bluuebunny/crossref_metadata_2025_split huggingface dataset:
Explaining among-country variation in COVID-19 case fatality rate
Authors: Sorci Gabriele , Faivre Bruno , Morand Serge 
Published: November 2020

AbstractWhile the epidemic of SARS-CoV-2 has spread worldwide, there is much concern over the mortality rate that the infection induces. Available data suggest that COVID-19 case fatality rate had varied temporally (as the epidemic has progressed) and spatially (among countries). Here, we attempted to identify key factors possibly explaining the variability in case fatality rate across countries. We used data on the temporal trajectory of case fatality rate provided by the European Center for Disease Prevention and Control, and country-specific data on different metrics describing the incidence of known comorbidity factors associated with an increased risk of COVID-19 mortality at the individual level. We also compiled data on demography, economy and political regimes for each country. We found that temporal trajectories of case fatality rate greatly vary among countries. We found several factors associated with temporal changes in case fatality rate both among variables describing comorbidity risk and demographic, economic and political variables. In particular, countries with the highest values of DALYs lost to cardiovascular, cancer and chronic respiratory diseases had the highest values of COVID-19 CFR. CFR was also positively associated with the death rate due to smoking in people over 70 years. Interestingly, CFR was negatively associated with share of death due to lower respiratory infections. Among the demographic, economic and political variables, CFR was positively associated with share of the population over 70, GDP per capita, and level of democracy, while it was negatively associated with number of hospital beds ×1000. Overall, these results emphasize the role of comorbidity and socio-economic factors as possible drivers of COVID-19 case fatality rate at the population level.
Antibiofilm activity of flavonoids on staphylococcal biofilms through targeting BAP amyloids
Authors: Matilla-Cuenca Leticia , Gil Carmen , Cuesta Sergio , Rapún-Araiz Beatriz , Žiemytė Miglė , Mira Alex , Lasa Iñigo , Valle Jaione 
Published: November 2020

AbstractThe opportunistic pathogen Staphylococcus aureus is responsible for causing infections related to indwelling medical devices, where this pathogen is able to attach and form biofilms. The intrinsic properties given by the self-produced extracellular biofilm matrix confer high resistance to antibiotics, triggering infections difficult to treat. Therefore, novel antibiofilm strategies targeting matrix components are urgently needed. The Biofilm Associated Protein, Bap, expressed by staphylococcal species adopts functional amyloid-like structures as scaffolds of the biofilm matrix. In this work we have focused on identifying agents targeting Bap-related amyloid-like aggregates as a strategy to combat S. aureus biofilm-related infections. We identified that the flavonoids, quercetin, myricetin and scutellarein specifically inhibited Bap-mediated biofilm formation of S. aureus and other staphylococcal species. By using in vitro aggregation assays and the cell-based methodology for generation of amyloid aggregates based on the Curli-Dependent Amyloid Generator system (C-DAG), we demonstrated that these polyphenols prevented the assembly of Bap-related amyloid-like structures. Finally, using an in vivo catheter infection model, we showed that quercetin and myricetin significantly reduced catheter colonization by S. aureus. These results support the use of polyphenols as anti-amyloids molecules that can be used to treat biofilm-related infections.
Machine learning approach for elucidating and predicting the role of synthesis parameters on the shape and size of TiO2 nanoparticles
Authors: Pellegrino Francesco , Isopescu Raluca , Pellutiè Letizia , Sordello Fabrizio , Rossi Andrea M. , Ortel Erik , Martra Gianmario , Hodoroaba Vasile-Dan , Maurino Valter 
Published: November 2020

AbstractIn the present work a series of design rules are developed in order to tune the morphology of TiO2 nanoparticles through hydrothermal process. Through a careful experimental design, the influence of relevant process parameters on the synthesis outcome are studied, reaching to the develop predictive models by using Machine Learning methods. The models, after the validation and training, are able to predict with high accuracy the synthesis outcome in terms of nanoparticle size, polydispersity and aspect ratio. Furthermore, they are implemented by reverse engineering approach to do the inverse process, i.e. obtain the optimal synthesis parameters given a specific product characteristic. For the first time, it is presented a synthesis method that allows continuous and precise control of NPs morphology with the possibility to tune the aspect ratio over a large range from 1.4 (perfect truncated bipyramids) to 6 (elongated nanoparticles) and the length from 20 to 140 nm.
The influence of the pore shape on the bulk modulus and the Biot coefficient of fluid-saturated porous rocks
Authors: Selvadurai A. P. S. , Suvorov A. P. 
Published: November 2020

AbstractFluid-saturated rocks are multi-phasic materials and the mechanics of partitioning the externally applied stresses between the porous skeleton of the rock and the interstitial fluids has to take into consideration the mechanical behaviour of the phases. In these studies the porosity of the multi-phasic material is important for estimating the multi-phasic properties and most studies treat the porosity as a scalar measure without addressing the influence of pore shape and pore geometry. This paper shows that both the overall bulk modulus of a porous medium and the Biot coefficient depend on the shape of the pores. Pores with shapes resembling either thin oblate spheroids or spheres are considered. The Mori–Tanaka and the self-consistent methods are used to estimate the overall properties and the results are compared with experimental data. The pore density and the aspect ratio of the spheroidal pores influence the porosity of the geomaterials. For partially saturated rocks, the equivalent bulk modulus of the fluid–gas mixture occupying the pore space can also be obtained. The paper also examines the influence of the pore shape in estimating the Biot coefficient that controls the stress partitioning in fluid-saturated poroelastic materials.
Catalytic liquefaction of sewage sludge to small molecular weight chemicals
Authors: Wang Yuehu , Tian Feihong , Guo Peimei , Fu Dazhen , Heeres Hero Jan , Tang Taotao , Yuan Huayu , Wang Bing , Li Jiang 
Published: November 2020

AbstractThe catalytic hydrotreatment of sewage sludge, the wet solid byproducts from wastewater treatment plants, using supported Ir, Pt, Pd, Ru catalysts had been investigated with different solvent conditions. Reactions were carried out in a batch set-up at elevated temperatures (400 °C) using a hydrogen donor (formic acid (FA) in isopropanol (IPA) or hydrogen gas), with sewage sludge obtained from different sampling places. Sewage sludge conversions of up to 83.72% were achieved using Pt/C, whereas the performance for the others catalysts is different and solvent had a strong effect on the conversion rate and product constitution. The sewage sludge oils were characterised using a range of analytical techniques (GC, GC–MS, GCxGC, GPC) and were shown to consist of monomers, mainly alkanes and higher oligomers.
Chitosan overlaid Fe3O4/rGO nanocomposite for targeted drug delivery, imaging, and biomedical applications
Authors: Karthika Viswanathan , AlSalhi Mohamad S. , Devanesan Sandhanasamy , Gopinath Kasi , Arumugam Ayyakannu , Govindarajan Marimuthu 
Published: November 2020

AbstractA hybrid and straightforward nanosystem that can be used simultaneously for cancer-targeted fluorescence imaging and targeted drug delivery in vitro was reported in this study. A chitosan (CS) polymer coated with reduced graphene oxide (rGO) and implanted with Fe3O4 nanoparticles was fabricated. The fundamental physicochemical properties were confirmed via FT-IR, XRD, FE-SEM, HR-TEM, XPS, and VSM analysis. The in vivo toxicity study in zebrafish showed that the nanocomposite was not toxic. The in vitro drug loading amount was 0.448 mg/mL−1 for doxorubicin, an anticancer therapeutic, in the rGO/Fe3O4/CS nanocomposite. Furthermore, the pH-regulated release was observed using folic acid. Cellular uptake and multimodal imaging revealed the benefit of the folic acid-conjugated nanocomposite as a drug carrier, which remarkably improves the doxorubicin accumulation inside the cancer cells over-express folate receptors. The rGO/Fe3O4/CS nanocomposite showed enhanced antibiofilm and antioxidant properties compared to other materials. This study's outcomes support the use of the nanocomposite in targeted chemotherapy and the potential applications in the polymer, cosmetic, biomedical, and food industries.
Short-term comparison of preoperative and postoperative pain after indirect decompression surgery and direct decompression surgery in patients with degenerative spondylolisthesis
Authors: Hiyama Akihiko , Katoh Hiroyuki , Sakai Daisuke , Tanaka Masahiro , Sato Masato , Watanabe Masahiko 
Published: November 2020

AbstractThe purpose of this study was to compare the short-term clinical outcomes between extreme lateral interbody fusion (XLIF) and minimally invasive surgery (MIS)–transforaminal interbody fusion (TLIF) in patients with degenerative spondylolisthesis with stenosis. One hundred-six patients were enrolled; 44 were treated with MIS–TLIF (direct decompression group; DP), and 62 were treated with XLIF (indirect decompression group; IDP). Perioperative indexes included operation time and intraoperative bleeding. Perioperative indexes preoperative and postoperative numeric rating scale (NRS) scores for low back pain (NRS-BP), leg pain (NRS-LP), and leg numbness (NRS-LN), and the preoperative score on the Japanese version of the painDETECT questionnaire (PDQ-J) were also assessed. The average follow-up period for the collection of NRS scores was 12.6 months. The operation time was significantly shorter in the IDP than in the DP group (109.9 ± 35.4 vs. 153.3 ± 50.9 min; p < 0.001). Intraoperative blood loss was also significantly less in the IDP group than in the DP group (85.4 ± 125.4 vs. 258.3 ± 220.4 mL; p < 0.001). The PDQ-J score and preoperative NRS scores (NRS-BP, NRS-LP, and NRS-LN) did not differ significantly between groups. Less improvement in the NRS-BP (ΔNRS-BP) was observed in the DP group than in the IDP group (p < 0.05). Although pain improved after surgery in both groups, IDP surgery was advantageous in minimizing bleeding and preserving posterior support elements such as the facet joints, lamina, and paraspinal muscles. These findings suggest that this may have contributed to the higher rate of improvement in low back pain compared with DP surgery.
The POLD1R689W variant increases the sensitivity of colorectal cancer cells to ATR and CHK1 inhibitors
Authors: Job Albert , Tatura Marina , Schäfer Cora , Lutz Veronika , Schneider Hanna , Lankat-Buttgereit Brigitte , Zielinski Alexandra , Borgmann Kerstin , Bauer Christian , Gress Thomas M. , Buchholz Malte , Gallmeier Eike 
Published: November 2020

AbstractInhibition of the kinase ATR, a central regulator of the DNA damage response, eliminates subsets of cancer cells in certain tumors. As previously shown, this is at least partly attributable to synthetic lethal interactions between ATR and POLD1, the catalytic subunit of the polymerase δ. Various POLD1 variants have been found in colorectal cancer, but their significance as therapeutic targets for ATR pathway inhibition remains unknown. Using CRISPR/Cas9 in the colorectal cancer cell line DLD-1, which harbors four POLD1 variants, we established heterozygous POLD1-knockout clones with exclusive expression of distinct variants to determine the functional relevance of these variants individually by assessing their impact on ATR pathway activation, DNA replication, and cellular sensitivity to inhibition of ATR or its effector kinase CHK1. Of the four variants analyzed, only POLD1R689W affected POLD1 function, as demonstrated by compensatory ATR pathway activation and impaired DNA replication. Upon treatment with ATR or CHK1 inhibitors, POLD1R689W strongly decreased cell survival in vitro, which was attributable at least partly to S phase impairment and apoptosis. Similarly, treatment with the ATR inhibitor AZD6738 inhibited growth of murine xenograft tumors, harboring the POLD1R689W variant, in vivo. Our POLD1-knockout model thus complements algorithm-based models to predict the pathogenicity of tumor-specific variants of unknown significance and illustrates a novel and potentially clinically relevant therapeutic approach using ATR/CHK1 inhibitors in POLD1-deficient tumors.
Pooling RT-qPCR testing for SARS-CoV-2 in 1000 individuals of healthy and infection-suspected patients
Authors: Hirotsu Yosuke , Maejima Makoto , Shibusawa Masahiro , Nagakubo Yuki , Hosaka Kazuhiro , Amemiya Kenji , Sueki Hitomi , Hayakawa Miyoko , Mochizuki Hitoshi , Tsutsui Toshiharu , Kakizaki Yumiko , Miyashita Yoshihiro , Omata Masao 
Published: November 2020

AbstractSevere acute respiratory coronavirus 2 (SARS-CoV-2) testing reagents are expected to become scarce worldwide. However, little is known regarding whether pooling of samples accurately detects SARS-CoV-2. To validate the feasibility of pooling samples, serial dilution analysis and spike-in experiments were conducted using synthetic DNA and nucleic acids extracted from SARS-CoV-2-positive and -negative patients. Furthermore, we studied 1000 individuals, 667 of whom were “healthy” individuals (195 healthcare workers and 472 hospitalized patients with disorders other than COVID-19 infection), and 333 infection-suspected patients with cough and fever. Serial dilution analysis showed a limit of detection of around 10–100 viral genome copies according to the protocol of the National Institute of Infectious Diseases, Japan. Spike-in experiments demonstrated that RT-qPCR detected positive signals in pooled samples with SARS-CoV-2-negative and -positive patients at 5-, 10-, 20-fold dilutions. By screening with this pooling strategy, by the end of April 2020 there were 12 SARS-CoV-2-positive patients in 333 infection-suspected patients (3.6%) and zero in 667 “healthy” controls. We obtained these results with a total of 538 runs using the pooling strategy, compared with 1000 standard runs. In a prospective study, we successfully detected SARS-CoV-2 using 10- to 20-fold diluted samples of nasopharyngeal swabs from eighteen COVID-19 patients with wide ranges of viral load. Pooling sample is feasible for conserving test reagents and detecting SARS-CoV-2 in clinical settings. This strategy will help us to research the prevalence infected individuals and provide infected-status information to prevent the spread of the virus and nosocomial transmission.
Bidirectional, non-necrotizing glomerular crescents are the critical pathology in X-linked Alport syndrome mouse model harboring nonsense mutation of human COL4A5
Authors: Song Jiang Ying , Saga Nobuyuki , Kawanishi Kunio , Hashikami Kentaro , Takeyama Michiyasu , Nagata Michio 
Published: November 2020

AbstractX-linked Alport syndrome (XLAS) is a progressive kidney disease caused by genetic abnormalities of COL4A5. Lack of collagen IV α5 chain staining and “basket-weave” by electron microscopy (EM) in glomerular basement membrane (GBM) are its typical pathology. However, the causal relationship between GBM defects and progressive nephropathy is unknown. We analyzed sequential pathology in a mouse model of XLAS harboring a human nonsense mutation of COL4A5. In mutant mice, nephropathy commenced from focal GBM irregularity by EM at 6 weeks of age, prior to exclusive crescents at 13 weeks of age. Low-vacuum scanning EM demonstrated substantial ragged features in GBM, and crescents were closely associated with fibrinoid exudate, despite lack of GBM break and podocyte depletion at 13 weeks of age. Crescents were derived from two sites by different cellular components. One was CD44 + cells, often with fibrinoid exudate in the urinary space, and the other was accumulation of α-SMA + cells in the thickened Bowman’s capsule. These changes finally coalesced, leading to global obliteration. In conclusion, vulnerability of glomerular and capsular barriers to the structural defect in collagen IV may cause non-necrotizing crescents via activation of PECs and migration of interstitial fibroblasts, promoting kidney disease in this model.
Three-dimensional reconstruction of laryngeal cancer with whole organ serial immunohistochemical sections
Authors: Tian Jun , Qian Bo , Zhang Sanmei , Guo Rui , Zhang Hui , Jeannon J.-P. , Jin Rongxiu , Feng Xiang , Zhan Yangni , Liu Jie , He Pengfei , Guo Jue , Li Le , Jia Yue , Huang Fuhui , Wang Binquan 
Published: November 2020

AbstractThree-dimensional (3D) image reconstruction of tumors based on serial histological sectioning is one of the most powerful methods for accurate high-resolution visualization of tumor structures. However, 3D histological reconstruction of whole tumor has not yet been achieved. We established a high-resolution 3D model of molecular marked whole laryngeal cancer by optimizing the currently available techniques. A series of 5,388 HE stained or immunohistochemically stained whole light microscopic images (200 ×) were acquired (15.61 TB).The data set of block-face images (96.2 GB) was also captured. Direct volume rendering of serial 6.25 × light microscopy images did not demonstrate the major characteristics of the laryngeal cancer as expected. Based on fusion of two datasets, the accurate boundary of laryngeal tumor bulk was visualized in an anatomically realistic context. In the regions of interest, micro tumor structure, budding, cell proliferation and tumor lymph vessels were well represented in 3D after segmentation, which highlighted the advantages of 3D reconstruction of light microscopy images. In conclusion, generating 3D digital histopathological images of a whole solid tumor based on current technology is feasible. However, data mining strategy should be developed for complete utilization of the large amount of data generated.
Identification of mesenchymal stromal cell survival responses to antimicrobial silver ion concentrations released from orthopaedic implants
Authors: Souter Paul , Vaughan John , Butcher Kerry , Dowle Adam , Cunningham Jim , Dodd James , Hall Michael , Wilson Darren , Horner Alan , Genever Paul 
Published: November 2020

AbstractAntimicrobial silver (Ag+) coatings on orthopaedic implants may reduce infection rates, but should not be to the detriment of regenerative cell populations, primarily mesenchymal stem/stromal cells (MSCs). We determined intramedullary silver release profiles in vivo, which were used to test relevant Ag+ concentrations on MSC function in vitro. We measured a rapid elution of Ag+ from intramedullary pins in a rat femoral implantation model, delivering a maximum potential concentration of 7.8 µM, which was below toxic levels determined for MSCs in vitro (EC50, 33 µM). Additionally, we present in vitro data of the reduced colonisation of implants by Staphylococcus aureus. MSCs exposed to Ag+ prior to/during osteogenic differentiation were not statistically affected. Notably, at clonal density, the colony-forming capacity of MSCs was significantly reduced in the presence of 10 µM Ag+, suggesting that a subpopulation of clonal MSCs was sensitive to Ag+ exposure. At a molecular level, surviving colony-forming MSCs treated with Ag+ demonstrated a significant upregulation of components of the peroxiredoxin/thioredoxin pathway and processes involved in glutathione metabolism compared to untreated controls. Inhibition of glutathione synthesis using l-buthionine sulfoxamine eliminated MSC clonogenicity in the presence of Ag+, which was rescued by exogenous glutathione.
Anti-herpes virus activity of the carnivorous botanical, Sarracenia purpurea
Authors: Kannan Latha , Kumar Ashok , Kumar Aradhana , Jacobs Bertram , Langland Jeffrey 
Published: November 2020

AbstractHerpes simplex virus type-1 (HSV-1), one of the most widely spread human viruses in the Herpesviridae family, causes herpes labialis (cold sores) and keratitis (inflammation of the cornea). Conventional treatment for HSV-1 infection includes pharmaceutical drugs, such as acyclovir and docosonal, which are efficacious but maintain the potential for the development of viral drug resistance. Extracts from the carnivorous pitcher plant,Sarracenia purpurea,have previously been shown to inhibit the replication of HSV-1. In this study, we demonstrate thatS. purpureaextracts can inhibit the replication of HSV-1 by two distinct mechanisms of action. These extracts directly inhibit extracellular virions or viral attachment to the human host cell as well as inhibiting the expression of viral immediate-early, early and late genes when added at various times post-infection. This botanical has previously been shown to inhibit the replication of poxviruses through the inhibition of early viral gene transcription. These results support a broader anti-viral activity ofS. purpureaextracts against both pox and herpes viruses.
Embryonic liver developmental trajectory revealed by single-cell RNA sequencing in the Foxa2eGFP mouse
Authors: Mu Tianhao , Xu Liqin , Zhong Yu , Liu Xinyu , Zhao Zhikun , Huang Chaoben , Lan Xiaofeng , Lufei Chengchen , Zhou Yi , Su Yixun , Xu Luang , Jiang Miaomiao , Zhou Hongpo , Lin Xinxin , Wu Liang , Peng Siqi , Liu Shiping , Brix Susanne , Dean Michael , Dunn Norris R. , Zaret Kenneth S. , Fu Xin-Yuan , Hou Yong 
Published: November 2020

AbstractThe liver and gallbladder are among the most important internal organs derived from the endoderm, yet the development of the liver and gallbladder in the early embryonic stages is not fully understood. Using a transgenic Foxa2eGFP reporter mouse line, we performed single-cell full-length mRNA sequencing on endodermal and hepatic cells isolated from ten embryonic stages, ranging from E7.5 to E15.5. We identified the embryonic liver developmental trajectory from gut endoderm to hepatoblasts and characterized the transcriptome of the hepatic lineage. More importantly, we identified liver primordium as the nascent hepatic progenitors with both gut and liver features and documented dynamic gene expression during the epithelial-hepatic transition (EHT) at the stage of liver specification during E9.5–11.5. We found six groups of genes switched on or off in the EHT process, including diverse transcripitional regulators that had not been previously known to be expressed during EHT. Moreover, we identified and revealed transcriptional profiling of gallbladder primordium at E9.5. The present data provides a high-resolution resource and critical insights for understanding the liver and gallbladder development.