bluuebunny/crossref_metadata_2025 huggingface dataset:
Genetic Analysis of Mingrelians Reveals Long-Term Continuity of Populations in Western Georgia (Caucasus)
Authors: Schurr Theodore G , Shengelia Ramaz , Shamoon-Pour Michel , Chitanava David , Laliashvili Shorena , Laliashvili Irma , Kibret Redate , Kume-Kangkolo Yanu , Akhvlediani Irakli , Bitadze Lia , Mathieson Iain , Yardumian Aram
Published: November 2023

To elucidate the population history of the Caucasus, we conducted a survey of genetic diversity in Samegrelo (Mingrelia), western Georgia. We collected DNA samples and genealogical information from 485 individuals residing in 30 different locations, the vast majority of whom being Mingrelian speaking. From these DNA samples, we generated mitochondrial DNA (mtDNA) control region sequences for all 485 participants (female and male), Y-short tandem repeat haplotypes for the 372 male participants, and analyzed all samples at nearly 590,000 autosomal single nucleotide polymorphisms (SNPs) plus around 33,000 on the sex chromosomes, with 27,000 SNP removed for missingness, using the GenoChip 2.0+ microarray. The resulting data were compared with those from populations from Anatolia, the Caucasus, the Near East, and Europe. Overall, Mingrelians exhibited considerable mtDNA haplogroup diversity, having high frequencies of common West Eurasian haplogroups (H, HV, I, J, K, N1, R1, R2, T, U, and W. X2) and low frequencies of East Eurasian haplogroups (A, C, D, F, and G). From a Y-chromosome standpoint, Mingrelians possessed a variety of haplogroups, including E1b1b, G2a, I2, J1, J2, L, Q, R1a, and R1b. Analysis of autosomal SNP data further revealed that Mingrelians are genetically homogeneous and cluster with other modern-day South Caucasus populations. When compared with ancient DNA samples from Bronze Age archaeological contexts in the broader region, these data indicate that the Mingrelian gene pool began taking its current form at least by this period, probably in conjunction with the formation of a distinct linguistic community.
Genomic Divergence and the Evolution of Ecotypes in Bottlenose Dolphins (Genus Tursiops)
Authors: Pratt Eleanor A L , Beheregaray Luciano B , Fruet Pedro , Tezanos-Pinto Gabriela , Bilgmann Kerstin , Zanardo Nikki , Diaz-Aguirre Fernando , Secchi Eduardo R , Freitas Thales R O , Möller Luciana M
Published: November 2023

Climatic changes have caused major environmental restructuring throughout the world's oceans. Marine organisms have responded to novel conditions through various biological systems, including genomic adaptation. Growing accessibility of next-generation DNA sequencing methods to study nonmodel species has recently allowed genomic changes underlying environmental adaptations to be investigated. This study used double-digest restriction-site associated DNA (ddRAD) sequence data to investigate the genomic basis of ecotype formation across currently recognized species and subspecies of bottlenose dolphins (genus Tursiops) in the Southern Hemisphere. Subspecies-level genomic divergence was confirmed between the offshore common bottlenose dolphin (T. truncatus truncatus) and the inshore Lahille's bottlenose dolphin (T. t. gephyreus) from the southwestern Atlantic Ocean (SWAO). Similarly, subspecies-level divergence is suggested between inshore (eastern Australia) Indo-Pacific bottlenose dolphin (T. aduncus) and the proposed Burrunan dolphin (T. australis) from southern Australia. Inshore bottlenose dolphin lineages generally had lower genomic diversity than offshore lineages, a pattern particularly evident for T. t. gephyreus, which showed exceptionally low diversity. Genomic regions associated with cardiovascular, musculoskeletal, and energy production systems appear to have undergone repeated adaptive evolution in inshore lineages across the Southern Hemisphere. We hypothesize that comparable selective pressures in the inshore environment drove similar adaptive responses in each lineage, supporting parallel evolution of inshore bottlenose dolphins. With climate change altering marine ecosystems worldwide, it is crucial to gain an understanding of the adaptive capacity of local species and populations. Our study provides insights into key adaptive pathways that may be important for the long-term survival of cetaceans and other organisms in a changing marine environment.
Selective Engagement in Preparations for Aging
Authors: Hess Thomas M , Park Jeongsoo , de Paula Couto M Clara P , Fung Helene H , Rothermund Klaus
Published: November 2023

Objectives

Preparing for old age is an adaptive behavior with positive consequences on well-being. This study examined; (a) the degree to which the importance associated with positive outcomes within specific domains of everyday functioning (e.g., social relationships, health) varies across ages and cultures; (b) the impact of importance on preparing for old age; and (c) whether the effects of importance were greater in later life.

Methods

Using data from adults aged 30–85 years in Germany (n = 623), Hong Kong (n = 317), and the United States (n = 313) collected over 5 years, we examined variations in importance ratings across age, cultures, and behavioral domains, and the extent to which age and importance predicted preparations.

Results

Importance ratings were found to vary with age, time of test, domains, and culture, reflecting the expected contextual effects. Importance also was a positive predictor of preparations, with the strength of prediction being somewhat greater in old age.

Discussion

The results provide evidence that the perceived importance of functioning within domains is affected by a number of contextual factors, including the domain of everyday function and culture. Given that importance also predicts preparations, such variation may help explain differences in preparations across contexts. In line with selective engagement theory, some support was also obtained for the prediction that older adults are more selective in engaging resources in support of preparations. Such selectivity can be viewed as an adaptive response to diminishing personal resources in later life.
Nurses can be key “REACH” accountable care organization partners to mitigate Medicare inequity
Authors: Rieselbach Richard , Sundwall David
Published: November 2023

We propose that Advanced Practice Registered Nurses (APRNs) can be key Accountable Care Organization (ACO) partners in mitigating Medicare inequity due to a shortage of primary care physicians. This shortage particularly impacts minority Medicare beneficiaries residing in urban and rural Health Professional Shortage Areas. In order to expand the primary care workforce to open the gateway to our health care system for these beneficiaries, we propose that APRNs provide primary care in a Medicare Neighborhood Clinic, as key partners of a modified “REACH” (Realizing Equity, Access, and Community Health) ACO model. We review the long history of ineffective efforts to alleviate the physician primary care shortage. After highlighting a report emphasizing the importance of nurses in achieving health equity, we describe the APRN role in a Medicare Neighborhood Clinic, and its potential for alleviating the primary care shortage. This clinic, as part of the modified “REACH” strategy, provides nurses with a key role in achieving Medicare equity. We contend that this strategy, as a means of APRNs providing value-based care to all Medicare beneficiaries while restraining the Medicare budget, contributes to transforming primary care for Medicare equity.
snRNA-seq analysis in multinucleated myogenic FSHD cells identifies heterogeneous FSHD transcriptome signatures associated with embryonic-like program activation and oxidative stress-induced apoptosis
Authors: Zheng Dongxu , Wondergem Annelot , Kloet Susan , Willemsen Iris , Balog Judit , Tapscott Stephen J , Mahfouz Ahmed , van den Heuvel Anita , van der Maarel Silvère M
Published: November 2023

The sporadic nature of DUX4 expression in FSHD muscle challenges comparative transcriptome analyses between FSHD and control samples. A variety of DUX4 and FSHD-associated transcriptional changes have been identified, but bulk RNA-seq strategies prohibit comprehensive analysis of their spatiotemporal relation, interdependence and role in the disease process. In this study, we used single-nucleus RNA-sequencing of nuclei isolated from patient- and control-derived multinucleated primary myotubes to investigate the cellular heterogeneity in FSHD. Taking advantage of the increased resolution in snRNA-sequencing of fully differentiated myotubes, two distinct populations of DUX4-affected nuclei could be defined by their transcriptional profiles. Our data provides insights into the differences between these two populations and suggests heterogeneity in two well-known FSHD-associated transcriptional aberrations: increased oxidative stress and inhibition of myogenic differentiation. Additionally, we provide evidence that DUX4-affected nuclei share transcriptome features with early embryonic cells beyond the well-described cleavage stage, progressing into the 8-cell and blastocyst stages. Altogether, our data suggests that the FSHD transcriptional profile is defined by a mixture of individual and sometimes mutually exclusive DUX4-induced responses and cellular state-dependent downstream effects.
Expanding the scope and roles of social sciences and humanities to support integrated ecosystem assessments and ecosystem-based management
Authors: Tam Jamie C , Parlee Courtenay E , Campbell-Miller Jill , Bellanger Manuel , Bentley Jacob , Pourfaraj Vahab , Andrews Evan J , Eger Sondra L , Cook Adam M , Beaulieu Gabrielle
Published: November 2023

Understanding social-ecological systems (SESs) is an important part of ecosystem-based management (EBM). One of the main decision support frameworks to develop scientific advice for EBM is integrated ecosystem assessments (IEAs). Human dimensions in SESs are primarily captured through indicators derived from three social sciences: economics, anthropology, and sociology. The breadth of social sciences and humanities (SSH) research is much greater than those three fields, but they are generally underused in natural science-based decision support processes such as IEAs. Greater contributions of SSHs can enhance IEAs through various direct (e.g. to develop indicators) and indirect ways (e.g. to establish and maintain ethical practices). We examine a wider range of SSH disciplines and conclude that scientific advice processes that inform EBM can benefit from broader integration of SSH theories and methods through themes of contextualizing, facilitating, communicating, evaluating, and anticipating. We see this an opportunity to both widen the vocabulary used to describe social scientists and those who work in humanities in IEAs, and apply the underlying worldviews used to conduct SSH research to fundamentally enhance the IEA process and to further progress in EBM.
Upcalling behaviour and patterns in North Atlantic right whales, implications for monitoring protocols during wind energy development
Authors: Davis G E , Tennant S C , Van Parijs S M
Published: November 2023

Offshore wind energy is rapidly developing in US waters, with construction underway off Southern New England (SNE), an important region for many species, including the critically endangered North Atlantic right whale (NARW). A data-driven understanding of NARW upcalling behaviour is presented here to help establish proper monitoring protocols for mitigating impacts. Analyses of individual upcalls from 2 years of acoustic recordings showed that NARWs were detected at least 1 day every week throughout both years, with highest NARW presence from October to April. Weeks with more days of acoustic presence typically had more hours with calling activity, but the number of upcalls within a day or hour was variable, reflective of the social function of the upcall. Within SNE, on average, 95% of the time NARWs persisted for 10 days, and reoccurred again within 11 days. An evaluation of the time period over which it is most effective to monitor prior to commencing pile driving activities showed that with 1 h of pre-construction monitoring there was only 4% likelihood of hearing a NARW, compared to 74% at 18 h. Therefore, monitoring for at least 24 h prior to activity will increase the likelihood of detecting an up-calling NARW.
Control and paralysis? A context-sensitive analysis of objections to supermajorities in constitutional adjudication
Authors: Rivera León Mauro Arturo
Published: November 2023

Supermajorities in judicial review are present in several countries, including the United States (at the state level), Mexico, Peru, the Czech Republic, Chile, and South Korea. Despite their prevalence, the theoretical legitimacy of supermajorities has been a topic of intense debate since the early twenty-first century. A notable gap exists between this theoretical discourse and empirical research that examines the supermajority models in practice. This article endeavors to bridge this gap. Focusing on two important concerns raised in comparative scholarship—namely that supermajorities might enable political branches to control the court through select appointments, and they could potentially paralyze constitutional courts—this article offers a nuanced examination of the Mexican scenario. It argues that specific mechanisms governing judicial appointments, such as staggered terms and pluralistic appointments, can effectively mitigate the risk of court control in supermajority settings. Furthermore, a thorough assessment of an ad hoc dataset on decisions in which the supermajority was applicable suggests that these majorities do not paralyze the court.
Constituent power: From Schmitt to Kantorowicz—Afterword to the Foreword by Sergio Verdugo
Authors: Barshack Lior
Published: November 2023

In his Foreword, Sergio Verdugo presents Schmitt’s account of constituent power as the conventional understanding of this concept. At the same time, he shows that Schmitt’s views are contested and hardly accepted as a matter of convention. Verdugo’s critiques of constituent power are leveled mainly against Schmitt’s (“conventional”) understanding of the concept. If Schmitt’s account is relaxed, various criticisms of constituent power seem overstated. We have good reasons to abandon Schmitt’s conception of constituent power as unlimited and permanently active. Several flaws of Schmitt’s model of constituent power have to do with its failure to account for the contribution of constituent power to world-building. A restless and omnipotent constituent power cannot contribute much to the construction of a public world. Schmitt’s unruly constituent power entraps society in a state of permanent worldlessnes (Arendt) or communitas (Turner). In order to allow for the reproduction of the public world, constituent power has to be limited and discontinuous. A theory of the constitution that is based on Kantorowicz’s account of the corporate body politic sheds light on the legal construction of public space and public time.
Multiple Ising Interfaces in Annulus and 2N-Sided Radial SLE
Authors: Feng Yu , Wu Hao , Yang Lu
Published: November 2023

We consider critical planar Ising model in annulus with alternating boundary conditions on the outer boundary and free boundary conditions in the inner boundary. As the size of the inner hole goes to zero, the event that all interfaces get close to the inner hole before they meet each other is a rare event. We prove that the law of the collection of the interfaces conditional on this rare event converges in total variation distance to the so-called $2N$-sided radial SLE$_{3}$, introduced by [ 16]. The proof relies crucially on an estimate for multiple chordal SLE. Suppose $(\gamma _{1}, \ldots , \gamma _{N})$ is chordal $N$-SLE$_{\kappa }$ with $\kappa \in (0,4]$ in the unit disc, and we consider the probability that all $N$ curves get close to the origin. We prove that the limit $\lim _{r\to 0+}r^{-A_{2N}}\mathbb{P}[\textrm{dist}(0,\gamma _{j})<r, 1\le j\le N]$ exists, where $A_{2N}$ is the so-called $2N$-arm exponents and $\textrm{dist}$ is Euclidean distance. We call the limit Green’s function for chordal $N$-SLE$_{\kappa }$. This estimate is a generalization of previous conclusions with $N=1$ and $N=2$ proved in [ 25, 26] and [ 32], respectively.
Modelling the dynamics and phenotypic consequences of tiller outgrowth and cessation in sorghum
Authors: Hammer Graeme L , McLean Greg , Kholová Jana , van Oosterom Erik
Published: November 2023

Tillering affects canopy leaf area, and hence crop growth via capture of light, water and nutrients. Depending on the season, variation in tillering can result in increased or decreased yield. Reduced tillering has been associated with water-saving and enhanced yield in water-limited conditions. The objective of this study was to develop a generic model of the dynamics of tillering in sorghum incorporating key genetic and environmental controls. The dynamic of tillering was defined in four key phases—pre-tillering, tiller emergence, cessation of tiller emergence and cessation of tiller growth. Tillering commenced at full expansion of leaf four and thereafter was synchronized with leaf appearance. The potential total number of tillers (TTN) was dependent on a genetic propensity to tiller and an index of assimilate availability dependent on the shoot source–sink balance. Cessation of tiller emergence could occur before TTN depending on extent of competition from neighbours. Subsequent cessation of growth of emerged tillers was related to the extent of internal competition for assimilate among plant organs, resulting in prediction of final fertile tiller number (FTN). The model predicted tillering dynamics well in an experiment with a range in plant density. Plausibility simulations of FTN conducted for diverse field conditions in the Australian sorghum belt reflected expectations. The model is able to predict FTN as an emergent property. Its utility to explore GxMxE crop adaptation landscapes, guide molecular discovery, provide a generic template for other cereals and link to advanced methods for enhancing genetic gain in crops were discussed.
Conditional Political Cycles in Africa: Myth or Reality?
Authors: Strong Christine O
Published: November 2023

This study tests for the presence of political cycles in Africa. Through an analysis encompassing data from 30 African nations over the period 1980–2020, we ask whether political incumbents in Africa rely on monetary and fiscal policy variables to improve their reelection prospects. In particular, we test for the existence of ‘conditional political cycles’, namely, we show that both government consumption and money growth go up during an election year, even when we account for critical institutional factors such as government attributes and political regimes. Our findings reveal a noticeable upswing in both government consumption and money growth during election years, a trend that holds consistent even after controlling for key institutional variables. Further exploration, however, unveils that this phenomenon is nuanced, particularly in the case of political monetary cycles; in particular, our analysis shows that when an African country is classified as a democracy during an election year, broad money falls. But although robust institutions can curtail the intensity of political monetary cycles, they do not exert a similar effect on fiscal variables. Finally, we test for the presence of ‘political credit cycles’ and find no empirical evidence that African incumbents manipulate credit markets to bolster their electoral outcomes.
Conceptualization Shapes Practice: Apostasy-Based Refugee Claims and International Human Rights Law
Authors: van Schaik Mirjam , Hillary Lynn
Published: November 2023

Freedom of religion or belief is guaranteed in international human rights law. Incorporating the right to apostasy as a fundamental aspect of religious freedom encounters challenges in different state practices. To study this phenomenon, this article explores the interaction of the conceptualization of the right to apostasy in international human rights law and in the context of apostasy-based refugee claims. The main argument of this article is that ambiguity in international human rights law exists on the concept of ‘apostasy’. This results in human rights protection gaps when states are unwilling to grant their inhabitants the right to apostasy. These gaps in protection are sometimes filled in by refugee law. However, in the specific context of apostasy-based refugee claims, this article identifies an issue with the identification and application of the concept of apostasy—and this conceptual ambiguity may lead to a lack of protection. Indeed, conceptualization shapes practice.
Navigating Asylum, Resettlement, and Integration: Syrian Refugees in France Beyond the Suffering Slot
Authors: Maddox Katherine
Published: November 2023

This article addresses the way that humanitarian conditioning continues in the lives of refugees after receiving asylum in Europe while also highlighting the perspective of refugees as they experience official and informal processes of integration. The ways the rhetoric of suffering must be invoked at various times throughout the asylum process are well documented. Less attention, however, has been paid to how asylum recipients in Europe continue to navigate these structures. Drawing on over 20 months of ethnographic research in Paris, France, this article explores the way that these resettled Syrian refugees encounter the rhetoric of suffering and other asylum structures in their everyday lives as an ongoing form of humanitarian conditioning. Through a focus on capabilities and aspirations, this article ultimately reveals how resettled refugees navigate this humanitarian conditioning to carve out lives and create new trajectories of integration in the wake of asylum in France.
Retroperitoneal spindle cell tumor: a case report
Authors: Kim Il D , Ahn Eun J , Yoon Jung-won , Choi Anna , Joo Sung H
Published: November 2023

Spindle cell tumors exhibit a relatively low occurrence rate and can manifest in various locations within the human body, including soft tissues and bones. The process of making a diagnosis is supported by conducting pathological and immunohistochemical tests. A 50-year-old female patient visited the hospital with abdominal pain that lasted about a week. Magnetic resonance imaging of the pelvis showed that this mass was independent and was not a lymph node mass, but a retroperitoneal sarcoma type mass. As part of the treatment, the mass was surgically excised, and a supracervical hysterectomy was carried out. The tumor was wrapped in a grayish-white capsule and showed a lobulating pattern. Retroperitoneal spindle cell tumors, particularly those occurring in abdominal soft tissues, are infrequently observed. Histopathological diagnosis is done in stages, and when cases are ambiguous, immunohistochemistry can provide valuable guidance in the right direction.
Evolution of the Spider Homeobox Gene Repertoire by Tandem and Whole Genome Duplication
Authors: Aase-Remedios Madeleine E , Janssen Ralf , Leite Daniel J , Sumner-Rooney Lauren , McGregor Alistair P
Published: November 2023

Gene duplication generates new genetic material that can contribute to the evolution of gene regulatory networks and phenotypes. Duplicated genes can undergo subfunctionalization to partition ancestral functions and/or neofunctionalization to assume a new function. We previously found there had been a whole genome duplication (WGD) in an ancestor of arachnopulmonates, the lineage including spiders and scorpions but excluding other arachnids like mites, ticks, and harvestmen. This WGD was evidenced by many duplicated homeobox genes, including two Hox clusters, in spiders. However, it was unclear which homeobox paralogues originated by WGD versus smaller-scale events such as tandem duplications. Understanding this is a key to determining the contribution of the WGD to arachnopulmonate genome evolution. Here we characterized the distribution of duplicated homeobox genes across eight chromosome-level spider genomes. We found that most duplicated homeobox genes in spiders are consistent with an origin by WGD. We also found two copies of conserved homeobox gene clusters, including the Hox, NK, HRO, Irx, and SINE clusters, in all eight species. Consistently, we observed one copy of each cluster was degenerated in terms of gene content and organization while the other remained more intact. Focussing on the NK cluster, we found evidence for regulatory subfunctionalization between the duplicated NK genes in the spider Parasteatoda tepidariorum compared to their single-copy orthologues in the harvestman Phalangium opilio. Our study provides new insights into the relative contributions of multiple modes of duplication to the homeobox gene repertoire during the evolution of spiders and the function of NK genes.
Opsin Gene Duplication in Lepidoptera: Retrotransposition, Sex Linkage, and Gene Expression
Authors: Mulhair Peter O , Crowley Liam , Boyes Douglas H , Lewis Owen T , Holland Peter W H
Published: November 2023

Color vision in insects is determined by signaling cascades, central to which are opsin proteins, resulting in sensitivity to light at different wavelengths. In certain insect groups, lineage-specific evolution of opsin genes, in terms of copy number, shifts in expression patterns, and functional amino acid substitutions, has resulted in changes in color vision with subsequent behavioral and niche adaptations. Lepidoptera are a fascinating model to address whether evolutionary change in opsin content and sequence evolution are associated with changes in vision phenotype. Until recently, the lack of high-quality genome data representing broad sampling across the lepidopteran phylogeny has greatly limited our ability to accurately address this question. Here, we annotate opsin genes in 219 lepidopteran genomes representing 33 families, reconstruct their evolutionary history, and analyze shifts in selective pressures and expression between genes and species. We discover 44 duplication events in opsin genes across ∼300 million years of lepidopteran evolution. While many duplication events are species or family specific, we find retention of an ancient long-wavelength-sensitive (LW) opsin duplication derived by retrotransposition within the speciose superfamily Noctuoidea (in the families Nolidae, Erebidae, and Noctuidae). This conserved LW retrogene shows life stage–specific expression suggesting visual sensitivities or other sensory functions specific to the early larval stage. This study provides a comprehensive order-wide view of opsin evolution across Lepidoptera, showcasing high rates of opsin duplications and changes in expression patterns.
BloodSpot 3.0: a database of gene and protein expression data in normal and malignant haematopoiesis
Authors: Gíslason Magnús H , Demircan Gül Sude , Prachar Marek , Furtwängler Benjamin , Schwaller Juerg , Schoof Erwin M , Porse Bo Torben , Rapin Nicolas , Bagger Frederik Otzen
Published: November 2023

BloodSpot is a specialised database integrating gene expression data from acute myeloid leukaemia (AML) patients related to blood cell development and maturation. The database and interface has helped numerous researchers and clinicians to quickly get an overview of gene expression patterns in healthy and malignant haematopoiesis. Here, we present an update to our framework that includes protein expression data of sorted single cells. With this update we also introduce datasets broadly spanning age groups, which many users have requested, with particular interest for researchers studying paediatric leukaemias. The backend of the database has been rewritten and migrated to a cloud-based environment to accommodate the growth, and provide a better user-experience for our many international users. Users can now enjoy faster transfer speeds and a more responsive interface. In conclusion, the continuing popularity of the database and emergence of new data modalities has prompted us to rewrite and futureproof the back-end, including paediatric centric views, as well as single cell protein data, allowing us to keep the database updated and relevant for the years to come. The database is freely available at www.bloodspot.eu.
SDRAP for annotating scrambled or rearranged genomes
Authors: Braun Jasper , Neme Rafik , Feng Yi , Landweber Laura F , Jonoska Nataša
Published: November 2023

Genomes sometimes undergo large-scale rearrangements. Programmed genome rearrangements in ciliates offer an extreme example, making them a compelling model system to study DNA rearrangements. Currently, available methods for genome annotation are not adequate for highly scrambled genomes. We present a theoretical framework and software implementation for the systematic extraction and analysis of DNA rearrangement annotations from pairs of genome assemblies corresponding to precursor and product versions. The software makes no assumptions about the structure of the rearrangements, and permits the user to select parameters to suit the data. Compared to previous approaches, this work achieves more complete precursor-product mappings, allows for full transparency and reproducibility, and can be adapted to genomic data from different sources.
Monitoring response to a clinically relevant IDH inhibitor in glioma—Hyperpolarized 13C magnetic resonance spectroscopy approaches
Authors: Hong Donghyun , Kim Yaewon , Mushti Chandrasekhar , Minami Noriaki , Wu Jing , Cherukuri Murali Krishna , Swenson Rolf E , Vigneron Daniel B , Ronen Sabrina M
Published: November 2023

Background

Mutant isocitrate dehydrogenase (IDHmut) catalyzes 2-hydroxyglutarate (2HG) production and is considered a therapeutic target for IDHmut tumors. However, response is mostly associated with inhibition of tumor growth. Response assessment via anatomic imaging is therefore challenging. Our goal was to directly detect IDHmut inhibition using a new hyperpolarized (HP) 13C magnetic resonance spectroscopy-based approach to noninvasively assess α-ketoglutarate (αKG) metabolism to 2HG and glutamate.

Methods

We studied IDHmut-expressing normal human astrocyte (NHAIDH1mut) cells and rats with BT257 tumors, and assessed response to the IDHmut inhibitor BAY-1436032 (n ≥ 4). We developed a new 13C Echo Planar Spectroscopic Imaging sequence with an optimized RF pulse to monitor the fate of HP [1-13C]αKG and [5-12C,1-13C]αKG with a 2.5 × 2.5 × 8 mm3 spatial resolution.

Results

Cell studies confirmed that BAY-1436032-treatment leads to a drop in HP 2HG and an increase in HP glutamate detectable with both HP substrates. Data using HP [5-12C,1-13C]αKG also demonstrated that its conversion to 2HG is detectable without the proximal 1.1% natural abundance [5-13C]αKG signal. In vivo studies showed that glutamate is produced in normal brains but no 2HG is detectable. In tumor-bearing rats, we detected the production of both 2HG and glutamate, and BAY-1436032-treatment led to a drop in 2HG and an increase in glutamate. Using HP [5-12C,1-13C]αKG we detected metabolism with an signal-to-noise ratio of 23 for 2HG and 17 for glutamate.

Conclusions

Our findings point to the clinical potential of HP αKG, which recently received FDA investigational new drug approval for research, for noninvasive localized imaging of IDHmut status.
Efficacy of Messenger RNA–1273 Against Severe Acute Respiratory Syndrome Coronavirus 2 Acquisition in Young Adults From March to December 2021
Authors: Stephenson Kathryn E , Marcelin Jasmine R , Pettifor Audrey E , Janes Holly , Brown Elizabeth , Neradilek Moni , Yen Catherine , Andriesen Jessica , Grunenberg Nicole , Espy Nicole , Trahey Meg , Fischer Rebecca S B , DeSouza Christopher A , Shisler Joanna L , Connick Elizabeth , Houpt Eric R , Chu Helen Y , McCulloh Russel J , Becker-Dreps Sylvia , Vielot Nadja A , Kalbaugh Corey A , Cherabuddi Kartik , Krueger Karen M , Rosenberg Molly , Greenberg Richard N , Joaquin Arnel , Immergluck Lilly Cheng , Corey Lawrence , Kublin James G
Published: November 2023

Background

The efficacy of messenger RNA (mRNA)–1273 against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is not well defined, particularly among young adults.

Methods

Adults aged 18–29 years with no known history of SARS-CoV-2 infection or prior vaccination for coronavirus disease 2019 (COVID-19) were recruited from 44 US sites from 24 March to 13 September 2021 and randomized 1:1 to immediate vaccination (receipt of 2 doses of mRNA-1273 vaccine at months 0 and 1) or the standard of care (receipt of COVID-19 vaccine). Randomized participants were followed up for SARS-CoV-2 infection measured by nasal swab testing and symptomatic COVID-19 measured by nasal swab testing plus symptom assessment and assessed for the primary efficacy outcome. A vaccine-declined observational group was also recruited from 16 June to 8 November 2021 and followed up for SARS-CoV-2 infection as specified for the randomized participants.

Results

The study enrolled 1149 in the randomized arms and 311 in the vaccine-declined group and collected >122 000 nasal swab samples. Based on randomized participants, the efficacy of 2 doses of mRNA-1273 vaccine against SARS-CoV-2 infection was 52.6% (95% confidence interval, −14.1% to 80.3%), with the majority of infections due to the Delta variant. Vaccine efficacy against symptomatic COVID-19 was 71.0% (95% confidence interval, −9.5% to 92.3%). Precision was limited owing to curtailed study enrollment and off-study vaccination censoring. The incidence of SARS-CoV-2 infection in the vaccine-declined group was 1.8 times higher than in the standard-of-care group.

Conclusions

mRNA-1273 vaccination reduced the incidence of SARS-CoV-2 infection from March to September 2021, but vaccination was only one factor influencing risk.

Clinical Trials Registration

NCT04811664.
Clinical Characteristics and Outcomes of Patients With Mpox Who Received Tecovirimat in a New York City Health System
Authors: Vo Christopher , Zomorodi Rustin , Silvera Richard , Bartram Logan , Lugo Luz Amarilis , Kojic Erna , Urbina Antonio , Aberg Judith , Sigel Keith , Chasan Rachel , Patel Gopi
Published: November 2023

Background

The 2022 global mpox outbreak was notable for transmission between persons outside of travel and zoonotic exposures and primarily through intimate contact. An understanding of the presentation of mpox in people with human immunodeficiency virus (HIV) and other immunocompromising conditions and knowledge of the efficacy of tecovirimat continue to evolve.

Methods

This retrospective study describes clinical features and outcomes of persons with mpox who received tecovirimat. Data were obtained via medical record review of patients prescribed tecovirimat in a health system in New York City during the height of the outbreak in 2022.

Results

One hundred thirty people received tecovirimat between 1 July and 1 October 2022. People with HIV (n = 80) experienced similar rates of recovery, bacterial superinfections, and hospitalization compared to patients without immunocompromising conditions. Individuals determined to be severely immunocompromised (n = 14) had a higher risk of hospitalization than those without severe immunocompromise (cohort inclusive of those with well-controlled HIV, excluding those without virologic suppression, n = 101): 50% versus 9% (P < .001). Hospitalized patients (n = 18 [13% of total]) were primarily admitted for bacterial superinfections (44.4%), with a median hospital stay of 4 days. Of those who completed follow-up (n = 85 [66%]), 97% had recovery of lesions at time of posttreatment assessment. Tecovirimat was well tolerated; there were no reported severe adverse events attributed to therapy.

Conclusions

There were no significant differences in outcomes between people with HIV when evaluated as a whole and patients without immunocompromising conditions. However, mpox infection was associated with higher rates of hospitalization in those with severe immunocompromise, including patients with HIV/AIDS. Treatment with tecovirimat was well tolerated.

Key Points: In our mpox cohort, people with HIV had similar rates of recovery and complications as those without HIV or other immunocompromising conditions. Severe immunocompromise was associated with a higher hospitalization rate. Tecovirimat was well tolerated, with minimal side effects.
Italian Opera in Late Eighteenth-Century London
Authors: Milhous Judith , Dideriksen Gabridla , Hume Robert D
Published: November 2023

Following on from the volume on the King’s Theatre, Haymarket (published by OUP in 1995), this interdisciplinary study of opera and ballet now turns to London’s Pantheon Opera during the period 1789-98. The discovery of six cartons of previously unknown manuscripts in the possession of the Duke of Bedford makes possible the rewriting of a hitherto dark and little understood chapter in the history of opera in London. The King’s Theatre, Haymarket, burnt down in 1789. To replace it, the fifth Duke of Bedford and the Marquis of Salisbury secretly backed a new opera company, to be housed in the Pantheon, an elegant exhibition hall hastily converted to house the venture. Part 1 of this book tells a tale of intrigue, blackmail, bankruptcy, arson, and high-society infighting against a background of exalted artistic aspirations and genuine love of opera. The Pantheon tried to engage Mozart to compete against Haydn, and hired some of the most notable singers and dancers in Europe. Mismanagement led to huge losses, and the theatre burnt in highly suspicious circumstances in 1792. The backers tried to impose an artistic vision and financial controls on the management of the rebuilt King’s Theatre, Haymarket, when opera returned there in 1793, but by 1795 their failure was evident. The second part of the book is a detailed analysis of the opera and ballet repertoire, personnel, management, costumes, staging practices, and finances of the company, based on the Bedford archive and a wealth of hitherto unused sources. What emerges is the fullest operational analysis ever published of any pre-nineteenth-century English theatre or opera company.
The Fire and the Little Haymarket Season, I79I-92
Authors: Milhous Judith , Dideriksen Gabridla , Hume Robert D
Published: November 2023

The present chapter moves from the reorganization at the end of the Pan the ones disastrous first season to the termination of the venture in the summer of 1792. The season of 1791--92 itself is virtually an epilogue, con ducted at the Little Haymarket after the Pantheon burnt down just four nights into the new season. The only reason that Italian opera did not instantly return to the King’s Theatre, Haymarket, in January 1792 was that William Taylor had rented it out to the Drury Lane actors while their theatre was being rebuilt.
The Ballet
Authors: Milhous Judith , Dideriksen Gabridla , Hume Robert D
Published: November 2023

The Nature of the Pantheon ballet company and the expectations it had to meet were established by the extraordinary changes that had occurred in the world of dance in London during the preceding decade. Ballet had become an increasingly important part of the opera company’s offerings during the 1770s, and large salaries were paid to obtain Continental stars, but dance made little effort to tell stories in detail.
African Countries
Authors: Harding Jeremy
Published: November 2023

Introducing a collection of African oral literature in 1988, the Nigerian polemicist and poet Chinweizu warned against any approach to the subject that reinforces ‘an Africa which European racism is flattered to imagine’. Instead, he suggests that ‘we [Africans] should listen to Africans talking to Africans about the world’. Writers like Chinweizu are concerned that the encounter between Africa and Europe is neither innocent nor symmetrical: slavery and the colonial past tilt this uneasy exchange in favour of non Africans. As outsiders, Europeans face a central problem when considering contemporary African writing: to think of it sui genms is to condescend to it; to compare it with other traditions-English, American, Indian, or French-is to disregard its specificity.
Arab Countries
Authors: Irwin Robert
Published: November 2023

The Naksa, or Israeli military victory over Egypt, Syria, and Jordan in 1967, was a major event in Arabic literature. The reality of disaster once again exposed the tawdry rhetoric of those who had led the Arabs to defeat and many now questioned the promises of the region’s nationalist and socialist leaders.
Australia
Authors: Craven Peter
Published: November 2023

There is no real substance in the belief that Australian writing only got going when national publishing began to sever itself from the essentially derivative, post-colonial, British variety in the 1970s. Australia’s three most formidable writers of fiction (four if one includes the short-story writer and memoirist Hal Porter) were active long before that date: Patrick White (1912-90) wrote three of his most ambitious novels in the 1950s, and Martin Boyd’s (1893-1972) Langton Quartet was largely composed during this same period. Christina Stead (1902-83) wrote her masterpiece in the 1940s though it was not discovered by her compatriots until 1966.
Brazil
Authors: Gledson John
Published: November 2023

Brazilian literature since 1960 has been dominated by political and social changes of great depth and, at times, violence. The military coup of 1964, and the subsequent ‘coup within a coup’ in 1968, which brought the pro-American Right to power, extended the practice of torture of political dissidents, and instituted severe censorship, delivering a traumatic shock to intellectuals as well as many others; and the ‘economic miracle’ of the late 1960s and early 1970s led to a sudden and massive urbanization, and the growth, in the south of the country above all, of a huge working class.
Czech Republic And Slovakia
Authors: Hájek Igor
Published: November 2023

When, in late December 1958, two weeks after its publication, Josef Škvorecký’s (b. 1924) first novel, The Cowards, was withdrawn from the bookshops and its author banned, it looked like the end of an all too brief period of grace in Czechoslovakia. Over the previous two years a remarkable thaw had occurred after the Stalinist freeze, enlivening both the Czech and the Slovak cultural scenes. In literature, quite a few new names had been introduced, some of whom were to stay in the forefront of interest for the next forty years: notably Miroslav Holub (b. 1923), Ivan Klima (b. 1931), and Milan Kundera (b. 1929).
England
Authors: Wood James
Published: November 2023

English writing in the 1960s and 1970s resembles a Victorian house whose windows have all been smashed: a solid structure timidly vandalized. Tom between nostalgia and rebellion, tradition and experiment, English writing of this period often lapsed into symmetrical failures: its Victorian solidity seems uninspiring and its experimentation only wanly successful. The Dickensian robustness of Angus Wilson’s (1913-82) novels, for instance, is not robust enough; but neither is his attempt to modernize or Post-Modernize the Dickensian tradition; Iris Murdoch’s (b. 1919) twentieth-century version of Tolstoyan realism has not been realized, nor could it have been, perhaps; but her philosophical dance around that realism has not been springy enough, and has attracted no partners; A. S. Byatt’s (b. 1936) desire to write what she calls ‘self-conscious realism’ seems too self-conscious and not real enough.
France
Authors: Taylor John
Published: November 2023

As the twentieth century draws to a close, French literature seems in a confusing state. The lamenters most often attribute this to the absence of ‘great writers’ who, having captured the international limelight, would compensate for the deaths of, say, Albert Camus (1913-60), Andre Breton (1896-1966), Francois Mauriac (1885-1970), Andre Malraux (1910-76), Jean-Paul Sartre (1905-80), and Simone de Beauvoir (1908-86). Other commentators add that no literary avant-gardes have stirred up world-wide excitement as intense as that created by the surrealists before the Second World War, by the existentialists after that war, or by the practitioners of the New Novel during the 1950s and early 1960s.
German-Speaking Countries
Authors: Williams Rhys
Published: November 2023

The writing covered in this chapter comes from four European states: East and West Germany, Austria, and Switzerland. Rather than try and cover it in national terms, I shall point up stylistic trends and themes that have been widely shared since 1960 among writers in the German language.
India
Authors: Cronin Richard
Published: November 2023

V. S. Naipaul pointed out in 1964 that Indian literature in English had ceased to exist: ‘The only writer who, while working from within the society, is yet able to impose on it a vision which is an acceptable type of comment, is R. Prawer Jhabvala. And she is European.’ He ought to have been right. That Indians had chosen to write in English must then have seemed simply a historical accident, a product of the Raj that would not long survive its passing. The government of India had committed itself to Hindi as the national language, and those who wrote in one of India’s twelve other major languages felt themselves engaged in a struggle against, not the pretensions of English, but the encroachments of Hindi. English remained as the first language of only one tiny and sadly disadvantaged Indian community, the Anglo-Indians.
Israel
Authors: Cheyette Bryan
Published: November 2023

In a typical contribution to the Hebrew Writers’ Association conference in 1968, Hayim Hazaz (1893-1972), a doyen of Hebrew literature, voiced his dissatisfaction with contemporary Israeli writing: ‘It goes without saying that Israeli literature should be a responsible literature ... Above all, books shouldn’t be mere books, writers shouldn’t be anonymous, shouldn’t be lukewarm, comfortable people ... they should be heroes of a national struggle, of a class-war, of culture; people of conviction and responsibility.’ Hazaz’s own contrived, overly rhetorical fiction, especially his novels of ideas, often bears out this programmatic statement, and contrasts unfavourably with the enigmatic modernism of his contemporary S. Y. Agnon (1888-1970). Agnon won the Nobel Prize for literature in 1966 for an oeuvre which, in its use of parables and its pervasive if unexplained Angst, is closely akin to Kafka. Much of Agnon’s fiction was published posthumously and, because of this, has continued to influence a good deal of contemporary Israeli literature.
Japan
Authors: Morris Mark
Published: November 2023

The most respected writer at work in Japan today is Oe Kenzaburo* (b. 1935), who in 1994 received the Nobel Prize for literature. Since the late 1950s, as part of a generation of talented writer-intellectuals, he has produced millions of words in the form of fiction, criticism, political essays, journalism, and several genres yet to be classified. Still this side of 60, Oe has hinted strongly all the same that he will one day probably stop writing fiction altogether..
Poland
Authors: Hyde George , Powaga With Wieslaw
Published: November 2023

The fate of writing in Poland has traditionally been to articulate and shape the national consciousness through long periods of oppression and suppression, from the first partition in 1772 to the short-lived Polish Republic after 1918, the horrors of the German invasion in 1939 and the Second World War, and the Communist take-over that followed. Communism, hopelessly inefficient and in the end bereft of all effective authority, stopped the cultural clock and made it possible to resurrect the myths and archetypes of the Romantic and modernist eras, which were deeply intertwined with the sense of national identity, especially in its revolutionary guise. The Communists handled this heritage with care, and tried to turn it to their own political and quasi-political ends.
Portugal
Authors: Guterres Maria
Published: November 2023

From 1925 to 1974 Portugal was a Fascist dictatorship, ruled first by Antonio de Oliveira Salazar and then, after Salazar had a stroke in 1968, by Marcelo Caetano, who essentially maintained the status quo. Salazar’s was a repressive and brutal regime, which crushed all opposition in violent fashion. Writers could be penalized or imprisoned if their work was considered to be of a subversive nature.