bluuebunny/crossref_metadata_2025_split huggingface dataset:
Integrative genomic analyses identify susceptibility genes underlying COVID-19 hospitalization
Authors: Pathak Gita A. , Singh Kritika , Miller-Fleming Tyne W. , Wendt Frank R. , Ehsan Nava , Hou Kangcheng , Johnson Ruth , Lu Zeyun , Gopalan Shyamalika , Yengo Loic , Mohammadi Pejman , Pasaniuc Bogdan , Polimanti Renato , Davis Lea K. , Mancuso Nicholas 
Published: July 2021

AbstractDespite rapid progress in characterizing the role of host genetics in SARS-Cov-2 infection, there is limited understanding of genes and pathways that contribute to COVID-19. Here, we integrate a genome-wide association study of COVID-19 hospitalization (7,885 cases and 961,804 controls from COVID-19 Host Genetics Initiative) with mRNA expression, splicing, and protein levels (n = 18,502). We identify 27 genes related to inflammation and coagulation pathways whose genetically predicted expression was associated with COVID-19 hospitalization. We functionally characterize the 27 genes using phenome- and laboratory-wide association scans in Vanderbilt Biobank (n = 85,460) and identified coagulation-related clinical symptoms, immunologic, and blood-cell-related biomarkers. We replicate these findings across trans-ethnic studies and observed consistent effects in individuals of diverse ancestral backgrounds in Vanderbilt Biobank, pan-UK Biobank, and Biobank Japan. Our study highlights and reconfirms putative causal genes impacting COVID-19 severity and symptomology through the host inflammatory response.
Impact of tiered restrictions on human activities and the epidemiology of the second wave of COVID-19 in Italy
Authors: Manica Mattia , Guzzetta Giorgio , Riccardo Flavia , Valenti Antonio , Poletti Piero , Marziano Valentina , Trentini Filippo , Andrianou Xanthi , Mateo-Urdiales Alberto , del Manso Martina , Fabiani Massimo , Vescio Maria Fenicia , Spuri Matteo , Petrone Daniele , Bella Antonino , Iavicoli Sergio , Ajelli Marco , Brusaferro Silvio , Pezzotti Patrizio , Merler Stefano 
Published: July 2021

AbstractTo counter the second COVID-19 wave in autumn 2020, the Italian government introduced a system of physical distancing measures organized in progressively restrictive tiers (coded as yellow, orange, and red) imposed on a regional basis according to real-time epidemiological risk assessments. We leverage the data from the Italian COVID-19 integrated surveillance system and publicly available mobility data to evaluate the impact of the three-tiered regional restriction system on human activities, SARS-CoV-2 transmissibility and hospitalization burden in Italy. The individuals’ attendance to locations outside the residential settings was progressively reduced with tiers, but less than during the national lockdown against the first COVID-19 wave in the spring. The reproduction number R(t) decreased below the epidemic threshold in 85 out of 107 provinces after the introduction of the tier system, reaching average values of about 0.95-1.02 in the yellow tier, 0.80-0.93 in the orange tier and 0.74-0.83 in the red tier. We estimate that the reduced transmissibility resulted in averting about 36% of the hospitalizations between November 6 and November 25, 2020. These results are instrumental to inform public health efforts aimed at preventing future resurgence of cases.
Super enhancer regulation of cytokine-induced chemokine production in alcoholic hepatitis
Authors: Liu Mengfei , Cao Sheng , He Li , Gao Jinhang , Arab Juan P. , Cui Huarui , Xuan Weixia , Gao Yandong , Sehrawat Tejasav S. , Hamdan Feda H. , Ventura-Cots Meritxell , Argemi Josepmaria , Pomerantz William C. K. , Johnsen Steven A. , Lee Jeong-Heon , Gao Fei , Ordog Tamas , Mathurin Philippe , Revzin Alexander , Bataller Ramon , Yan Huihuang , Shah Vijay H. 
Published: July 2021

AbstractAlcoholic hepatitis (AH) is associated with liver neutrophil infiltration through activated cytokine pathways leading to elevated chemokine expression. Super-enhancers are expansive regulatory elements driving augmented gene expression. Here, we explore the mechanistic role of super-enhancers linking cytokine TNFα with chemokine amplification in AH. RNA-seq and histone modification ChIP-seq of human liver explants show upregulation of multiple CXCL chemokines in AH. Liver sinusoidal endothelial cells (LSEC) are identified as an important source of CXCL expression in human liver, regulated by TNFα/NF-κB signaling. A super-enhancer is identified for multiple CXCL genes by multiple approaches. dCas9-KRAB-mediated epigenome editing or pharmacologic inhibition of Bromodomain and Extraterminal (BET) proteins, transcriptional regulators vital to super-enhancer function, decreases chemokine expression in vitro and decreases neutrophil infiltration in murine models of AH. Our findings highlight the role of super-enhancer in propagating inflammatory signaling by inducing chemokine expression and the therapeutic potential of BET inhibition in AH treatment.
Field-free spin-orbit torque-induced switching of perpendicular magnetization in a ferrimagnetic layer with a vertical composition gradient
Authors: Zheng Zhenyi , Zhang Yue , Lopez-Dominguez Victor , Sánchez-Tejerina Luis , Shi Jiacheng , Feng Xueqiang , Chen Lei , Wang Zilu , Zhang Zhizhong , Zhang Kun , Hong Bin , Xu Yong , Zhang Youguang , Carpentieri Mario , Fert Albert , Finocchio Giovanni , Zhao Weisheng , Khalili Amiri Pedram 
Published: July 2021

AbstractCurrent-induced spin-orbit torques (SOTs) are of interest for fast and energy-efficient manipulation of magnetic order in spintronic devices. To be deterministic, however, switching of perpendicularly magnetized materials by SOT requires a mechanism for in-plane symmetry breaking. Existing methods to do so involve the application of an in-plane bias magnetic field, or incorporation of in-plane structural asymmetry in the device, both of which can be difficult to implement in practical applications. Here, we report bias-field-free SOT switching in a single perpendicular CoTb layer with an engineered vertical composition gradient. The vertical structural inversion asymmetry induces strong intrinsic SOTs and a gradient-driven Dzyaloshinskii–Moriya interaction (g-DMI), which breaks the in-plane symmetry during the switching process. Micromagnetic simulations are in agreement with experimental results, and elucidate the role of g-DMI in the deterministic switching processes. This bias-field-free switching scheme for perpendicular ferrimagnets with g-DMI provides a strategy for efficient and compact SOT device design.
Oncogene-induced senescence in hematopoietic progenitors features myeloid restricted hematopoiesis, chronic inflammation and histiocytosis
Authors: Biavasco Riccardo , Lettera Emanuele , Giannetti Kety , Gilioli Diego , Beretta Stefano , Conti Anastasia , Scala Serena , Cesana Daniela , Gallina Pierangela , Norelli Margherita , Basso-Ricci Luca , Bondanza Attilio , Cavalli Giulio , Ponzoni Maurilio , Dagna Lorenzo , Doglioni Claudio , Aiuti Alessandro , Merelli Ivan , Di Micco Raffaella , Montini Eugenio 
Published: July 2021

ABSTRACTActivating mutations in the BRAF-MAPK pathway have been reported in histiocytoses, hematological inflammatory neoplasms characterized by multi-organ dissemination of pro-inflammatory myeloid cells. Here, we generate a humanized mouse model of transplantation of human hematopoietic stem and progenitor cells (HSPCs) expressing the activated form of BRAF (BRAFV600E). All mice transplanted with BRAFV600E-expressing HSPCs succumb to bone marrow failure, displaying myeloid-restricted hematopoiesis and multi-organ dissemination of aberrant mononuclear phagocytes. At the basis of this aggressive phenotype, we uncover the engagement of a senescence program, characterized by DNA damage response activation and a senescence-associated secretory phenotype, which affects also non-mutated bystander cells. Mechanistically, we identify TNFα as a key determinant of paracrine senescence and myeloid-restricted hematopoiesis and show that its inhibition dampens inflammation, delays disease onset and rescues hematopoietic defects in bystander cells. Our work establishes that senescence in the human hematopoietic system links oncogene-activation to the systemic inflammation observed in histiocytic neoplasms.
Surface enrichment and diffusion enabling gradient-doping and coating of Ni-rich cathode toward Li-ion batteries
Authors: Yu Haifeng , Cao Yueqiang , Chen Long , Hu Yanjie , Duan Xuezhi , Dai Sheng , Li Chunzhong , Jiang Hao 
Published: July 2021

AbstractCritical barriers to layered Ni-rich cathode commercialisation include their rapid capacity fading and thermal runaway from crystal disintegration and their interfacial instability. Structure combines surface modification is the ultimate choice to overcome these. Here, a synchronous gradient Al-doped and LiAlO2-coated LiNi0.9Co0.1O2 cathode is designed and prepared by using an oxalate-assisted deposition and subsequent thermally driven diffusion method. Theoretical calculations, in situ X-ray diffraction results and finite-element simulation verify that Al3+ moves to the tetrahedral interstices prior to Ni2+ that eliminates the Li/Ni disorder and internal structure stress. The Li+-conductive LiAlO2 skin prevents electrolyte penetration of the boundaries and reduces side reactions. These help the Ni-rich cathode maintain a 97.4% cycle performance after 100 cycles, and a rapid charging ability of 127.7 mAh g−1 at 20 C. A 3.5-Ah pouch cell with the cathode and graphite anode showed more than a 500-long cycle life with only a 5.6% capacity loss.
Synergistic broad-spectrum antibacterial activity of Hypoxis hemerocallidea-derived silver nanoparticles and streptomycin against respiratory pathobionts
Authors: Aremu Oluwole S. , Qwebani-Ogunleye T. , Katata-Seru Lebogang , Mkhize Zimbili , Trant John F. 
Published: July 2021

AbstractRespiratory tract infections arise due to the introduction of microbes into the airway, disrupting the normal, healthy, complex interdependent microbiome. The selective disruption of this community can be either beneficial or dangerous. Nanoparticles are a potential tool for modifying this population. Coated silver nanoparticles (AgNPs) were synthesized using ethanolic extracts of Hypoxis hemerocallidea (EEHH), a Southern African plant used extensively in traditional medicine and the source of many bioactive secondary metabolites. The room temperature reaction between silver nitrate and EEHH forms largely spherical AgNPs with an average diameter of 6–20 nm. These nanoparticles show similar levels of antibacterial activity as the broad-spectrum antibiotic streptomycin against Bacillus cereus, Streptococcus pneumonia, Escherichia coli, Pseudomonas aeuroginosa, and Moraxella catarrhalis. However, the AgNPs synergistically increase the antibacterial activity of streptomycin when they are applied in combination (30–52%). AgNPs are reiterated to be promising dual-function antibiotics, synergistically enhancing activity while also acting as delivery agents for small molecules.
Size conservation emerges spontaneously in biomolecular condensates formed by scaffolds and surfactant clients
Authors: Sanchez-Burgos Ignacio , Joseph Jerelle A. , Collepardo-Guevara Rosana , Espinosa Jorge R. 
Published: July 2021

AbstractBiomolecular condensates are liquid-like membraneless compartments that contribute to the spatiotemporal organization of proteins, RNA, and other biomolecules inside cells. Some membraneless compartments, such as nucleoli, are dispersed as different condensates that do not grow beyond a certain size, or do not present coalescence over time. In this work, using a minimal protein model, we show that phase separation of binary mixtures of scaffolds and low-valency clients that can act as surfactants—i.e., that significantly reduce the droplet surface tension—can yield either a single drop or multiple droplets that conserve their sizes on long timescales (herein ‘multidroplet size-conserved’ scenario’), depending on the scaffold to client ratio. Our simulations demonstrate that protein connectivity and condensate surface tension regulate the balance between these two scenarios. The multidroplet size-conserved scenario spontaneously arises at increasing surfactant-to-scaffold concentrations, when the interfacial penalty for creating small liquid droplets is sufficiently reduced by the surfactant proteins that are preferentially located at the interface. In contrast, low surfactant-to-scaffold concentrations enable continuous growth and fusion of droplets without restrictions. Overall, our work proposes one thermodynamic mechanism to help rationalize how size-conserved coexisting condensates can persist inside cells—shedding light on the roles of protein connectivity, binding affinity, and droplet composition in this process.
Robust topological designs for extreme metamaterial micro-structures
Authors: Chatterjee Tanmoy , Chakraborty Souvik , Goswami Somdatta , Adhikari Sondipon , Friswell Michael I. 
Published: July 2021

AbstractWe demonstrate that the consideration of material uncertainty can dramatically impact the optimal topological micro-structural configuration of mechanical metamaterials. The robust optimization problem is formulated in such a way that it facilitates the emergence of extreme mechanical properties of metamaterials. The algorithm is based on the bi-directional evolutionary topology optimization and energy-based homogenization approach. To simulate additive manufacturing uncertainty, combinations of spatial variation of the elastic modulus and/or, parametric variation of the Poisson’s ratio at the unit cell level are considered. Computationally parallel Monte Carlo simulations are performed to quantify the effect of input material uncertainty to the mechanical properties of interest. Results are shown for four configurations of extreme mechanical properties: (1) maximum bulk modulus (2) maximum shear modulus (3) minimum negative Poisson’s ratio (auxetic metamaterial) and (4) maximum equivalent elastic modulus. The study illustrates the importance of considering uncertainty for topology optimization of metamaterials with extreme mechanical performance. The results reveal that robust design leads to improvement in terms of (1) optimal mean performance (2) least sensitive design, and (3) elastic properties of the metamaterials compared to the corresponding deterministic design. Many interesting topological patterns have been obtained for guiding the extreme material robust design.
Determination of the characteristic inactivation fluence for SARS-CoV-2 under UV-C radiation considering light absorption in culture media
Authors: Martínez-Antón Juan Carlos , Brun Alejandro , Vázquez Daniel , Moreno Sandra , Fernández-Balbuena Antonio A. , Alda Javier 
Published: July 2021

AbstractThe optical absorption coefficient of culture media is critical for the survival analysis of pathogens under optical irradiation. The quality of the results obtained from experiments relies on the optical analysis of the spatial distribution of fluence which also depends on the geometry of the sample. In this contribution, we consider both the geometrical shape and the culture medium’s absorption coefficient to evaluate how the spatial distribution of optical radiation affects pathogens/viruses. In this work, we exposed SARS-CoV-2 to UV-C radiation ($$\lambda$$
λ
= 254 nm) and we calculated—considering the influence of the optical absorption of the culture medium—a characteristic inactivation fluence of $$F_i$$

F
i

= 4.7 J/m2, or an equivalent 10% survival (D90 dose) of 10.8 J/m2. Experimentally, we diluted the virus into sessile drops of Dulbecco’s Modified Eagle Medium to evaluate pathogen activity after controlled doses of UV irradiation. To validate the optical absorption mode, we carried out an additional experiment where we varied droplet size. Our model—including optical absorption and geometrical considerations—provides robust results among a variety of experimental situations, and represents our experimental conditions more accurately. These results will help to evaluate the capability of UV disinfecting strategies applied to a variety of everyday situations, including the case of micro-droplets generated by respiratory functions.
Structural colors of pearls
Authors: Ozaki Ryotaro , Kikumoto Kei , Takagaki Masataka , Kadowaki Kazunori , Odawara Kazushi 
Published: July 2021

AbstractThe luster is the most important characteristic of pearls, whose colors depend on periodic structures of aragonite crystal layers and conchiolin sheets. We here propose an optical model for analyzing the structural colors of pearls that includes the transmission, reflection, and scattering of light in pearls. Unlike other structural color materials, internal light scattering and its transmission are the keys to understanding the optical properties of pearls. The appearance of pearls is determined by the superposition of transmitted and reflected light. The transmission and reflection spectra of pearls calculated using the proposed model show good agreement with experimental results. We also demonstrate the rendering of images of pearls using the calculated spectra. Furthermore, the appearance of pearls with different layer thicknesses are predicted by calculation based on the optical model.
Quantitative multiparametric MRI as a non-invasive stratification tool in children and adolescents with autoimmune liver disease
Authors: Janowski Kamil , Shumbayawonda Elizabeth , Cheng Lin , Langford Caitlin , Dennis Andrea , Kelly Matt , Pronicki Maciej , Grajkowska Wieslawa , Wozniak Malgorzata , Pawliszak Piotr , Chełstowska Sylwia , Jurkiewicz Elzbieta , Banerjee Rajarshi , Socha Piotr 
Published: July 2021

AbstractAutoimmune hepatitis (AIH) and autoimmune sclerosing cholangitis (ASC) are two very closely related autoimmune liver diseases with overlapping clinical features and similar management strategies. The purpose of this study was to assess the utility of quantitative imaging markers to distinguish ASC from AIH in paediatrics. 66 participants (N = 52 AIH, N = 14 ASC) aged 14.4 ± 3.3 years scheduled to undergo routine biopsy and baseline serum liver biochemistry testing were invited to undergo MRI (non-contrast abdominal MRI and 3D fast spin-echo MRCP). Multiparametric MRI was used to measure fibro-inflammation with corrected T1 (cT1), while the biliary tree was modelled using quantitative MRCP (MRCP +). Mann–Whitney U tests were performed to compare liver function tests with imaging markers between patient groups (ASC vs AIH). Receiver operating characteristic curves and stepwise logistic regressions were used to identify the best combination of markers to discriminate between ASC and AIH. Correlations between liver function tests and imaging markers were performed using Spearman’s rank correlation. cT1 was significantly correlated with liver function tests (range 0.33 ≤ R ≤ 56, p < 0.05), as well as with fibrosis, lobular and portal inflammation (range 0.31 ≤ R ≤ 42, p < 0.05). 19 MRCP + metrics correlated significantly with liver function tests (range 0.29 ≤ R ≤ 0.43, p < 0.05). GGT and MRCP + metrics were significantly higher in ASC compared to those with AIH. The best multivariable model for distinguishing ASC from AIH included total number of ducts and the sum of relative severity of both strictures and dilatations AUC: 0.91 (95% CI 0.78–1). Quantitative MRCP metrics are a good discriminator of ASC from AIH.
Diverse effects of pan-ROCK and ROCK2 inhibitors on 2 D and 3D cultured human trabecular meshwork (HTM) cells treated with TGFβ2
Authors: Watanabe Megumi , Ida Yosuke , Ohguro Hiroshi , Ota Chiaki , Hikage Fumihito 
Published: July 2021

AbstractA pan-ROCK-inhibitor, ripasudil (Rip), and a ROCK2 inhibitor, KD025, were used To study the effects of Rho-associated coiled-coil containing protein kinase (ROCK)1 and 2 on two-dimensional (2D) and three-dimensional (3D) cultures of a TGFβ2-treated human trabecular meshwork (HTM) cells. In the presence of 5 ng/mL TGFβ2, the effects of these inhibitors were characterized by transendothelial electrical resistance (TEER), FITC-dextran permeability, and the size and stiffness of 3D sphenoids, the expression of extracellular matrix (ECM) including collagen1, 4 and 6, and fibronectin, α-smooth muscle actin, a tissue inhibitor of metalloproteinase (TIMP)1–4, and matrix metalloproteinase (MMP)2, 9 and 14. TGFβ2 caused a significant increase in the TEER values, and decrease in FITC-dextran permeability, as well as a decrease in the sizes and stiffness of the 3D sphenoids. In the presence of ROCK inhibitors, the TGFβ2-induced effects of the TEER and FITC-dextran permeability were inhibited, especially by KD025. Rip induced a significant increase in sizes and a decrease in the stiffness of the TGFβ2-treated 3D sphenoids, although the effects of KD025 were weaker. Gene expressions of most of the ECMs, TIMP2 and MMP9 of 2D and 3D HTM cells were significantly up-regulated by TGFβ2. Those were significantly and differently modulated by Rip or KD025.
Negative potential energy content analysis in cracked rotors whirl response
Authors: AL-Shudeifat Mohammad A. , Alhammadi Fatima K. 
Published: July 2021

AbstractAppearance of transverse cracks in rotor systems mainly affects their stiffness content. The stability of such systems at steady-state running is usually analyzed by using the Floquet’s theory. Accordingly, the instability zones of rotational speeds are dominated by negative stiffness content in the whirl response in the vicinity of critical rotational speeds. Consequently, an effective stiffness measure is introduced here to analyze the effect of the crack and the unbalance force vector orientation on the intensity of negative potential and stiffness content in the whirl response. The effective stiffness expression is obtained from the direct integration of the equations of motion of the considered cracked rotor system. The proposed effective stiffness measure is applied for steady-state and transient operations using the Jeffcott rotor model with open and breathing crack models. The intensity of negative potential and stiffness content in the numerical and experimental whirl responses is found to be critically depending on the propagation level of the crack and the unbalance force vector orientation. Therefore, this can be proposed as a crack detection tool in cracked rotor systems that either exhibit recurrent passage through the critical rotational speeds or steady-state running.
Extent of impact of deep-sea nodule mining midwater plumes is influenced by sediment loading, turbulence and thresholds
Authors: Muñoz-Royo Carlos , Peacock Thomas , Alford Matthew H. , Smith Jerome A. , Le Boyer Arnaud , Kulkarni Chinmay S. , Lermusiaux Pierre F. J. , Haley Patrick J. , Mirabito Chris , Wang Dayang , Adams E. Eric , Ouillon Raphael , Breugem Alexander , Decrop Boudewijn , Lanckriet Thijs , Supekar Rohit B. , Rzeznik Andrew J. , Gartman Amy , Ju Se-Jong 
Published: July 2021

AbstractDeep-sea polymetallic nodule mining research activity has substantially increased in recent years, but the expected level of environmental impact is still being established. One environmental concern is the discharge of a sediment plume into the midwater column. We performed a dedicated field study using sediment from the Clarion Clipperton Fracture Zone. The plume was monitored and tracked using both established and novel instrumentation, including acoustic and turbulence measurements. Our field studies reveal that modeling can reliably predict the properties of a midwater plume in the vicinity of the discharge and that sediment aggregation effects are not significant. The plume model is used to drive a numerical simulation of a commercial-scale operation in the Clarion Clipperton Fracture Zone. Key takeaways are that the scale of impact of the plume is notably influenced by the values of environmentally acceptable threshold levels, the quantity of discharged sediment, and the turbulent diffusivity in the Clarion Clipperton Fracture Zone.