bluuebunny/crossref_metadata_2025 huggingface dataset:
Collaboration between the Fab and Fc contribute to maximal protection against SARS-CoV-2 in nonhuman primates following NVX-CoV2373 subunit vaccine with Matrix-M™ vaccination
Authors: Gorman Matthew J , Patel Nita , Guebre-Xabier Mimi , Zhu Alex , Atyeo Caroline , Pullen Krista M. , Loos Carolin , Goez-Gazi Yenny , Carrion Ricardo , Tian Jing-Hui , Yaun Dansu , Bowman Kathryn , Zhou Bin , Maciejewski Sonia , McGrath Marisa E. , Logue James , Frieman Matthew B. , Montefiori David , Mann Colin , Schendel Sharon , Amanat Fatima , Krammer Florian , Saphire Erica Ollmann , Lauffenburger Douglas , Greene Ann M. , Portnoff Alyse D. , Massare Michael J. , Ellingsworth Larry , Glenn Gregory , Smith Gale , Alter Galit
Published: February 2021

Recently approved vaccines have already shown remarkable protection in limiting SARS-CoV-2 associated disease. However, immunologic mechanism(s) of protection, as well as how boosting alters immunity to wildtype and newly emerging strains, remain incompletely understood. Here we deeply profiled the humoral immune response in a cohort of non-human primates immunized with a stable recombinant full-length SARS-CoV-2 spike (S) glycoprotein (NVX-CoV2373) at two dose levels, administered as a single or two-dose regimen with a saponin-based adjuvant Matrix-M™. While antigen dose had some effect on Fc-effector profiles, both antigen dose and boosting significantly altered overall titers, neutralization and Fc-effector profiles, driving unique vaccine-induced antibody fingerprints. Combined differences in antibody effector functions and neutralization were strongly associated with distinct levels of protection in the upper and lower respiratory tract, pointing to the presence of combined, but distinct, compartment-specific neutralization and Fc-mechanisms as key determinants of protective immunity against infection. Moreover, NVX-CoV2373 elicited antibodies functionally target emerging SARS-CoV-2 variants, collectively pointing to the critical collaborative role for Fab and Fc in driving maximal protection against SARS-CoV-2. Collectively, the data presented here suggest that a single dose may prevent disease, but that two doses may be essential to block further transmission of SARS-CoV-2 and emerging variants.

Highlights

NVX-CoV2373 subunit vaccine elicits receptor blocking, virus neutralizing antibodies, and Fc-effector functional antibodies.

The vaccine protects against respiratory tract infection and virus shedding in non-human primates (NHPs).

Both neutralizing and Fc-effector functions contribute to protection, potentially through different mechanisms in the upper and lower respiratory tract.

Both macaque and human vaccine-induced antibodies exhibit altered Fc-receptor binding to emerging mutants.
Small in size, big on taste: metabolomics analysis of flavor compounds from Philippine garlic
Authors: Molino Ralph John Emerson J. , Rellin Klidel Fae B. , Nellas Ricky B. , Junio Hiyas A.
Published: February 2021

Philippine garlic (Allium sativum L.) is arguably known to pack flavor and aroma in smaller bulbs compared to imported varieties saturating the local market. In this study, ethanolic extracts of Philippine garlic cultivars were profiled using ultra-high performance liquid chromatography-quadrupole time-of-flight mass spectrometry (UHPLC-QTOF). γ-Glu dipeptides, oligosaccharides and lipids were determined in Philippine garlic cultivars through bioinformatics analysis in GNPS Molecular Networking Platform and fragmentation analysis. Multivariate statistical analysis using XCMS Online showed the abundance of γ-Glu allyl cysteine in Batanes-sourced garlic while γ-Glu propenyl cysteine, γ-Glu methyl cysteine, and alliin are enriched in the Ilocos cultivar. Principal component analysis showed that the γ-Glu dipeptides found in local garlic influenced their distinct separation across PC1 from imported varieties. This presence of high levels of γ-Glu dipeptides and probiotic oligosaccharides may potentially contribute to the superior flavor and nutritional benefits of Philippine garlic.
The impacts of hydropower on freshwater macroinvertebrate richness: A global meta-analysis
Authors: Trottier Gabrielle , Turgeon Katrine , Boisclair Daniel , Bulle Cécile , Margni Manuele
Published: February 2021

Hydroelectric dams and their reservoirs have been suggested to affect freshwater biodiversity. However, studies investigating the consequences of hydroelectric dams and reservoirs on macroinvertebrate richness have reached opposite conclusions. We carried out a meta-analysis devised to elucidate the effects of hydropower dams and their reservoirs on macroinvertebrates richness while accounting for the potential role played by moderators such as biomes, impact types, study designs, sampling seasons and gears. We used a random and mixed effect model, combined with robust variance estimation, to conduct the meta-analysis on 72 pairs of observations (i.e., impacted versus reference) extracted from 17 studies (more than one observation per study). We observed a large range of effect sizes, from very negative to very positive impacts of hydropower. However, according to this meta-analysis, hydropower dams and their reservoirs did not have an overall clear, directional and statistically significant effect on macroinvertebrate richness. We tried to account for the large variability in effect sizes using moderators, but none of the moderators included in the meta-analysis had statistically significant effect. This suggests that some other moderators, which were unavailable for the 17 studies included in this meta-analysis, might be important (e.g., temperature, granulometry, wave disturbance and macrophytes) and that macroinvertebrate richness may be driven by local, smaller scale processes. As new studies become available, it would be interesting to keep enriching this meta-analysis, as well as collecting local habitat variables, to see if we could finally draw statistically significant conclusions about the impacts of hydropower on macroinvertebrate richness.
Furin cleavage of the SARS-CoV-2 spike is modulated by O-glycosylation
Authors: Zhang Liping , Mann Matthew , Syed Zulfeqhar , Reynolds Hayley M. , Tian E , Samara Nadine L. , Zeldin Darryl C. , Tabak Lawrence A. , Ten Hagen Kelly G.
Published: February 2021

The SARS-CoV-2 coronavirus responsible for the global pandemic contains a unique furin cleavage site in the spike protein (S) that increases viral infectivity and syncytia formation. Here, we show that O-glycosylation near the furin cleavage site is mediated by specific members of the GALNT enzyme family and is dependent on the novel proline at position 681 (P681). We further demonstrate that O-glycosylation of S decreases furin cleavage. Finally, we show that GALNT family members capable of glycosylating S are expressed in human respiratory cells that are targets for SARS-CoV-2 infection. Our results suggest that O-glycosylation may influence viral infectivity/tropism by modulating furin cleavage of S and provide mechanistic insight into the potential role of P681 mutations in the recently identified, highly transmissible B.1.1.7 variant.
Performance measurement in-fourth party reverse logistics
Authors: Öz Halil Hilmi , Özyörük Bahar
Published: February 2021

Purpose

This paper aims to develop a performance measurement (PM) system for fourth-party reverse logistics (RL). In this regard, it proposes simultaneous utilization of a procedural approach and hybrid use of existing performance frameworks.

Design/methodology/approach

The paper first describes fundamentals of RL and PM approaches in literature to build a basis for further discussion. It then carries out a systematic review of the literature on PM in RL to highlight current trends and approaches in this regard. At last, it develops a PM system for fourth-party RL by exploring relevant performance frameworks and by defining a procedure in detail.

Findings

The paper identifies the ongoing interest in development PM in RL, and the gap and the need for the development of comprehensive PM system for fourth-party RL. It also identifies the best approach is to use existing performance frameworks in literature and a procedural approach together as they complement each other rather than contradicting.

Research limitations/implications

The paper fills a gap in literature by developing a comprehensive PM framework for the fourth-party RL. The presented procedure is well suited to be used as part of strategic management process in any fourth-party RL organization. It forces users a top-down approach, from strategies to measures, so that a strong linkage is established in the process. When used together with the proposed PM framework, it guarantees a comprehensive and balanced PM system.

Practical implications

The paper identifies the need for the development of a PM framework as well as a measurement system for the fourth-party RL in the literature. In this regard, it develops a PM framework first, and then a procedure on how to implement it. As a result, users can effectively use them as a part of strategic management process of their organizations.

Social implications

The fourth-party RL is growing and very promising mode of RL for well-being of society, by offering a strong path to sustainable development in the midst of diminishing resources in the world. The existence of a well measurement system is crucial for the healthy operations and development of fourth-party RL organizations. The paper is offering a strong PM model in this regard.

Originality/value

The paper fulfills an identified need to study how to develop a PM system for fourth-party RL.
Personality and pace‐of‐life: Ecological lessons learnt from free‐ranging lemon sharks
Authors: Dingemanse Niels J.
Published: February 2021

In Focus: Dhellemmes, F., Finger J.S., Smukall M.J., Gruber S.H., Guttridge T.L., Laskowski K.L., & J. Krause. (2020) Personality‐driven life‐history trade‐offs differ in two subpopulations of free‐ranging predators. Journal of Animal Ecology, 90, 260–272. Life‐history theory predicts that explorative individuals live‐fast‐but‐die‐young as they take risks to rapidly accumulate resources. Dhellemmes et al. (2020) show that fast‐exploring sharks forage in risky habitats, where they grow‐fast‐but‐die‐young. In higher risk environments, however, this personality‐related pace‐of‐life‐syndrome does not exist because neither fast‐ nor slow‐exploring types venture out into risky areas. The study thereby reveals the key role of ecology as a mediator of personality‐related pace‐of‐life‐syndromes in the wild.
Genetic relationship between tetraploids and pentaploids in the agamospermous species Taraxacum albidum Dahlst., clarified by enzyme electrophoresis
Authors: Morita Tatsuyoshi , Misawa Kyoko , Nishino Takako
Published: February 2021

In order to reveal the genetic relationship of tetraploids and pentaploids in the agamospermous species Taraxacum albidum Dahlst., an allozyme study was carried out. Approximately 200 plants putatively identified as T. albidum were collected mainly from the Kyushu Island of Japan, and analyzed by enzyme electrophoresis. Two multilocus genotypes at 14 presumptive loci of nine enzymes, Type A and Type B, were detected. Most of the sample plants showed uniclonal Type A, which corresponds to “T. albidum” as reported in our previous paper. Type B, which is also uniclonal, was found at fewer localities and was clearly different from Type A in the allele composition of pgi‐2 and pgm‐1, as well as in the allele dosage at mdh and sod‐1. By means of flow cytometry and chromosome count, the ploidy levels of Type A and Type B were shown to be pentaploid and tetraploid, respectively. A comparison of the allele composition suggests a hybrid origin of pentaploid T. albidum (Type A) from an unreduced gamete of Type B and a reduced gamete of any diploid Taraxacum species.
Current state of athalassohaline deep‐sea hypersaline anoxic basin research—recommendations for future work and relevance to astrobiology
Authors: Fisher Luke A. , Pontefract Alexandra , M. Som Sanjoy , Carr Christopher E. , Klempay Benjamin , E. Schmidt Britney , S. Bowman Jeff , Bartlett Douglas H.
Published: February 2021

Deep‐sea hypersaline anoxic basins (DHABs) are uniquely stratified polyextreme environments generally found in enclosed seas. These environments select for elusive and widely uncharacterized microbes that may be living below the currently recognized window of life on Earth. Still, there is strong evidence of highly specialized active microbial communities in the Kryos, Discovery, and Hephaestus basins located in the Eastern Mediterranean Sea; the only known athalassohaline DHABs. Life is further constrained in these DHABs as near‐saturated concentrations of magnesium chloride significantly reduces water activity (aw) and exerts extreme chaotropic stress, the tendency of a solution to disorder biomolecules. In this review, we provide an overview of microbial adaptations to polyextremes focusing primarily on chaotropicity, summarize current evidence of microbial life within athalassohaline DHABs and describe the difficulties of life detection approaches and sampling within these environments. We also reveal inconsistent measurements of chaotropic activity in the literature highlighting the need for a new methodology. Finally, we generate recommendations for future investigations and discuss the importance of athalassohaline DHAB research to help inform extraterrestrial life detection missions.
Carbohydrate‐dependent sulfur respiration in halo(alkali)philic archaea
Authors: Sorokin Dimitry Y. , Messina Enzo , Smedile Francesco , La Cono Violetta , Hallsworth John E. , Yakimov Michail M.
Published: February 2021

Archaea are environmentally ubiquitous on Earth, and their extremophilic and metabolically versatile phenotypes make them useful as model systems for astrobiology. Here, we reveal a new functional group of halo(natrono)archaea able to utilize alpha‐d‐glucans (amylopectin, amylose and glycogen), sugars, and glycerol as electron donors and carbon sources for sulfur respiration. They are facultative anaerobes enriched from hypersaline sediments with either amylopectin, glucose or glycerol as electron/carbon sources and elemental sulfur as the terminal electron acceptor. They include 10 strains of neutrophilic haloarchaea from circum pH‐neutral lakes and one natronoarchaeon from soda‐lake sediments. The neutrophilic isolates can grow by fermentation, although addition of S0 or dimethyl sulfoxide increased growth rate and biomass yield (with a concomitant decrease in H2). Natronoarchaeal isolate AArc‐S grew only by respiration, either anaerobically with S0 or thiosulfate as the terminal electron acceptor, or aerobically. Through genome analysis of five representative strains, we detected the full set of enzymes required for the observed catabolic and respiratory phenotypes. These findings provide evidence that sulfur‐respiring haloarchaea partake in biogeochemical sulfur cycling, linked to terminal anaerobic carbon mineralization in hypersaline anoxic habitats. We discuss the implications for life detection in analogue environments such as the polar subglacial brine‐lakes of Mars.
Concentrations of toxic elements (As, Cd, Hg and Pb) in cow milk: A review of the recent scientific literature
Authors: Domingo Jose L.
Published: February 2021

A continued intake of milk with certain contents of environmental pollutants/toxicants can mean health risks for the consumers. This paper is mainly focused on reviewing recent studies on the concentrations of As, Cd, Hg and Pb in cow milk of different countries. As expected, notable differences in the metal levels in cow milk samples, depending on the countries and the specific areas of collection, have been found. In general terms, based on the studies here reviewed, human exposure to As, Cd, Hg and Pb by frequent consumption of cow milk should not mean significant health risks for the consumers.
How to Lose Weight well, According to How to Lose Weight well
Authors: Stubbs Joshua E. , Stubbs Toby C. T.
Published: February 2021

Authorities in the UK hope to “tackle obesity” by encouraging people to “eat better and move more”. But what sort of dietary changes are most effective? Joshua E. Stubbs and Toby C. T. Stubbs look to a TV show for answers
Passionate Statisticians
Authors: Aldrich John
Published: February 2021

The phrase “passionate statistician” is usually reserved for Florence Nightingale. But she was not the first to be described as such, as John Aldrich explains
Editorial
Authors: Tarran Brian
Published: February 2021

Another round?
COVID-19: One Year On…
Authors: Fricker Ronald D.
Published: February 2021

Ron Fricker assesses the impact of the pandemic in the United States by calculating the number of “excess deaths”
What's the Big Idea? “Big Data” and its Origins
Authors: Diebold Francis X.
Published: February 2021

Against the background of explosive growth in data volume, velocity, and variety, Francis X. Diebold investigates the origins of the term “Big Data”
Career Story
Authors: Isaac William
Published: February 2021

“It is almost a necessity for researchers to collaborate and interact with people from other disciplines”
COVID-19: A View from the Sidelines
Authors: Hoffman Katherine
Published: February 2021

Katherine Hoffman is a biostatistician in the pulmonary and critical care team of a New York City hospital, who found herself part of the Covid-19 response when the outbreak first hit in March 2020. This is her story
Review article: Developing the Australian and New Zealand Guideline for Mild to Moderate Head Injuries in Children: An adoption/adaption approach
Authors: Tavender Emma , Ballard Dustin W , Wilson Agnes , Borland Meredith L , Oakley Ed , Cotterell Elizabeth , Wilson Catherine L , Ring Jenny , Dalziel Stuart R , Babl Franz E ,   Paediatric Research in Emergency Departments International Collaborative (PREDICT)
Published: February 2021

The Paediatric Research in Emergency Departments International Collaborative (PREDICT) released the Australian and New Zealand Guideline for Mild to Moderate Head Injuries in Children in 2021. We describe innovative and practical methods used to develop this guideline. Informed by GRADE‐ADOLOPMENT and ADAPTE frameworks, we adopted or adapted recommendations from multiple high‐quality guidelines or developed de novo recommendations. A Guideline Steering Committee and a multidisciplinary Guideline Working Group of 25 key stakeholder representatives formulated the guideline scope and developed 33 clinical questions. We identified four relevant high‐quality source guidelines; their recommendations were mapped to clinical questions. The choice of guideline recommendation, if more than one guideline addressed a question, was based on its appropriateness, currency of the literature, access to evidence, and relevance. Updated literature searches identified 440 new studies and key new evidence identified. The decision to develop adopted, adapted or de novo recommendations was based on the supporting evidence‐base and its transferability to the local setting. The guideline underwent a 12‐week consultation period. The final guideline consisted of 35 evidence‐informed and 17 consensus‐based recommendations and 19 practice points. An algorithm to inform imaging and observation decision‐making was also developed. The resulting process was an efficient and rigorous way to develop a guideline based on existing high‐quality guidelines from different settings.
Angiogenic markers predict kidney injury and obstetric complications in women with preeclampsia and pregnancy‐related acute kidney injury
Authors: Shemies Rasha Samir , Gaber Tamer Zaki , Baiomy Azza , Aladle Doaa A. , Mosbah Alaa , Abdel‐hady El‐Said , Sayed‐Ahmed Nagy , Sobh Mohammed
Published: February 2021

Pregnancy‐related acute kidney injury (PRAKI) particularly on top of preeclampsia (PE) represents a major cause of maternal and fetal morbidity and mortality. Reliable diagnostic tools are needed to further evaluate the diagnosis and prognosis of PRAKI. Our objective was to study the diagnostic and prognostic value of angiogenic markers (e.g., stromal cell‐derived factor 1 (SDF‐1), vascular endothelial growth factor (VEGF), alarmins as uric acid) in women with PE and PRAKI. This prospective study included three groups; PRAKI, PE patients, and healthy controls that were compared regarding serum levels of the studied markers correlated to renal, maternal, and fetal outcomes. SDF‐1, VEGF, and uric acid levels were significantly different between the three included groups and predicted PRAKI diagnosis. Patients with hemolysis, elevated liver enzymes, and low platelet (HELLP) syndrome exhibited the highest titers of SDF‐1 and VEGF. A positive correlation was found between SDF‐1 and renal recovery. Conclusively, serum assays of SDF‐1, VEGF, and uric acid may add a diagnostic value in PRAKI and PE.
Analysis of dietary intake, diet cost and food group expenditure from a 24‐hour food record collected in a sample of Australian university students
Authors: McCartney Danielle , Desbrow Ben , Khalesi Saman , Irwin Christopher
Published: February 2021

Aim

University students often cite increased monetary cost as a major barrier to improved eating behaviours. Here, we examine food expenditure behaviours in a sample of Australian university students.

Methods

Students (n = 147) collected and analysed a 24‐hour food record to determine their food group and nutrient intakes, then costed the food and non‐tap water beverages consumed in the amounts recorded. Diet cost and food group expenditure (absolute and relative to total diet cost) were calculated and compared across socio‐demographic characteristics. Spearman's Rho correlations and partial correlations (controlling for energy intake) were also used to identify associations between diet cost and intake.

Results

The median (IQR) 24‐hour diet cost was $12.42 ($7.06). However, students who worked ≥20 h·wk−1 had a higher diet cost than those who worked <20 h·wk−1 (P = .002) or were unemployed (P = .002). Relative food group expenditure also differed by sex, employment status and whether special dietary requirements were reported (P's < .05). For instance, males reported spending a smaller relative amount on the fruit and vegetables food groups and a larger relative amount on discretionary choices than females (P's < 0.05). Higher diet costs were also associated with greater intakes of the fruit, vegetables and lean meat and alternatives food groups, protein, alcohol, water and calcium, and lower intakes of the grain foods food group and carbohydrate (P's < .05).

Conclusions

These findings provide insight into university students' food expenditure behaviours and may assist health professionals to develop targeted strategies and tailored advice aimed at improving their dietary behaviours.
Why the History of Parliament Has Not Been Written*
Authors: Seaward Paul
Published: February 2021

There have been legions of individual studies of the history of the English/British/United Kingdom parliament, which is not surprising, since its history is widely acknowledged to be so closely bound up with the history of the nation state itself. But there have been remarkably few attempts to put the story together, to try to consider the long‐term development of parliament as an institution. What would such a story look like? This essay discusses some of the critiques of the whiggish narrative of constitutional and parliamentary development to recognise a common theme in whiggism's tendency to anthropomorphise parliament, to describe it as a single organism with agency and purpose. To forgo that temptation, however, makes it difficult to provide a satisfying narrative of parliament over time. The essay tries to imagine how one might construct a history of parliament as an institution which no longer sees it as an actor in its own story, but, instead, a complex collection of ideas, processes, customs, and conventions, which competing forces struggle to organise in order to achieve their goals, and which is also an arena and forum for that competition.
A.F. Pollard*
Authors: Cavill Paul
Published: February 2021

A.F. Pollard is now better remembered for founding the Institute of Historical Research than he is for his scholarship. In his heyday, however, Pollard was a formidable and prolific historian, primarily of parliament and the Tudor period. Pollard has been characterised both as a modernist and as a whig historian. Rejecting romantic invocations of liberty, he extolled instead the sovereign nation state, pinpointing the 16th century as the moment when it was achieved. Pollard rejected anachronistic accounts of parliament's development: for him, the assembly had grown by accident (out of the medieval king's council), rather than by design. This adaptability had ensured parliament's longevity and would preserve it into the future. Pollard revered the English parliament all the more for its embodiment of this national good fortune. Pollard helped to professionalise the discipline of history, but his own writings could be found wanting when measured against the standards that he had advocated. Criticism of his approach and assumptions comes easily now. Yet, upon reacquaintance, historians of parliament may find enduring interest in Pollard's shrewd and extensive work.
Constitutionalists, Despots, Whigs, and Revisionists: Tudor Parliamentary History in the 20th Century
Authors: Kyle Chris R.
Published: February 2021

The 20th century was the great age of Tudor parliamentary history. This essay examines the contributions and profound changes to the field made by the leading historians of the era, especially Sir John Neale and Sir Geoffrey Elton. Taking as its starting point the whiggish ideas of Stubbs's Constitutional History of England, it traces the impact of A.F. Pollard, G.M. Trevelyan, and Sir Lewis Namier on the field. At its core, though, lie the often acrimonious differences of opinion between Neale and his pupil, Elton. For Neale the Elizabethan parliaments were characterised by an increasingly puritanical Commons eager to wrest control of debates on religion and the succession away from the queen. In so doing this created a constitutional clash that would eventually lead to civil war in the mid 17th century. This ‘orthodoxy’ was savagely critiqued by a revisionist ‘school’ led by Elton that dismantled the interpretation of Neale and replaced it with an institution that was not dominated by political conflict but by largely consensual politics. It was also a position that gave equal weight to the Lords and to the importance of the business of parliament – legislation. The revisionists were masters of critique and highly effective at demolishing Neale, but did little to replace his theories or to explain religio‐political conflict – in doing so it could be argued that they killed the subject. The essay ends by suggesting some new approaches to Tudor parliaments that could help revitalise the subject.
Writing Scottish Parliamentary History, c.1500–1707
Authors: Blakeway Amy , Stewart Laura A.M.
Published: February 2021

In the 19th and 20th centuries, scholarship on the Scottish parliament was heavily informed by a narrative of ‘failure’, directed at explaining why its members voted it out of existence in 1707. Part of the problem was the tendency to see any deviation from the practices of the Westminster parliament as weakness. By reappraising parliament in terms of its utility to those who comprised its membership, notably the titled peerage and the monarch, historians have revealed its adaptability and inventiveness, especially in times of crisis. This essay considers how fresh approaches both to what constituted the parliamentary record and what can – and cannot – be found within it have exerted a transformative influence on our understanding of parliament's evolving role in Scottish political life. Although the Reformation crisis of 1560 and the accession of the ruling house of Stewart to the English throne in 1603 effected profound changes on parliamentary culture, this essay emphasises how parliament sustained its legitimacy and relevance, in part, by drawing on past practices and ideas. Historians have become more attentive in recent years to the means by which social groupings ordinarily excluded from formal parliamentary activity were nonetheless able to engage with, and influence, its proceedings. Gaps remain in our knowledge, however. Some periods have been more intensively studied than others, while certain aspects of parliamentary culture are understudied. The writing of Scottish parliamentary history will continue to offer rich possibilities in future.
‘High Politics’ and its Intellectual Contexts*
Authors: Middleton Alex
Published: February 2021

Recent interest in the historiography of ‘high politics’ has centred mainly on historians writing in the 1960s and 1970s, above all Maurice Cowling. Less attention has been paid to the modified agendas pursued by the next generation of scholars. This essay explores some pioneering attempts to make sense of the structural relationships between 19th‐century British ‘high politics’ and its ‘intellectual’ contexts, focusing on a cluster of seminal 1980s studies by the historians Michael Bentley, Richard Brent, Boyd Hilton, and Jonathan Parry. Together, these works demanded a fundamental rethinking of how Victorian politics operated.
An Irish Party and the British Parliament: Conor Cruise O'Brien's Parnell and His Party
Authors: Bull Philip
Published: February 2021

This essay reassesses the importance of Conor Cruise O'Brien's Parnell and His Party, 1880–90, originally published in 1957, with particular reference to its significance in the history of the British parliament. While establishing the book's continuing relevance, both as a study of a specific political phenomenon and as a model for analysing political movements, the essay questions aspects which do not hold up in the light of subsequent research. In particular, O'Brien's account and interpretation of Parnell's behaviour in 1890–1 in the aftermath of the O'Shea divorce case is shown to be inadequate in the light of more recent research and writing.
Stereotactic ablative radiotherapy as single treatment for early stage non‐small cell lung cancer: A single institution analysis
Authors: Zheng Xiaoli , Sun Yanan , Ye Ke , Fan Chengcheng , Wang Xiaohui , Yang Yang , Jiao Ruidi , Ge Hong
Published: February 2021

Background

Stereotactic ablative radiotherapy (SABR) is the current standard‐of‐care in cases of inoperable early stage non‐small cell lung cancer (ES‐NSCLC). This study aimed to assess the survival outcomes and recurrence patterns after SABR for ES‐NSCLC in a hospital setting.

Methods

A single‐institution retrospective study was performed which included 109 patients who had undergone SABR. The main study endpoints were overall survival (OS), cancer specific survival (CSS), local recurrence‐free survival (LRFS), regional recurrence free survival (RRFS) and distant metastasis‐free survival (DMFS). Univariate and multivariate analysis were conducted to explore the potential factors which might be related to patient survival.

Results

A total of 109 patients were enrolled into the study. Median follow‐up was 44 months (range: 2–93 months). (i) Recurrence results: Among 45 patients with recurrence, 30 patients (28%) had distant metastasis (DM), 17 patients (16%) had local recurrence (LR), 10 patients (9%) had regional recurrence (RR) of lymph nodes and two patients (2%) had second primary lung cancer (SPLC). (ii) Survival results: Median OS, CSS, PFS was 78 months, 78 and 40 months. Two‐year OS, CSS, PFS, LRFS, RRFS and DMFS was 84.7%, 87.1%, 69.2%, 86.8%, 92.7% and 78.0%, respectively. Four‐year OS, CSS, PFS, LRFS, RRFS and DMFS was 55.6%, 60.7%, 37.3%, 76.3%, 88.4% and 59.4%, respectively. (iii) Univariate and multivariate analyses indicated that age was a prognostic factor of CSS in patients aged <75 years (P = 0.04 HR 2.12 95% confidence interval [CI]: 1.04–4.33).

Conclusions

Although high survival rates can be achieved in ES‐NSCLC patients treated with SABR, using SABR on its own may not be enough. Prolonged surveillance and adjuvant therapy is therefore needed.
Clinical influence of switching companion diagnostic tests for EGFR‐TKs from Therascreen to Cobas v2
Authors: Uchibori Ken , Takano Natsuki , Manabe Ryo , Tsugitomi Ryosuke , Ogusu Shinsuke , Tozuka Takehiro , Sakamoto Hiroaki , Yoshida Hiroshi , Amino Yoshiaki , Ariyasu Ryo , Kitazono Satoru , Yanagitani Noriko , Nishio Makoto
Published: February 2021

Background

Several companion diagnostic (CDx) tests for epidermal growth factor receptor tyrosine kinase inhibitors (EGFR‐TKIs) have been approved. In our institute, the CDx test for EGFR‐TKIs was changed from the Therascreen test (Therascreen) to the Cobas EGFR v2 test (Cobas) because only Cobas was approved for the use of osimertinib in patients with EGFR‐mutated non‐small cell lung cancer (NSCLC) with T790M mutations. The clinical influence of switching the CDx test has not yet been examined comprehensively.

Methods

All serial patients with lung cancer tested for EGFR mutations with CDx tests between February 2014 and February 2016 at the Cancer Institute Hospital of the Japanese Foundation for Cancer Research (JFCR) were enrolled in this analysis.

Results

Therascreen was used as a CDx test for EGFR‐TKI therapy in 607 patients between February 2014 and January 2015, and Cobas was used in 621 patients between February 2015 and February 2016. EGFR mutations were detected in 218 patients (35.9%) and 244 patients (39.3%) tested with Therascreen and Cobas, respectively. At the initial diagnosis, 400 and 459 patients were tested with Therascreen and Cobas, respectively. EGFR mutation subtypes, including del19, L858R, and others, were detected in 13.0%, 17.0%, and 2.5% of patients using Therascreen and 17.4%, 14.4%, and 1.5% of patients using Cobas, respectively.

Conclusions

No significant impact of switching from Therascreen to Cobas as the CDx test for EGFR mutations in clinical practice was observed. However, the detection pattern of the EGFR mutation subtypes between the two CDx tests was slightly different.

Key points

Significant findings of the study

We examined the influence of changing the EGFR test in 1228 patients in total. The detection rate of EGFR mutations was similar. However, the detection pattern for EGFR subtype mutations was slightly different between the two tests.

What this study adds

Switching CDx tests from target polymerase chain reaction (PCR)‐ to next‐generation sequencing (NGS)‐based methods may lead to obvious changes in clinical practice. When the CDx test is required to change, the investigation of this influence is warranted in future studies.
Clinical impact of rebiopsy among patients with epidermal growth factor receptor‐mutant lung adenocarcinoma in a real‐world clinical setting
Authors: Nam Yunha , Kim Ho Cheol , Kim Young‐Chul , Jang Seung Hun , Lee Kye Young , Lee Shin Yup , Lee Sang Hoon , Lee Sung Yong , Yoon Seong Hoon , Ryu Jeong‐Seon , Jang Tae Won , Chang Yoon Soo , Kim Seung Joon , Park Chan Kwon , Lee Jeong Eun , Jung Chi Young , Choi Chang‐Min
Published: February 2021

Background

In this study, we investigated the risk factors of acquired T790M mutation among patients with lung adenocarcinoma with epidermal growth factor receptor (EGFR) tyrosine mutation who were treated with EGFR‐tyrosine kinase inhibitors (TKIs). The aim was to identify the clinical impact of rebiopsy.

Methods

This multicenter, retrospective cohort study was conducted in South Korea from January 2007 to June 2017. Patients with adenocarcinoma with EGFR mutation who underwent rebiopsy and were treated with EGFR‐TKIs were included.

Results

Of a total of 352 patients, T790M mutation was identified in 156 (41.9%) at the time of rebiopsy. The median duration from initial biopsy to rebiopsy was 17 months. Univariate logistic regression analysis revealed associations of exon 19 deletion (odds ratio [OR], 1.643; p = 0.026), absence of L858R (OR, 0.627; p = 0.042), and previous EGFR‐TKI treatment duration (OR, 1.039; p < 0.001) with T790M mutation. Previous EGFR‐TKI treatment duration (OR, 3.580; p < 0.001) was independently associated with T790M mutation. A multivariate Cox proportional hazard model revealed that brain metastasis at initial diagnosis (hazard ratio, 1.390; p = 0.050) tended to be associated with T790M mutation. Among the patients with T790M mutation at rebiopsy, the osimertinib user group (n = 90) had a better one‐year survival (68.7 vs. 58.3%, p = 0.048) than the osimertinib nonuser group (n = 66).

Conclusions

Rebiopsy might affect the clinical course of patients with EGFR‐mutant adenocarcinoma who receive EGFR‐TKIs.
Malignant pleural mesothelioma in a patient with pneumothorax: A cumbersome subtype both clinically and pathologically
Authors: Fukui Takafumi , Okubo Takako , Tanimoto Naoki , Okuma Hiromichi , Shiina Yoshitaka , Kohama Mizuki , Yamada Jun , Funada Yasuhiro , Ikura Yoshihiro
Published: February 2021

Here, we report a case of malignant pleural mesothelioma (MPM) that was very difficult to diagnose. A 62‐year‐old woman with a surgical history of recurrent bilateral pneumothorax was admitted to our hospital with severe dysphagia. Computed tomography (CT) detected stenosis in the lower esophagus. Immunohistochemical examination of a biopsy sample from the stenotic region was suggestive of MPM. Chemotherapy was initiated, but the patient soon weakened and died. Autopsy revealed atypical cells, identical to those seen in the biopsy sample which had spread into the stenotic esophagus and entire thoracic cavity. Although neither pleural thickening/nodules nor asbestos bodies were observed, we finally diagnosed the tumor as a biphasic‐type MPM. We re‐examined previous surgical specimens of pneumothorax and acknowledged foci of bland mesothelial cell proliferation which had the same pathological findings as tumor cells at autopsy. The lack of asbestos exposure and pleural thickening, an initial manifestation of pneumothorax, and faint cytological atypia prevented an early diagnosis. In cases of recurrent pneumothorax in elderly patients, MPM should be included in the differential diagnosis.
Impacts of cutting frequency and position to tree line on herbage accumulation in silvopastoral grassland reveal potential for grassland conservation based on land use and cover information
Authors: Schmiedgen Andrea , Komainda Martin , Kowalski Katja , Hostert Patrick , Tonn Bettina , Kayser Manfred , Isselstein Johannes
Published: February 2021

In agricultural grassland, high herbage utilisation efficiency (HEFF), which is the proportion of gross live‐green herbage production that is utilised before entering senescence, is ensured by frequent defoliation. The decision upon which defoliation frequency to apply depends on the farming intensity. Assuming a reduced total herbage accumulation near trees in silvopastoral systems, frequent defoliations with high HEFF become less worthwhile—at least in specific spatial configurations. This makes an extensive management near trees an interesting option because it promotes other grassland‐related ecosystem services such as biodiversity. The present study first analysed the interaction between defoliation frequency and position to trees on the total, dead and live herbage accumulation and the HEFF at two silvopastoral sites with short‐rotation coppices in Germany. In addition, the total grassland–tree interface in Germany was assessed from land use and land cover maps of Germany based on satellite data to approximate the potential of grassland extensification near trees. The total herbage accumulation near trees declined by up to 41% but the HEFF was not affected by the position. Consequently, any intensification is not paid‐off by adequate productivity and herbage quality in terms of HEFF and tree‐related losses in herbage accumulation are expected up to a distance of 4.5–6 m. Applying a 4.5 m border on satellite data, we found that up to 4.4% (approximately 2200 km2) of the total grassland area in Germany is at a tree interface and potentially suitable for extensification. These findings indicate substantial potential for biodiversity conservation in grasslands with low trade‐off for high‐quality yield.
Novel DNA methylation marker discovery by assumption‐free genome‐wide association analysis of cognitive function in twins
Authors: Mohammadnejad Afsaneh , Soerensen Mette , Baumbach Jan , Mengel‐From Jonas , Li Weilong , Lund Jesper , Li Shuxia , Christiansen Lene , Christensen Kaare , Hjelmborg Jacob V. B. , Tan Qihua
Published: February 2021

Privileged by rapid increase in available epigenomic data, epigenome‐wide association studies (EWAS) are to make a profound contribution to understand the molecular mechanism of DNA methylation in cognitive aging. Current statistical methods used in EWAS are dominated by models based on multiple assumptions, for example, linear relationship between molecular profiles and phenotype, normal distribution for the methylation data and phenotype. In this study, we applied an assumption‐free method, the generalized correlation coefficient (GCC), and compare it to linear models, namely the linear mixed model and kinship model. We use DNA methylation associated with a cognitive score in 400 and 206 twins as discovery and replication samples respectively. DNA methylation associated with cognitive function using GCC, linear mixed model, and kinship model, identified 65 CpGs (p < 1e‐04) from discovery sample displaying both nonlinear and linear correlations. Replication analysis successfully replicated 9 of these top CpGs. When combining results of GCC and linear models to cover diverse patterns of relationships, we identified genes like KLHDC4, PAPSS2, and MRPS18B as well as pathways including focal adhesion, axon guidance, and some neurological signaling. Genomic region‐based analysis found 15 methylated regions harboring 11 genes, with three verified in gene expression analysis, also the 11 genes were related to top functional clusters including neurohypophyseal hormone and maternal aggressive behaviors. The GCC approach detects valuable methylation sites missed by traditional linear models. A combination of methylation markers from GCC and linear models enriched biological pathways sensible in neurological function that could implicate cognitive performance and cognitive aging.
Concurrent chronic hyperplastic candidosis and oral lichenoid lesion as adverse events of secukinumab therapy
Authors: Farah CS
Published: February 2021

Secukinumab (Cosentyx®) is an IL‐17A inhibitor which is used for the management of psoriasis, active psoriatic arthritis or ankylosing spondylitis. Oral adverse events of secukinumab therapy are not widely appreciated. This article highlights the presentation of two concurrent oral adverse events of secukinumab therapy; namely chronic hyperplastic candidosis (CHC) and oral lichenoid lesion (OLL). This is the first documented case report of CHC occurring as a consequence of secukinumab therapy, and represents a new adverse effect which general and specialist oral health practitioners should be aware of. This case highlights the importance of correlating the presence of oral lesions with the patient’s medical history, keeping up to date with the development of new medications and pharmacotherapeutics, having a deep understanding of underlying biological processes related to various oral diseases, and appreciating the use of clinical adjunctive devices. Accurate diagnosis is key to formulating a correct management plan.
A comparative analysis of sphenoid bone between domestic sheep (ovis aries) and goat (capra hircus) using geometric morphometrics
Authors: Parés‐Casanova Pere M. , Domènech‐Domènech Xènia
Published: February 2021

The sphenoid bone forms the rostral part of the base of the neurocranium and is composed of two segments, the presphenoid [os praesphenoidale] and the basisphenoid [os basisphenoidale]. Rarely studied in osteology, we tested whether it can provide distinctive features between domestic sheep (Ovis aries L., 1758) and goat (Capra hircus L., 1758). For this goal, we studied a sample comprised by 53 dry modern skulls of adult sheep (n = 36) and goat (n = 17) subjects from a modern comparative collection by means of geometric morphometric techniques using a total of 26 anatomical points (2 saggital landmarks and 24 semilandmarks). Results showed that form (size + shape) differences appear between both species: sphenoid among sheep tends to be bigger, longer and wider than in goats, differences of width being mainly located on basisphenoid width.
The lumbosacral Plexus of the Barn Owl (tyto alba): Formation, branches and distribution
Authors: Demiraslan Yasin , Gürbüz İftar , Demircioğlu İsmail , Dayan Mustafa Orhun
Published: February 2021

The aim of the present study is to reveal the anatomical structure of lumbosacral plexus of barn owl. Six barn owls were included in the study. Nerves originating from plexus were dissected individually, and findings of innervation areas of nerves were determined. Lumbosacral plexus of barn owl was observed to be formed by ventral rami of ten synsacral spinal nerves. It was found that while the r. cutaneus femoris lateralis, the n. obturatorius, the n. coxalis cranialis, the r. cutaneus femoris medialis, the n. cutaneus femoris cranialis and the n. femoralis originated from the lumbar plexus, the n. isciofemoralis, the n. cutaneus femoris caudalis, the n. coxalis caudalis and the n. ischiadicus originated from the sacral plexus. Consequently, when the results of the study were compared with information of different avian species, it was observed that differences focused on the formation of the lumbar and sacral plexuses and innervation level of digits.
Biogeography of the Egyptian mongoose Herpestes ichneumon (Linnaeus, 1758) in Africa, with first records for Laikipia County, central Kenya
Authors: Ngatia Dedan Kabuu , Webala Paul Waswa , Mware Mugo J. , Butynski Thomas M. , de Jong Yvonne A. , Ferguson Adam Wesley
Published: February 2021

The paucity of studies on Egyptian mongoose Herpestes ichneumon (Linnaeus, 1758) in Africa highlights the need for baseline information on the geographic range of this species as well as factors that may determine its distribution. This study presents eight novel locality records of H. ichneumon in Laikipia County, central Kenya, addresses questions on the species’ distribution in Africa, and predicts environmental (climatic) suitability across its range. From a total of 4,822 H. ichneumon occurrence records, we used 4,432 georeferenced records to generate distribution maps, conduct ecological niche modelling, and identify environmental limits for this species across its range with a focus on Africa. 20% of all records originate from continental Africa, including 121 records for Kenya. Despite extensive field research and predicted habitat suitability, H. ichneumon has not been previously reported in Laikipia County. Our niche models, however, predicted parts of Laikipia to be environmentally suitable for H. ichneumon. Similarly, our new distribution maps show extended geographic ranges both in Laikipia and Kenya as compared to the 2016 IUCN map. The eight Laikipia records underscore the limited knowledge for this species, its distribution, and its environmental requirements in Africa.
Liquidity Management During the Covid‐19 Pandemic*
Authors: Almeida Heitor
Published: February 2021

With the help of the United States Government and committed funding from bank credit lines, the United States corporate sector responded to the Covid‐19 cash flow shock by issuing long‐term debt to increase cash holdings. I use a case study, evidence from recent research, and a theoretical model to explain the logic behind the changes in corporate financial policy that happened during 2020, and to discuss the importance of United States Government policies to support the market for long‐term debt. I also point to open research questions about liquidity management, in particular questions that were highlighted by how companies reacted to the Covid‐19 pandemic.