bluuebunny/crossref_metadata_2025 huggingface dataset:
Literary Cosmopolitanism in the English Fin de Siècle
Authors: Evangelista Stefano
Published: August 2021

Derived from the ancient Greek for ‘world citizenship’, cosmopolitanism offers a radical alternative to identities and cultural practices built on the idea of the nation: cosmopolitans imagine themselves instead as part of a global community that cuts across national and linguistic boundaries. This book argues that fin-de-siècle writing in English witnessed an extensive and heated debate about cosmopolitanism, which transformed readers’ attitudes towards national identity, foreign literatures, translation, and the idea of world literature. It offers a critical examination of cosmopolitanism as a field of controversy. While some writers and readers embraced the creative, imaginative, emotional, and political potentials of world citizenship, hostile critics denounced it as a politically and morally suspect ideal, and stressed instead the responsibilities of literature towards the nation. In this age of empire and rising nationalism, world citizenship came to enshrine a paradox: it simultaneously connoted positions of privilege and marginality, connectivity and non-belonging. Chapters on Oscar Wilde, Lafcadio Hearn, George Egerton, the periodical press, and artificial languages bring to light a variety of literary responses. The book interrogates cosmopolitanism as a liberal ideology that celebrates human diversity and as a social identity linked to worldliness. It investigates its effect on gender, ethics, and the emotions. It presents English-language literature of the fin de siècle as a dynamic space of exchange and mediation, and argues that our own approach to literary studies should become less national in focus.
Glossary (1578)
Authors: Nappi Carla
Published: August 2021

Chapter 1 tells the story of the Translators’ College (Siyi guan) and Interpreters’ Station (Huitong guan) in Ming Dynasty China. It follows the story of the translators who worked at the Siam Translation Bureau to explain the history of the College, the Station, the translators that they trained and employed, and the ways that their work laid a foundation for the later history of translation and oral interpretation in China. It also pays special attention to the ways that glossaries and dictionaries can be read as historical documents.
Dispersal
Authors: Nappi Carla
Published: August 2021

This interlude concludes the book. It considers various types of dispersal models for understanding how the story ends.
The ‘History of Everyday Life’ on BBC Radio
Authors: Carter Laura
Published: August 2021

The second part of this book, which starts with this chapter, is about the ‘history of everyday life’ in practice. This opening chapter is about the broadcasting of history on BBC radio before the 1960s, drawing on programme schedules, scripts, and production documents. The ‘history of everyday life’ flourished as part of the BBC’s educational, citizen-making project, underpinned by the ethos of John Reith, the BBC’s first Director-General between 1922 and 1938. This chapter reveals how the ‘history of everyday life’ was bound up with the concentration of female talent within the inter-war BBC and the emergence of new radiophonic technologies during the 1930s. Sound effects, music, and femininity helped to construct a genre of ‘light’ social history broadcasting, designed to appeal to ordinary listeners across both schools and general programming. This trend is highlighted through a focus on the work of Rhoda Power, a BBC educationaist. A particular shift is identified during the period from the 1940s to the 1960s, when history content on the radio became stratified between the ‘expert’ and the ‘popular’ due to gendered and professionalizing impulses within the BBC. As a consequence, the ‘history of everyday life’ came to be regarded as history for leisure in the post-1945 period.
‘Histories of Everyday Life’ in Local Museums
Authors: Carter Laura
Published: August 2021

The second part of this book, of which this chapter is part, is about the ‘history of everyday life’ in practice. This chapter examines the ‘history of everyday life’ in local community settings. It argues that folk museums were the museological vehicles of popular social history in mid-twentieth-century Britain. The British folk museum movement is traced via museum case studies in Luton, Cambridge, York, and the Highlands. Collecting practices, curation, visitors, and the educational programmes within each museum are analysed. The practices of several curator-collectors of everyday life, notably Enid Porter and Isabel Grant, are explored in depth. The chapter argues that folk history, so often thought of as a talisman of the extreme right, was recast at a community level into a feminized and conservative ‘history of everyday life’ for ordinary people. The final part of the chapter connects the ‘history of everyday life’ to debates about the emergence of commercial and industrial heritage in Britain during the 1960s and 1970s.
Foreign Judgments and Contracts: The Anti-enforcement Injunction
Authors: Yeo Tiong Min
Published: August 2021

This essay examines, within the common law world, the practice of courts in England and Wales and in Singapore of granting injunctions to restrain the enforcement of foreign judgments, with particular reference to cases in which the injunction is sought to protect a contractual right. It considers the approach in recent case law, contrasting the ‘anti-enforcement injunction’ with the more frequently granted ‘anti-suit injunction’. It further seeks to differentiate cases where the proceedings leading to the foreign judgment had been brought in breach of a choice of court or arbitration agreement from cases where the reliance on the foreign judgment is the breach of contract.
‘A Peculiarly Pointless Line of Division’: Recognition of Proceedings and Non-proceedings Divorces under the Family Law Act 1986
Authors: Shúilleabháin Máire Ní
Published: August 2021

This essay critically examines the distinction within the overseas divorce recognition scheme in Part II of the Family Law Act 1986 between divorces obtained by ‘judicial or other proceedings’ and divorces obtained ‘otherwise than by means of proceedings’. It examines the English courts’ approach to this distinction, and argues for a different alignment within the rules for recognising overseas divorces. The essay also considers, and criticises, the distinction between ‘mono-territorial’ and transnational divorces under the 1986 Act.
International Representation of the EU
Authors: Wouters Jan , Hoffmeister Frank , Baere Geert De , Ramopoulos Thomas
Published: August 2021

This chapter provides an overview of the specific provisions of the Treaties, secondary law, and practice that determine which actors are tasked to externally represent the Union in third states, international organizations, and international fora, as well as international dispute settlement mechanisms and diplomatic exchanges. It starts with the constitutional principles that govern the international representation of the EU, in particular the principles of sincere cooperation, consistency, and unity. Secondly, it delves into the institutional framework for the international representation of the EU, as simplified and rendered more continuous by the Treaty of Lisbon. Specific attention is given to the role of the High Representative of the Union for Foreign Affairs and Security Policy/Vice-President of the Commission, and to the European External Action Service. The post-Lisbon practice on delivering statements in multilateral organizations is noted. The legal underpinnings of the diplomatic practice of the EU are considered in detail. Last but not least, the representation of the EU in international judicial proceedings is discussed.
Treaty-making Procedures
Authors: Wouters Jan , Hoffmeister Frank , Baere Geert De , Ramopoulos Thomas
Published: August 2021

This chapter provides an overview of the treaty-making procedures in the European Union. It explains the historical evolution of primary law in the field and gives examples for each step under Article 218 TFEU (negotiation, signature, provisional application, and conclusion). Excerpts of European Court of Justice (ECJ) case law illustrate how these provisions are interpreted and applied in practice. The chapter also discusses the principles covering suspension and termination of EU agreements, and the ever more important system that allows the EU to contribute to the adoption of international secondary law under Article 218, paragraph 9 Treaty on the Functioning of the European Union (TFEU). A final section describes EU practice for adopting non-legally binding instruments and reproduces the new guidance of December 2017 issued by the Council and the Commission in this respect after the ECJ’s judgment in the case relating to the EU–Swiss Memorandum of Understanding.
Common Commercial Policy
Authors: Wouters Jan , Hoffmeister Frank , Baere Geert De , Ramopoulos Thomas
Published: August 2021

This chapter provides an overview of the historical evolution and contemporary legal framework of the EU’s common commercial policy (CCP). A structured presentation of the most important European Court of Justice (ECJ) case law in the field recalls the scope and objectives of the CCP. Specific attention is paid to the unilateral regulation of trade, that is, the EU’s regulations on imports (including trade defence) and exports, services, intellectual property, and foreign direct investment. The chapter also presents the trade barriers and enforcement regulations in their context. Finally, it provides an outline of the main points in the EU’s Free Trade and Investment Agreements with third countries.
Cooperation Policies beyond Trade
Authors: Wouters Jan , Hoffmeister Frank , Baere Geert De , Ramopoulos Thomas
Published: August 2021

This chapter provides an overview of the cooperation policies of the Union beyond trade. In particular, it focuses on the neighbourhood policy, development cooperation and cooperation with developed countries, and humanitarian aid. It presents and analyses their development in time and the case law of the Court of Justice on their nature and scope, situating them within the overall scheme of the Treaties. It further examines the tools at the disposal of the Union to implement them. These comprise unilateral thematic and geographic instruments and the proposed Neighbourhood, Development and International Cooperation Instrument that is to apply from 2021 to 2027. They further include international agreements concluded with third countries.
Generalized Linear Models (GLM)
Authors: Touchon Justin C.
Published: August 2021

Chapter 7 introduces one of the most useful statistical frameworks for the modern life scientist: the generalized linear model (GLM). GLMs extend the linear model to an array of non-normally distributed data such as Poisson, negative binomial, binomial, and Gamma distributed data. These models dramatically improve the breadth of data that can be properly analysed without resorting to non-parametric statistics. Using the same RxP dataset, readers learn how to assess the error distribution of their data and evaluate competing models to achieve the best, most robust analysis possible. Diagnostic plots and assessing model fit is continually taught as is how to interpret the model output and calculate summary statistics. Plotting non-normal error distributions with ggplot2 is taught, as is using the predict() function.
Mixed Effects Models
Authors: Touchon Justin C.
Published: August 2021

Mixed effects models are powerful techniques for controlling for non-independence of data or repeated measures, and can be harnessed for both normal and non-normal data structures. Chapter 8 teaches readers how to code, assess, interpret, and troubleshoot both linear and generalized linear mixed models using the same RxP dataset which has been used throughout the book, although now it is viewed through a new lens. Readers are taught how to code likelihood ratio tests to calculate statistical significance and how to use multiple packages, such as lme4 and glmmTMB.
Language-Mastery and the Sorites Paradox
Authors: Wright Crispin
Published: August 2021

This chapter, originally written for Gareth Evans’s and John McDowell’s edited anthology of papers, Truth and Meaning, on the philosophical issues raised by Davidsonian truth-theoretic semantics for natural language, reprises the key arguments of Chapter 1, but with a more explicit focus on the question: what is the nature of linguistic competence? Can it, at least at the most basic level, be viewed as consisting in propositional knowledge of, and a consequent ability to follow, semantic and syntactic rules? The suggestion is that the Davidsonian programme is implicitly invested in a positive answer to that question, and that one lesson of the Sorites is to make that answer seriously doubtful, mandating a ‘more purely behaviouristic’ conception of basic linguistic competence.
Hairier than Putnam Thought
Authors: Read Stephen
Published: August 2021

This chapter is a short note, co-written with Stephen Read, reacting to Hilary Putnam’s observation in his ‘Vagueness and Alternative Logic’ that intuitionistic logic would block the transition from the negation of the usual universally quantified conditional form of major premise for a Sorites to the assertion of a sharp boundary to the target predicate in the series concerned, and would thus allow the paradox to be reconceived as a straightforward reductio of its major premise. It is pointed out that a Sorites need not employ that form of major premise but can instead proceed, in intuitionistic logic, from the negation of the existential claim that the series in question contains a sharp boundary and that, while an intuitionistically suspect double negation elimination step would still be needed to enforce the unpalatable conclusion that the predicate in question indeed has a sharp boundary, nothing like the semantic motivation that the Intuitionists have favoured in mathematics for a restriction on double negation elimination can be operative in this context.
Further Reflections on the Sorites Paradox
Authors: Wright Crispin
Published: August 2021

This chapter revisits certain of the issues of Chapters 1 and 2. It is argued that Dummett’s ‘incoherentist’ response to the Sorites is unacceptable, and urges that we should distinguish a variety of types of Sorites, as individuated by the differing motivations for their various respective major premises, including what are here termed the No Sharp Boundaries paradox and the Tachometer paradox. The chapter rejects Christopher Peacocke’s contention that the major premises for Sorites can be motivated under the aegis of a behaviouristic conception of linguistic competence, so that jettison of the Governing View is beside the point as a response to Sorites paradoxes. It musters six objections to Peacocke’s own treatment of the Sorites, as representative of degree-theoretic approaches to vagueness in general. The chapter includes further discussion of the relationship between tolerance and observationality.
The Arabidopsis PeptideAtlas: Harnessing worldwide proteomics data to create a comprehensive community proteomics resource
Authors: van Wijk Klaas J , Leppert Tami , Sun Qi , Boguraev Sascha S , Sun Zhi , Mendoza Luis , Deutsch Eric W
Published: August 2021

We developed a resource, the Arabidopsis PeptideAtlas (www.peptideatlas.org/builds/arabidopsis/), to solve central questions about the Arabidopsis thaliana proteome, such as the significance of protein splice forms and post-translational modifications (PTMs), or simply to obtain reliable information about specific proteins. PeptideAtlas is based on published mass spectrometry (MS) data collected through ProteomeXchange and reanalyzed through a uniform processing and metadata annotation pipeline. All matched MS-derived peptide data are linked to spectral, technical, and biological metadata. Nearly 40 million out of ∼143 million MS/MS (tandem MS) spectra were matched to the reference genome Araport11, identifying ∼0.5 million unique peptides and 17,858 uniquely identified proteins (only isoform per gene) at the highest confidence level (false discovery rate 0.0004; 2 non-nested peptides ≥9 amino acid each), assigned canonical proteins, and 3,543 lower-confidence proteins. Physicochemical protein properties were evaluated for targeted identification of unobserved proteins. Additional proteins and isoforms currently not in Araport11 were identified that were generated from pseudogenes, alternative start, stops, and/or splice variants, and small Open Reading Frames; these features should be considered when updating the Arabidopsis genome. Phosphorylation can be inspected through a sophisticated PTM viewer. PeptideAtlas is integrated with community resources including TAIR, tracks in JBrowse, PPDB, and UniProtKB. Subsequent PeptideAtlas builds will incorporate millions more MS/MS data.
Reduced blood circulating calcium level is an outstanding biomarker for preeclampsia among 48 types of human diseases
Authors: Xu S , Zhang M , Cong J , He Y , Zhang L , Guo Y , Li X
Published: August 2021

Background

Calcium ion (Ca2+) is essential for human physiology by regulating various signal transduction pathways inside all cells and in the blood circulation.

Aim

We compared circulating Ca2+ levels in the healthy control against 48 different types of human diseases.

Design

A total of 144 201 independent test results of Ca2+ levels from 48 clinically defined diseases and 141 679 independent test results of Ca2+ from healthy individuals who came to the hospital for annual physical examination were retrieved during the past 5 years.

Methods

Ca2+ was determined by the standard ‘Arsenazo III method’ in the clinical laboratory of Affiliated Hospital of Qingdao University. We analyzed all data using RStudio V.1.3.1073 and python libraries 3.8.

Results

All 48 types of diseases had decreased Ca2+ levels than the healthy control based on either mean or median values. Patients suffering from preeclampsia had the lowest Ca2+ levels among all 48 diseases. The perfect area under the curve, sensitivity, and specificity values of 1.0, 0.96 and 0.96 indicated that Ca2+ was an excellent biomarker for diagnosing preeclampsia. Extremely low Ca2+ was present in patients suffering kidney-related diseases. Since the correlation between each disease on the statistical features is proportional to their vector distance, the two-component analysis revealed that preeclampsia, sepsis and chronic obstructive pulmonary disease were closely related among 48 diseases.

Conclusions

All human diseases were associated with reduced circulating Ca2+ levels, where the decreased Ca2+ was a perfect biomarker for preeclampsia. Kidney-related conditions were related to over-down-regulation of Ca2+ levels. The resemblance of preeclampsia to sepsis and chronic obstructive pulmonary disease based on two-component analysis suggested that the three unrelated diseases might share a similar mechanism of the circulating Ca2+ regulation.
Photocrosslinking silver nanoparticles–aloe vera–silk fibroin composite hydrogel for treatment of full-thickness cutaneous wounds
Authors: Liu Yangkun , Fan JinChuan , Lv MingQi , She Kepeng , Sun Jiale , Lu Qingqing , Han Changhao , Ding SongTao , Zhao Shuang , Wang GuiXue , Zhang YuChan , Zang GuangChao
Published: August 2021

Damage to the skin causes physiological and functional issues. The most effective treatment approach is the use of wound dressings. Silk fibroin (SF) is a promising candidate biomaterial for regulating wound healing; however, its antibacterial properties and biological activity must be further improved. In this study, a photocrosslinking hydrogel was developed to treat full-thickness cutaneous wounds. The composite hydrogel (Ag–AV–SF hydrogel) was prepared by introducing the silver nanoparticles (AgNPs) and aloe vera (AV) as the modifiers. In vitro study exhibited great antibacterial ability, biocompatibility and cell-proliferation and -migration-promoting capacities. It also showed the pH-response releasing properties which release more AgNPs in a simulated chronic infection environment. The healing effect evaluation in vivo showed the healing-promoting ability of the Ag–AV–SF hydrogel was stronger than the single-modifiers groups, and the healing rate of it reached 97.02% on Day 21, higher than the commercial wound dressing, silver sulfadiazine (SS) cream on sale. Additionally, the histological and protein expression results showed that the Ag–AV–SF hydrogel has a greater effect on the pro-healing regenerative phenotype with M2 macrophages at the early stage, reconstructing the blood vessels networks and inhibiting the formation of scars. In summary, the Ag–AV–SF hydrogel developed in this study had good physical properties, overwhelming antibacterial properties, satisfactory biocompatibility and significantly promoting effect on cell proliferation, migration and wound healing. Overall, our results suggest that the Ag–AV–SF hydrogel we developed has great potential for improving the wound healing in clinical treatment.
COVID-19 instructional approaches (in-person, online, hybrid), school start times, and sleep in over 5,000 U.S. adolescents
Authors: Meltzer Lisa J , Saletin Jared M , Honaker Sarah M , Owens Judith A , Seixas Azizi , Wahlstrom Kyla L , Wolfson Amy R , Wong Patricia , Carskadon Mary A
Published: August 2021

Study Objectives

To examine associations among instructional approaches, school start times, and sleep during the COVID-19 pandemic in a large, nationwide sample of U.S. adolescents.

Methods

Cross-sectional, anonymous self-report survey study of a community-dwelling sample of adolescents (grades 6–12), recruited through social media outlets in October/November 2020. Participants reported on instructional approach (in-person, online/synchronous, online/asynchronous) for each weekday (past week), school start times (in-person or online/synchronous days), and bedtimes (BT) and wake times (WT) for each identified school type and weekends/no school days. Sleep opportunity was calculated as BT-to-WT interval. Night-to-night sleep variability was calculated with mean square successive differences.

Results

Respondents included 5,245 racially and geographically diverse students (~50% female). BT and WT were earliest for in-person instruction; followed by online/synchronous days. Sleep opportunity was longer on individual nights students did not have scheduled instruction (>1.5 h longer for online/asynchronous than in-person). More students obtained sufficient sleep with later school start times. However, even with the same start times, more students with online/synchronous instruction obtained sufficient sleep than in-person instruction. Significantly greater night-to-night variability in sleep-wake patterns was observed for students with in-person hybrid schedules versus students with online/synchronous + asynchronous schedules.

Conclusions

These findings provide important insights regarding the association between instructional approach and school start times on the timing, amount, and variability of sleep in U.S. adolescents. Given the public health consequences of short and variable sleep in adolescents, results may be useful for education and health policy decision-making for post-pandemic secondary schools.
The Association Between the Decision to Withdraw Life-Sustaining Therapy and Patient Mortality in U.K. ICUs*
Authors: Maharaj Ritesh , Harrison David A. , Rowan Kathryn
Published: August 2021

OBJECTIVES:

Differences in decisions to limit life-sustaining therapy are often supported by perceptions that patients receive unnecessary and expensive treatment which provide negligible survival benefit. However, the assumption behind those beliefs—that is, that life-sustaining therapy provides no significant marginal survival benefit—remains unproven. Our objective was to quantify the effects of variations in decisions to withdraw or withhold life-sustaining treatment on 180-day mortality in critically ill patients.

DESIGN:

Retrospective observational cohort study of a national clinical database.

SETTING:

Adult ICUs participating in the Intensive Care National Audit and Research Center Case Mix Program in the United Kingdom.

PATIENTS:

Adult patients admitted to general ICUs between April 1, 2009, and March 31, 2016.

MEASUREMENTS AND MAIN RESULTS:

During the study period, 795,721 patients were admitted to 247 ICUs across the United Kingdom. A decision to withdraw or withhold life-sustaining treatment was made for 92,327 patients (11.6%). A multilevel model approach was used to estimate ICU-level practice variation. The ICU-level practice variation was then used as an instrument to measure the effects of decision to withdraw or withhold life-sustaining treatment on 180-day mortality. The marginal population was estimated to be 5.9% of the total cohort. A decision to withdraw or withhold life-sustaining treatment was associated with a marginal increase in 180-day mortality of 25.6% (95% CI, 23.2–27.9%).

CONCLUSIONS:

Decision to withdraw or withhold life-sustaining treatment in critically ill adults in the United Kingdom was associated with increased 180-day mortality in the marginal patients. The increased mortality from a decision to withdraw or withhold life-sustaining treatment in the marginal patient may be informative when establishing patients’ preferences and evaluating the cost-effectiveness of intensive treatments.
The effect of a nurse-led advice line and virtual clinic on inflammatory bowel disease service delivery: an Australian study
Authors: Karimi Neda , Sechi Alexandra J. , Harb Martin , Sawyer Elise , Williams Astrid-Jane , Ng Watson , Connor Susan J.
Published: August 2021

Background

This retrospective cohort study investigated the economic impact of implementing a nurse-led inflammatory bowel disease (IBD) advice-line and virtual clinic on the Australian healthcare system. The advice line is a telephone and email service managed by IBD specialist nurses. The virtual clinic is a planned, formal communication between the gastroenterologist and the specialist IBD nurse the result of which is communicated to the patient electronically

Methods

Advice line telephone calls and virtual clinic consultations registered between 1 June 2015 and 1 June 2016 were reviewed and analyzed in terms of outcome: avoidance of general practitioner (GP) consultation, IBD outpatient consultation, emergency department (ED) presentation, or hospital admission. Cost-benefit analysis was conducted to estimate financial savings.

Results

During the study period, 220 calls were received through the advice line and 1017 virtual clinic consultations occurred. The advice line resulted in the avoidance of 53 GP visits, 159 IBD outpatient department visits, six ED presentations, and one hospital admission. The virtual clinic resulted in the avoidance of four GP visits, 954 IBD outpatient department visits, and 58 ED presentations. This led to an estimated annual cost saving of AUD 169 376.80, with the annual costs incurred estimated to be $58 713. Thus, the annual net benefit of implementing the advice line and the virtual clinic was estimated to be $110 663.80.

Conclusion

Specialized-IBD-nurse-led advice line and virtual clinic improves IBD patients’ access to services and reduces healthcare costs. This highlights the importance of a proactive multidisciplinary approach in optimizing the care of patients with IBD.
Natural selection on a carbon cycling trait drives ecosystem engineering by
Sphagnum
(peat moss)
Authors: Piatkowski Bryan T. , Yavitt Joseph B. , Turetsky Merritt R. , Shaw A. Jonathan
Published: August 2021

Sphagnum
peat mosses have an extraordinary impact on the global carbon cycle as they control long-term carbon sequestration in boreal peatland ecosystems.
Sphagnum
species engineer peatlands, which harbour roughly a quarter of all terrestrial carbon, through peat accumulation by constructing their own niche that allows them to outcompete other plants. Interspecific variation in peat production, largely resulting from differences in tissue decomposability, is hypothesized to drive niche differentiation along microhabitat gradients thereby alleviating competitive pressure. However, little empirical evidence exists for the role of selection in the creation and maintenance of such gradients. In order to document how niche construction and differentiation evolved in
Sphagnum
, we quantified decomposability for 54 species under natural conditions and used phylogenetic comparative methods to model the evolution of this carbon cycling trait. We show that decomposability tracks the phylogenetic diversification of peat mosses, that natural selection favours different levels of decomposability corresponding to optimum niche and that divergence in this trait occurred early in the evolution of the genus prior to the divergence of most extant species. Our results demonstrate the evolution of ecosystem engineering via natural selection on an extended phenotype, of a fundamental ecosystem process, and one of the Earth's largest soil carbon pools.
A large and unusually thick-shelled turtle egg with embryonic remains from the Upper Cretaceous of China
Authors: Ke Yuzheng , Wu Rui , Zelenitsky Darla K. , Brinkman Don , Hu Jinfeng , Zhang Shukang , Jiang Haishui , Han Fenglu
Published: August 2021

Turtle eggs containing embryos are exceedingly rare in the fossil record. Here, we provide the first description and taxonomic identification, to our knowledge, of a fossilized embryonic turtle preserved in an egg, a fossil recovered from the Upper Cretaceous Xiaguan Formation of Henan Province, China. The specimen is attributed to the Nanhsiungchelyidae (Pan-Trionychia), an extinct group of large terrestrial turtles (possibly the speciesYuchelys nanyangensis). The egg is rigid, spherical, and is one of the largest and thickest shelled Mesozoic turtle eggs known. Importantly, this specimen allowed identification of other nanhsiungchelyid egg clutches and comparison to those of Adocidae, as Nanhsiungchelyidae and Adocidae form the basal extinct clade Adocusia of the Pan-Trionychia (includes living soft-shelled turtles). Despite the differences in habitat adaptations, nanhsiungchelyids (terrestrial) and adocids (aquatic) shared several reproductive traits, including relatively thick eggshells, medium size clutches and relatively large eggs, which may be primitive for trionychoids (including Adocusia and Carrettochelyidae). The unusually thick calcareous eggshell of nanhsiungchelyids compared to those of all other turtles (including adocids) may be related to a nesting style adaptation to an extremely harsh environment.
Increase in marine provinciality over the last 250 million years governed more by climate change than plate tectonics
Authors: Kocsis Ádám T. , Reddin Carl J. , Scotese Christopher R. , Valdes Paul J. , Kiessling Wolfgang
Published: August 2021

Amidst long-term fluctuations of the abiotic environment, the degree to which life organizes into distinct biogeographic provinces (provinciality) can reveal the fundamental drivers of global biodiversity. Our understanding of present-day biogeography implies that changes in the distribution of continents across climatic zones have predictable effects on habitat distribution, dispersal barriers and the evolution of provinciality. To assess marine provinciality through the Phanerozoic, here we (a) simulate provinces based on palaeogeographic reconstructions and global climate models and (b) contrast them with empirically derived provinces that we define using network analysis of fossil occurrences. Simulated and empirical patterns match reasonably well and consistently suggest a greater than 15% increase in provinciality since the Mesozoic era. Although both factors played a role, the simulations imply that the effect of the latitudinal temperature gradient has been twice as important in determining marine provinciality as continental configuration.
Wild ciliates differ in susceptibility to Legionella pneumophila JR32
Authors: Kawashiro Airi , Okubo Torahiko , Nakamura Shinji , Thapa Jeewan , Miyake Masaki , Yamaguchi Hiroyuki
Published: August 2021

We investigated how

Legionella pneumophila

(Lp) JR32 interacts with Anteglaucoma CS11A and Colpoda E6, two ciliates that we isolated from sewage and sink trap sludge, respectively, using a handmade maze device containing a 96-well crafting plate. Our 18S rDNA-based phylogenetic analysis showed that Anteglaucoma CS11A and Colpoda E6 formed distinct clades. Scanning electron microscopy showed that Anteglaucoma CS11A had a bigger-sized body than Colpoda E6 and, unlike Tetrahymena IB (the reference strain), neither ciliate produced pellets, which are extracellular vacuoles. Fluorescence microscopic observations revealed that although the intake amounts differed, all three ciliates rapidly ingested LpJR32 regardless of the presence or absence of the icm/dot virulence genes, indicating that they all interacted with LpJR32. In co-cultures with Anteglaucoma CS11A, the LpJR32 levels were maintained but fell dramatically when the co-culture contained the LpJR32 icm/dot deletion mutant instead. Anteglaucoma CS11A died within 2 days of co-culture with LpJR32, but survived co-culture with the deletion mutant. In co-cultures with Colpoda E6, LpJR32 levels were maintained but temporarily decreased independently of the virulence gene. Concurrently, the Colpoda E6 ciliates survived by forming cysts, which may enable them to resist harsh environments, and by diminishing the sensitivity of trophozoites to Lp. In the Tetrahymena IB co-cultures with LpJR32 or Δicm/dot, the Lp levels were maintained, albeit with temporal decreases, and the Tetrahymena IB levels were also maintained. We conclude that unlike Tetrahymena IB with pellet production, Anteglaucoma CS11A can be killed by LpJR32 infection, and Colpoda E6 can resist LpJR32 infection through cyst formation and the low sensitivity of trophozoites to Lp. Thus, the two ciliates that we isolated had different susceptibilities to LpJR32 infection.
The influence of SARS-CoV-2 variants of concern on national case fatality rates
Authors: Barletta William A.
Published: August 2021

Background

During 2021 several new variants of the SARS-CoV-2 virus appeared with both increased levels of transmissibility and virulence with respect to the original wild variant. The Delta (B.1.617.2) variation, first seen in India, dominates COVID-19 infections in several large countries including the United States and India. Most recently, the Lambda variant of interest with increased resistance to vaccines has spread through much of South America.

Objective

This research explores the degree to which new variants of concern 1) generate spikes and waves of fluctuations in the daily case fatality rates (CFR) across countries in several regions in the face of increasing levels of vaccination of national populations and 2) may increase the vulnerability of persons with certain comorbidities.

Methods

This study uses new, openly available, epidemiological statistics reported to the relevant national and international authorities for countries across the Americas, Europe, Africa, Asia and the Middle East. Daily CFRs and correlations of fatal COVID-19 infections with potential cofactors are computed for the first half of 2021 that has been dominated by the wide spread of several “variants of concern” as denoted by the World Health Organization.

Results

The analysis yields a new quantitative measure of the temporal dynamics of mortality due to SARS-CoV-2 infections in the form of variations of a proxy case fatality rate compared on a country to-country basis in the same region. It also finds minimal variation of correlation between the cofactors based on WHO data and on the average apparent case fatality rate.
Immunogenicity and safety of inactivated whole virion Coronavirus vaccine with CpG (VLA2001) in healthy adults aged 18 to 55: a randomised phase 1 /2 clinical trial
Authors: Lazarus Rajeka , Taucher Christian , Brown Claire , Corbic Irena , Danon Leon , Dubischar Katrin , Duncan Christopher J.A. , Eder-Lingelbach Susanne , Faust Saul N , Green Christopher , Gokani Karishma , Hochreiter Romana , Wright Johanna Kellett , Kwon Dowan , Middleditch Alexander , Munro Alasdair P.S. , Naker Kush , Penciu Florentina , Price David , Querton Benedicte , Riaz Tawassal , Ross-Russell Amy , Sanchez-Gonzalez Amada , Wardle Hayley , Warren Sarah , Finn Adam ,   the Valneva Phase 1 Trial Group
Published: August 2021

Background

We assessed the safety, tolerability and immunogenicity of VLA2001 is a whole-virion inactivated SARS-CoV-2 vaccine adsorbed to alum with a toll-like receptor 9 agonist adjuvant in healthy volunteers aged 18-55.

Methods

The first 15 participants were enrolled, in groups of 5, to receive two doses, separated by 21 days, of one of three dose concentrations, administered intramuscularly. 138 further participants were randomised 1:1:1 to receive the same 3 dose concentrations, in a double blinded manner. Primary outcomes were solicited adverse reactions 7 days after each vaccination and neutralising antibody geometric mean titres (GMT) against SARS-CoV-2, 2 weeks after the second vaccination (day 36), measured by live microneutralisation assay against wild-type virus (MNA50). Secondary outcomes included unsolicited adverse events, and humoral and cellular responses at day 36, measured by IgG ELISA against Spike protein and interferon-γ secreting T-cells by ELISpot stimulated with multiple SARS-CoV-2 antigens. (ClinicalTrials.govNCT04671017, ISRCTN 82411169)

Findings

Between December 16, 2020 and January 21, 2021, 153 participants were enrolled and randomised evenly between the dose groups. The rates of solicited reactions were similar after the first and second doses and between the three dose groups. The most frequent local reactions were tenderness (58·2%) and pain (41·8%) and systemic reactions were headache (46%) and fatigue (39·2%).

In the high dose group, two weeks following the second dose, the geometric mean titres were 530.4 (95% CI: 421·49, 667·52) for neutralizing antibodies and 2147·9 (95% CI: 1705·98, 2704·22) for S-binding antibodies. There was a dose dependent response with 90·0% (95% CI:78·0%.,97·0%) seroconversion (4-fold rise) at day 36 in the high dose group, which was significantly higher than rates in both the medium (73.5%; 95% CI: 59%,85%), CIs) and low dose (51%; 95%CI: 37%,65%) rate, CIs) groups (both p < 0.001). Antigen-specific interferon-γ T-cells reactive against the S, M and N proteins were observed in 76, 36 and 49% of high dose recipients, respectively.

Interpretation

VLA2001-201 was well tolerated and produced both humoral and cellular immune responses, with a clear dose-response effect.

Funding

This study was funded by the Department of Health and Social Care, UK

The funder had no role in the study design, implementation or analysis.
Food interactions observed in a pharmacokinetic investigation comparing two marketed cold preparations (BNO1016 and ELOM-080) after administration to male beagle dogs
Authors: Seibel Jan , Neumann Astrid , Müller Anne , Wonnemann Meinolf
Published: August 2021

The cold remedies Sinupret extract (BNO 1016) and Gelomyrtol forte (ELOM-080) represent the two top-selling cold remedies in Germany nowadays. Whereas BNO 1016 is a typical immediate release coated tablet, ELOM-080 is an enteric-coated soft gelatin capsule. The latter formulation, however, is at risk of pharmacokinetic interactions affecting absorption especially in the case of concomitant food intake. In the present pilot study, we investigated the risk of a possible food effect on BNO 1016 in comparison to ELOM-080 in three male beagle dogs. Single doses of BNO 1016 and ELOM-80 at 80 mg/kg and 160 mg/kg, respectively, were administered under fasting and fed conditions according to a 4-period, 4-treatment within-design. Blood sampling took place until up to 30 hp.a.and plasma concentrations of gentiopicroside, verbenalin and from a further marker analyte (BNO 1016 analytes) as well as 1,8-cineole, limonene and perillic acid (ELOM-080 analytes) were determined. Pharmacokinetic parameters focusing on rate and extent of absorption were derived. BNO 1016 analytes demonstrated a homogenous course in all animals in both, the fasted and fed state. Pharmacokinetic characteristics of a typical immediate release drug formulation were observed for all analytes and a food effect could be ruled out. ELOM-080 analytes also showed a homogeneous picture in the fasted state. However, lag-times (tlag) of up to 2 hp.a.with corresponding tmaxvalues of 3 to 4 h were observed, reflecting a longer gastric residence time of the formulation. In the fed state, ELOM-080 showed significant pharmacokinetic characteristics suggesting a clear food effect. A major observation was a double peak phenomenon that could be observed in two out of three dogs. Furthermore, lag-times of some analytes up to 3-4 h and corresponding tmaxvalues of up to 6-8 h occurred. In contrast to BNO 1016, these findings suggest that, as with other enteric-coated formulations, there may be a significant risk for food effects with ELOM-080 also in humans.
Covid-19 vaccine immunogenicity in people living with HIV-1
Authors: Nault Lauriane , Marchitto Lorie , Goyette Guillaume , Tremblay-Sher Daniel , Fortin Claude , Martel-Laferrière Valérie , Trottier Benoît , Richard Jonathan , Durand Madeleine , Kaufmann Daniel , Finzi Andrés , Tremblay Cécile
Published: August 2021

Introduction

COVID-19 vaccine efficacy has been evaluated in large clinical trials and in real-world situation. Although they have proven to be very effective in the general population, little is known about their efficacy in immunocompromised patients. HIV-infected individuals’ response to vaccine may vary according to the type of vaccine and their level of immunosuppression. We evaluated immunogenicity of an mRNA anti-SARS CoV-2 vaccine in HIV-positive individuals.

Methods

HIV-positive individuals (n=121) were recruited from HIV clinics in Montreal and stratified according to their CD4 counts. A control group of 20 health care workers naïve to SARS CoV-2 was used. The participants’ Anti-RBD IgG responses were measured by ELISA at baseline and 3 to 4 weeks after receiving the first dose of an mRNA vaccine).

Results

Eleven of 121 participants had anti-COVID-19 antibodies at baseline, and a further 4 had incomplete data for the analysis. Mean anti-RBD IgG responses were similar between between the HIV negative control group (n=20) and the combined HIV+ group (n=106) (p = 0.72). However, these responses were significantly lower in the group with <250 CD4 cells/mm3. (p<0.0001). Increasing age was independently associated with decreased immunogenicity.

Conclusion

HIV-positive individuals with CD4 counts over 250 cells/mm3have an anti-RBD IgG response similar to the general population. However, HIV-positive individuals with the lowest CD4 counts (<250 cells/mm3) have a weaker response. These data would support the hypothesis that a booster dose might be needed in this subgroup of HIV-positive individuals, depending on their response to the second dose.
Nucleoporin107 mediates female sexual differentiation via Dsx
Authors: Shore Tikva , Levi Tgst , Kalifa Rachel , Dreifuss Amatzia , Rekler Dina , Weinberg-Shukron Ariella , Nevo Yuval , Bialistoky Tzofia , Moyal Victoria , Gold Merav Yaffa , Leebhoff Shira , Zangen David , Deshpande Girish , Gerlitz Offer
Published: August 2021

We recently identified a missense mutation in Nucleoporin107 (Nup107; D447N) underlying XX-ovarian-dysgenesis, a rare disorder characterized by underdeveloped and dysfunctional ovaries. Modelling of the human mutation in Drosophila or specific knockdown of Nup107 in the gonadal soma resulted in ovarian-dysgenesis-like phenotypes. Transcriptomic analysis identified the somatic sex-determination gene doublesex (dsx) as a target of Nup107. Establishing Dsx as a primary relevant target of Nup107, either loss or gain of Dsx in the gonadal soma is sufficient to mimic or rescue the phenotypes induced by Nup107 loss. Importantly, the aberrant phenotypes induced by compromising either Nup107 or dsx are reminiscent of BMP signaling hyperactivation. Remarkably, in this context, the metalloprotease AdamTS-A, a transcriptional target of both Dsx and Nup107, is necessary for the calibration of BMP signaling. As modulation of BMP signaling is a conserved critical determinant of soma-germline interaction, the sex and tissue specific deployment of Dsx-F by Nup107 seems crucial for the maintenance of the homeostatic balance between the germ cells and somatic gonadal cells.
The dynamic interaction of systemic inflammation and the hypothalamic-pituitary-adrenal (HPA) axis during and after major surgery
Authors: Galvis Daniel , Zavala Eder , Walker Jamie J. , Upton Thomas , Lightman Stafford L. , Angelini Gianni D. , Evans Jon , Rogers Chris A. , Phillips Kirsty , Gibbison Ben
Published: August 2021

Major surgery and critical illness produce a potentially life threatening systemic inflammatory response. The hypothalamic-pituitary-adrenal (HPA) axis is one of the key physiological systems that counterbalances this systemic inflammation through changes in adrenocorticotrophic hormone (ACTH) and cortisol. These hormones normally exhibit highly correlated ultradian pulsatility with an amplitude modulated by circadian processes. However, these dynamics are disrupted by major surgery and critical illness. In this work, we characterise the inflammatory, ACTH and cortisol responses of patients undergoing cardiac surgery and show that the HPA axis response can be classified into one of three phenotypes: single-pulse, two-pulses and multiple-pulses dynamics. We develop a mathematical model of cortisol secretion and metabolism that predicts the physiological mechanisms responsible for these different phenotypes. We show that the effects of inflammatory mediators are important only in the single-pulse pattern in which normal pulsatility is lost – suggesting that this phenotype could be indicative of the greatest inflammatory response. Investigating whether and how these phenotypes are correlated with clinical outcomes will be critical to patient prognosis and designing interventions to improve recovery.
Desolvation Energy Explains Partitioning of Client Proteins into Condensates
Authors: Villegas José A. , Levy Emmanuel D.
Published: August 2021

Membraneless organelles are cellular compartments that form by liquid-liquid phase separation of one or more components. Other molecules, such as other proteins and nucleic acids, will distribute between the cytoplasm and the liquid compartment in accordance with the thermodynamic drive to lower the free energy of the system. The resulting distribution colocalizes molecular species, to carry out a diversity of functions. Two factors could drive this partitioning: the difference in solvation between the dilute versus dense phase, and intermolecular interactions between the client and scaffold proteins. Here, we develop a set of knowledge-based potentials that allow for the direct comparison between desolvation energy and pairwise interaction energy terms, and use these to examine experimental data from two systems: protein cargo dissolving within phase-separated droplets made from FG repeat proteins of the nuclear pore complex, and client proteins dissolving within phase-separated FUS droplets. We find close agreement between desolvation energies of the client proteins and the experimentally determined values of the partition coefficients, while pairwise interaction energies between client and scaffold show weaker correlations. These results show that client stickiness is sufficient to explain differential partitioning of clients within these two phase-separated systems without taking into account the composition of the condensate. This suggests that selective trafficking of client proteins to distinct membraneless organelles requires recognition elements beyond the client sequence composition.