]-AgN3 structure is composed of armchair–antiarmchair N-chain, in which all the N atoms are sp2 hybridization. The inherent stability of the armchair–antiarmchair chain and the anion–cation interaction between the N-chain and Ag atom induce a high stability of the [Formula: see text]-AgN3 phase, which can be captured at ambient conditions and hold its stable structure up to 1400 K. The exhibited high energy density (1.88 KJ/g) and prominent detonation properties ([Formula: see text] Km/s; [Formula: see text] GPa) of the [Formula: see text]-AgN3 phase make it a potentially high energy density material.
SOX11 Inhibitors Are Cytotoxic in Mantle Cell Lymphoma
Authors: Jatiani Shashidhar S. , Christie Stephanie , Leshchenko Violetta V. , Jain Rinku , Kapoor Abhijeet , Bisignano Paola , Lee Clement , Kaniskan H. Ümit , Edwards Donna , Meng Fanye , Laganà Alessandro , Youssef Youssef , Wiestner Adrian , Alinari Lapo , Jin Jian , Filizola Marta , Aggarwal Aneel K. , Parekh Samir 
Published: June 2021

AbstractPurpose:Mantle cell lymphoma (MCL) is a fatal subtype of non–Hodgkin lymphoma. SOX11 transcription factor is overexpressed in the majority of nodal MCL. We have previously reported that B cell–specific overexpression of SOX11 promotes MCL pathogenesis via critically increasing BCR signaling in vivo. SOX11 is an attractive target for MCL therapy; however, no small-molecule inhibitor of SOX11 has been identified to date. Although transcription factors are generally considered undruggable, the ability of SOX11 to bind to the minor groove of DNA led us to hypothesize that there may exist cavities at the protein–DNA interface that are amenable to targeting by small molecules.Experimental Design:Using a combination of in silico predictions and experimental validations, we report here the discovery of three structurally related compounds (SOX11i) that bind SOX11, perturb its interaction with DNA, and effect SOX11-specific anti-MCL cytotoxicity.Results:We find mechanistic validation of on-target activity of these SOX11i in the inhibition of BCR signaling and the transcriptional modulation of SOX11 target genes, specifically, in SOX11-expressing MCL cells. One of the three SOX11i exhibits relatively superior in vitro activity and displays cytotoxic synergy with ibrutinib in SOX11-expressing MCL cells. Importantly, this SOX11i induces cytotoxicity specifically in SOX11-positive ibrutinib-resistant MCL patient samples and inhibits Bruton tyrosine kinase phosphorylation in a xenograft mouse model derived from one of these subjects.Conclusions:Taken together, our results provide a foundation for therapeutically targeting SOX11 in MCL by a novel class of small molecules.
The Radiosensitizing Effect of AZD0530 in Glioblastoma and Glioblastoma Stem-Like Cells
Authors: Yun Hong Shik , Lee Jennifer , Kil Whoon Jong , Kramp Tamalee R. , Tofilon Philip J. , Camphausen Kevin 
Published: June 2021

Abstract
AZD0530, a potent small-molecule inhibitor of the Src kinase family, is an anticancer drug used in the treatment of various cancers. In the case of glioblastoma (GBM), where resistance to radiotherapy frequently occurs, Src kinase is known as one of the molecules responsible for imparting radioresistance to GBM. Thus, we evaluated the effect of AZD0530 on the radiosensitivity of human GBM cells and human glioblastoma stem-like cells (GSCs). We show that Src activity of GBM and GSC is increased by radiation and inhibited by AZD0530, and using clonogenic assays, AZD0530 enhances the radiosensitivity of GBM and GSCs. Also, AZD0530 induced a prolongation of radiation-induced γH2AX without specific cell cycle and mitotic index changes, suggesting that AZD0530-induced radiosensitization in GBM cells and GSCs results from the inhibition of DNA repair. In addition, AZD0530 was shown to inhibit the radiation-induced EGFR/PI3K/AKT pathway, which is known to promote and regulate radioresistance and survival of GBM cells by radiation. Finally, mice bearing orthotopic xenografts initiated from GBM cells were then used to evaluate the in vivo response to AZD0530 and radiation. The combination of AZD0530 and radiation showed the longest median survival compared with any single modality. Thus, these results show that AZD0530 enhances the radiosensitivity of GBM cells and GSCs and suggest the possibility of AZD0530 as a clinical radiosensitizer for treatment of GBM.
ATE1 Inhibits Liver Cancer Progression through RGS5-Mediated Suppression of Wnt/β-Catenin Signaling
Authors: Xu Cong , Li Yi-Ming , Sun Bo , Zhong Fang-Jing , Yang Lian-Yue 
Published: June 2021

Abstract

Arginyltransferase (ATE1) plays critical roles in many biological functions including cardiovascular development, angiogenesis, adipogenesis, muscle contraction, and metastasis of cancer. However, the role of ATE1 in hepatocellular carcinoma (HCC) remains unknown. In this study, we find that ATE1 plays an essential role in growth and malignancy of liver cancer. ATE1 expression is significantly reduced in human HCC samples compared with normal liver tissue. In addition, low ATE1 expression is correlated with aggressive clinicopathologic features and is an independent poor prognostic factor for overall survival and disease-free survival of patients with HCC. Lentivirus-mediated ATE1 knockdown significantly promoted liver cancer growth, migration, and disease progression in vitro and in vivo. Opposing results were observed when ATE1 was upregulated. Mechanistically, ATE1 accelerated the degradation of β-catenin and inhibited Wnt signaling by regulating turnover of Regulator of G Protein Signaling 5 (RGS5). Loss- and gain-of-function assays confirmed that RGS5 was a key effector of ATE1-mediated regulation of Wnt signaling. Further studies indicated that RGS5 might be involved in regulating the activity of GSK3-β, a crucial component of the cytoplasmic destruction complex. Treatment with a GSK inhibitor (CHIR99021) cooperated with ablation of ATE1 or RGS5 overexpression to promote Wnt/β-catenin signaling, but overexpression of ATE1 or RGS5 knockdown did not reverse the effect of GSK inhibitor.

Implications:
ATE1 inhibits liver cancer progression by suppressing Wnt/β-catenin signaling and can serve as a potentially valuable prognostic biomarker for HCC.
Identification of Autophagy-Related Genes as Targets for Senescence Induction Using a Customizable CRISPR-Based Suicide Switch Screen
Authors: Schepers Arnout , Jochems Fleur , Lieftink Cor , Wang Liqin , Pogacar Ziva , Leite de Oliveira Rodrigo , De Conti Giulia , Beijersbergen Roderick L. , Bernards Rene 
Published: June 2021

Abstract

Pro-senescence therapies are increasingly being considered for the treatment of cancer. Identifying additional targets to induce senescence in cancer cells could further enable such therapies. However, screening for targets whose suppression induces senescence on a genome-wide scale is challenging, as senescent cells become growth arrested, and senescence-associated features can take 1 to 2 weeks to develop. For a screen with a whole-genome CRISPR library, this would result in billions of undesirable proliferating cells by the time the senescent features emerge in the growth arrested cells. Here, we present a suicide switch system that allows genome-wide CRISPR screening in growth-arrested subpopulations by eliminating the proliferating cells during the screen through activation of a suicide switch in proliferating cells. Using this system, we identify in a genome-scale CRISPR screen several autophagy-related proteins as targets for senescence induction. We show that inhibiting macroautophagy with a small molecule ULK1 inhibitor can induce senescence in cancer cell lines of different origin. Finally, we show that combining ULK1 inhibition with the senolytic drug ABT-263 leads to apoptosis in a panel of cancer cell lines.

Implications:
Our suicide switch approach allows for genome-scale identification of pro-senescence targets, and can be adapted to simplify other screens depending on the nature of the promoter used to drive the switch.
The Cell Surface Receptors Ror1/2 Control Cardiac Myofibroblast Differentiation
Authors: Chavkin Nicholas W. , Sano Soichi , Wang Ying , Oshima Kosei , Ogawa Hayato , Horitani Keita , Sano Miho , MacLauchlan Susan , Nelson Anders , Setia Karishma , Vippa Tanvi , Watanabe Yosuke , Saucerman Jeffrey J. , Hirschi Karen K. , Gokce Noyan , Walsh Kenneth 
Published: June 2021

Background
A hallmark of heart failure is cardiac fibrosis, which results from the injury‐induced differentiation response of resident fibroblasts to myofibroblasts that deposit extracellular matrix. During myofibroblast differentiation, fibroblasts progress through polarization stages of early proinflammation, intermediate proliferation, and late maturation, but the regulators of this progression are poorly understood. Planar cell polarity receptors, receptor tyrosine kinase–like orphan receptor 1 and 2 (Ror1/2), can function to promote cell differentiation and transformation. In this study, we investigated the role of the Ror1/2 in a model of heart failure with emphasis on myofibroblast differentiation.

Methods and Results
The role of Ror1/2 during cardiac myofibroblast differentiation was studied in cell culture models of primary murine cardiac fibroblast activation and in knockout mouse models that underwent transverse aortic constriction surgery to induce cardiac injury by pressure overload. Expression of Ror1 and Ror2 were robustly and exclusively induced in fibroblasts in hearts after transverse aortic constriction surgery, and both were rapidly upregulated after early activation of primary murine cardiac fibroblasts in culture. Cultured fibroblasts isolated from Ror1/2 knockout mice displayed a proinflammatory phenotype indicative of impaired myofibroblast differentiation. Although the combined ablation of Ror1/2 in mice did not result in a detectable baseline phenotype, transverse aortic constriction surgery led to the death of all mice by day 6 that was associated with myocardial hyperinflammation and vascular leakage.

Conclusions
Together, these results show that Ror1/2 are essential for the progression of myofibroblast differentiation and for the adaptive remodeling of the heart in response to pressure overload.
Mitral Valve Prolapse and Its Motley Crew‐Syndromic Prevalence, Pathophysiology, and Progression of a Common Heart Condition
Authors: Morningstar Jordan E. , Nieman Annah , Wang Christina , Beck Tyler , Harvey Andrew , Norris Russell A. 
Published: June 2021

Abstract
Mitral valve prolapse (MVP) is a commonly occurring heart condition defined by enlargement and superior displacement of the mitral valve leaflet(s) during systole. Although commonly seen as a standalone disorder, MVP has also been described in case reports and small studies of patients with various genetic syndromes. In this review, we analyzed the prevalence of MVP within syndromes where an association to MVP has previously been reported. We further discussed the shared biological pathways that cause MVP in these syndromes, as well as how MVP in turn causes a diverse array of cardiac and noncardiac complications. We found 105 studies that identified patients with mitral valve anomalies within 18 different genetic, developmental, and connective tissue diseases. We show that some disorders previously believed to have an increased prevalence of MVP, including osteogenesis imperfecta, fragile X syndrome, Down syndrome, and Pseudoxanthoma elasticum, have few to no studies that use up‐to‐date diagnostic criteria for the disease and therefore may be overestimating the prevalence of MVP within the syndrome. Additionally, we highlight that in contrast to early studies describing MVP as a benign entity, the clinical course experienced by patients can be heterogeneous and may cause significant cardiovascular morbidity and mortality. Currently only surgical correction of MVP is curative, but it is reserved for severe cases in which irreversible complications of MVP may already be established; therefore, a review of clinical guidelines to allow for earlier surgical intervention may be warranted to lower cardiovascular risk in patients with MVP.
Perceiving Intersensory and Emotional Qualities of Everyday Objects: A Study on Smoothness or Sharpness Features with Line Drawings by Designers
Authors: Sinico Michele , Bertamini Marco , Soranzo Alessandro 
Published: June 2021

Abstract
A large number of studies have focused on the aesthetic value of smoothly curved objects. By contrast, angular shapes tend to be associated with tertiary qualities such as threat, hardness, loudness, nervousness, etc. The present study focuses on the effect of curvilinearity vs angularity on the aesthetic experience of design artefacts. We used the drawings of everyday objects with novel shapes created by 56 designers (IUAV image dataset). Each drawing had two versions: a smooth and an angular version. To test new tertiary associations, beyond aesthetic value, we obtained ratings for seven characteristics (‘soft/hard, sad/cheerful, male/female, bad/good, aggressive/peaceful, agitated/serene, useless/useful’) from 174 naïve observers. Importantly, each naïve rater saw only one of the two versions of an object. The results confirmed a significant relation between smoothness and hardness as well as other (tertiary) associations. The link between smoothness and usefulness confirms that perceptual utility is significantly influenced by the shape of the object. This finding suggests that tertiary qualities convey both static and functional information about design objects. The role of perceptual constraints in drawing design artefacts is also discussed.
The impact of coupled data assimilation on Madden-Julian Oscillation predictability initialized from coupled satellite-era reanalysis
Authors: Yao Junchen , Vitart Frédéric , Balmaseda Magdalena Alonso , Wu Tongwen , Liu Xiangwen 
Published: June 2021

AbstractThis study investigates the impact of coupled initialization on the extended-range prediction of the Madden-Julian Oscillation (MJO). A set of reforecasts using combinations of the oceanic and atmospheric initial conditions produced with coupled and uncoupled data assimilation (DA) are conducted to evaluate the impact of coupling in the different domains, from the perspective of MJO forecasts. The coupled initial conditions are provided by CERA-SAT pilot coupled reanalysis for the satellite era recently produced by ECMWF. We focus on the prediction skill of the MJO using the Real-time Outgoing Long-wave Radiation (OLR) MJO index in a series of re-forecasts. The impact of atmospheric initial conditions produced by coupled DA shows slight benefit for the MJO prediction. However, compared with the operational ocean reanalysis, the ocean initial conditions created by CERA-SAT degrade the MJO prediction skill during the first 2-3 weeks of the re-forecast by 1.5% to 5.8%. A moist static energy budget analysis revealed that the underestimation of 0.2 K sea surface temperature, 1.4 W m-2 top of atmosphere downward longwave radiation, and 3.8 W m-2 latent heat flux over the Maritime Continent lead to small but statistically significant degradation of the MJO forecast skill. The results demonstrate that the MJO is sensitive to ocean initial conditions, and illustrate the value of the extended range MJO prediction for evaluating the quality of coupled data assimilation, and suggest that future efforts on coupled data assimilation pay special attention to the balance of air-sea interaction processes over the warm pool area, in terms of modeling, observational needs and system.
Healthcare-associated infections over an eight year period in a large university hospital in Sicily (Italy, 2011–2018)
Authors: Russo Fiorino Giusy , Maniglia Marialuisa , Marchese Valentina , Aprea Luigi , Torregrossa Maria V , Campisi Fabio , Favaro Dario , Calamusa Giuseppe , Amodio Emanuele 
Published: June 2021

Background: Up to 7% of hospitalised patients acquire at least one healthcare-associated infection (HAI). The aim of the present study was to quantify the burden of HAIs in an Italian hospital, identifying involved risk factors. Methods: Prevalence point study carried out from 2011 to 2018. For each recruited patient, a data entry form was compiled including information on demographics, hospital admission, risk factors, antimicrobial treatment, and infection if present. Results: A total of 2844 patients were included and 218 (7.03%) reported an infection. HAI prevalence rates showed a significant increase (average annual per cent change (AAPC) +33.9%; p=0.018) from 2011 to 2014 whereas from 2014 to 2018 a gradual decline was observed (AAPC –6.15%; p=0.35). Urinary tract infection was the most common HAI (25.2%) and a total of 166 (76.1%) pathogens were isolated from 218 infections. Enterococcus and Klebsiella species were the most prevalent pathogens, causing 15.1% and 14.5% of HAIs, respectively. A significant higher risk of HAIs was found in patients exposed to central catheter (adjusted odds ratio (adj-OR)=5.40), peripheral catheter (adj-OR=1.89), urinary catheter (adj-OR=1.46), National Healthcare Safety Network surgical intervention (adj-OR=1.48), ultimately fatal disease (adj-OR=2.19) or rapidly fatal disease (adj-OR=2.09) and in patients with longer hospital stay (adj-OR=1.01). Conclusion: Intervention programmes based on guidelines dissemination and personnel training can contribute to reduce the impact of HAI. Moreover, McCabe score can be a very powerful and efficient predictor of risk for HAI. Finally, an unexpected very high burden of disease due to Enterobacteriaceae and Gram positive cocci that could be related to the frequent use of carbapenems and third generation cephalosporins in this hospital was found.