bluuebunny/crossref_metadata_2025_split huggingface dataset:
Co-delivery of IOX1 and doxorubicin for antibody-independent cancer chemo-immunotherapy
Authors: Liu Jing , Zhao Zhihao , Qiu Nasha , Zhou Quan , Wang Guowei , Jiang Haiping , Piao Ying , Zhou Zhuxian , Tang Jianbin , Shen Youqing 
Published: April 2021

AbstractAnti-programmed cell death-1 (PD-1)/programmed cell death-ligand 1 (PD-L1) antibodies are currently used in the clinic to interupt the PD-1/PD-L1 immune checkpoint, which reverses T cell dysfunction/exhaustion and shows success in treating cancer. Here, we report a histone demethylase inhibitor, 5-carboxy-8-hydroxyquinoline (IOX1), which inhibits tumour histone demethylase Jumonji domain-containing 1A (JMJD1A) and thus downregulates its downstream β-catenin and subsequent PD-L1, providing an antibody-independent paradigm interrupting the PD-1/PD-L1 checkpoint. Synergistically, IOX1 inhibits cancer cells’ P-glycoproteins (P-gp) through the JMJD1A/β-catenin/P-gp pathway and greatly enhances doxorubicin (DOX)-induced immune-stimulatory immunogenic cell death. As a result, the IOX1 and DOX combination greatly promotes T cell infiltration and activity and significantly reduces tumour immunosuppressive factors. Their liposomal combination reduces the growth of various murine tumours, including subcutaneous, orthotopic, and lung metastasis tumours, and offers a long-term immunological memory function against tumour rechallenging. This work provides a small molecule-based potent cancer chemo-immunotherapy.
Genomic profile of advanced breast cancer in circulating tumour DNA
Authors: Kingston Belinda , Cutts Rosalind J. , Bye Hannah , Beaney Matthew , Walsh-Crestani Giselle , Hrebien Sarah , Swift Claire , Kilburn Lucy S. , Kernaghan Sarah , Moretti Laura , Wilkinson Katie , Wardley Andrew M. , Macpherson Iain R. , Baird Richard D. , Roylance Rebecca , Reis-Filho Jorge S. , Hubank Michael , Faull Iris , Banks Kimberly C. , Lanman Richard B. , Garcia-Murillas Isaac , Bliss Judith M. , Ring Alistair , Turner Nicholas C. 
Published: April 2021

AbstractThe genomics of advanced breast cancer (ABC) has been described through tumour tissue biopsy sequencing, although these approaches are limited by geographical and temporal heterogeneity. Here we use plasma circulating tumour DNA sequencing to interrogate the genomic profile of ABC in 800 patients in the plasmaMATCH trial. We demonstrate diverse subclonal resistance mutations, including enrichment of HER2 mutations in HER2 positive disease, co-occurring ESR1 and MAP kinase pathway mutations in HR + HER2− disease that associate with poor overall survival (p = 0.0092), and multiple PIK3CA mutations in HR + disease that associate with short progression free survival on fulvestrant (p = 0.0036). The fraction of cancer with a mutation, the clonal dominance of a mutation, varied between genes, and within hotspot mutations of ESR1 and PIK3CA. In ER-positive breast cancer subclonal mutations were enriched in an APOBEC mutational signature, with second hit PIK3CA mutations acquired subclonally and at sites characteristic of APOBEC mutagenesis. This study utilises circulating tumour DNA analysis in a large clinical trial to demonstrate the subclonal diversification of pre-treated advanced breast cancer, identifying distinct mutational processes in advanced ER-positive breast cancer, and novel therapeutic opportunities.
Kidney intercalated cells are phagocytic and acidify internalized uropathogenic Escherichia coli
Authors: Saxena Vijay , Gao Hongyu , Arregui Samuel , Zollman Amy , Kamocka Malgorzata Maria , Xuei Xiaoling , McGuire Patrick , Hutchens Michael , Hato Takashi , Hains David S. , Schwaderer Andrew L. 
Published: April 2021

AbstractKidney intercalated cells are involved in acid-base homeostasis via vacuolar ATPase expression. Here we report six human intercalated cell subtypes, including hybrid principal-intercalated cells identified from single cell transcriptomics. Phagosome maturation is a biological process that increases in biological pathway analysis rank following exposure to uropathogenicEscherichia coliin two of the intercalated cell subtypes. Real time confocal microscopy visualization of murine renal tubules perfused with green fluorescent protein expressingEscherichia colior pHrodo GreenE. coliBioParticles demonstrates that intercalated cells actively phagocytose bacteria then acidify phagolysosomes. Additionally, intercalated cells have increased vacuolar ATPase expression following in vivo experimental UTI. Taken together, intercalated cells exhibit a transcriptional response conducive to the kidney’s defense, engulf bacteria and acidify the internalized bacteria. Intercalated cells represent an epithelial cell with characteristics of professional phagocytes like macrophages.
Inhibition of polar actin assembly by astral microtubules is required for cytokinesis
Authors: Chen Anan , Ulloa Severino Luisa , Panagiotou Thomas C. , Moraes Trevor F. , Yuen Darren A. , Lavoie Brigitte D. , Wilde Andrew 
Published: April 2021

AbstractDuring cytokinesis, the actin cytoskeleton is partitioned into two spatially distinct actin isoform specific networks: a β-actin network that generates the equatorial contractile ring, and a γ-actin network that localizes to the cell cortex. Here we demonstrate that the opposing regulation of the β- and γ-actin networks is required for successful cytokinesis. While activation of the formin DIAPH3 at the cytokinetic furrow underlies β-actin filament production, we show that the γ-actin network is specifically depleted at the cell poles through the localized deactivation of the formin DIAPH1. During anaphase, CLIP170 is delivered by astral microtubules and displaces IQGAP1 from DIAPH1, leading to formin autoinhibition, a decrease in cortical stiffness and localized membrane blebbing. The contemporaneous production of a β-actin contractile ring at the cell equator and loss of γ-actin from the poles is required to generate a stable cytokinetic furrow and for the completion of cell division.
Optical information transmission through complex scattering media with optical-channel-based intensity streaming
Authors: Ruan Haowen , Xu Jian , Yang Changhuei 
Published: April 2021

AbstractFor the past decade, optical wavefront shaping has been the standard technique to control light through scattering media. Implicit in this dominance is the assumption that manipulating optical interference is a necessity for optical control through scattering media. In this paper, we challenge this assumption by reporting on an alternate approach for light control through a disordered scattering medium – optical-channel-based intensity streaming (OCIS). Instead of actively tuning the interference between the optical paths via wavefront shaping, OCIS controls light and transmits information through scattering media through linear intensity operations. We demonstrate a set of OCIS experiments that connect to some wavefront shaping implementations, i.e. iterative wavefront optimization, digital optical phase conjugation, image transmission through transmission matrix, and direct imaging through scattering media. We experimentally created focus patterns through scattering media on a sub-millisecond timescale. We also demonstrate that OCIS enables a scattering medium mediated secure optical communication application.
Protein design and variant prediction using autoregressive generative models
Authors: Shin Jung-Eun , Riesselman Adam J. , Kollasch Aaron W. , McMahon Conor , Simon Elana , Sander Chris , Manglik Aashish , Kruse Andrew C. , Marks Debora S. 
Published: April 2021

AbstractThe ability to design functional sequences and predict effects of variation is central to protein engineering and biotherapeutics. State-of-art computational methods rely on models that leverage evolutionary information but are inadequate for important applications where multiple sequence alignments are not robust. Such applications include the prediction of variant effects of indels, disordered proteins, and the design of proteins such as antibodies due to the highly variable complementarity determining regions. We introduce a deep generative model adapted from natural language processing for prediction and design of diverse functional sequences without the need for alignments. The model performs state-of-art prediction of missense and indel effects and we successfully design and test a diverse 105-nanobody library that shows better expression than a 1000-fold larger synthetic library. Our results demonstrate the power of the alignment-free autoregressive model in generalizing to regions of sequence space traditionally considered beyond the reach of prediction and design.
Augmenting ideational fluency in a creativity task across multiple transcranial direct current stimulation montages
Authors: Chrysikou Evangelia G. , Morrow Hannah M. , Flohrschutz Austin , Denney Lauryn 
Published: April 2021

AbstractNeuroimaging and transcranial direct current stimulation (tDCS) research has revealed that generating novel ideas is associated with both reductions and increases in prefrontal cortex (PFC) activity, and engagement of posterior occipital cortex, among other regions. However, there is substantial variability in the robustness of these tDCS‐induced effects due to heterogeneous sample sizes, different creativity measures, and methodological diversity in the application of tDCS across laboratories. To address these shortcomings, we used twelve different montages within a standardized tDCS protocol to investigate how altering activity in frontotemporal and occipital cortex impacts creative thinking. Across four experiments, 246 participants generated either the common or an uncommon use for 60 object pictures while undergoing tDCS. Participants also completed a control short-term memory task. We applied active tDCS for 20 min at 1.5 mA through two 5 cm × 5 cm electrodes over left or right ventrolateral prefrontal (areas F7, F8) or occipital (areas O1, O2) cortex, concurrent bilateral stimulation of these regions across polarities, or sham stimulation. Cathodal stimulation of the left, but not right, ventrolateral PFC improved fluency in creative idea generation, but had no effects on originality, as approximated by measures of semantic distance. No effects were obtained for the control tasks. Concurrent bilateral stimulation of the ventrolateral PFC regardless of polarity direction, and excitatory stimulation of occipital cortex did not alter task performance. Highlighting the importance of cross-experimental methodological consistency, these results extend our past findings and contribute to our understanding of the role of left PFC in creative thinking.
Subseafloor sulphide deposit formed by pumice replacement mineralisation
Authors: Nozaki Tatsuo , Nagase Toshiro , Takaya Yutaro , Yamasaki Toru , Otake Tsubasa , Yonezu Kotaro , Ikehata Kei , Totsuka Shuhei , Kitada Kazuya , Sanada Yoshinori , Yamada Yasuhiro , Ishibashi Jun-ichiro , Kumagai Hidenori , Maeda Lena ,   the D/V Chikyu Expedition 909 Scientists, Fuchida Shigeshi , Fukuhara Tatsuo , Ikehata Kei , Ishibashi Jun-ichiro , Kato Hirokazu , Kawachi Masanobu , Kawaguchi Shinji , Kawakida Ryuhei , Kitada Kazuya , Komori Shogo , Koshikawa Hiroshi , Kret Kakda , Kumagai Hidenori , Maeda Lena , Masaki Yuka , Matsui Yohei , McIntosh Iona , Minamide Kana , Miyahara Rena , Mukae Nobuhiro , Nagase Toshiro , Nakamura Shunsuke , Nozaki Tatsuo , Ohno Masao , Otake Tsubasa , Saitoh Masafumi , Sanada Yoshinori , Takaya Yutaro , Toki Tomohiro , Torimoto Junji , Totsuka Shuhei , Tsutsumi Akihi , Uehara Riki , Uza Hirotaka , Watanabe Masayuki , Yamada Yasuhiro , Yamagishi Takahiro , Yamamoto Hirofumi , Yamasaki Toru , Yonezu Kotaro 
Published: April 2021

AbstractSeafloor massive sulphide (SMS) deposits, modern analogues of volcanogenic massive sulphide (VMS) deposits on land, represent future resources of base and precious metals. Studies of VMS deposits have proposed two emplacement mechanisms for SMS deposits: exhalative deposition on the seafloor and mineral and void space replacement beneath the seafloor. The details of the latter mechanism are poorly characterised in detail, despite its potentially significant role in global metal cycling throughout Earth’s history, because in-situ studies require costly drilling campaigns to sample SMS deposits. Here, we interpret petrographic, geochemical and geophysical data from drill holes in a modern SMS deposit and demonstrate that it formed via subseafloor replacement of pumice. Samples from the sulphide body and overlying sediment at the Hakurei Site, Izena Hole, middle Okinawa Trough indicate that sulphides initially formed as aggregates of framboidal pyrite and matured into colloform and euhedral pyrite, which were replaced by chalcopyrite, sphalerite and galena. The initial framboidal pyrite is closely associated with altered material derived from pumice, and alternating layers of pumiceous and hemipelagic sediments functioned as a factory of sulphide mineralisation. We infer that anhydrite-rich layers within the hemipelagic sediment forced hydrothermal fluids to flow laterally, controlling precipitation of a sulphide body extending hundreds of meters.
Geometry of turbulent dissipation and the Navier–Stokes regularity problem
Authors: Rafner Janet , Grujić Zoran , Bach Christian , Bærentzen Jakob Andreas , Gervang Bo , Jia Ruo , Leinweber Scott , Misztal Marek , Sherson Jacob 
Published: April 2021

AbstractThe question of whether a singularity can form in an initially regular flow, described by the 3D incompressible Navier–Stokes (NS) equations, is a fundamental problem in mathematical physics. The NS regularity problem is super-critical, i.e., there is a ‘scaling gap’ between what can be established by mathematical analysis and what is needed to rule out a singularity. A recently introduced mathematical framework—based on a suitably defined ‘scale of sparseness’ of the regions of intense vorticity—brought the first scaling reduction of the NS super-criticality since the 1960s. Here, we put this framework to the first numerical test using a spatially highly resolved computational simulation performed near a ‘burst’ of the vorticity magnitude. The results confirm that the scale is well suited to detect the onset of dissipation and provide numerical evidence that ongoing mathematical efforts may succeed in closing the scaling gap.
Study on the characteristics of nitrogen dioxide adsorption and storage of coal residue in coal-fired power plants in goaf
Authors: Wang Xuefeng , Qiao Ling , Deng Cunbao , Chu Ge , Li Xiaofeng , Zhao Qi , Wang Guoli 
Published: April 2021

AbstractIn order to realize the storage of the residual coal in the goaf on the flue gas of the power plant, the adsorption characteristics of nitrogen dioxide in the flue gas of the power plant were studied. The Gaussian09 was used to study the adsorption process of NO2 molecules on coal at the density functional (DFT) B3LYP/6-311G level, and the model of NO2 adsorption by coal was established. Different quantities were obtained using orbital energy changes and molecular bond length changes. According to the principle of molecular adsorption, the adsorption of NO2 by coal is considered to be physical adsorption with endothermic heat. On the basis of simulation, using self-organized experimental devices, the single-component NO2 gas and the simulated coal-fired power plant flue gas were introduced into anthracite, bituminous coal and lignite. In single-component adsorption, the adsorption of NO2 by lignite increases with time. The time to reach equilibrium is related to the properties of the coal itself. In the process of simulated flue gas adsorption, the order of the adsorption amount of coal to flue gas is CO2 > NO2 > N2 > O2. In the simulated flue gas, coal is easy to absorb NO2 and CO2, and the competition between gases reduces the frequency of contact between NO2 and the coal surface. Simulation and experimental results show that coal has obvious adsorption characteristics for NO2, and it is feasible for the residual coal in the goaf to adsorb NO2 in the flue gas of power plants.
A probabilistic method for mapping earth fissure hazards
Authors: Zang Mingdong , Peng Jianbing , Xu Nengxiong , Jia Zhijie 
Published: April 2021

AbstractEarth fissures caused by tectonic forces, human activities, or both seriously threaten the safety of people’s lives and properties. The Taiyuan Basin, a Cenozoic downfaulted basin located in the centre of the Fen-Wei Basin tectonic belt, in northwestern China, presents the ideal study area for a hazard assessment of earth fissures. A total of 104 earth fissures have been observed in the Taiyuan Basin, with a total length of approximately 128 km. In this paper, we proposed a probabilistic method for mapping earth fissure hazards by integrating the analytic hierarchy process (AHP), the area under the curve (AUC), and the certainty factor model (CFM). Geomorphic units, geologic formations, active faults and land subsidence zones of the Taiyuan Basin were mapped in detail. Correlations between these factors and earth fissures were evaluated through spatial modelling in ArcGIS. The AUC was introduced into the AHP to weight each factor and thus, to derive an earth fissure susceptibility map. Finally, the modelled earth fissure susceptibility was compared with a digital inventory of earth fissures to develop a probability function and map the spatial variability in failure probability through the CFM. The study indicates that active faults have the greatest contribution to the generation of earth fissures. Earth fissures are prone to develop in the piedmont alluvial-diluvial clinoplain and the transitional zone near the geomorphic boundary. This mapping procedure can assist in making rational decisions regarding urban planning and infrastructure development in areas susceptible to earth fissures.
Picking up the hydrothermal whisper at Ischia Island in the Covid-19 lockdown quiet
Authors: Falanga Mariarosaria , Cusano Paola , De Lauro Enza , Petrosino Simona 
Published: April 2021

AbstractIn this paper, we analyse the seismic noise at Ischia Island (Italy) with the objective of detecting the hydrothermal source signals taking advantage of the Covid-19 quiescence due to lockdown (strong reduction of anthropogenic noise). We compare the characteristics of the background noise in pre-, during and post-lockdown in terms of spectral content, energy release (RMS) and statistical moments. The continuous noise is decomposed into two independent signals in the 1−2 Hz and 2−4 Hz frequency bands, becoming sharpened around 1 Hz and 3 Hz respectively in lockdown. We propose a conceptual model according to which a dendritic system of fluid-permeated fractures plays as neighbour closed organ pipes, for which the fundamental mode provides the persistent whisper and the first higher mode is activated in concomitance with energy increases. By assuming reasonable values for the sound speed in low vapor–liquid mass fraction for a two-phase fluid and considering temperatures and pressures of the shallow aquifer fed by sea, meteoric and deep hydrothermal fluids, we estimate pipe lengths in the range 200–300 m. In this scheme, Ischia organ-like system can play both continuous whisper and transients, depending on the energy variations sourced by pressure fluctuations in the hydrothermal fluids.
Safety of traditional Chinese medicine injection based on spontaneous reporting system from 2014 to 2019 in Hubei Province, China
Authors: Huang Rui , Cai Yuanxuan , Yang Linhui , Shangguan Xiaofang , Ghose Bishwajit , Tang Shangfeng 
Published: April 2021

AbstractTraditional Chinese medicine (TCM) injection is widely used in clinical settings, but its adverse drug reactions (ADRs) can be a serious public health concern. The objective is to study the safety of TCM injection and provide suggestions for clinical use. ADR reports collected by the Hubei Adverse Drug Reaction Monitoring Center from 2014 to 2019 were analysed. The safety of TCM injections was described by descriptive analysis and three signal mining methods, including the reporting odd ratio (ROR), proportional reporting ratio (PRR) and comprehensive standard method (MHRA). The findings indicate that the age groups of 0–10 and 41–80 years had the highest rates of reporting ADRs. A total of 96.41% of the ADRs occurred within one week, mostly on the same day that the injection was administered. Among the 60 TCM injections, Shenmai, Xiangdan, Salvia, Shengmai, Astragalus and Xuebijing injection had an above average ratio of severe ADRs (12.63%). A total of 99.24% of the cases improved after treatment. There were 9 deaths whose ADRs were mainly anaphylactic shock, dyspnoea and anaphylactoid reaction. In signal mining, the three methods produced 19 signals that were the same, and 14 of them were off-label ADRs. The frequency of TCM injections in children and elderly patients should be reduced and monitored strictly. Close observation is necessary during the first seven days after receiving the injection. The clinical use of Shenmai, Xiangdan, Salvia, Shengmai, Astragalus and Xuebijing injections should be investigated. Signal mining and more research are needed on TCM injections.
Aggressive and recurrent ovarian cancers upregulate ephrinA5, a non-canonical effector of EphA2 signaling duality
Authors: Jukonen Joonas , Moyano-Galceran Lidia , Höpfner Katrin , Pietilä Elina A. , Lehtinen Laura , Huhtinen Kaisa , Gucciardo Erika , Hynninen Johanna , Hietanen Sakari , Grénman Seija , Ojala Päivi M. , Carpén Olli , Lehti Kaisa 
Published: April 2021

AbstractErythropoietin producing hepatocellular (Eph) receptors and their membrane-bound ligands ephrins are variably expressed in epithelial cancers, with context-dependent implications to both tumor-promoting and -suppressive processes in ways that remain incompletely understood. Using ovarian cancer tissue microarrays and longitudinally collected patient cells, we show here that ephrinA5/EFNA5 is specifically overexpressed in the most aggressive high-grade serous carcinoma (HGSC) subtype, and increased in the HGSC cells upon disease progression. Among all the eight ephrin genes, high EFNA5 expression was most strongly associated with poor overall survival in HGSC patients from multiple independent datasets. In contrast, high EFNA3 predicted improved overall and progression-free survival in The Cancer Genome Atlas HGSC dataset, as expected for a canonical inducer of tumor-suppressive Eph receptor tyrosine kinase signaling. While depletion of either EFNA5 or the more extensively studied, canonically acting EFNA1 in HGSC cells increased the oncogenic EphA2-S897 phosphorylation, EFNA5 depletion left unaltered, or even increased the ligand-dependent EphA2-Y588 phosphorylation. Moreover, treatment with recombinant ephrinA5 led to limited EphA2 tyrosine phosphorylation, internalization and degradation compared to ephrinA1. Altogether, our results suggest a unique function for ephrinA5 in Eph-ephrin signaling and highlight the clinical potential of ephrinA5 as a cell surface biomarker in the most aggressive HGSCs.