bluuebunny/crossref_metadata_2025 huggingface dataset:
Balfour's World
Authors: Ellenberger Nancy W.
Published: May 2021

Arthur James Balfour (1848-1930) was born toward the beginning of Queen Victoria's long reign. At her death in 1901, he was a year away from becoming the first prime minister of the Edwardian era. Inthe quarter century after his entry into political life in the 1870s, Britain experienced material changes and a sense of intensifying human interactions as dramatic to his generation as the forces ofglobalization are today. Aristocrats watched anxiously as gifted boys from the middle classes rose to the top in professional life. Culture wars over male and female behaviours erupted at home, as small wars of empire proliferated overseas. Politicians came to terms with electioneering among the masses and with a boisterous print culture that prefigured the mass media of the next century. The first great era of advanced, international capitalism affected every segment of British and imperial society, including the rarefied domain of Arthur Balfour. That changes of the magnitude that Balfour's generation faced would demand different skills, career paths or political alignments is not surprising. That they might also result in the creation of different emotional sets and interiorworlds may be more so. Balfour's World provides an intimate history of how Arthur and his friends - George Herbert, 13th Earl of Pembroke; Laura and Margot (later Lady Asquith) Tennant; Mary and George Wyndham - helped to construct a new 'emotional regime' among Britain's political elites at the fin de si�cle. The rich diaries, letters and publications they left allow access both to publicselves and to inner landscapes, and the mix of psychological patterns and cultural assumptions that mediated their responses to the world. As the new century began, the demeanours modelled by habitu�s of Balfour's world would characterize many in the imperial elite, marking them as a clear bridge between the Victorians and the moderns in Britain's twentieth-century political culture. NANCY W. ELLENBERGER is Professor of History at the United States Naval Academy, Annapolis, Maryland.
Carajicomedia: Parody and Satire in Early Modern Spain
Authors: Domínguez Frank A.
Published: May 2021

Since Carajicomedia was published in 1519, it has been largely ignored by critics because of its strong sexual content. The author of Carajicomedia: Parody and Satire in Early Modern Spain believes that it is a sophisticated and complex composition that provides as good a vantage point from which to examine the ideology of the period as does La Celestina. In their poems,the writers of Carajicomedia inadvertently reveal the deep worries of the knights and nobles who opposed the regencies of Ferdinand the Catholic and Francisco Jiménez de Cisneros pending the arrival of Charles V. Carajicomedia is therefore a harbinger of the War of the Comuneros, the great popular revolt that convulsed Spain in 1520.  In this book's chapters, the author examinesthe parodic relationship between the text of Juan de Mena's El Laberinto de Fortuna, the glosses of Hernán Núñez's Las Trezientas, and Carajicomedia. He then turns to its actualwriters and their settings, and shows how their satirical attitudes towards males, females, and conversos reveals the failure of the societal mechanisms in place to control desire and miscegenation. Carajicomedia: Parody and Satire in Early Modern Spain concludes with a paleographic edition of the text and appendices that contain a modern Spanish version and its English translation, as wellas examine Carajicomedia's language.  Frank A. Domínguez is a professor of medieval Spanish literature and culture at the University of North Carolina at Chapel Hill.
A Companion to Juan Rulfo
Authors: Boldy Steven
Published: May 2021

A comprehensive study of the Mexican writer considered one of the finest novelists and short-story writers in 20th-century Latin America.
A comparison of coronavirus disease 2019 (COVID-19) versus influenza during the pandemic: Can we distinguish COVID-19 from flu?
Authors: Nichols Lindsey K. , Maki Safa B. , Szpunar Susan M. , Bhargava Ashish , Saravolatz Louis D.
Published: May 2021

We conducted a retrospective chart review examining the demographics, clinical history, physical findings, and comorbidities of patients with influenza and patients with coronavirus disease 2019 (COVID-19). Older patients, male patients, patients reporting fever, and patients with higher body mass indexes (BMIs) were more likely to have COVID-19 than influenza.
Surface meltwater drainage and ponding on Amery Ice Shelf, East Antarctica, 1973–2019
Authors: Spergel Julian J. , Kingslake Jonathan , Creyts Timothy , van Wessem Melchior , Fricker Helen A.
Published: May 2021

Surface melting on Amery Ice Shelf (AIS), East Antarctica, produces an extensive supraglacial drainage system consisting of hundreds of lakes connected by surface channels. This drainage system forms most summers on the southern portion of AIS, transporting meltwater large distances northward, toward the ice front and terminating in lakes. Here we use satellite imagery, Landsat (1, 4 and 8), MODIS multispectral and Sentinel-1 synthetic aperture radar to examine the seasonal and interannual evolution of the drainage system over nearly five decades (1972–2019). We estimate seasonal meltwater input to one lake by integrating output from the regional climate model [Regional Atmospheric Climate Model (RACMO 2.3p2)] over its catchment defined using the Reference Elevation Model of Antarctica. We find only weak positive relationships between modeled seasonal meltwater input and lake area and between meltwater input and lake volume. Consecutive years of extensive melting lead to year-on-year expansion of the drainage system, potentially through a link between melt production, refreezing in firn and the maximum extent of the lakes at the downstream termini of drainage. These mechanisms are important when evaluating the potential of drainage systems to grow in response to increased melting, delivering meltwater to areas of ice shelves vulnerable to hydrofracture.
Social Origins of Dictatorships: Elite Networks and Political Transitions in Haiti
Authors: NAIDU SURESH , ROBINSON JAMES A. , YOUNG LAUREN E.
Published: May 2021

Existing theories of democratic reversals emphasize that elites mount actions like coups when democracy is particularly threatening to their interests. However, existing theory has been largely silent on the role of elite social networks, which interact with economic incentives and may facilitate antidemocratic collective action. We develop a model where coups generate rents for elites and show that the effort an elite puts into a coup is increasing in their network centrality. We empirically explore the model using an original dataset of Haitian elite networks that we linked to firm-level data. We show that central families were more likely to be accused of participating in the 1991 coup against the democratic Aristide government. We then find that the retail prices of staple goods that are imported by such elites differentially increase during subsequent periods of nondemocracy. Our results suggest that elite social structure is an important factor in democratic reversals.
A FICTIVE MEMBERSHIP RUSH AND CURATORIAL FRAUD IN THE LEX OF THE COLLEGIVM OF IVORY AND CITRUS-WOOD MERCHANTS (CIL 6.3885 = ILS 7214)
Authors: Last Richard
Published: May 2021

The law of the collegium of ivory and citrus-wood merchants is best known for its suspected prohibition against outsiders or non-practitioners. The present study argues that the regulation in question actually prohibits curatores from enrolling outsiders—the text curiously labels such an offense ‘fraud’. Rather than banning outsiders altogether, the law provides that only quinquennales shall have the authority to admit non-practitioners. It is still a rather unusual law, and since it conveys the impression that this collegium is wildly popular even among non-practitioners, and headed by quinquennales who excel in the virtue of orderliness, its audience and function are both scrutinized here.
Stochastic comparison of parallel systems with Pareto components
Authors: Naqvi Sameen , Ding Weiyong , Zhao Peng
Published: May 2021

Pareto distribution is an important distribution in extreme value theory. In this paper, we consider parallel systems with Pareto components and study the effect of heterogeneity on skewness of such systems. It is shown that, when the lifetimes of components have different shape parameters, the parallel system with heterogeneous Pareto component lifetimes is more skewed than the system with independent and identically distributed Pareto components. However, for the case when the lifetimes of components have different scale parameters, the result gets reversed in the sense of star ordering. We also establish the relation between star ordering and dispersive ordering by extending the result of Deshpande and Kochar [(1983). Dispersive ordering is the same as tail ordering. Advances in Applied Probability 15(3): 686–687] from support $(0, \infty )$ to general supports $(a, \infty )$, $a > 0$. As a consequence, we obtain some new results on dispersion of order statistics from heterogeneous Pareto samples with respect to dispersive ordering.
Observational measures of early irritability predict children's psychopathology risk
Authors: Mohamed Ali Ola , Gabel Lindsay N. , Stanton Kasey , Kaufman Erin A. , Klein Daniel N. , Hayden Elizabeth P.
Published: May 2021

Irritability is a transdiagnostic feature of diverse forms of psychopathology and a rapidly growing literature implicates the construct in child maladaptation. However, most irritability measures currently used are drawn from parent-report questionnaires not designed to measure irritability per se; furthermore, parent report methods have several important limitations. We therefore examined the utility of observational ratings of children's irritability in predicting later psychopathology symptoms. Four-hundred and nine 3-year-old children (208 girls) completed observational tasks tapping temperamental emotionality and parents completed questionnaires assessing child irritability and anger. Parent-reported child psychopathology symptoms were assessed concurrently to the irritability assessment and when children were 5 and 8 years old. Children's irritability observed during tasks that did not typically elicit anger predicted their later depressive and hyperactivity symptoms, above and beyond parent-reported irritability and context-appropriate observed anger. Our findings support the use of observational indices of irritability and have implications for the development of observational paradigms designed to assess this construct in childhood.
High take-off right coronary artery in a patient with tetralogy of Fallot
Authors: Terlemez Semiha , Kula Serdar , Oğuz Deniz
Published: May 2021

High take-off coronary artery anomaly is a quite rare anomaly which is usually seen in isolated form and diagnosed incidentally. Association with tetralogy of Fallot is also rare and it is not one of the well-known coronary anomalies seen in this disease. Here, we describe high take-off right coronary artery in a 10-month-old female patient with tetralogy of Fallot which was diagnosed during catheter angiography. It is very important to show this anomaly sometimes with additional imaging techniques as it alters all the surgical approach including aortic cannulation.
Atrioesophageal Fistula as a Complication of Radiofrequency Ablation for Atrial Fibrillation
Authors: Canakci Mustafa Emin , Ovali Cengiz , Aydogdu İrem , Tiryaki Bastug Betul , Ahmadzai Obaidullah , Bozdogan Ramazan Faruk
Published: May 2021

Atrioesophageal fistula (AEF) is an important complication of radiofrequency ablation (RFA). Delayed diagnosis is associated with increased morbidity and mortality. Despite the name “atrioesophageal fistula,” fistulas functionally act esophageal to atrial, which accounts for the neurologic and infectious complications. This report presents the management of a 60-year-old male patient who was admitted to the emergency department (ED) with AEF-caused gastrointestinal bleeding. The patient was operated urgently, but he had serious comorbidities and died after the operation. The aim of this case was to evaluate patients who underwent RFA, within 10 days to two months, carefully in the ED and to know the possible complications.
Contagious ecthyma: how serious is the disease worldwide?
Authors: Lawan Zaharaddeen , Bala Jamilu Abubakar , Bukar Alhaji Modu , Balakrishnan Krishnan Nair , Mangga Hassana Kyari , Abdullah Faez Firdaus Jesse , Noordin Mustapha Mohamed , Mohd-Azmi Mohd Lila
Published: May 2021

Contagious ecthyma (CE) is an infectious disease of small ruminants caused by a parapoxvirus of family Poxviridae subfamily Chordopoxvirinae. The disease is obviously distinguished by an establishment of scabby lesions and ulcerative formation on less hairy areas including muzzle, ears, nostril, and sometimes on genitalia. The disease is endemic in sheep and goats. The virus is transmissible to other ruminants and is a public health concern in humans. Although the disease is known as self-limiting, it may cause a significant economic threat and financial losses due to lower productivity in livestock production. Information with regard to the risk of the disease and epidemiology in most parts of the world is underreported. This paper aims to provide relevant information about the epidemiology of CE in selected regions of Europe, South America, North America, Asia, Africa, and Australia. An in-depth comprehension of virus infection, diagnoses, and management of the disease will enable farmers, researchers, veterinarians, abattoir workers, health personnel, and border controllers to improve their measures, skills, and effectiveness toward disease prevention and control, toward reducing unnecessary economic loss among farmers. A herd health program for significant improvement in management and productivity of livestock demands a well planned extension program that ought to encourage farmers to equip themselves with adequate skills for animal healthcare.
Seeking the Seekers
Authors: Ryrie Alec
Published: May 2021

The Seekers, a supposed sect which flourished in late 1640s England, have generally been neglected by historians, with the exception of Quaker historiography, in which the Seekers play a pivotal but supporting role. This article argues that the Seeker phenomenon is worth attending to in its own right. Perhaps deriving from spiritualist, radical and Dutch Collegiant roots, it also represents the logical outcome of English Baptists and other radicals trying and failing to find ecclesiological certainty, and being driven to the conclusion that no true church exists or (for some Seekers) can exist. The article concludes by examining how the Seeker life was lived, whether as austere, apophatic withdrawal; a veering into libertinism; or by forming provisional communities, communities which did, in some cases, serve as a gateway to Quakerism.
Inspiration and Institution in Catholic Missionary Martyrdom Accounts: Japan and New France, 1617–49
Authors: Teather Rhiannon
Published: May 2021

This article focuses on the martyrdoms of the French Jesuit Antoine Daniel in New France and the Spanish friars Alonso Navarrete and Hernando Ayala in Japan. Drawing upon the accounts written by the missionaries Paul Ragueneau and Jacinto Orfanel, it shows how they adapted apostolic teaching and the Tridentine vision of the priesthood to interpret the acts of their brethren as sources of inspiration and models of renewed institutional identity. It argues that martyrdom was viewed as a pastoral responsibility in the missions to New France and Japan. Martyrs were portrayed as divinely inspired to lay down their lives for their communities, while the act of martyrdom was viewed as a literal, semi-liturgical sacrifice imbued with the sacramentality of the priesthood. Martyrdom was perceived both to fulfil an urgent pastoral need within communities and to model the apostolic vision of the Roman Catholic Church.
Effects of chromium supplementation on oxidative stress biomarkers
Authors: Amini Mohammad Reza , Sheikhhossein Fatemeh , Djafari Farhang , Jafari Alireza , Djafarian Kurosh , Shab-Bidar Sakineh
Published: May 2021

Abstract: Aim: This systematic review and meta-analysis aimed to evaluate the effects of chromium supplementation on oxidative stress biomarkers such as superoxide dismutase (SOD), glutathione (GSH), glutathione peroxidase (GPX), malondialdehyde (MDA), total antioxidant status (TAS), thiobarbituric acid reactive substances (TBARS), catalase (CAT), nitric oxide (NO), total antioxidant capacity (TAC) and protein carbonyl. Methods: Relevant studies, published from inception until July 2019, were searched through PubMed/Medline, Scopus, ISI Web of Science, Embase, and Google Scholar. All randomized clinical trials investigating the effect of chromium supplementation on oxidative stress were included. Results: Out of 252 citations, 10 trials that enrolled 595 subjects were included. Chromium supplementation resulted in a significant increase in GSH (WMD: 64.79 mg/dl, 95% CI: 22.43 to 107.15; P=0.003) but no significant change in MDA, TAS, TBARS levels, SOD, CAT levels and GPX. Chromium picolinate supplementation resulted in a significant increase in TAC while failing to have a significant effect on NO. Moreover, both chromium picolinate and chromium dinicocysteinate supplementation reduced protein carbonyl levels. Conclusion: Overall, this meta-analysis demonstrated that chromium supplementation increased GSH without any significant changes in the mean of GPX, MDA, TAS, TBARS, CAT and SOD.
CME-Dermatologie 23: Hidradenitis suppurativa
Authors: Dahmen Robert A. , Lautenschlager Stephan
Published: May 2021

Zusammenfassung. Hidradenitis suppurativa (Acne inversa) ist eine chronische Hauterkrankung, die durch wiederkehrende entzündliche Knötchen, Abszesse und Narben in den intertriginösen Bereichen gekennzeichnet ist. Die Prävalenz der Erkrankung wird weltweit auf 0,05 bis 4,1 % geschätzt, wobei Frauen häufiger betroffen sind. Die genaue Pathogenese bleibt unklar, aber der Verschluss und die Entzündung der Haarfollikel scheinen die auslösenden Ereignisse zu sein. Es wurden verschiedene epidemiologische Korrelationen mit Rauchen und Fettleibigkeit sowie Mutationen in Gamma-Sekretase-Genen beschrieben. Die Therapie hängt von der Ausdehnung der Krankheit ab und sollte die aktuellen Richtlinien einhalten. Topisches Clindamycin ist für milde Formen der Krankheit geeignet, während mittelschwere bis schwere Krankheiten eine systemische entzündungshemmende Behandlung erfordern. Ein chirurgischer Eingriff ist derzeit die einzige endgültige Behandlung für Hidradenitis suppurativa.
Der Forschungsbeitrag der deutschsprachigen Klinischen Psychologie zu Themen der psychischen Störungen und Psychotherapie
Authors: Richter Jan , Bittermann André , Christiansen Hanna , Krämer Lena V. , Kuhberg-Lasson Veronika , Schneider Silvia
Published: May 2021

Zusammenfassung. Die Klinische Psychologie ist essentieller Bestandteil interdisziplinärer Forschung im Bereich psychischer Störungen. Ziel der präsentierten Analyse war es, den individuellen Beitrag der Psychologie abzubilden. Wir bestimmten daher objektive Indikatoren für die Mitwirkung der deutschsprachigen Klinischen Psychologie und ihrer psychologischen Nachbardisziplinen an den Forschungsthemen zu psychischen Störungen. Eine themenbezogene Drittmittelanalyse für den Zeitraum 2000 – 2018 identifizierte 85 Großprojekte unter klinisch-psychologischer Leitung sowie 10 Personenförderungen mit einem Gesamtfördervolumen von 156 Millionen Euro. Weiterhin zeigte eine Publikationsanalyse, dass in den Jahren 1980 – 2018 die 150 deutschsprachigen Autor_innen mit den meisten themenrelevanten Publikationen mehrheitlich (63 %) einen akademischen Abschluss in Psychologie hatten. Die Anzahl der Publikationen nahm unter den psychologischen Autor_innen insgesamt jährlich zu. Wir identifizierten ein breites Forschungsfeld in störungsspezifischer, verfahrensspezifischer und neurowissenschaftlich fundierter Forschung. Die Ergebnisse verdeutlichen den substantiellen Beitrag der Psychologie in der Grundlagen- und Behandlungsforschung zu psychischen Störungen.
Rien van Genuchten Receives 2020 Robert E. Horton Medal
Authors:   AGU
Published: May 2021

Rien van Genuchten was awarded the 2020 Robert E. Horton Medal at the virtual AGU Fall Meeting in December 2020. The medal is for “outstanding contributions to hydrology.”
Your Summer Outlook: Cloudy with an Above-Normal Chance of Hurricanes
Authors: Duncombe Jenessa
Published: May 2021

Get ready for another above-average hurricane season, but it likely won’t be as busy as last year.
Prompt Response of the Dayside Magnetosphere to Discrete Structures Within the Sheath Region of a Coronal Mass Ejection
Authors: Blum L. W. , Koval A. , Richardson I. G. , Wilson L. B. , Malaspina D. , Greeley A. , Jaynes A. N.
Published: May 2021

A sequence of discrete solar wind structures within the sheath region of an interplanetary coronal mass ejection on November 6, 2015, caused a series of compressions and releases of the dayside magnetosphere. Each compression resulted in a brief adiabatic enhancement of ions (electrons) driving bursts of electromagnetic ion cyclotron (EMIC; whistler mode chorus) wave growth across the dayside magnetosphere. Fine‐structured rising tones were observed in the EMIC wave bursts, resulting in nonlinear scattering of relativistic electrons in the outer radiation belt. Multipoint observations allow us to study the spatial structure and evolution of these sheath structures as they propagate Earthward from L1 as well as the spatio‐temporal characteristics of the magnetospheric response. This event highlights the importance of fine‐scale solar wind structure, in particular within complex sheath regions, in driving dayside phenomena within the inner magnetosphere.
Origin of Electron Boomerang Stripes: Statistical Study
Authors: Zhao X. X. , Hao Y. X. , Zong Q.‐G. , Zhou X.‐Z. , Yue C. , Chen X. R. , Liu Y. , Liu Z.‐Y. , Blake J. B. , Claudepierre S. G. , Reeves G. D.
Published: May 2021

In the outer radiation belt, localized ultralow frequency (ULF) waves can interact with energetic electrons by drift resonance, leading to quasiperiodic oscillations. The oscillations in the pitch angle spectrum can be characterized by either boomerang‐shaped or straight stripes. Previous studies have shown that boomerang‐shaped stripes evolve from straight ones when electrons drift away from the localized wave interaction region. Based on the time‐of‐flight technique on the pitch angle‐dependent drift velocity, the origin can be remotely identified from the pitch angle dispersion. We report 27 straight stripe events and 86 boomerang‐shaped events observed by Van Allen Probes from January 1, 2013, to December 31, 2017. Statistical study shows a good coincidence between the locations of straight ones and traceback regions from boomerang‐shaped ones. These locations, mainly located in noon‐to‐dusk region, coincide well with the plasmaspheric plumes. Thus, localized ULF waves trapped in the plume may result in the preference of localized ULF wave‐electron interactions at noon‐to‐dusk region.
Statistical Properties of Current, Energy Conversion, and Electron Acceleration in Flux Ropes in the Terrestrial Magnetotail
Authors: Jiang K. , Huang S. Y. , Yuan Z. G. , Deng X. H. , Wei Y. Y. , Xiong Q. Y. , Xu S. B. , Zhang J. , Zhang Z. H. , Lin R. T. , Yu L.
Published: May 2021

We perform a statistical analysis on current density, energy conversion, and electron acceleration in the primary flux ropes (PFRs) and the secondary flux ropes (SFRs) distinguished by out‐of‐plane electron current, respectively. It is found that current filaments are plentiful in both PFRs and SFRs. The closer to the center of the SFRs, the stronger the |J| is. The J•E′ is intermittent in the PFRs. However, J•E′ almost stays positive in the SFRs. The local adiabatic acceleration of the electrons in the PFRs and the SFRs are explored. Fermi and betatron acceleration are closely related to the adjacent magnetic field and bulk flow which can lead to the contraction/relaxation of the PFRs and SFRs and enhance/reduce the gradient of the magnetic field. The acceleration by the parallel electric field is significant in the SFRs. Our results can help to improve the understanding of the PFRs and SFRs and their roles in the magnetotail dynamics.
Gut microbiota restoration through fecal microbiota transplantation: a new atopic dermatitis therapy
Authors: Kim Jong-Hwa , Kim Kiyoung , Kim Wonyong
Published: May 2021

The pathogenesis of atopic dermatitis (AD) involves complex factors, including gut microbiota and immune modulation, which remain poorly understood. The aim of this study was to restore gut microbiota via fecal microbiota transplantation (FMT) to ameliorate AD in mice. FMT was performed using stool from donor mice. The gut microbiota was characterized via 16S rRNA sequencing and analyzed using Quantitative Insights into Microbial Ecology 2 with the DADA2 plugin. Gut metabolite levels were determined by measuring fecal short-chain fatty acid (SCFA) contents. AD-induced allergic responses were evaluated by analyzing blood parameters (IgE levels and eosinophil percentage, eosinophil count, basophil percentage, and monocyte percentage), the levels of Th1 and Th2 cytokines, dermatitis score, and the number of mast cells in the ileum and skin tissues. Calprotectin level was measured to assess gut inflammation after FMT. FMT resulted in the restoration of gut microbiota to the donor state and increases in the levels of SCFAs as gut metabolites. In addition, FMT restored the Th1/Th2 balance, modulated Tregs through gut microbiota, and reduced IgE levels and the numbers of mast cells, eosinophils, and basophils. FMT is associated with restoration of gut microbiota and immunologic balance (Th1/Th2) along with suppression of AD-induced allergic responses and is thus a potential new therapy for AD.
Healthy eating and lifestyle in pregnancy (HELP): a cluster randomised trial to evaluate the effectiveness of a weight management intervention for pregnant women with obesity on weight at 12 months postpartum
Authors: Simpson Sharon A. , Coulman Elinor , Gallagher Dunla , Jewell Karen , Cohen David , Newcombe Robert G. , Huang Chao , Robles-Zurita José Antonio , Busse Monica , Owen-Jones Eleri , Duncan Donna , Williams Nefyn , Stanton Helen , Avery Amanda , McIntosh Emma , Playle Rebecca
Published: May 2021

Objective

To assess whether a weight management intervention for pregnant women with obesity was effective in reducing body mass index (BMI) 12 months after giving birth.

Methods

Pragmatic, cluster randomised controlled trial (RCT) with embedded cost-effectiveness analysis. 598 women with a BMI of ≥30 kg/m2(between 12 and 20 weeks gestation) were recruited from 20 secondary care maternity units in England and Wales. BMI at 12 months postpartum was the primary outcome. A range of clinical and behavioural secondary outcomes were examined.

Interventions

Women attending maternity units randomised to intervention were invited to a weekly weight management group, which combined expertise from a commercial weight loss programme with clinical advice from midwives. Both intervention and control participants received usual care and leaflets on diet and physical activity in pregnancy.

Results

Mean (SD) BMI at 12 months postpartum was 36.0 kg/m2(5.2) in the control group, and 37.5 kg/m2(6.7) in the intervention group. After adjustment for baseline BMI, the intervention effect was −0.02 (95% CI −0.04 to 0.01). The intervention group had an improved healthy eating score (3.08, 95% CI 0.16 to 6.00,p < 0.04), improved fibre score (3.22, 1.07 to 5.37,p < 0.01) and lower levels of risky drinking at 12 months postpartum compared to the control group (OR 0.45, 0.27 to 0.74,p < 0.002). The net incremental monetary benefit was not statistically significantly different between arms, although the probability of the intervention being cost-effective was above 60%, at policy-relevant thresholds.

Conclusions

There was no significant difference between groups on the primary outcome of BMI at 12 months. Analyses of secondary outcomes indicated improved healthy eating and lower levels of risky drinking.

Trial registration: Current Controlled Trials ISRCTN25260464.
JAK2 unmutated erythrocytosis: current diagnostic approach and therapeutic views
Authors: Gangat Naseema , Szuber Natasha , Pardanani Animesh , Tefferi Ayalew
Published: May 2021

JAK2unmutated or non-polycythemia vera (PV) erythrocytosis encompasses both hereditary and acquired conditions. A systematic diagnostic approach begins with documentation of historical hematocrit (Hct)/hemoglobin (Hgb) measurements and classification of the process as life-long/unknown duration or acquired. Further investigation in both categories is facilitated by determination of serum erythropoietin level (EPO). Workup for hereditary/congenital erythrocytosis requires documentation of family history and laboratory screening for high-oxygen affinity hemoglobin variants, 2, 3 biphosphoglycerate deficiency, and germline mutations that are known to alter cellular oxygen sensing (e.g.,PHD2, HIF2A, VHL) or EPO signaling (e.g.,EPORmutations); the latter is uniquely associated with subnormal EPO. Acquired erythrocytosis is often elicited by central or peripheral hypoxia resulting from cardiopulmonary disease/high-altitude dwelling or renal artery stenosis, respectively; EPO in the former instance is often normal (compensated by negative feed-back). Other conditions associated with acquired erythrocytosis include EPO-producing tumors and the use of drugs that promote erythropoiesis (e.g., testosterone, erythropoiesis stimulating agents). “Idiopathic erythrocytosis” loosely refers to an otherwise not explained situation. Historically, management of non-PV erythrocytosis has been conflicted by unfounded concerns regarding thrombosis risk, stemming from limited phenotypic characterization, save for Chuvash polycythemia, well-known for its thrombotic tendency. In general, cytoreductive therapy should be avoided and phlebotomy is seldom warranted where frequency is determined by symptom control rather than Hct threshold. Although not supported by hard evidence, cardiovascular risk optimization and low-dose aspirin use are often advised. Application of modern genetic tests and development of controlled therapeutic intervention trials are needed to advance current clinical practice.
Mitochondrial proteome of mouse oocytes and cisplatin-induced shifts in protein profile
Authors: Zhang Na , Sun An-di , Sun Si-man , Yang Rui , Shi Yan-yan , Wang Qi-long , Li Xin-yu , Ma Ji-hong , Yue Wei , Xie Bing-teng , Qiao Jie , Li Mo
Published: May 2021

Mitochondria are essential organelles that provide energy for mammalian cells and participate in multiple functions, such as signal transduction, cellular differentiation, and regulation of apoptosis. Compared with the mitochondria in somatic cells, oocyte mitochondria have an additional level of importance since they are required for germ cell maturation, dysfunction in which can lead to severe inherited disorders. Thus, a systematic proteomic profile of oocyte mitochondria is urgently needed to support the basic and clinical research, but the acquisition of such a profile has been hindered by the rarity of oocyte samples and technical challenges associated with capturing mitochondrial proteins from live oocytes. Here, in this work, using proximity labeling proteomics, we established a mitochondria-specific ascorbate peroxidase (APEX2) reaction in live GV-stage mouse oocytes and identified a total of 158 proteins in oocyte mitochondria. This proteome includes intrinsic mitochondrial structural and functional components involved in processes associated with “cellular respiration”, “ATP metabolism”, “mitochondrial transport”, etc. In addition, mitochondrial proteome capture after oocyte exposure to the antitumor chemotherapeutic cisplatin revealed differential changes in the abundance of several oocyte-specific mitochondrial proteins. Our study provides the first description of a mammalian oocyte mitochondrial proteome of which we are aware, and further illustrates the dynamic shifts in protein abundance associated with chemotherapeutic agents.
Qki activates Srebp2-mediated cholesterol biosynthesis for maintenance of eye lens transparency
Authors: Shin Seula , Zhou Hao , He Chenxi , Wei Yanjun , Wang Yunfei , Shingu Takashi , Zeng Ailiang , Wang Shaobo , Zhou Xin , Li Hongtao , Zhang Qiang , Mo Qinling , Long Jiafu , Lan Fei , Chen Yiwen , Hu Jian
Published: May 2021

Defective cholesterol biosynthesis in eye lens cells is often associated with cataracts; however, how genes involved in cholesterol biosynthesis are regulated in lens cells remains unclear. Here, we show that Quaking (Qki) is required for the transcriptional activation of genes involved in cholesterol biosynthesis in the eye lens. At the transcriptome level, lens-specific Qki-deficient mice present downregulation of genes associated with the cholesterol biosynthesis pathway, resulting in a significant reduction of total cholesterol level in the eye lens. Mice with Qki depletion in lens epithelium display progressive accumulation of protein aggregates, eventually leading to cataracts. Notably, these defects are attenuated by topical sterol administration. Mechanistically, we demonstrate that Qki enhances cholesterol biosynthesis by recruiting Srebp2 and Pol II in the promoter regions of cholesterol biosynthesis genes. Supporting its function as a transcription co-activator, we show that Qki directly interacts with single-stranded DNA. In conclusion, we propose that Qki-Srebp2–mediated cholesterol biosynthesis is essential for maintaining the cholesterol level that protects lens from cataract development.
Sedimentary ancient DNA reveals a threat of warming-induced alpine habitat loss to Tibetan Plateau plant diversity
Authors: Liu Sisi , Kruse Stefan , Scherler Dirk , Ree Richard H. , Zimmermann Heike H. , Stoof-Leichsenring Kathleen R. , Epp Laura S. , Mischke Steffen , Herzschuh Ulrike
Published: May 2021

Studies along elevational gradients worldwide usually find the highest plant taxa richness in mid-elevation forest belts. Hence, an increase in upper elevation diversity is expected in the course of warming-related treeline rise. Here, we use a time-series approach to infer past taxa richness from sedimentary ancient DNA from the south-eastern Tibetan Plateau over the last ~18,000 years. We find the highest total plant taxa richness during the cool phase after glacier retreat when the area contained extensive and diverse alpine habitats (14–10 ka); followed by a decline when forests expanded during the warm early- to mid-Holocene (10–3.6 ka). Livestock grazing since 3.6 ka promoted plant taxa richness only weakly. Based on these inferred dependencies, our simulation yields a substantive decrease in plant taxa richness in response to warming-related alpine habitat loss over the next centuries. Accordingly, efforts of Tibetan biodiversity conservation should include conclusions from palaeoecological evidence.
Diversity-oriented functionalization of 2-pyridones and uracils
Authors: Shang Yong , Wu Chenggui , Gao Qianwen , Liu Chang , Li Lisha , Zhang Xinping , Cheng Hong-Gang , Liu Shanshan , Zhou Qianghui
Published: May 2021

Heterocycles 2-pyridone and uracil are privileged pharmacophores. Diversity-oriented synthesis of their derivatives is in urgent need in medicinal chemistry. Herein, we report a palladium/norbornene cooperative catalysis enabled dual-functionalization of iodinated 2-pyridones and uracils. The success of this research depends on the use of two unique norbornene derivatives as the mediator. Readily available alkyl halides/tosylates and aryl bromides are utilized as ortho-alkylating and -arylating reagents, respectively. Widely accessible ipso-terminating reagents, including H/DCO2Na, boronic acid/ester, terminal alkene and alkyne are compatible with this protocol. Thus, a large number of valuable 2-pyridone derivatives, including deuterium/CD3-labeled 2-pyridones, bicyclic 2-pyridones, 2-pyridone-fenofibrate conjugate, axially chiral 2-pyridone (97% ee), as well as uracil and thymine derivatives, can be quickly prepared in a predictable manner (79 examples reported), which will be very useful in new drug discovery.
Transcriptional signature in microglia associated with Aβ plaque phagocytosis
Authors: Grubman Alexandra , Choo Xin Yi , Chew Gabriel , Ouyang John F. , Sun Guizhi , Croft Nathan P. , Rossello Fernando J. , Simmons Rebecca , Buckberry Sam , Landin Dulce Vargas , Pflueger Jahnvi , Vandekolk Teresa H. , Abay Zehra , Zhou Yichen , Liu Xiaodong , Chen Joseph , Larcombe Michael , Haynes John M. , McLean Catriona , Williams Sarah , Chai Siew Yeen , Wilson Trevor , Lister Ryan , Pouton Colin W. , Purcell Anthony W. , Rackham Owen J. L. , Petretto Enrico , Polo Jose M.
Published: May 2021

The role of microglia cells in Alzheimer’s disease (AD) is well recognized, however their molecular and functional diversity remain unclear. Here, we isolated amyloid plaque-containing (using labelling with methoxy-XO4, XO4+) and non-containing (XO4−) microglia from an AD mouse model. Transcriptomics analysis identified different transcriptional trajectories in ageing and AD mice. XO4+microglial transcriptomes demonstrated dysregulated expression of genes associated with late onset AD. We further showed that the transcriptional program associated with XO4+microglia from mice is present in a subset of human microglia isolated from brains of individuals with AD. XO4−microglia displayed transcriptional signatures associated with accelerated ageing and contained more intracellular post-synaptic material than XO4+microglia, despite reduced active synaptosome phagocytosis. We identified HIF1α as potentially regulating synaptosome phagocytosis in vitro using primary human microglia, and BV2 mouse microglial cells. Together, these findings provide insight into molecular mechanisms underpinning the functional diversity of microglia in AD.
Allostery through DNA drives phenotype switching
Authors: Rosenblum Gabriel , Elad Nadav , Rozenberg Haim , Wiggers Felix , Jungwirth Jakub , Hofmann Hagen
Published: May 2021

Allostery is a pervasive principle to regulate protein function. Growing evidence suggests that also DNA is capable of transmitting allosteric signals. Yet, whether and how DNA-mediated allostery plays a regulatory role in gene expression remained unclear. Here, we show that DNA indeed transmits allosteric signals over long distances to boost the binding cooperativity of transcription factors. Phenotype switching in Bacillus subtilis requires an all-or-none promoter binding of multiple ComK proteins. We use single-molecule FRET to demonstrate that ComK-binding at one promoter site increases affinity at a distant site. Cryo-EM structures of the complex between ComK and its promoter demonstrate that this coupling is due to mechanical forces that alter DNA curvature. Modifications of the spacer between sites tune cooperativity and show how to control allostery, which allows a fine-tuning of the dynamic properties of genetic circuits.
High-throughput single-cell chromatin accessibility CRISPR screens enable unbiased identification of regulatory networks in cancer
Authors: Pierce Sarah E. , Granja Jeffrey M. , Greenleaf William J.
Published: May 2021

Chromatin accessibility profiling can identify putative regulatory regions genome wide; however, pooled single-cell methods for assessing the effects of regulatory perturbations on accessibility are limited. Here, we report a modified droplet-based single-cell ATAC-seq protocol for perturbing and evaluating dynamic single-cell epigenetic states. This method (Spear-ATAC) enables simultaneous read-out of chromatin accessibility profiles and integrated sgRNA spacer sequences from thousands of individual cells at once. Spear-ATAC profiling of 104,592 cells representing 414 sgRNA knock-down populations reveals the temporal dynamics of epigenetic responses to regulatory perturbations in cancer cells and the associations between transcription factor binding profiles.
Sex as an important factor in nanomedicine
Authors: Hajipour Mohammah Javad , Aghaverdi Haniyeh , Serpooshan Vahid , Vali Hojatollah , Sheibani Sara , Mahmoudi Morteza
Published: May 2021

Nanomedicine has demonstrated substantial potential to improve the quality and efficacy of healthcare systems. Although the promise of nanomedicine to transform conventional medicine is evident, significant numbers of therapeutic nanomedicine products have failed in clinical trials. Most studies in nanomedicine have overlooked several important factors, including the significance of sex differences at various physiological levels. This report attempts to highlight the importance of sex in nanomedicine at cellular and molecular level. A more thorough consideration of sex physiology, among other critical variations (e.g., health status of individuals), would enable researchers to design and develop safer and more-efficient sex-specific diagnostic and therapeutic nanomedicine products.
Deep learning predicts cardiovascular disease risks from lung cancer screening low dose computed tomography
Authors: Chao Hanqing , Shan Hongming , Homayounieh Fatemeh , Singh Ramandeep , Khera Ruhani Doda , Guo Hengtao , Su Timothy , Wang Ge , Kalra Mannudeep K. , Yan Pingkun
Published: May 2021

Cancer patients have a higher risk of cardiovascular disease (CVD) mortality than the general population. Low dose computed tomography (LDCT) for lung cancer screening offers an opportunity for simultaneous CVD risk estimation in at-risk patients. Our deep learning CVD risk prediction model, trained with 30,286 LDCTs from the National Lung Cancer Screening Trial, achieves an area under the curve (AUC) of 0.871 on a separate test set of 2,085 subjects and identifies patients with high CVD mortality risks (AUC of 0.768). We validate our model against ECG-gated cardiac CT based markers, including coronary artery calcification (CAC) score, CAD-RADS score, and MESA 10-year risk score from an independent dataset of 335 subjects. Our work shows that, in high-risk patients, deep learning can convert LDCT for lung cancer screening into a dual-screening quantitative tool for CVD risk estimation.
Optimized CRISPR tools and site-directed transgenesis towards gene drive development in Culex quinquefasciatus mosquitoes
Authors: Feng Xuechun , López Del Amo Víctor , Mameli Enzo , Lee Megan , Bishop Alena L. , Perrimon Norbert , Gantz Valentino M.
Published: May 2021

Culex mosquitoes are a global vector for multiple human and animal diseases, including West Nile virus, lymphatic filariasis, and avian malaria, posing a constant threat to public health, livestock, companion animals, and endangered birds. While rising insecticide resistance has threatened the control of Culex mosquitoes, advances in CRISPR genome-editing tools have fostered the development of alternative genetic strategies such as gene drive systems to fight disease vectors. However, though gene-drive technology has quickly progressed in other mosquitoes, advances have been lacking in Culex. Here, we develop a Culex-specific Cas9/gRNA expression toolkit and use site-directed homology-based transgenesis to generate and validate a Culex quinquefasciatus Cas9-expressing line. We show that gRNA scaffold variants improve transgenesis efficiency in both Culex quinquefasciatus and Drosophila melanogaster and boost gene-drive performance in the fruit fly. These findings support future technology development to control Culex mosquitoes and provide valuable insight for improving these tools in other species.
Deep learning the structural determinants of protein biochemical properties by comparing structural ensembles with DiffNets
Authors: Ward Michael D. , Zimmerman Maxwell I. , Meller Artur , Chung Moses , Swamidass S. J. , Bowman Gregory R.
Published: May 2021

Understanding the structural determinants of a protein’s biochemical properties, such as activity and stability, is a major challenge in biology and medicine. Comparing computer simulations of protein variants with different biochemical properties is an increasingly powerful means to drive progress. However, success often hinges on dimensionality reduction algorithms for simplifying the complex ensemble of structures each variant adopts. Unfortunately, common algorithms rely on potentially misleading assumptions about what structural features are important, such as emphasizing larger geometric changes over smaller ones. Here we present DiffNets, self-supervised autoencoders that avoid such assumptions, and automatically identify the relevant features, by requiring that the low-dimensional representations they learn are sufficient to predict the biochemical differences between protein variants. For example, DiffNets automatically identify subtle structural signatures that predict the relative stabilities of β-lactamase variants and duty ratios of myosin isoforms. DiffNets should also be applicable to understanding other perturbations, such as ligand binding.
The poleward enhanced Arctic Ocean cooling machine in a warming climate
Authors: Shu Qi , Wang Qiang , Song Zhenya , Qiao Fangli
Published: May 2021

As a cooling machine of the Arctic Ocean, the Barents Sea releases most of the incoming ocean heat originating from the North Atlantic. The related air-sea heat exchange plays a crucial role in both regulating the climate and determining the deep circulation in the Arctic Ocean and beyond. It was reported that the cooling efficiency of this cooling machine has decreased significantly. In this study, we find that the overall cooling efficiency did not really drop: When the cooling efficiency decreased in the southern Barents Sea, it increased in the northern Barents and Kara Seas, indicating that the cooling machine has expanded poleward. According to climate model projections, it is very likely that the cooling machine will continue to expand to the Kara Sea and then to the Arctic Basin in a warming climate. As a result, the Arctic Atlantification will be enhanced and pushed poleward in the future.
Transcriptome-wide association study uncovers the role of essential genes in anthracycline-induced cardiotoxicity
Authors: Scott Erika N. , Wright Galen E. B. , Drögemöller Britt I. , Hasbullah Jafar S. , Gunaretnam Erandika P. , Miao Fudan , Bhavsar Amit P. , Shen Fei , Schneider Bryan P. , Carleton Bruce C. , Ross Colin J. D.
Published: May 2021

Anthracyclines are highly effective chemotherapeutic agents; however, their clinical utility is limited by severe anthracycline-induced cardiotoxicity (ACT). Genome-wide association studies (GWAS) have uncovered several genetic variants associated with ACT, but the impact of these findings requires further elucidation. We conducted a transcriptome-wide association study (TWAS) using our previous GWAS summary statistics (n = 280 patients) to identify gene expression-related associations with ACT. We identified a genetic association between decreased expression of GDF5 and ACT (Z-score = −4.30, P = 1.70 × 10−5), which was replicated in an independent cohort (n = 845 patients, P = 3.54 × 10−3). Additionally, cell viability of GDF5-silenced human cardiac myocytes was significantly decreased in response to anthracycline treatment. Subsequent gene set enrichment and pathway analyses of the TWAS data revealed that genes essential for survival, cardioprotection and response to anthracyclines, as well as genes involved in ribosomal, spliceosomal and cardiomyopathy pathways are important for the development of ACT.