bluuebunny/crossref_metadata_2025_split huggingface dataset:
Rationale for concurrent chemoradiotherapy for patients with stage III non-small-cell lung cancer
Authors:   on behalf of AstraZeneca UK Limited, Conibear John 
Published: December 2020

AbstractWhen treating patients with unresectable stage III non-small-cell lung cancer (NSCLC), those with a good performance status and disease measured within a radical treatment volume should be considered for definitive concurrent chemoradiotherapy (cCRT). This guidance is based on key scientific rationale from two large Phase 3 randomised studies and meta-analyses demonstrating the superiority of cCRT over sequential (sCRT). However, the efficacy of cCRT comes at the cost of increased acute toxicity versus sequential treatment. Currently, there are several documented approaches that are addressing this drawback, which this paper outlines. At the point of diagnosis, a multidisciplinary team (MDT) approach can enable accurate assessment of patients, to determine the optimal treatment strategy to minimise risks. In addition, reviewing the Advisory Committee on Radiation Oncology Practice (ACROP) guidelines can provide clinical oncologists with additional recommendations for outlining target volume and organ-at-risk delineation for standard clinical scenarios in definitive cCRT (and adjuvant radiotherapy). Furthermore, modern advances in radiotherapy treatment planning software and treatment delivery mean that radiation oncologists can safely treat substantially larger lung tumours with higher radiotherapy doses, with greater accuracy, whilst minimising the radiotherapy dose to the surrounding healthy tissues. The combination of these advances in cCRT may assist in creating comprehensive strategies to allow patients to receive potentially curative benefits from treatments such as immunotherapy, as well as minimising treatment-related risks.
The E3 ligase UBR2 regulates cell death under caspase deficiency via Erk/MAPK pathway
Authors: Villa Elodie , Paul Rachel , Meynet Ophélie , Volturo Sophie , Pinna Guillaume , Ricci Jean-Ehrland 
Published: December 2020

AbstractEscape from cell death is a key event in cancer establishment/progression. While apoptosis is often considered as the main cell death pathway, upon caspase inhibition, cell death is rather delayed than blocked leading to caspase-independent cell death (CICD). Although described for years, CICD’s underlying mechanism remains to be identified. Here, we performed a genome-wide siRNA lethality screening and identified the RING-Type E3 Ubiquitin Transferase (UBR2) as a specific regulator of CICD. Strikingly, UBR2 downregulation sensitized cells towards CICD while its overexpression was protective. We established that UBR2-dependent protection from CICD was mediated by the MAPK/Erk pathway. We then observed that UBR2 is overexpressed in several cancers, especially in breast cancers and contributes to CICD resistance. Therefore, our work defines UBR2 as a novel regulator of CICD, found overexpressed in cancer cells, suggesting that its targeting may represent an innovative way to kill tumor cells.
A blood transcriptome-based analysis of disease progression, immune regulation, and symptoms in coronavirus-infected patients
Authors: Sadanandam Anguraj , Bopp Tobias , Dixit Santosh , Knapp David J. H. F. , Emperumal Chitra Priya , Vergidis Paschalis , Rajalingam Krishnaraj , Melcher Alan , Kannan Nagarajan 
Published: December 2020

AbstractCOVID-19 patients show heterogeneity in clinical presentation and outcomes that makes pandemic control and strategy difficult; optimizing management requires a systems biology approach of understanding the disease. Here we sought to potentially understand and infer complex disease progression, immune regulation, and symptoms in patients infected with coronaviruses (35 SARS-CoV and 3 SARS-CoV-2 patients and 57 samples) at two different disease progression stages. Further, we compared coronavirus data with healthy individuals (n = 16) and patients with other infections (n = 144; all publicly available data). We applied inferential statistics (the COVID-engine platform) to RNA profiles (from limited number of samples) derived from peripheral blood mononuclear cells (PBMCs). Compared to healthy individuals, a subset of integrated blood-based gene profiles (signatures) distinguished acute-like (mimicking coronavirus-infected patients with prolonged hospitalization) from recovering-like patients. These signatures also hierarchically represented multiple (at the system level) parameters associated with PBMC including dysregulated cytokines, genes, pathways, networks of pathways/concepts, immune status, and cell types. Proof-of-principle observations included PBMC-based increases in cytokine storm-associated IL6, enhanced innate immunity (macrophages and neutrophils), and lower adaptive T and B cell immunity in patients with acute-like disease compared to those with recovery-like disease. Patients in the recovery-like stage showed significantly enhanced TNF, IFN-γ, anti-viral, HLA-DQA1, and HLA-F gene expression and cytolytic activity, and reduced pro-viral gene expression compared to those in the acute-like stage in PBMC. Besides, our analysis revealed overlapping genes associated with potential comorbidities (associated diabetes) and disease-like conditions (associated with thromboembolism, pneumonia, lung disease, and septicemia). Overall, our COVID-engine inferential statistics platform and study involving PBMC-based RNA profiling may help understand complex and variable system-wide responses displayed by coronavirus-infected patients with further validation.
FN-EDA mediates angiogenesis of hepatic fibrosis via integrin-VEGFR2 in a CD63 synergetic manner
Authors: Su Xiaonan , Ma Xiaowen , Xie Xiaoyu , Wu Hao , Wang Le , Feng Yuemin , Yu Zhen , Liu Chenxi , Qi Jianni , Zhu Qiang 
Published: December 2020

AbstractPathological angiogenesis is an important component of hepatic fibrosis along with fibrous deposition, but its role is not well understood. Here, we demonstrated that fibronectin containing extra domain A(FN-EDA), a fibronectin splice variant highly expressed in hepatic fibrosis, mediated angiogenesis in disease progression. FN-EDA was positively correlated with pathological angiogenesis in hepatic fibrosis, and a reduction in FN-EDA expression was associated with diminished intrahepatic angiogenesis and fibrosis. FN-EDA mostly colocalized with hepatic stellate cells (HSCs) and interference or blockage of FN-EDA attenuated migration and tube formation in co-cultured endothelial cells. Mechanistic studies indicated that FN-EDA was secreted to promote phosphorylation of VEGFR2 with the assistance of integrin and CD63. Targeting FN-EDA-integrin combination postponed the progression of hepatic angiogenesis and fibrosis in vivo. These results indicated that FN-EDA plays an emerging role in angiogenesis in hepatic fibrosis and could be a potential therapeutic intervention for the disease.
B7-CD28 co-stimulation modulates central tolerance via thymic clonal deletion and Treg generation through distinct mechanisms
Authors: Watanabe Masashi , Lu Ying , Breen Michael , Hodes Richard J. 
Published: December 2020

AbstractThe molecular and cellular mechanisms mediating thymic central tolerance and prevention of autoimmunity are not fully understood. Here we show that B7-CD28 co-stimulation and B7 expression by specific antigen-presenting cell (APC) types are required for clonal deletion and for regulatory T (Treg) cell generation from endogenous tissue-restricted antigen (TRA)-specific thymocytes. While B7-CD28 interaction is required for both clonal deletion and Treg induction, these two processes differ in their CD28 signaling requirements and in their dependence on B7-expressing dendritic cells, B cells, and thymic epithelial cells. Meanwhile, defective thymic clonal deletion due to altered B7-CD28 signaling results in the accumulation of mature, peripheral TRA-specific T cells capable of mediating destructive autoimmunity. Our findings thus reveal a function of B7-CD28 co-stimulation in shaping the T cell repertoire and limiting autoimmunity through both thymic clonal deletion and Treg cell generation.
Structure of native glycolipoprotein filaments in honeybee royal jelly
Authors: Mattei Simone , Ban Arvid , Picenoni Armin , Leibundgut Marc , Glockshuber Rudi , Boehringer Daniel 
Published: December 2020

AbstractRoyal jelly (RJ) is produced by honeybees (Apis mellifera) as nutrition during larval development. The high viscosity of RJ originates from high concentrations of long lipoprotein filaments that include the glycosylated major royal jelly protein 1 (MRJP1), the small protein apisimin and insect lipids. Using cryo-electron microscopy we reveal the architecture and the composition of RJ filaments, in which the MRJP1 forms the outer shell of the assembly, surrounding stacked apisimin tetramers harbouring tightly packed lipids in the centre. The structural data rationalize the pH-dependent disassembly of RJ filaments in the gut of the larvae.
Tumor derived UBR5 promotes ovarian cancer growth and metastasis through inducing immunosuppressive macrophages
Authors: Song Mei , Yeku Oladapo O. , Rafiq Sarwish , Purdon Terence , Dong Xue , Zhu Lijing , Zhang Tuo , Wang Huan , Yu Ziqi , Mai Junhua , Shen Haifa , Nixon Briana , Li Ming , Brentjens Renier J. , Ma Xiaojing 
Published: December 2020

AbstractImmunosuppressive tumor microenvironment (TME) and ascites-derived spheroids in ovarian cancer (OC) facilitate tumor growth and progression, and also pose major obstacles for cancer therapy. The molecular pathways involved in the OC-TME interactions, how the crosstalk impinges on OC aggression and chemoresistance are not well-characterized. Here, we demonstrate that tumor-derived UBR5, an E3 ligase overexpressed in human OC associated with poor prognosis, is essential for OC progression principally by promoting tumor-associated macrophage recruitment and activation via key chemokines and cytokines. UBR5 is also required to sustain cell-intrinsic β-catenin-mediated signaling to promote cellular adhesion/colonization and organoid formation by controlling the p53 protein level. OC-specific targeting of UBR5 strongly augments the survival benefit of conventional chemotherapy and immunotherapies. This work provides mechanistic insights into the novel oncogene-like functions of UBR5 in regulating the OC-TME crosstalk and suggests that UBR5 is a potential therapeutic target in OC treatment for modulating the TME and cancer stemness.
Comparison of computed tomographic imaging-guided hook wire localization and electromagnetic navigation bronchoscope localization in the resection of pulmonary nodules: a retrospective cohort study
Authors: Tian Yu , Wang Cong , Yue Weiming , Lu Ming , Tian Hui 
Published: December 2020

AbstractThe resection of nodules by thoracoscopic surgery is difficult because the nodules may be hard to identify. Preoperative localization of pulmonary nodules is widely used in the clinic. In this study, we retrospectively compared CT-guided hook wire localization and electromagnetic navigation bronchoscopy (ENB) localization of small pulmonary nodules before resection. Patients who underwent localization with CT-guided hook wire or ENB followed by video-assisted thoracoscopic surgery (VATS) at Qilu Hospital of Shandong University between January 2016 and December 2019 were retrospectively included. Clinical parameters, complication and failure rate, and localization time were compared between two groups. A total of 157 patients underwent the localization procedure successfully. Pulmonary nodules were localized by CT-guided hook wire in 105 patients and by ENB in 52 patients. The nodule size in ENB group was smaller than that in CT-guided localization group (P < 0.001). Both CT-guided localization and ENB localization were well tolerated in all patients, while ENB localization leaded to less complications (P = 0.0058). In CT-guided localization group, 6 patients failed to be located while none failed in ENB group (P = 0.079). The procedure time was 15.15 ± 3.70 min for CT-guided localization and 21.29 ± 4.00 min for ENB localization (P < 0.001). CT-guided localization is simple and feasible for uncertain pulmonary nodules before surgery. ENB localization could identify small lung nodules with high accuracy and achieve lower incidence of complications.
SARS-CoV-2 receptor ACE2 is co-expressed with genes related to transmembrane serine proteases, viral entry, immunity and cellular stress
Authors: Wruck Wasco , Adjaye James 
Published: December 2020

AbstractThe COVID-19 pandemic resulting from the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) which emerged in December 2019 in Wuhan in China has placed immense burden on national economies and global health. At present neither vaccination nor therapies are available. Here, we performed a meta-analysis of RNA-sequencing data from three studies employing human lung epithelial cells. Of these one focused on lung epithelial cells infected with SARS-CoV-2. We aimed at identifying genes co-expressed with angiotensin I converting enzyme 2 (ACE2) the human cell entry receptor of SARS-CoV-2, and unveiled several genes correlated or inversely correlated with high significance, among the most significant of these was the transmembrane serine protease 4 (TMPRSS4). Serine proteases are known to be involved in the infection process by priming the virus spike protein. Pathway analysis revealed virus infection amongst the most significantly correlated pathways. Gene Ontologies revealed regulation of viral life cycle, immune responses, pro-inflammatory responses- several interleukins such as IL6, IL1, IL20 and IL33, IFI16 regulating the interferon response to a virus, chemo-attraction of macrophages, and cellular stress resulting from activated Reactive Oxygen Species. We believe that this dataset will aid in a better understanding of the molecular mechanism(s) underlying COVID-19.
Metagenomic analysis reveals rapid development of soil biota on fresh volcanic ash
Authors: Song Hokyung , Kerfahi Dorsaf , Takahashi Koichi , Nixon Sophie L. , Tripathi Binu M. , Kim Hyoki , Tateno Ryunosuke , Adams Jonathan 
Published: December 2020

AbstractLittle is known of the earliest stages of soil biota development of volcanic ash, and how rapidly it can proceed. We investigated the potential for soil biota development during the first 3 years, using outdoor mesocosms of sterile, freshly fallen volcanic ash from the Sakurajima volcano, Japan. Mesocosms were positioned in a range of climates across Japan and compared over 3 years, against the developed soils of surrounding natural ecosystems. DNA was extracted from mesocosms and community composition assessed using 16S rRNA gene sequences. Metagenome sequences were obtained using shotgun metagenome sequencing. While at 12 months there was insufficient DNA for sequencing, by 24 months and 36 months, the ash-soil metagenomes already showed a similar diversity of functional genes to the developed soils, with a similar range of functions. In a surprising contrast with our hypotheses, we found that the developing ash-soil community already showed a similar gene function diversity, phylum diversity and overall relative abundances of kingdoms of life when compared to developed forest soils. The ash mesocosms also did not show any increased relative abundance of genes associated with autotrophy (rbc, coxL), nor increased relative abundance of genes that are associated with acquisition of nutrients from abiotic sources (nifH). Although gene identities and taxonomic affinities in the developing ash-soils are to some extent distinct from the natural vegetation soils, it is surprising that so many of the key components of a soil community develop already by the 24-month stage. In this system, however, rapid development may be facilitated by the relatively moderate pH of the Sakurajima ash, proximity of our mesocosms to propagule sources, and the rapid establishment of a productive bryophyte and lichen layer on the surface. Ash from other volcanoes richer in acids or more distant from propagule sources could show a different pattern and slower soil biota development.
Complimentary action of structured and unstructured domains of epsin supports clathrin-mediated endocytosis at high tension
Authors: Joseph Jophin G. , Osorio Carlos , Yee Vivian , Agrawal Ashutosh , Liu Allen P. 
Published: December 2020

AbstractMembrane tension plays an inhibitory role in clathrin-mediated endocytosis (CME) by impeding the transition of flat plasma membrane to hemispherical clathrin-coated structures (CCSs). Membrane tension also impedes the transition of hemispherical domes to omega-shaped CCSs. However, CME is not completely halted in cells under high tension conditions. Here we find that epsin, a membrane bending protein which inserts its N-terminus H0 helix into lipid bilayer, supports flat-to-dome transition of a CCS and stabilizes its curvature at high tension. This discovery is supported by molecular dynamic simulation of the epsin N-terminal homology (ENTH) domain that becomes more structured when embedded in a lipid bilayer. In addition, epsin has an intrinsically disordered protein (IDP) C-terminus domain which induces membrane curvature via steric repulsion. Insertion of H0 helix into lipid bilayer is not sufficient for stable epsin recruitment. Epsin’s binding to adaptor protein 2 and clathrin is critical for epsin’s association with CCSs under high tension conditions, supporting the importance of multivalent interactions in CCSs. Together, our results support a model where the ENTH and unstructured IDP region of epsin have complementary roles to ensure CME initiation and CCS maturation are unimpeded under high tension environments.
Dependency of solvation effects on metal identity in surface reactions
Authors: Zare Mehdi , Saleheen Mohammad , Kundu Subrata Kumar , Heyden Andreas 
Published: December 2020

AbstractSolvent interactions with adsorbed moieties involved in surface reactions are often believed to be similar for different metal surfaces. However, solvents alter the electronic structures of surface atoms, which in turn affects their interaction with adsorbed moieties. To reveal the importance of metal identity on aqueous solvent effects in heterogeneous catalysis, we studied solvent effects on the activation free energies of the O–H and C–H bond cleavages of ethylene glycol over the (111) facet of six transition metals (Ni, Pd, Pt, Cu, Ag, Au) using an explicit solvation approach based on a hybrid quantum mechanical/molecular mechanical (QM/MM) description of the potential energy surface. A significant metal dependence on aqueous solvation effects was observed that suggests solvation effects must be studied in detail for every reaction system. The main reason for this dependence could be traced back to a different amount of charge-transfer between the adsorbed moieties and metals in the reactant and transition states for the different metal surfaces.
Spin-constrained optoelectronic functionality in two-dimensional ferromagnetic semiconductor heterojunctions
Authors: Guo Yilv , Zhang Yehui , Zhou Zhaobo , Zhang Xiwen , Wang Bing , Yuan Shijun , Dong Shuai , Wang Jinlan 
Published: December 2020

A new type of spin-constrained optoelectronic device model implemented using 2D ferromagnetic semiconductor heterostructures is proposed, which utilizes the coupling between the interlayer magnetic orientation and the spin-polarized band structure.
Language Differentiation Using Augmentative and Alternative Communication: An Investigation of Spanish–English Bilingual Children With and Without Language Impairments
Authors: King Marika R. , Romski MaryAnn , Sevcik Rose A. 
Published: December 2020

PurposeChildren with severe speech and language impairments growing up in dual language environments may communicate in more than one language using augmentative and alternative communication (AAC). This study investigated predictors of bilingual children's ability to differentiate between Spanish and English using an AAC iPad app during a cued language-switching task and examined whether switching between languages using AAC incurred a cognitive cost.MethodParticipants were 58 Spanish–English bilingual children ages 4;0–6;11 (years;months; 23 with language impairments). Children received standardized language and cognitive assessments and completed an experimental language-switching task in which they were asked to differentiate between languages using an AAC iPad app containing English and Spanish vocabulary layouts paired with voice output.ResultsResults of a binary logistic regression indicated that, when controlling for age, processing speed significantly predicted whether children were classified as high or low performers on the experimental task. Nonparametric tests indicated that switching between languages did not incur a cognitive cost as evidenced by similar response times on trials where participants were required to switch between languages compared to trials where they did not switch.ConclusionThis study contributes to the understanding of how young bilingual children with and without language impairments conceptualize and discriminate between languages represented in a visual–graphic modality paired with speech output.Supplemental Materialhttps://doi.org/10.23641/asha.13289330
Fixed‐time orientation estimation and network localisation of multi‐agent systems
Authors: John Younghun , Oh Kwang‐Kyo , Fidan Bariş , Ahn Hyo‐Sung 
Published: December 2020

AbstractAmong different distributed network localisation methods, displacement‐based network localisation with orientation estimation is an effective approach because it does not require global information and yet asymptotically produces accurate estimates. In this paper, to improve transient performance of this approach, non‐linear laws to achieve fixed‐time orientation estimation and fixed‐time displacement‐based localisation are proposed. A sequential algorithm ensuring fixed‐time convergence property and show uniform asymptotic stability of a fixed‐time network localisation with simultaneous fixed‐time orientation estimation is further provided. Simulation results verify that the proposed laws achieve network localisation of multi‐agent systems within fixed settling time.
Stable thin‐wire model of buried pipe‐type power distribution cables for 3D FDTD transient simulation
Authors: Li Binghao , Ding Yuxuan , Du Yaping , Chen Mingli 
Published: December 2020

Underground cables such as pipe‐type cables are widely used in urban power industry. In this study, an advanced thin‐wire model of the pipe‐type cables is 3D FDTD simulations. In this model, the multi‐conductor cables are represented with two‐level transmission line equations. A stabilising technique with a 1D spatial low‐pass filter is proposed to maintain computational stability. Frequency‐dependent losses are fully considered by using a vector‐fitting technique. The proposed thin‐wire model is validated with the multi‐conductor transmission line theory analytically and the traditional FDTD method numerically. Good agreements are observed. It is found that the simulation maintains stability for 360,000‐time steps. Compared to the traditional FDTD method, the memory space and computation time of the proposed model can be reduced by 73% and 98%, respectively. Induced lightning currents in a cable connection station are analysed. It is found that, without considering soil ionisation and soil stratification, the peak current in the metallic armour is 1.54 times as much as the one with considering these non‐linear effects. It can be reduced by 9.04% and 18.6% if the cable is buried at depths of 1 m and 1.5 m, compared with the case of a 0.5 m buried depth.