bluuebunny/crossref_metadata_2025 huggingface dataset:
Detection of SARS‐CoV‐2 in respiratory samples from cats in the UK associated with human‐to‐cat transmission
Authors: Hosie Margaret J. , Epifano Ilaria , Herder Vanessa , Orton Richard J. , Stevenson Andrew , Johnson Natasha , MacDonald Emma , Dunbar Dawn , McDonald Michael , Howie Fiona , Tennant Bryn , Herrity Darcy , Da Silva Filipe Ana , Streicker Daniel G. ,   the COVID‐19 Genomics UK (COG‐UK) consortium, Willett Brian J. , Murcia Pablo R. , Jarrett Ruth F. , Robertson David L. , Weir William
Published: April 2021

Objectives: The aim of the study was to find evidence of SARS‐CoV‐2 infection in UK cats.

Design: Tissue samples were tested for SARS‐CoV‐2 antigen using immunofluorescence and for viral RNA by in situ hybridisation. A set of 387 oropharyngeal swabs that had been submitted for routine respiratory pathogen testing was tested for SARS‐CoV‐2 RNA using reverse transcriptase quantitative PCR.

Results: Lung tissue collected post‐mortem from cat 1 tested positive for both SARS‐CoV‐2 nucleocapsid antigen and RNA. SARS‐CoV‐2 RNA was detected in an oropharyngeal swab collected from cat 2 that presented with rhinitis and conjunctivitis. High throughput sequencing of the viral genome revealed five single nucleotide polymorphisms (SNPs) compared to the nearest UK human SARS‐CoV‐2 sequence, and this human virus contained eight SNPs compared to the original Wuhan‐Hu‐1 reference sequence. An analysis of the viral genome of cat 2 together with nine other feline‐derived SARS‐CoV‐2 sequences from around the world revealed no shared cat‐specific mutations.

Conclusions: These findings indicate that human‐to‐cat transmission of SARS‐CoV‐2 occurred during the COVID‐19 pandemic in the UK, with the infected cats developing mild or severe respiratory disease. Given the ability of the new coronavirus to infect different species, it will be important to monitor for human‐to‐cat, cat‐to‐cat and cat‐to‐human transmission.
‘Gender discrimination is stopping women pursuing leadership roles in our profession’
Authors: Moore Alice
Published: April 2021

Alice Moore argues that gender discrimination is still a big problem in the veterinary profession and that the tendency to focus purely on the gender pay gap is not helpful in solving the wider issues.
Ian Geofrey Newlands Smith
Authors: Smith Fergus
Published: April 2021

Born in Africa, Geof came to the UK to study veterinary medicine at Edinburgh, before returning to Kenya where he ultimately became assistant director of the country's veterinary service.
A 2021 update on cancer image analytics with deep learning
Authors: Cherian Kurian Nikhil , Sethi Amit , Reddy Konduru Anil , Mahajan Abhishek , Rane Swapnil Ulhas
Published: April 2021

Deep learning (DL)‐based interpretation of medical images has reached a critical juncture of expanding outside research projects into translational ones, and is ready to make its way to the clinics. Advances over the last decade in data availability, DL techniques, as well as computing capabilities have accelerated this journey. Through this journey, today we have a better understanding of the challenges to and pitfalls of wider adoption of DL into clinical care, which, according to us, should and will drive the advances in this field in the next few years. The most important among these challenges are the lack of an appropriately digitized environment within healthcare institutions, the lack of adequate open and representative datasets on which DL algorithms can be trained and tested, and the lack of robustness of widely used DL training algorithms to certain pervasive pathological characteristics of medical images and repositories. In this review, we provide an overview of the role of imaging in oncology, the different techniques that are shaping the way DL algorithms are being made ready for clinical use, and also the problems that DL techniques still need to address before DL can find a home in clinics. Finally, we also provide a summary of how DL can potentially drive the adoption of digital pathology, vendor neutral archives, and picture archival and communication systems. We caution that the respective researchers may find the coverage of their own fields to be at a high‐level. This is so by design as this format is meant to only introduce those looking in from outside of deep learning and medical research, respectively, to gain an appreciation for the main concerns and limitations of these two fields instead of telling them something new about their own.

This article is categorized under:

Technologies > Artificial Intelligence

Algorithmic Development > Biological Data Mining
Geometrizing non-relativistic bilinear deformations
Authors: Hansen Dennis , Jiang Yunfeng , Xu Jiuci
Published: April 2021

Abstract

We define three fundamental solvable bilinear deformations for any massive non-relativistic 2d quantum field theory (QFT). They include the $$ \mathrm{T}\overline{\mathrm{T}} $$
T

T
¯

deformation and the recently introduced hard rod deformation. We show that all three deformations can be interpreted as coupling the non-relativistic QFT to a specific Newton-Cartan geometry, similar to the Jackiw-Teitelboim-like gravity in the relativistic case. Using the gravity formulations, we derive closed-form deformed classical Lagrangians of the Schrödinger model with a generic potential. We also extend the dynamical change of coordinate interpretation to the non-relativistic case for all three deformations. The dynamical coordinates are then used to derive the deformed classical Lagrangians and deformed quantum S-matrices.
Burden of respiratory syncytial virus bronchiolitis on the Dutch pediatric intensive care units
Authors: Linssen Rosalie S. , Bem Reinout A. , Kapitein Berber , Rengerink Katrien Oude , Otten Marieke H. , den Hollander Bibiche , Bont Louis , van Woensel Job B. M. ,   on behalf of the PICE Study Group, Wösten-van Asperen Roelie M. , Klein Richard H. , Kneyber Martin C. J. , Kuiper Jan Willem , Verlaat Carin , van Heerde Marc , Riedijk Maaike A. , van Waardenburg Dick A.
Published: April 2021

Respiratory syncytial virus (RSV) bronchiolitis causes substantial morbidity and mortality in young children, but insight into the burden of RSV bronchiolitis on pediatric intensive care units (PICUs) is limited. We aimed to determine the burden of RSV bronchiolitis on the PICUs in the Netherlands. Therefore, we identified all children ≤ 24 months of age with RSV bronchiolitis between 2003 and 2016 from a nationwide PICU registry. Subsequently we manually checked their patient records for correct diagnosis and collected patient characteristics, additional clinical data, respiratory support modes, and outcome. In total, 2161 children were admitted to the PICU for RSV bronchiolitis. The annual number of admissions increased significantly during the study period (β 4.05, SE 1.27, p = 0.01), and this increase was mostly driven by increased admissions in children up to 3 months old. Concomitantly, non-invasive respiratory support significantly increased (β 7.71, SE 0.92, p < 0.01), in particular the use of high flow nasal cannula (HFNC) (β 6.69, SE 0.96, p < 0.01), whereas the use of invasive ventilation remained stable.

Conclusion: The burden of severe RSV bronchiolitis on PICUs has increased in the Netherlands. Concomitantly, the use of non-invasive respiratory support, especially HFNC, has increased.

What is Known:• RSV bronchiolitis is a major cause of childhood morbidity and mortality and may require pediatric intensive care unit admission.• The field of pediatric critical care for severe bronchiolitis has changed due to increased non-invasive respiratory support options.

What is New:• The burden of RSV bronchiolitis for the Dutch PICUs has increased. These data inform future strategic PICU resource planning and implementation of RSV preventive strategies.• There was a significant increase in the use of high flow nasal cannula at the PICU, but the use of invasive mechanical ventilation did not decrease.
Calculations on Mode Eigenvalues in a Corrugated Waveguide with Varying Diameter and Corrugation Depth
Authors: Haas Daniel , Thumm Manfred , Jelonnek John
Published: April 2021

The present paper addresses numerical calculations on the eigenvalues of hybrid modes in corrugated circular waveguides with varying diameter and corrugation depth. Such calculations are essential for the numerical optimization of advanced mode converters and diameter tapers for future low-loss high-power microwave applications, like broadband high-power radar sensors for space debris observation in low earth orbit (LEO). Corresponding mode converters and diameter tapers may be synthesized based on coupled mode theory. Of particular importance here is the ability to consider varying mode eigenvalues along the perturbed waveguide. The procedure presented here is able to consider arbitrary variations of the corrugation depth as well as the waveguide diameter and therefore is highly flexible. The required computational effort is low. Limitations of the method are discussed.
A Categorification of the Ribbon Element in Quantum sl(2)
Authors: Beliakova Anna , Habiro Kazuo
Published: April 2021

We define a bicomplex whose Euler characteristic is the idempotented version of the ribbon element of quantum sl(2). We show that properties of this bicomplex descend to the centrality, invertibility, and symmetries of the ribbon element after decategorification.
Think, Do, and Communicate Environmental Science
Authors: Ivanochko Tara
Published: April 2021

Many students find it daunting to move from studying environmental science, to designing and implementing their own research proposals. This book provides a practical introduction to help develop scientific thinking, aimed at undergraduate and new graduate students in the earth and environmental sciences. Students are guided through the steps of scientific thinking using published scientific literature and real environmental data. The book starts with advice on how to effectively read scientific papers, before outlining how to articulate testable questions and answer them using basic data analysis. The Mauna Loa CO2 dataset is used to demonstrate how to read metadata, prepare data, generate effective graphs and identify dominant cycles on various timescales. Practical, question-driven examples are explored to explain running averages, anomalies, correlations and simple linear models. The final chapter provides a framework for writing persuasive research proposals, making this an essential guide for students embarking on their first research project.
Taxing the Digital Economy
Authors: Elliffe Craig
Published: April 2021

The question of how to tax multinational companies that operate highly digitalised business models is one of the most contested areas of international taxation. The tax paid in the jurisdictions in which these companies operate has not kept pace with their immense growth and the OECD has proposed a new international tax compromise that will allocate taxing rights to market jurisdictions and remove the need to have a physical presence in the taxing jurisdictions in order to sustain taxability. In this work, Craig Elliffe explains the problems with the existing international tax system and its inability to respond to challenges posed by digitalised companies. In addition to looking at how the new international tax rules will work, Elliffe assesses their likely effectiveness and highlights features that are likely to endure in the next waves of international tax reform.
Full and Partial Grounding
Authors: TROGDON KELLY , WITMER D. GENE
Published: April 2021

While controversy about the nature ofgroundingabounds, our focus is on a question for which a particular answer has attracted something like a consensus. The question concerns the relation betweenpartialgrounding andfullgrounding. The apparent consensus is that the former is to be defined in terms of the latter. In this article, we argue that the standard way of doing this faces a significant problem and that we ought to pursue the reverse project of defining full grounding in terms of partial grounding. The guiding idea behind the definition we propose is that full grounding is what happens when partial grounding works in a way that ensures that the grounded is nothing over and above the grounds. We ultimately understand this idea in terms of iterated ‘nothing over and above’ claims.
Mock Mockers: Cynicism, Suffering, Irish Modernism
Authors: McDonald Ronan
Published: April 2021

Cynicism styles itself as the answer to the mental suffering produced by disillusionment, disappointment, and despair. It seeks to avoid them by exposing to ridicule naive idealism or treacherous hope. Modern cynics avoid the vulnerability produced by high ideals, just as their ancient counterparts eschewed dependence on all but the most essential of material needs. The philosophical tradition of the Cynics begins with the Ancients, including Diogenes and Lucian, but has found contemporary valence in the work of cultural theorists such as Peter Sloterdijk. This article uses theories of cynicism to analyze postcolonial disappointment in Irish modernism. It argues that in the “ambi-colonial” conditions of early-twentieth-century Ireland, the metropolitan surety of and suaveness of a cynical attitude is available but precarious. We therefore find a recursive cynicism that often turns upon itself, finding the self-distancing and critical sure-footedness of modern, urbane cynicism a stance that itself should be treated with cynical scepticism. The essay detects this recursive cynicism in a number of literary works of post-independence Ireland, concluding with an extended consideration of W. B. Yeats’s great poem of civilizational precarity, “Nineteen Hundred and Nineteen.”
On Antigone’s Suffering
Authors: Mukherjee Ankhi
Published: April 2021

Examining the contestation of interpretations around this work, I argue that the proliferation of exegetical material on Sophocles’sAntigoneis related to a noncomprehension of the human motives behind her transgressive action. Did she ever love, and is there any suffering in her piety? If she didn’t love (her brother), could she have suffered? I read the play alongside Kamila Shamsie’s postcolonial rewriting of it inHome Fireto elaborate on the relationship between personal loss and collective (and communal) suffering, particularly as it is focalized in the novel by the figure of a young woman who is both a bereaved twin and a vengeful fury.
New variable martingale Hardy spaces
Authors: Jiao Yong , Zeng Dan , Zhou Dejian
Published: April 2021

We investigate various variable martingale Hardy spaces corresponding to variable Lebesgue spaces$\mathcal {L}_{p(\cdot )}$defined by rearrangement functions. In particular, we show that the dual of martingale variable Hardy space$\mathcal {H}_{p(\cdot )}^{s}$with$0<p_{-}\leq p_{+}\leq 1$can be described as a BMO-type space and establish martingale inequalities among these martingale Hardy spaces. Furthermore, we give an application of martingale inequalities in stochastic integral with Brownian motion.
NEW POETIC FRAGMENTS FROM A NEGLECTED WITNESS OF PS.-TRYPHO'SDE TROPIS: CALLIMACHUS, PS.-HESIOD, PS.-SIMONIDES
Authors: Pontani Filippomaria , Sandri Maria Giovanna
Published: April 2021

A treatise on rhetorical tropes is attributed in manuscripts to the first-century grammarian Trypho: this article considers for the first time a fifteenth-century manuscript of this work (Leiden, BPG 74G), which turns out to be the only complete witness of its hitherto unknown original version; this version (very fragmentarily transmitted by a fifth-century papyrus scrap) is also partly found in another fifteenth-century manuscript now kept in Olomouc (M 79). Four interesting poetic fragments are quoted in this newly discovered, fuller version of Ps.-Trypho'sDe Tropis: some lines from Callimachus’ fifth and fourthIambi(23–9 and 90–2 respectively: a radically new light is shed by this new witness on the parallel papyrus fragments carrying Callimachus’ text), an epigram dubiously attributed to Simonides (FGE44 Page, probably to be dated to the Hellenistic period: the text can be now restored to its complete form), and some enigmatic lines of “Hesiod”'sWedding of Keyx, which the new witness finally makes fully understandable.
Motivation, self-efficacy beliefs, and speaking anxiety in language MOOCs
Authors: Bárkányi Zsuzsanna
Published: April 2021

This paper examines the role of motivation, anxiety, and self-efficacy beliefs and their interplay with regard to speaking on beginners’ Spanish LMOOCs. It answers three research questions: (1) what are learners’ motivations and goals for joining these LMOOCs and how do these relate to foreign language speaking anxiety; (2) how do learners’ self-efficacy beliefs and anxiety levels change as a result of course completion; and (3) is there a correlation between motivation, foreign language speaking anxiety, and self-efficacy beliefs in this context? A mixed-methods research design used quantitative and qualitative data gathered from self-reflective questionnaires and forum discussions. The results reveal that learners with intrinsic motivation are more likely to complete the courses than those who sign up to manage a personal situation or advance in their career or studies. No direct correlation was, however, found between motivation and the other variables under scrutiny. Learners present higher self-efficacy beliefs at the end of the courses than at the beginning, while anxiety levels are affected to a much smaller degree by course completion. Although spoken interactions in this learning environment are not synchronous, apprehension and anxiety prevent many learners from fully participating in the speaking activities.
The Spatiality of Politics: Cesare Battisti's Regional and International Thought, 1900–1916
Authors: Rosenboim Or
Published: April 2021

This article concerns the conceptualization of political spaces in early twentieth-century European political thought. The main figure is the Italian geographer and political thinker Cesare Battisti (1875–1916). Drawing on his geographical knowledge of his native region of Trentino, then in the Austro-Hungarian Empire, Battisti envisioned an alternative political order in Central Europe. In a series of geographical surveys and political essays, he described his idea of the region as a meaningful political space, that could become an alternative to both empire and nation-state as part of a continental democratic federation. The article argues that through this new spatial conceptualization of region and federation, Battisti sought to reinterpret the political categories of authority and community. The article examines Battisti's ideas in their historical and intellectual context, arguing that he offers original insights on the evolution of European international and regional thought in the twentieth century.
The Relationships Between Risk-Taking, Depression, and Alcohol Use in the Experience of Suicidal Ideation Among Adults in the General Population
Authors: Li Juliann , Bornheimer Lindsay A. , Fernandez Lindsay , Dagher Jenna
Published: April 2021

Abstract. Risk-taking is associated with suicide among depressed adolescents. In the United States, alcohol is among the most used substances resulting in need for treatment. While alcohol use relates to greater depression and suicidality, less is known about these relationships with risk-taking tendencies, particularly among adult populations. The current study examined suicidal ideation, alcohol use, depression, and risk-taking tendencies among adults 18–65 years old who participated in the 2017 National Survey on Drug Use and Health. Structural equation modeling was used to examine the specific aims in Mplus8. A total of 1,740 (21.4%) participants endorsed suicidal ideation. The model demonstrated good fit and findings indicate increases in alcohol abuse or dependence ( b = 0.094, SE = 0.01, p < .001), depression ( b = 0.036, SE = 0.01, p < .001), and risk-taking ( b = 0.044, SE = 0.01, p < .001) all independently related to increased odds of ideation. Increases in alcohol abuse or dependence ( b = 0.210, SE = 0.02, p < .001) and depression ( b = 0.026, SE = 0.01, p < .05) also related to elevated risk-taking. Based on the joint significance test, risk-taking tendencies served as a partial mediator, functioning as a mechanism in the relationships between alcohol use, depression, and ideation. Risk-taking thus serves as an important treatment target in the prevention of suicide. Implications for practice and future research are discussed.
Maritime Cloud and Drizzle Microphysical Properties Retrieved From Ship‐Based Observations During MAGIC
Authors: Brendecke Jordann , Dong Xiquan , Xi Baike , Wu Peng
Published: April 2021

The Marine ARM GPCI Investigation of Clouds (MAGIC) field campaign provided a wealth of information looking at the stratocumulus to cumulus transition (SCT) over the Eastern‐North Pacific (ENP), however, the lack of cloud in situ measurements gave limited information. Using the observations of Marine W‐band ARM cloud radar, ceilometer, and three‐channel microwave radiometer onboard the ship, we retrieve the single‐layer, low‐level cloud‐droplet effective radius and drizzle median radius (rc and rm,d), number concentration (Nc and Nd), and liquid water content (LWCc and LWCd) using the methods in Wu et al. (2020, https://doi.org/10.1029/2019JD032205). Based on the results during MAGIC, we found that both cloud base and top heights increase approximately 0.75 km from Los Angeles (LA) until cloud breakup (CB) before leveling off. Low cloud fractions (CFs) ranged from ∼85% halfway between LA and CB to ∼20% near Hawaii. Retrieved rc values decreased approximately 2 μm from peak CF to Hawaii while rm,d increased more than 20 μm over the same path. Mean values of rc, rm,d, Nc, Nd, LWCc, and LWCd during MAGIC are 12.1 μm, 55.8 μm, 97.9 cm−3, 0.09 cm−3, 0.40 g m−3, and 0.05 g m−3, respectively. Compared to the mean values over the Azores in Wu et al. (2020, https://doi.org/10.1029/2019JD032205), the mean cloud and drizzle microphysical properties during MAGIC, except LWCd which is roughly equal, are greater due to higher liquid water path and warmer sea surface temperature. This information allows for a better understanding of the SCT over the ENP and can be used to better improve model simulations.
Coherent Satellite Monitoring of the Water Cycle Over the Amazon. Part 1: Methodology and Initial Evaluation
Authors: Pellet Victor , Aires Filipe , Yamazaki Dai , Papa Fabrice
Published: April 2021

Monitoring coherently the Amazon Water Cycle (WC) using satellite observations is crucial for climate and water resources studies. The SAtellite Water Cycle (SAWC) integration methodology is introduced to optimize the satellite datasets. In this paper, the WC budget is balanced simultaneously over 10 sub‐basins by constraining the horizontal water exchanges between them. Compared to an actual assimilation analysis, SAWC benefits from the use of water storage observations from Gravity Recovery and Climate Experiment. SAWC corrects the satellite evapotranspiration datasets that tend to under‐estimate the water‐limited evaporation over the central Amazon and to over‐estimate the energy‐limited evaporation over the northern Amazon. The SAWC precipitation estimates are evaluated against gauge measurements and show good overall results with a correlation varying from 0.94 to 0.99 and root‐mean‐square deviation between 16 and 41 mm/month (≃10% of precipitation estimate).
Fate of Artificially Injected Oxygen in the Hypolimnion of a Two‐Basin Lake: Amisk Lake, Revisited
Authors: Toledo J. C. , Singleton V. L. , Little J. C. , Lawrence G. A. , Ramón C. L. , Rueda F. J.
Published: April 2021

Bubble‐plume diffusers are increasingly used to add dissolved oxygen (DO) to the hypolimnion of lakes and reservoirs. Bubble plumes are successful at replenishing hypolimnetic DO, but they also introduce mixing energy that induces subtle changes in the thermal structure of the reservoir, driving changes in plume behavior. To account for this complex plume‐reservoir interaction, a double bubble‐plume model is coupled with a three‐dimensional hydrodynamic model. The coupled model is used to reassess a field‐scale analysis of the bubble‐plume diffuser in two‐basin Amisk Lake, aiming at evaluating the relative role of bubble‐induced circulation and internal‐seiching in driving inter‐basin transport under stratified conditions. A large‐scale plume‐induced circulation was previously thought to be the main driver of inter‐basin oxygen transport. This interpretation was based on the attribution of the time‐averaged circulation in the channel due to plume operation. However, the intrinsic complexity of the hydraulic system and the sparseness of the field data introduced large uncertainties in the previous analysis. Here, we demonstrate that the time‐averaged circulation is primarily the result of wind‐driven internal seiches. Oxygen exchange is shown to be controlled by the interaction between internal seiche‐driven horizontal transport along the channel, and, the rate at which added oxygen reaches the layers above the sill, which is mainly controlled by plume‐induced circulation. Internal‐seiche driven transport through basin constrictions will vary depending on the magnitude of the wind forcing, depth of the thermocline and the channel geometry. These results highlight the importance of understanding water movement prior to introducing restoration actions in lakes.
Physical Controls of Summer Variations in Bottom Layer Oxygen Concentrations in the Coastal Hypoxic Region off the Northeastern Shandong Peninsula in the Yellow Sea
Authors: Zhai Fangguo , Liu Zizhou , Li Peiliang , Gu Yanzhen , Sun Liyuan , Hu Luoyu , Liu Xingchuan , Wu Wenfan
Published: April 2021

Hypoxia has been observed worldwide and causes great damage to marine ecosystems. In the northeastern mariculture areas of the Shandong Peninsula, summer oxygen depletion and even hypoxia have been observed in the bottom layer, but the underlying dynamics are still poorly understood. In the current study, the physical controls of variations in bottom layer oxygen concentrations in summer and their interannual variations in the northeastern mariculture areas of the Shandong Peninsula were first investigated using in situ observations collected during 2016–2020. Over the past 5 years, the dissolved oxygen (DO) concentrations of the bottom layer have ranged from 0.8 to 13.0 mg L−1 and exhibited a robust annual cycle, with the lowest value occurring in August. Hypoxia events covering several days were observed intermittently in the summers of 2016 and 2017. Summer oxygen depletion was caused by the combined effects of ocean stratification and enhanced biogeochemical oxygen consumption. At the interannual time scale, stratification and bottom layer DO concentrations showed synchronous variations and both peaked in 2018. The underlying mechanism was related to bottom layer currents, which were created by southerly monsoon winds. Strong/weak southerly surface winds induced a strong/weak bottom shoreward advection of cold, oxygen‐rich water and resulted in strong/weak stratification and high/low DO concentrations. The results provide a good reference for coastal mariculture management in the Shandong Province and enrich our understanding of the global distribution of coastal hypoxia.
Ketogenic diet alleviates colitis by reduction of colonic group 3 innate lymphoid cells through altering gut microbiome
Authors: Kong Cheng , Yan Xuebing , Liu Yongqiang , Huang Linsheng , Zhu Yefei , He Jide , Gao Renyuan , Kalady Matthew F. , Goel Ajay , Qin Huanlong , Ma Yanlei
Published: April 2021

Accumulating evidence suggests that ketogenic diets (KDs) mediate the rise of circulating ketone bodies and exert a potential anti-inflammatory effect; however, the consequences of this unique diet on colitis remain unknown. We performed a series of systematic studies using a dextran sulfate sodium (DSS) animal model of inflammatory colitis. Animals were fed with a KD, low-carbohydrate diet (LCD), or normal diet (ND). Germ-free mice were utilized in validation experiments. Colon tissues were analyzed by transcriptome sequencing, RT2 profiler PCR array, histopathology, and immunofluorescence. Serum samples were analyzed by metabolic assay kit. Fecal samples were analyzed by 16S rRNA gene sequencing, liquid chromatography–mass spectrometry and gas chromatography–mass spectrometry. We observed that KD alleviated colitis by altering the gut microbiota and metabolites in a manner distinct from LCD. Quantitative diet experiments confirmed the unique impact of KD relative to LCD with a reproducible increase inAkkermansia, whereas the opposite was observed forEscherichia/Shigella. After colitis induction, the KD protected intestinal barrier function, and reduced the production of RORγt+CD3−group 3 innate lymphoid cells (ILC3s) and related inflammatory cytokines (IL-17α, IL-18, IL-22, Ccl4). Finally, fecal microbiota transplantation into germ-free mice revealed that the KD- mediated colitis inhibition and ILC3 regulation were dependent on the modification of gut microbiota. Taken together, our study presents a global view of microbiome-metabolomics changes that occur during KD colitis treatment, and identifies the regulation of gut microbiome and ILC3s as novel targets involving in IBD dietary therapy.
Indium phosphide magic-sized clusters: chemistry and applications
Authors: Kwon Yongju , Kim Sungjee
Published: April 2021

This paper reviews developments in the synthesis of InP quantum dots (QDs) and research on InP magic-sized clusters (MSCs), which occur as intermediates during the growth of InP QDs. We classify research on InP MSCs into (1) synthesis and characterization and (2) applications. Several InP MSCs have been developed using low reaction temperatures or strong binding ligands. InP MSCs passivated by carboxylate, amine or phosphonate ligands and InP MSCs that incorporate heterogeneous atoms (Cl or Zn) have been synthesized. We also review tools to characterize MSCs and show the intermediate characteristics of InP MSCs. InP MSCs have been used as synthesis precursors for spherical InP QDs and nonspherical InP nanostructures, such as elongated, branched, and hyperbranched/dendrimer-like morphologies. We also present MSC-mediated growth mechanisms involving fragments, monomers or other nanoclusters. Research on the chemistry and applications of InP MSCs has uncovered the formation process of InP nanomaterials. Developments in the luminescent properties of InP MSCs, InP QDs and elongated InP nanostructures would be useful in displays.
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

Anti-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

The 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.
Publisher Correction: A meta-analysis of genome-wide association studies identifies multiple longevity genes
Authors: Deelen Joris , Evans Daniel S. , Arking Dan E. , Tesi Niccolò , Nygaard Marianne , Liu Xiaomin , Wojczynski Mary K. , Biggs Mary L. , van der Spek Ashley , Atzmon Gil , Ware Erin B. , Sarnowski Chloé , Smith Albert V. , Seppälä Ilkka , Cordell Heather J. , Dose Janina , Amin Najaf , Arnold Alice M. , Ayers Kristin L. , Barzilai Nir , Becker Elizabeth J. , Beekman Marian , Blanché Hélène , Christensen Kaare , Christiansen Lene , Collerton Joanna C. , Cubaynes Sarah , Cummings Steven R. , Davies Karen , Debrabant Birgit , Deleuze Jean-François , Duncan Rachel , Faul Jessica D. , Franceschi Claudio , Galan Pilar , Gudnason Vilmundur , Harris Tamara B. , Huisman Martijn , Hurme Mikko A. , Jagger Carol , Jansen Iris , Jylhä Marja , Kähönen Mika , Karasik David , Kardia Sharon L. R. , Kingston Andrew , Kirkwood Thomas B. L. , Launer Lenore J. , Lehtimäki Terho , Lieb Wolfgang , Lyytikäinen Leo-Pekka , Martin-Ruiz Carmen , Min Junxia , Nebel Almut , Newman Anne B. , Nie Chao , Nohr Ellen A. , Orwoll Eric S. , Perls Thomas T. , Province Michael A. , Psaty Bruce M. , Raitakari Olli T. , Reinders Marcel J. T. , Robine Jean-Marie , Rotter Jerome I. , Sebastiani Paola , Smith Jennifer , Sørensen Thorkild I. A. , Taylor Kent D. , Uitterlinden André G. , van der Flier Wiesje , van der Lee Sven J. , van Duijn Cornelia M. , van Heemst Diana , Vaupel James W. , Weir David , Ye Kenny , Zeng Yi , Zheng Wanlin , Holstege Henne , Kiel Douglas P. , Lunetta Kathryn L. , Slagboom P. Eline , Murabito Joanne M.
Published: April 2021

A Correction to this paper has been published: https://doi.org/10.1038/s41467-021-22613-2
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

Kidney 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

During 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

For 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

The 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

Neuroimaging 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

Seafloor 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

The 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

In 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.