bluuebunny/crossref_metadata_2025 huggingface dataset:
Leaving Things to Take their Chances: Cause and Disposition Grounded in Chance
Authors: Barker Stephen
Published: November 2023

Chances, causes, counterfactuals, and dispositions are related in some way that is revelatory of their natures, but which way? Impressed by the power of counterfactuals as an analytic tool, many have thought that both cause and disposition are grounded in counterfactual facts. Think of causes as facts to do with what wouldn’t have been if certain events had not occurred. Think of dispositions as analysed in terms of facts about what would have been if certain events had occurred. Now refine this idea by bringing in chances to deal with indeterministic elements that may attend both cause and disposition, and contrive more complicated counterfactual conditions to cater for pre-emption, finks, antidotes, and other disruptive phenomena. One has therein the current counterfactual-theoretic program to tame cause and disposition. Its practitioners don’t agree about how it should work, or whether it really can. I shall argue that the question of its fate does not rest with their sorting out the details; it turns on a deeper matter. A closer look at chance shows that the whole counterfactual reductive program starts on the wrong foot.
From Muscovy towards St Petersburg 1598–1689
Authors: Torke Hans-Joachim
Published: November 2023

The seventeenth century has long been a focus of historiographic debate. Impressed by the broad-ranging reforms of Peter the Great (1689–1725), most early historians tended to emphasize the ‘break’, juxtaposing a traditional Muscovy of the seventeenth century to a Westernizing state of the eighteenth. But for over a century specialists have realized that the Petrine reforms built upon changes initiated by his predecessors in the seventeenth century. The army, finances, state administration—favourite areas of Petrine reform—were also the subject of government reforms in the seventeenth century.
Pre-Reform Russia 1801–1855
Authors: Ransel David L
Published: November 2023

If the murder of Tsar Paul in 1801 brought instant relief to the political élite of Russia, it did not have the same healthy effect on the new ruler, Alexander I, son of the murdered tsar. Alexander was himself a conspirator, for he had authorized the overthrow of his father, if not his assassination, and the new tsar initially expressed despair about the killing, feelings of incompetence about ruling, and stark fear that he too might be killed. The recent series of executions and overturns of European rulers had made royalty insecure everywhere in Europe.
Reform and Counter Reform 1855–1890
Authors: Freeze Gregory L
Published: November 2023

The period 1855–90 marks Russia’s transition from counter- revolution to revolution—from the ‘Gendarme of Europe’ to the bastion of revolutionary forces. That transition reflected the profound impact of the ‘Great Reforms’, which brought not only far-reaching changes (the emancipation of serfs and a host of other Westernizing, modernizing reforms), but also a new kind of politics and relationship between state and society. In so many respects, the epoch of reform and counter-reform encapsulated the fundamental processes at work in the history of Russia: the dangerous and unpredictable consequences of reform, the awakening of unfulfilled expectations, the unleashing of liberal and revolutionary movements, and the powerful, implosive impact of borderland minorities on politics in the central heartland.
Building Stalinism 1929–1941
Authors: Siegelbaum Lewis
Published: November 2023

The 1930s have long represented a watershed in the grand narratives of Soviet history. According to the Marxist-Leninist version, de rigueur in the Soviet Union until the late 1980s, it was the decade of ‘socialist construction’. Under the leadership of I. V. Stalin (or in the post-1956 de-Stalinized variant, the Communist Party), the Soviet people confounded sceptics, both domestic and foreign, by rapidly and enthusiastically constructing gigantic factories and dams, transforming backward villages into collective farms, and in the process becoming citizens of a genuinely socialist society. Their achievement was celebrated and formalized in the ‘Stalin Constitution’ of 1936, which guaranteed civil rights and equality among all the peoples of the USSR.
A Modern ‘Time of Troubles’
Authors: Freeze Gregory L
Published: November 2023

The fourteen and half years between Chernenko’s death and Putin’s presidency loomed like a redux of the ‘Time of Troubles’ in the early seventeenth century. What began as systemic reform turned into systemic collapse—dissolution of the Soviet Union, disastrous economic regression, profound social upheavals, and loss of superpower status. Mikhail Gorbachev initiated the reforms, aiming to reinvigorate and ultimately transform the Soviet system. His ‘perestroika’, however, unleashed forces and expectations even as it failed to satisfy minimal requirements.
Rebuilding Russia
Authors: Freeze Gregory L
Published: November 2023

The first years of the twenty-first century witnessed a spectacular recovery in Russia—the rebuilding of central state power, a fast- paced economic boom, and reassertion of that country’s status as a major global power. Leading this renaissance was Vladimir Putin, former KGB officer and Boris Yeltsin’s anointed successor, a man determined to restore Russia to its ‘rightful’ place in the world. He benefited from the fortuitous surge in the global economy (which generated an insatiable demand for Russia’s abundant energy resources); that windfall enabled Putin not only to claim responsibility for reversing a decade of catastrophic economic decline but also to re-establish a centralized state.
Introduction
Authors: Clark Peter
Published: November 2023

Since the Middle Ages, Europe has been one of the most urbanized continents on the planet and its cities have stamped their imprint on the European economy, as well as on European social, political, and cultural life. Rarely sprawling mega-cities like those of present-day Latin America or Asia, mostly compact and coherent, they have been communities of heavy mortality (until the twentieth century) and of high immigration.
Economy 1800 – 2000
Authors: Clark Peter
Published: November 2023

The two centuries after 1800 saw the urbanizing of the European economy. Agriculture lost its primacy and urban economic life moved from its earlier dependency on the countryside to a new world increasingly shaped by national and international forces. Though the relationship of cities and globalization has become a controversial issue in recent years, the international impact on cities was long-term and dynamic for much of the modern period (as it had been on a more limited basis since the high Middle Ages). Internationalization played a vital role in the rise of urban manufacturing during the nineteenth and twentieth centuries, and in the industrial crisis in European cities after the 1970s.
Who can take the Pill, who can’t, and Who Needs Careful Monitoring?
Authors: Guillebaud John , Maccregor Anne
Published: November 2023

As you’ve seen in previous chapters, the pill is safe for the majority of women, but for others the balance of risks outweighs the benefits. If you answer ‘yes’ to any of the questions in Box 9.1, you will know from Chapters 7 and 8 that the risks of taking the pill outweigh the potential benefits and you should use a different method of contraception, at least until the risk factor goes away (e.g. more than 3 weeks since having a baby or losing weight to a BMI of 29 or less).
Emergency Contraception
Authors: Guillebaud John , Maccregor Anne
Published: November 2023

Available from nurses, doctors, and over-the-counter from pharmacists, the emergency pill—known as ̔Levonelle®̕, containing LNG 1500 mcg—is often called the ̔morning-after pill̕. This name is unhelpful because, although it works better the earlier it is taken, it can also be started much laterthan the next morning after unprotected sex—up to 72 hours (sometimes even 120 hours) later.
Popular Opinion in Russia Under Pre-war Stalinism
Authors: Fitzpatrick Sheila
Published: November 2023

What is popular opinion? One approach would assume that it corresponds to some some kind of general will, in other words, something unitary. That’s the way people thought about it in the French Revolution. By contrast, orthodox Marxists in the Soviet Union and elsewhere dismissed the idea that there was a single ‘people’ (narod), hence a single popular opinion; instead, there was necessarily an array ofclassopinions (bourgeois, proletarian, kulak, poor peasant, etc.). However, the apparent breadth of the array often concealed a binary: proletarian/bourgeois, good/bad; and so it was with opinion— meaning essentially opinion about the government— where the binary was ‘positive’ (pro-Soviet, ‘proletarian’) and ‘negative’ (anti-Soviet, ‘bourgeois’).
Popular Opinion in Nazi Germany: Mobilization, Experience, Perceptions:The View from the Württemberg Countryside
Authors: Stephenson Jill
Published: November 2023

Popular opinion’ fascinates historians of dictatorships in which censorship, propaganda, police controls and sanctions prevent the open expression of citizens’ views of both public events and their own conditions. In regimes where the aim is simply to prevent the expression of views that are alternative or opposed to those of the ruling monarch or oligarchy, the monitoring of ‘popular opinion’ is generally of little interest. In Nazi Germany, however, the regime’s aim was actively to mould the views of ‘valuable’ Germans in order to elicit both enthusiasm for and collaboration with its structures, policies and projects. As different agencies of party and government became aware that they had no clear idea of how successful their efforts were, their response was to establish an increasing number of monitoring agencies to try to find out what ‘valuable’ Germans were privately saying and thinking. Robert Ley’s boast that ‘The only person in Germany who still has a private life is a person who’s sleeping’ was bombastic rhetoric which scarcely concealed the frustration of dedicated functionaries at their ignorance of what the popular mood actually was. The great irony of this aspiring totalitarian state was, then, that it endeavoured to suppress spontaneous expressions of popular opinion, but its success in doing so meant that it lacked the barometers of the popular mood— free elections, independent newspapers, opposition political literature, among others— that afforded political leaders in pluralist polities some insight into the popular reception of both their policies and circumstances beyond their control.
Demography, Opportunity or Ideological Conversion? Reflections on the Role of the ‘Second Hitler Youth Generation’, or ‘1929ers’, in the GDR
Authors: Fulbrook Mary
Published: November 2023

The relative balance of coercion, commitment, consent, complicity, compromise, conformity, passive or active resistance and dissent in the two German dictatorships has long been the topic of debate among historians. Simplistic models seeking to make clear distinctions between ‘regime’ and ‘people’, ‘state’ and ‘society’, ‘support’ and ‘opposition’ are clearly inadequate to explore the complex and often ambivalent ways in which people interact with, respond to, and make their way through dictatorial regimes, where they may approve of some policies, be adversely affected by others, and have a variety of conflicting opinions and changing motives as they are caught up in and seek to live their lives through a constantly changing apparatus of mobilization and control.
The Semantics of Clause Linking in Galo
Authors: Post Mark
Published: November 2023

Galo is a Tibeto-Burman language of the Tani branch spoken by around 30,000–40,000 hill tribespeople in central Arunachal Pradesh state, north-east India. There are two major dialects, Lare (laree) and Pugo (puugóo), and several minor dialects and subdialects; this chapter is based on the majority Lare dialect, as described by Post (2007). Galo’s historical contacts with non-Tani languages appear to have been inextensive; within the last fifty to sixty years, contacts with Indo-European languages such as Assamese, English, and most recently Hindi have increased dramatically.
The Semantics of Clause Linking in Ojibwe
Authors: Valentine J Randolph
Published: November 2023

Ojibwe is a general term for a group of closely related Algonquian languages and dialects that were spoken in the northern Great Lakes region of North America at the time of contact with Europeans in the early seventeenth century. In this chapter I will present data exclusively from the variety still spoken along the shores of Lake Huron, identified by its speakers as Nishnaabemwin, and by linguists as Ottawa or Odawa. The language is spoken fluently and robustly by several hundred speakers on Manitoulin Island, in northern Lake Huron, but is not being actively learned by children, so the present generation of speakers will probably be the last to use the language vitally. There are also limited numbers of speakers at other communities around Lake Huron, such as Walpole Island and Cape Croker, Ontario. Text collections are available, most notably those collected by linguists such as Leonard Bloomfield (Bloomfield 1957 and Williams 1991) and Carl Voegelin, e.g., in Nichols (1988). The Lake Huron dialects of Ojibwe are described in detail in Valentine (2001), to which the reader is referred for additional details.
The Semantics of Clause Linking in Toqabaqita
Authors: Lichtenberk Frantisek
Published: November 2023

Toqabaqita is an Oceanic language spoken on the island of Malaita in the Solomon Islands. Ethnologue, where the name of the language appears as To’abaita, gives the number of speakers as 12,572 in 1999 (Gordon 2005). Toqabaqita is a nominative-accusative language, almost exclusively head marking. The basic constituent orders in verbal clauses are shown in (1). ‘V-complex’ stands for ‘verb complex’ (see further below). The O element designates lexical (not pronominal) noun phrases.
The Semantics of Clause Linking in Goemai
Authors: Hellwig Birgit
Published: November 2023

This chapter discusses the semantics of clause linking in Goemai, a West Chadic language (Afroasiatic, Chadic, West Chadic A, Angas-Goemai, Southern Branch) that is spoken south of the Jos Plateau in Central Nigeria.
Semantics and Grammar in Clause Linking
Authors: Aikhenvald Alexandra Y
Published: November 2023

All the semantic relations between clauses—outlined in Chapter 1—can in some way be expressed in each ofthe languages discussed within this volume. This is akin to a lay assumption that anything can be said in any language. It is, however, the case that some relations are expressed more readily and more frequently than others. Temporal relations between clauses are a prime example. In contrast, semantic relations of possible consequence, manner, or addition may not have a way of expression of their own.
Protein sequence alignment and database scanning
Authors: Barton Geoffreyj
Published: November 2023

In the context of protein structure prediction, there are two principle reasons for comparing and aligning protein sequences: (a) To obtain an accurate alignment. This may be for protein modelling by comparison to proteins of known three-dimensional structure. (b) To scan a database with a newly determined protein sequence and identify possible functions for the protein by analogy with well-characterized proteins. In this chapter I review the underlying principles and techniques for sequence comparison as applied to proteins and used to satisfy these two aims.
Antibody combining sites: structure and prediction
Authors: Rees Anthony R , Searle stephen J , Henry andrew H , Whitelegg Nicholas , Pedersen Jan
Published: November 2023

Antibodies possess a vast repertoire of specificity and affinity. To understand the molecular basis of antibody function requires a knowledge of the structures of free and antigen-bound antibodies, determined by X-ray crystallography or NMR, or ideally both. Although the number of antibody structures is increasing rapidly—at the time of writing 48 structures have been deposited in the Brookhaven Protein Database (PDB) (1)—the rate of structure determination will never match that of sequence acquisition. Thus, to explore fully the structural variability of antibody combining sites, encoded in immunoglobulin variable region sequences, effective structural prediction methods have become essential. Such models will have increasing utility where the structural effects of point mutations within the antibody combining site need to be assessed, where minimal perturbation strategies for the grafting of complementarity determining regions (CDRs) during the process of ‘humanization’ are required, and even where the residues to be targeted for random mutation in the gene library methods now available (e.g. phage libraries) are selected in a more rational manner on the basis of their likely accessibility to antigen. In time, when the antibody sequence/structure relationship is fully understood, de nova design of antibodies will also become possible (2).
Immunological detection of proteins of known sequence
Authors: Scheidtmann Karl Heinz , Reinartz, Silke , Schlebusch Harald
Published: November 2023

Many proteins were first identified as antigens or neo-antigens, such as viral or tumour-specific proteins in infected or transformed cells, which in the carrier organism induced an immune response. In those cases, sera from infected animals or patients provided the tools for identification of the antigenic proteins.
Hydrodynamic properties of proteins
Authors: Harding Stephen E
Published: November 2023

Since the first edition of this book, there has been something of a renaissance of hydrodynamic methods for the determination of the mass, quaternary structure, gross conformation, and interaction properties of proteins and other macromolecules in solution. By ‘hydrodynamic’ (Greek for ‘watermovement’) techniques, we mean any technique involving motion of a macromolecule with or relative to the aqueous solvent in which it is dissolved or suspended. This therefore includes not only gel filtration, viscometry, sedimentation (velocity and equilibrium), and rotational diffusion probes (fluorescence anisotropy depolarization and electric-optical methods), but also ‘classical’ and ‘dynamic’ light scattering, which both derive from the relative motions of the macromolecular solute in relation to the solvent. This definition also includes electrophoretic methods (considered in Chapter 8 and not covered here), which are powerful tools for separation, purification, and identification of proteins, but also, with ‘SDS’ methodology, provide an estimate of polypeptide molecular weight (see Chapter I). The present chapter therefore considers the hydrodynamic determination of ‘molar mass’ or molecular weight and quaternary structure (subunit composition and arrangement, self-association phenomena. and polydispersity). It will also consider the measurement of protein conformation in dilute solution with particular reference to the use of the analytical ultracentrifuge, a technique although of considerable antiquity (70th birthday in 1993) that has been the centre of the revival of hydrodynamic methodology.
Purification for crystallography
Authors: Wood S P , Coker A R
Published: November 2023

In the early days of protein biochemistry, crystallization was often employed as a purification technique and crystallinity was considered an index of purity. Crystallographic studies were focused on a selection of proteins whose principle qualification was their abundance and ease of crystallization. The techniques of protein crystallography have now developed to such a degree that a complete three-dimensional structure analysis may not be a long task. Indeed it is often the production of suitable crystals that is rate limiting for the study of many proteins. High purity of the protein preparation used for crystallization is often one of the most important factors for growing diffraction quality crystals. Many crystallization trials have run into difficulties due to protein preparations which are not as homogeneous as first thought. Even for those proteins that can be purified from very impure mixtures by crystallization, crystal quality improves with each recrystallization as the purity increases. Crystal growing procedures and methods of purification have developed to cope with ever smaller quantities of protein derived from expression systems in bacteria, yeast, fungi, and cultured eukaryotic cells. This has allowed structure investigations of molecules that do not occur in nature or molecules or fragments whose natural abundance is very low. These expression systems often generate particular challenges in purification. The relationship of homogeneity and crystal growth is not well documented in the literature. Reports of successful crystal growth are numerous, but many of the problems encountered are not fully recorded.
Protein purifications from mammalian cell culture
Authors: Cartwright Terry
Published: November 2023

Health care in the last decades of the twentieth century has been revolutionized by our capacity to produce recombinant proteins and viruses for therapeutic, vaccine, and diagnostic use. The greatest challenge has been the production of complex proteins for administration to humans in order to replace or augment deficient endogenous proteins. In many cases, the complexity of the protein structure involved, particularly where post-translational modifications such as glycosylation are required, is such that only mammalian cells can perform all of the synthetic steps required to produce truly authentic copies of the natural human protein. One of the major successes of the biotechnology industry is the speed with which mammalian cell culture has been developed into a viable biopharmaceutical production process from its beginnings in the 1960s. Today approximately half of the multi-billion dollar biopharmaceutical industry is based on products derived from cultured mammalian cells.
Protein purification from microbial cell culture
Authors: Levison Peter R
Published: November 2023

This chapter discusses some of the issues associated with the purification of proteins and related biomolecules from microbial sources. The emphasis in the examples described is on the scale-up of these processes to produce commercial quantities of the proteins. The protein purification steps can best be separated into upstream and downstream processes. For simplicity, we will delineate downstream processes into those using clarified feedstocks suitable for chroma-tography whereas upstream processes are those preceding clarification, i.e. cell harvesting, lysis, inclusion body concentration, etc. The scope of this chapter is restricted to downstream processes with upstream processes being well described elsewhere (1, 2).
Protein purification from animal tissue
Authors: Hooper Nigel M
Published: November 2023

Numerous proteins have been purified from almost every conceivable animal tissue. In this chapter, I deal with the principles involved in isolating proteins from animal tissue, covering such issues as the choice of tissue, methods used to disrupt the tissue, and procedures for isolating the appropriate subcellular fraction. Most of the procedures that I detail have been used to isolate mg quantities of a particular protein from relatively large (50-200 g) amounts of tissue, but can readily be scaled down for smaller amounts. Also covered are the use of protease inhibitors to prevent unwanted proteolysis, and the use of detergents, proteases, and phospholipases to solubilize membrane proteins. The chapter finishes with three example purifications of animal proteins-the isolation of angiotensin converting enzyme and aminopeptidase P from pig kidney cortex membranes, and offructose-1,6-bisphosphatase from pig liver cytosol.
Protein purification from plant sources
Authors: Bolwell G Paul
Published: November 2023

There is a prevailing perception that plants pose special problems with respect to protein purification. These problems occur as a result of lower protein per unit volume than animals or prokaryotes, the occurrence of natural products that interfere with purification and oxidative processes brought into play by tissue disruption that lead to enzyme inactivation. This chapter highlights how some of these problems may be overcome. Often a careful selection of source material and preliminary work to determine the time window of maximum expression of the target protein can improve the chances of purification to homogeneity significantly. Plants tend to regulate protein levels by changes in gene expression and turnover and these can often be in response to developmental and environmental factors. Prior knowledge of regulation of appearance of a particular protein is, particularly, advantageous. A second consideration, which is probably more important for plant sources, is the initial tissue disruption strategy and this requires some knowledge of the source material. Once the protein has been isolated in a form which allows fractionation however, plant proteins can be treated like any other and general chromatography matrices and methods are applicable.
Application of three-dimensional printing in cardiovascular diseases: a bibliometric analysis
Authors: Zhang Xin , Yi Kang , Xu Jian-Guo , Wang Wen-Xin , Liu Cheng-Fei , He Xiao-Long , Wang Fan-Ning , Zhou Guo-Lei , You Tao
Published: November 2023

Aim:

This paper aimed to explore the application of Three-dimensional (3D) printing in cardiovascular diseases, to reach an insight in this field and prospect the future trend.

Methods:

The articles were selected from the Web of Science Core Collection database. Excel 2019, VOSviewer 1.6.16, and CiteSpace 6.1.R6 were used to analyze the information.

Results:

A total of 467 papers of 3D printing in cardiovascular diseases were identified, and the first included literature appeared in 2000. A total of 692 institutions from 52 countries participated in the relevant research, while the United States of America contributed to 160 articles and were in a leading position. The most productive institution was Curtin University , and Zhonghua Sun who has posted the most articles (n=8) was also from there. The Frontiers in Cardiovascular Medicine published most papers (n=25). The Journal of Thoracic and Cardiovascular Surgery coveted the most citations (n=520). Related topics of frontiers will still focus on congenital heart disease, valvular heart disease, and left atrial appendage closure.

Conclusions:

We summarized the publication information of the application of 3D printing in cardiovascular diseases related literature from 2000 to 2023, including country and institution of origin, authors, and publication journal. This study can reflect the current hotspots and novel directions for the application of 3D printing in cardiovascular diseases.
Dynamic Regulation of Innate Lymphoid Cell Development During Ontogeny
Authors: Wu Tao , Chen Sijie , Ma Jie , Zhu Xinyi , Luo Maocai , Wang Yuanhao , Tian Yujie , Sun Qingqing , Guo Xiaohuan , Zhang Jianhong , Zhang Xuegong , Zhu Yunping , Wu Li
Published: November 2023

Innate lymphoid cells (ILCs) are crucial for maintaining tissue homeostasis. The dynamic composition of ILC subsets during ontogeny has been observed for over a decade, yet the underlying mechanisms remain incompletely understood. Here, we combined differentiation assay and scRNA-seq analysis to compare the fetal and adult ILC development, and assessed their contribution to the dynamic change of ILC subsets. We revealed the preference for LTi cell differentiation in fetal hematopoietic progenitors, contrasted with a non-LTi differentiation bias in adult stages. Our analyses elucidated that the two stages shared a conserved differentiation trajectory and regulatory programs but used different controlling logic. Through computational prediction and dose-response experiments, we proposed a model where a transition from fetal RORγt-dominant states to adult Notch-GATA3-dominant states orchestrates these changes. This study suggests that ILC development can be modulated to accommodate the varying demands for specific ILC subsets within the body at different developmental stages.

Highlight

The ratio of LTi cells to non-LTi ILCs decreases from fetal to adult stage

Modified fate determination of ILC progenitors contributes to this decrease of LTi cell ratio during ontogeny

A conserved trajectory exists from early αLPs to Innate Lymphoid Cell Precursors (ILCPs) during both fetal and adult ILC development

Enhanced activity of Notch-GATA3 signaling in ILC precursors accounts for the transition of their differentiation from LTi cells in the fetal to non-LTi ILCs in adults.

Graphical abstract
Conservation applications of niche modeling: native and naturalized ferns may compete for limited Hawaiian dryland habitat
Authors: Edwards-Calma Krystalyn , Jiménez Laura , Zenil-Ferguson Rosana , Heyduk Karolina , Thomas Miles K. , Tribble Carrie M.
Published: November 2023

Premise

Competition from naturalized species and habitat loss are common threats to native biodiversity and may act synergistically to increase competition for decreasing habitat availability. We use Hawaiian dryland ferns as a model for the interactions between land-use change and competition from naturalized species in determining habitat availability.

Methods

We use fine-resolution climatic variables and carefully curated occurrence data from herbaria and community science repositories to estimate the distributions of Hawaiian dryland ferns. We quantify the degree to which naturalized ferns tend to occupy native species suitable area and map remaining available habitat given land-use change.

Results

Of all native species,Doryopteris angelicahas the lowest percentage of occurrences of naturalized species in its suitable area whileD. decorahas the highest. However, allDoryopterisspp. had a higher percentage overlap—whilePellaea ternifoliahad a lower percentage overlap—than expected by chance.D. decoraandD. decipienshave the lowest proportions (<20%) of suitable area covering native habitat.

Discussion

Areas characterized by shared environmental preferences of native and naturalized ferns may also decrease due to human development and fallowed agricultural lands. Our study demonstrates the value of placed-based application of a recently developed correlative ecological niche modeling approach for conservation risk assessment in a rapidly changing and urbanized island ecosystem.
Prevalence of TEM and SHV Genes inKlebsiella pneumoniaeisolated from different Clinical specimens in Khartoum, Sudan
Authors: Hussein Saad A. S , Salih Mutassim A.M. , Adlan Hind M.E , Abdalla Abualgasim E.
Published: November 2023

Objective

The aim of this study is to determine the prevalence of ESBL producingKlebsiella pneumoniaeisolated from different clinical specimens gathered from different clinics in Khartoum State.

Settings and Design

This is a descriptive cross-sectional study conducted in Khartoum State during a period from February to May 2018.

Methods and Materials

Klebsiella pneumoniaeisolated from patients attending to health-care settings with different infections, which was re-identiGied by conventional methods and screened for ESBL production by modiGied Kirby-Bauer’s method. The TEM and SHV genes were detected by PCR.

Results

Out of 100K. pneumoniaeisolates, 85% (85/100) were ESBL producing strains. The highest prevalence of ESBL production was in blood 100% (6/6) as well as stool 100% (4/4) followed by sputum 91% (21/23), wound 85% (12/14) and urine 82%(40\49) samples, while the lowest was noted in CSF 50% (2/4). The isolatedK. pneumoniaeshowed high resistance to Ceftazidime 85% followed by Cefotaxime and Cefpodoxime 80% for each and 73% for Aztreonam. Furthermore, we found that 88% of isolates were resistant to Colistin and 33% were resistant to Meropenem. TEM and SHV genes were detected in 9.4% (8/85) and 1.2% (1/85) of ESBL producing strains, respectively. However, SHV was also detected in 6.7% (1/15) of non-ESBL-producingK. pneumoniae.

Conclusions

A high prevalence of ESBL-producingK. pneumoniaewas detected in this study Which is 85%. TEM and SHV genes were found in some strains of ESBL producingK. pneumoniae. The Gindings of this study alarm the physicians to take ESBL producing strains ofK. pneumoniaeunder consideration before making treatment decisions.
Transcranial ultrasound stimulation effect in the redundant and synergistic networks consistent across macaques
Authors: Gatica Marilyn , Atkinson-Clement Cyril , Mediano Pedro A. M. , Alkhawashki Mohammad , Ross James , Sallet Jèrôme , Kaiser Marcus
Published: November 2023

Low-intensity transcranial ultrasound stimulation (TUS) is a non-invasive technique that safely alters neural activity, reaching deep brain areas with good spatial accuracy. We investigated the effects of TUS at the level of macaque using a recent metric, the synergy minus redundancy rank gradient, that quantifies different kinds of causal neural information processing. We analyzed this high-order quantity on the fMRI data after TUS in two targets: the supplementary motor area (SMA-TUS) and the frontal polar cortex (FPC-TUS). The TUS produced specific changes at the limbic network at FPC-TUS and the motor network at SMA-TUS and altered, in both targets, the sensorimotor, temporal, and frontal networks, consistent across macaques. Moreover, there was a reduction in the structural and functional coupling after both stimulations. Finally, the TUS changed the intrinsic high-order network topology, decreasing the modular organization of the redundancy at SMA-TUS and increasing the synergistic integration at FPC-TUS.
Genetic Influences on Educational Attainment Through the Lens of the Evolving Swedish Welfare State: A cross-level gene-environment interaction study based on polygenic indices and longitudinal register data
Authors: Pettersson Oskar
Published: November 2023

Gene-environment interaction with regards to educational attainment has received increasing attention during the last few years. However, the potential interdependence between different types of environments in gene-environment interaction models has mostly been neglected. Using high-quality register data for an extensive panel of Swedish twins, born during most of the twentieth century, this study explores how genetic propensities for educational attainment, as measured by a polygenic index, interact with both macro-level institutional and sociopolitical context, and with socioeconomic background. The analyses, which combine between-family and causally robust within-family models, suggest that the average association between genetic propensities and educational attainment has increased in Sweden during the twentieth century, along with the expansion of the educational system and decreased economic inequality. There is also evidence of a positive interaction between genetic propensities and socioeconomic background, but only in the oldest cohorts in the sample, and that were born before the Swedish welfare state had been fully established. This implies that micro-level gene-environment interactions can be significantly dependent on macro-level context, an insight that has arguably not yet been given sufficient attention in the literature. Acknowledging limitations of polygenic indices, and the arbitrariness of the genetic lottery, the results may nevertheless indicate a development towards higher equality of opportunity in Sweden during the twentieth century.
Sufficient COVID-19 quarantine and testing on international travelers from China
Authors: Bojja Dinesh , Zuo Scott , Townsend Jeffrey P.
Published: November 2023

Objectives

Removal of zero-COVID restrictions in China led to a surge in COVID-19 cases. In response, countries imposed restrictions on Chinese travelers. However, border policies may not provide substantial benefits and their assessment depends on accurate prevalence data.

Methods

We analyzed quarantines and testing sufficient to prevent additional in-country transmission for February 13–19, 2023 based on World Health Organization (WHO) and self-reported infection rates to estimate prevalence.

Results

Here we have shown that self-reported prevalence data indicated more stringent border restrictions compared to WHO-published prevalence statistics. No travel restrictions were required for Singapore for infections to not be greater than in complete border closure, while a 1-day quarantine, 2-day quarantine, and a 3-day quarantine were indicated for England, Germany, and Scotland respectively. A 10-day quarantine, 11-day quarantine, and 13-day quarantine were required for Italy, Japan, and France, respectively, to prevent an increase in the number of within-country infections due to travel, while South Korea required a complete border shutdown.

Conclusions

Our results demonstrated the necessity for accurate and timely reporting of pandemic statistics to prevent an increase in viral spread. Through the minimum-quarantine analysis, countries can use science to determine policy, minimize international friction, and improve the cost-efficiency of interventions.
Cross-sectional associations between prenatal maternal per- and poly-fluoroalkyl substances and bioactive lipids in three Environmental influences on Child Health Outcomes (ECHO) cohorts
Authors: Suthar Himal , Manea Tomás , Pak Dominic , Woodbury Megan , Eick Stephanie M. , Cathey Amber , Watkins Deborah J. , Strakovsky Rita S. , Ryva Brad A. , Pennathur Subramaniam , Zeng Lixia , Weller David , Park June-Soo , Smith Sabrina , DeMicco Erin , Padula Amy , Fry Rebecca C. , Mukherjee Bhramar , Aguiar Andrea , Geiger Sarah Dee , Ng Shukhan , Huerta-Montanez Gredia , Vélez-Vega Carmen , Rosario Zaira , Cordero Jose F. , Zimmerman Emily , Woodruff Tracey J. , Morello-Frosch Rachel , Schantz Susan L. , Meeker John D. , Alshawabkeh Akram , Aung Max T.
Published: November 2023

Background

Per- and poly-fluoroalkyl substances (PFAS) exposure can occur through ingestion of contaminated food and water, and inhalation of indoor air contaminated with these chemicals from consumer and industrial products. Prenatal PFAS exposures may confer risk for pregnancy-related outcomes such as hypertensive and metabolic disorders, preterm birth, and impaired fetal development through intermediate metabolic and inflammation pathways.

Objective

Estimate associations between maternal pregnancy PFAS exposure (individually and as a mixture) and bioactive lipids.

Methods

Our study included pregnant women in the Environmental influences on Child Health Outcomes Program: Chemicals in our Bodies cohort (CiOB, n=73), Illinois Kids Developmental Study (IKIDS, n=287), and the ECHO-PROTECT cohort (n=54). We measured twelve PFAS in serum and 50 plasma bioactive lipids (parent fatty acids and eicosanoids derived from cytochrome p450, lipoxygenase, and cyclooxygenase) during pregnancy (median 17 gestational weeks). Pairwise associations across cohorts were estimated using linear mixed models and meta-analysis. Associations between the PFAS mixture and individual bioactive lipids were estimated using quantile g-computation.

Results

PFDeA, PFOA, and PFUdA were associated (p<0.05) with changes in bioactive lipid levels in all three enzymatic pathways (cyclooxygenase [n=6 signatures]; cytochrome p450 [n=5 signatures]; lipoxygenase [n=7 signatures]) in at least one combined cohort analysis. The strongest signature indicated that a doubling in PFOA corresponded with a 24.3% increase (95% CI [7.3%, 43.9%]) in PGD2 (cyclooxygenase pathway) in the combined cohort. In the mixtures analysis, we observed nine positive signals across all pathways associated with the PFAS mixture. The strongest signature indicated that a quartile increase in the PFAS mixture was associated with a 34% increase in PGD2 (95% CI [8%, 66%]), with PFOS contributing most to the increase.

Conclusions

Bioactive lipids were revealed as biomarkers of PFAS exposure and could provide mechanistic insights into PFAS’ influence on pregnancy outcomes, informing more precise risk estimation and prevention strategies.
Role of Cardiorespiratory Fitness and Mitochondrial Energetics in Reduced Walk Speed of Older Adults with Diabetes in the Study of Muscle, Mobility and Aging (SOMMA)
Authors: Ramos Sofhia V. , Distefano Giovanna , Lui Li-Yung , Cawthon Peggy M. , Kramer Philip , Sipula Ian J. , Bello Fiona M. , Mau Theresa , Jurczak Michael J. , Molina Anthony J. , Kershaw Erin E. , Marcinek David J. , Toledo Frederico G.S. , Newman Anne B. , Hepple Russell T. , Kritchevsky Stephen B. , Goodpaster Bret H. , Cummings Steven R. , Coen Paul M.
Published: November 2023

Rationale

Cardiorespiratory fitness and mitochondrial energetics are associated with reduced walking speed in older adults. The impact of cardiorespiratory fitness and mitochondrial energetics on walking speed in older adults with diabetes has not been clearly defined.

Objective

To examine differences in cardiorespiratory fitness and skeletal muscle mitochondrial energetics between older adults with and without diabetes. We also assessed the contribution of cardiorespiratory fitness and skeletal muscle mitochondrial energetics to slower walking speed in older adults with diabetes.

Findings

Participants with diabetes had lower cardiorespiratory fitness and mitochondrial energetics when compared to those without diabetes, following adjustments for covariates including BMI, chronic comorbid health conditions, and physical activity. 4-m and 400-m walking speeds were slower in those with diabetes. Mitochondrial oxidative capacity alone or combined with cardiorespiratory fitness mediated ∼20-70% of the difference in walk speed between older adults with and without diabetes. Further adjustments of BMI and co-morbidities further explained the group differences in walk speed.

Conclusions

Skeletal muscle mitochondrial energetics and cardiorespiratory fitness contribute to slower walking speeds in older adults with diabetes. Cardiorespiratory fitness and mitochondrial energetics may be therapeutic targets to maintain or improve mobility in older adults with diabetes.

ARTICLE HIGHLIGHTS

Why did we undertake this study?

To determine if mitochondrial energetics and cardiorespiratory fitness contribute to slower walking speed in older adults with diabetes.

What is the specific question(s) we wanted to answer?

Are mitochondrial energetics and cardiorespiratory fitness in older adults with diabetes lower than those without diabetes? How does mitochondrial energetics and cardiorespiratory fitness impact walking speed in older adults with diabetes?

What did we find?

Mitochondrial energetics and cardiorespiratory fitness were lower in older adults with diabetes compared to those without diabetes, and energetics, and cardiorespiratory fitness, contributed to slower walking speed in those with diabetes.

What are the implications of our findings?

Cardiorespiratory fitness and mitochondrial energetics may be key therapeutic targets to maintain or improve mobility in older adults with diabetes.

Graphical Abstract
Curating Retrospective Multimodal and Longitudinal Data for Community Cohorts at Risk for Lung Cancer
Authors: Li Thomas Z. , Xu Kaiwen , Chada Neil C. , Chen Heidi , Knight Michael , Antic Sanja , Sandler Kim L. , Maldonado Fabien , Landman Bennett A. , Lasko Thomas A.
Published: November 2023

Large community cohorts are useful for lung cancer research, allowing for the development and validation of predictive models. A robust methodology for (1) identifying lung cancer and pulmonary nodules from electronic health record (EHRs) as well as (2) associating longitudinal data with these conditions is needed to optimally curate cohorts at scale from clinical data. Both objectives present the challenge of labeling noisy multimodal data while minimizing assumptions about the data structure specific to any institution. In this study, we leveraged (1) SNOMED concepts to develop ICD-based decision rules for building a cohort that captured lung cancer and pulmonary nodules and (2) clinical knowledge to define time windows for collecting longitudinal imaging and clinical concepts. We curated three cohorts with clinical concepts and repeated imaging for subjects with pulmonary nodules from our Vanderbilt University Medical Center. Our approach achieved an estimated sensitivity 0.930 (95% CI: [0.879, 0.969]), specificity of 0.996 (95% CI: [0.989, 1.00]), positive predictive value of 0.979 (95% CI: [0.959, 1.000]), and negative predictive value of 0.987 (95% CI: [0.976, 0.994]). for distinguishing lung cancer from subjects with SPNs. This work represents a strategy for high-throughput curation of multi-modal longitudinal cohorts at risk for lung cancer from routinely collected EHRs.
Meta-analysis of RNA sequencing data from 534 skin samples shows substantial IL-17 effects in non-lesional psoriatic skin
Authors: Solvin Åshild Øksnevad , Chawla Konika , Jenssen Marita , Olsen Lene Christin , Furberg Anne-Sofie , Danielsen Kjersti , Saunes Marit , Hveem Kristian , Sætrom Pål , Løset Mari
Published: November 2023

Psoriasis is a common chronic inflammatory skin disease characterized by disturbed interactions between infiltrating immune cells and keratinocytes. To enhance our understanding of the underlying molecular and cellular mechanisms driving psoriasis pathobiology, and to identify potential biomarkers for disease severity, we conducted RNA sequencing of skin biopsies from 75 patients with psoriasis vulgaris and 46 non-psoriatic controls. To increase the robustness of the results, we meta-analysed our data with four publicly available datasets, bringing the total number of samples to 534. By comparing lesional psoriatic (PP) to healthy control (NN) skin, we identified 2269 differentially expressed genes (DEGs) (|log2FC|>1.0, FDR <0.1), and 58 DEGs when comparing non-lesional psoriatic (PN) to NN skin. We also identified 54 DEGs associated with disease severity (PASI ≥10 vs. PASI <10). Cellular deconvolution analysis showed that differentiated keratinocytes emerged as the most prominent cell type among the DEGs in PP/NN. Functional enrichment analysis in PN/NN revealed several IL-17 related pathways and confirmed a previously reported ‘pre-inflammatory signature’ across all psoriatic skin. This study provides insights into the psoriasis transcriptome and identifies a severity-specific signature, which may serve as candidate for future studies aimed at identifying psoriasis biomarkers and predicting disease progression.