bluuebunny/crossref_metadata_2025 huggingface dataset:
Competition for DNA binding between the genome protector replication protein A and the genome modifying APOBEC3 single-stranded DNA deaminases
Authors: Wong Lai , Sami Alina , Chelico Linda
Published: November 2022

The human APOBEC family of eleven cytosine deaminases use RNA and single-stranded DNA (ssDNA) as substrates to deaminate cytosine to uracil. This deamination event has roles in lipid metabolism by altering mRNA coding, adaptive immunity by causing evolution of antibody genes, and innate immunity through inactivation of viral genomes. These benefits come at a cost where some family members, primarily from the APOBEC3 subfamily (APOBEC3A-H, excluding E), can cause off-target deaminations of cytosine to form uracil on transiently single-stranded genomic DNA, which induces mutations that are associated with cancer evolution. Since uracil is only promutagenic, the mutations observed in cancer genomes originate only when uracil is not removed by uracil DNA glycosylase (UNG) or when the UNG-induced abasic site is erroneously repaired. However, when ssDNA is present, replication protein A (RPA) binds and protects the DNA from nucleases or recruits DNA repair proteins, such as UNG. Thus, APOBEC enzymes must compete with RPA to access their substrate. Certain APOBEC enzymes can displace RPA, bind and scan ssDNA efficiently to search for cytosines, and can become highly overexpressed in tumor cells. Depending on the DNA replication conditions and DNA structure, RPA can either be in excess or deficient. Here we discuss the interplay between these factors and how despite RPA, multiple cancer genomes have a mutation bias at cytosines indicative of APOBEC activity.
Podcasts and Social Work
Authors: Singer Jonathan B. , Gomez Astrid J.
Published: November 2022

A podcast is a series of audio files that users can subscribe to, download, and listen to. Although social workers have traditionally been late adopters to technology, the first social work podcast was published on 12 January 2007, less than eighteen months after Apple added a podcast category to its iTunes store. Podcasts are used in social work education, as a study resource for licensure exams, as a tool for learning about best practices, and to amplify traditionally marginalized or silenced voices. Most scholarship on podcasting comes from allied disciplines outside of social work, with a focus on education, distance learning, and professional development.
Utilitarianism
Authors: Eggleston Ben
Published: November 2022

Utilitarianism is a moral theory that judges actions based on their consequences—specifically, based on their effects on well-being. Most utilitarians take well-being to be constituted largely by happiness, and historically utilitarianism has been known by the phrase “the greatest happiness for the greatest number.” As the second part of this phrase suggests, utilitarianism is concerned with the well-being of all people, not just the person who performs an action or the people most directly affected; in fact, because nonhuman animals can also experience pleasure and pain, their well-being also counts in the moral assessment of actions, according to most utilitarians. Thus, a simple statement of the utilitarian view is that an action is right if and only if it brings about at least as much overall well-being as any action the agent could have performed instead. Controversially, this means that, according to utilitarianism, in principle, any type of action—such as lying, stealing, or even killing someone—could conceivably be condoned by utilitarianism if, in the particular circumstances, it would produce at least as much overall well-being as anything else the agent could have done. Utilitarians tend to condemn such actions because they tend to reduce overall well-being, but they hold that the impact on well-being is what makes such actions wrong—not their being prohibited by conventionally accepted moral rules, the commands of a deity, principles of human rights, or other considerations that can conflict with the fundamental moral goal of maximizing overall well-being. In addition to the straightforward form of utilitarianism summarized above, there are other forms of the view, such as ones that judge acts not in terms of their direct effects on overall well-being, but in terms of their compliance with rules whose general acceptance tends to promote well-being. All forms of the view, however, hold that the moral assessment of acts derives directly or indirectly from the fundamental utilitarian moral criterion of the maximization of overall well-being.
Giovanni Caboto (John Cabot)
Authors: Bruscoli Francesco Guidi
Published: November 2022

Giovanni Caboto (John Cabot, b. c. 1450–d. c. 1500) was an Italian navigator credited to be the first European to set foot in North America after the Norse, during an expedition of 1497 carried out under the English flag. Little is known about his origins, although he certainly took up Venetian citizenship, implying origin elsewhere. He was known as Zuan Chabotto in Venice, and he presented himself as a Venetian when he moved to England. As early as the late sixteenth/early seventeenth century, Richard Hakluyt and Samuel Purchas praised Caboto’s pioneering “discoveries” (despite some confusion between the role of Giovanni and that of his son). But it was especially from 1897 (the 400th anniversary of his landing) that—following new archival discoveries—his achievement as an explorer was celebrated. Until then his role had been overshadowed by that of his son Sebastian, who in part because of the influence of Sebastian’s own accounts, had been credited with being in charge of the voyages. It was in particular Henry Harrisse, in John Cabot, the Discoverer of North America, and Sebastian his Son: A Chapter of the Maritime History of England under the Tudors, 1496–1557 (London: Stevens, 1896), who revived the figure of Giovanni, while at the same time lambasting Sebastiano as an impostor. In the same period, more or less co-incident with the 400th anniversary of Columbus’s 1492 voyage, general interest in voyages of exploration revived also in Italy, although studies on Caboto mainly focused on his origin. In the 1940s new documentary discoveries threw some light on Caboto’s years both in Spain and in Venice. In the 1950s the discovery of John Day’s letter in the Simancas archive stimulated a new wave of studies, for the letter hints at a previously unknown voyage of 1496, provides many technical details concerning the 1497 voyage (thus opening debate on the latitude of the landing), and alludes to earlier discoveries. The most important study, still a crucial reference for studies on Caboto, is James A. Williamson’s The Cabot Voyages and Bristol Discovery under Henry VII (Cambridge: Cambridge University Press/Hakluyt Society, 2nd Series, vol. 120, 1962). For the 500th anniversary of the landing, in 1997, several conferences were organized, in many cases leading to the publication of proceedings. The most relevant recent advances, however, have been made within the framework of the Cabot Project, based at the University of Bristol. Following unpublished leads left behind by deceased scholar Alwyn Ruddock, Evan Jones and others have proposed new hypotheses, and uncovered the first known financiers of the 1497 voyage.
Thomas Babington Macaulay
Authors: Adams Edward
Published: November 2022

Thomas Babington Macaulay (b. 1800–d. 1859) accumulated an unprecedented series of successes—both in sales and critical acclaim—as an English poet, essayist, orator, and, most triumphantly, historian. In addition, he presided over important though controversial reforms in education and law in India and served as a leading politician at home in Parliament and an influential figure abroad for the British East India Company. Like his contemporary and antithesis Thomas Carlyle, to whom he is often contrasted, Macaulay has suffered an equally remarkable descent. In the twenty-first century, much of the shrinking scholarly attention has turned frankly judgmental, especially regarding his role in first helping build and then loudly celebrating a liberal capitalist Britain and British Empire as the then acme (in his eyes) of Western progressive civilization. The question of the reasons for Macaulay’s lifetime successes and posthumous reversals runs through much Macaulay scholarship. The 20th-century turn against grand or totalizing historical narratives, particularly of progress, has produced a context in which Macaulay’s championing of this narrative, indeed his nationalist embodiment of it, has steadily worked against not for him. Considerable scholarly work, moreover, has explored his famously clear, highly rhetorical, and smoothly narrative style—popularizing qualities that originally elevated his fame but soon helped consign him to a sub-canonical status. As his career developed from his essays (mostly novella-length biographies of English literary and political figures), his influential speeches (above all, in support of the First Reform Bill), and his popular historical ballads and thence toward his systematic planning for a long epic history, Macaulay’s aspiration was to join the select club of great narrative historians. The ancient Greek Thucydides emerged as his favorite, and Macaulay seemed poised to become the English Thucydides of the Napoleonic Wars abroad and political reform at home—for both of which he had been an observer and participant. Instead, he designed a far more ambitious project. His History of England, whose sales broke records in England and then America, would sweep from the 17th-century Glorious Revolution to the 19th-century Reform Bill. Such Humean or Gibbonian grandeur combined with cutting-edge novelistic detailing enabled by his archival work proved impossibly ambitious. But here, too, his history’s unfinished state and the story of its evolution have become subjects of fascinating inquiry into Macaulay’s central lifework.
Simpson's Paradox in Psychology
Authors: Mangalam Madhur
Published: November 2022

Simpson’s paradox—also called the reversal paradox and amalgamation paradox—is a statistical phenomenon in which an apparent paradox arises because aggregate data at the group level (or at the level of a set of groups) can support a conclusion that is either not observed or is opposite from that suggested by the same data before aggregation at the individual level (or at the level of groups). The paradox is resolved when the data are stratified by groups in the statistical modeling. An intuitive example of Simpson’s paradox is the correlation between typing speed and typos. At the group level, the correlation is negative—experienced typists type faster and make fewer typos. However, at the individual level, the correlation is positive—the faster an individual types, the greater the number of typos he/she makes. Thus, it would be fallacious to conclude that the relationship between typing speed and typos observed at the group level holds at the individual level. Simpson’s paradox is especially problematic in physical and social sciences, where statistical trends in point data observed at the group level are often fallaciously used to derive inferences about individuals, or relatively less often, the other way round. Hence, equivalence at the group and individual levels must be explicitly tested.
Corporate Taxation and International Financial Integration: U.S. evidence from a consolidated perspective
Authors: Bénétrix Agustín , Sanchez Pacheco André
Published: November 2022

We document a robust relation between corporate tax differentials and US international financial integration (IFI). While this is the case for traditional IFI based on cross-border positions, the positive link also emerges for its larger consolidated-by-nationality version. The gap between these IFI measures, the key outcome variable in our analysis, exhibits a strong positive correlation with tax differentials too. This is in part due to consolidated assets of multinational enterprises being more strongly correlated with tax differentials than their cross-border counterpart. We interpret this as indirect evidence of US multinationals taking advantage of tax differentials in ways that go beyond what is captured by traditional Balance of Payments procedures.

JEL: F36, F21, F23, H87.
Mantle-Derived Cargo vs Liquid Line of Descent: Reconstructing the P–T–fO2–X Path of the Udachnaya–East Kimberlite Melts during Ascent in the Siberian Sub-Cratonic Lithosphere
Authors: Casetta Federico , Asenbaum Rene , Ashchepkov Igor , Abart Rainer , Ntaflos Theodoros
Published: November 2022

Disentangling the physico-chemical evolution of the melts that give rise to kimberlites during their genesis, ascent through the sub-cratonic lithosphere and emplacement in the crust is challenging. This is because the extensive entrainment and assimilation of, and reaction with, mantle-derived material makes kimberlites mixtures of xenocrystic, magmatic components and alteration minerals, rarely preserving evidence of their original melt composition. Here, a detailed textural and compositional study of coherent and volcaniclastic kimberlite units from the Udachnaya–East pipe (Siberian craton) was performed to reconstruct the pressure–temperature–oxygen fugacity-compositional (P–T–fO2–X) path of kimberlite melts during their ascent through the sub-cratonic lithosphere. Routine and high-precision electron microprobe analyses of olivine, phlogopite and Fe–Ti oxides enabled to discriminate the mantle-derived cargo from the magmatic components, and thus make inferences on the liquid line of descent (LLD) of proto-kimberlite to kimberlite melts. Most of the olivine cores in Udachnaya–East kimberlite are xenocrystic and record conditions of last equilibration in the Siberian sub-cratonic lithospheric mantle at T–P ranging from 812–1227°C at 3.1–5.4 GPa, to 871–1170°C at 4.6–7.0 GPa, depending on the chosen model geotherm (35 mW/m2 vs 40 mW/m2). Based on their Ni, Cr, Mn, Al and P vs Mg/Fe systematics, olivine core populations were associated to the sheared, granular garnet-bearing or spinel-bearing cratonic peridotites. The occurrence of olivine Internal Zones (I) having the same composition as Fe-rich cores, as well as rare mantle-derived xenocrystic cores of phlogopite, bear witness of mantle metasomatism preceding kimberlite ascent. The assimilation of mantle material by initially H2O- and P-rich proto-kimberlitic melts is recorded by the cotectic formation of magmatic olivine Internal Zones (II) and phlogopite Internal Zones around resorbed xenocrystic cores. The LLD then evolved by inducing cotectic precipitation of olivine, phlogopite rims and Cr-spinel at P of 1.5–3.0 GPa, T of 1120–1250°C and fO2 from −2.8 to −1.6 ΔFMQ. Ilmenite–magnetite pairs in the groundmass record the later conditions of crystallization that occurred at P of ~1.0 GPa, T from 1133°C down to 1000°C and fO2 of +0.3 to +0.9 ΔFMQ. These results confirm the progressive oxidation of the melt that finally led to the formation of calcite, apatite and Mg-rich olivine and phlogopite rinds. The F-enrichment of phlogopite rinds reflects a late decrease of the H2O/CO2 activity of the melt that evolved toward alkali-carbonated composition. Our results showed that the crystal cargo of kimberlites can be used to track all processes acting in between the melt-rock reactions in the mantle and the emplacement in the crust.
Genetic variability, biomass parameters, elemental composition and energy content of the non-indigenous hydromedusa Craspedacusta sowerbii in North America
Authors: Lüskow Florian , Boersma Maarten , López-González Pablo J , Pakhomov Evgeny A
Published: November 2022

The freshwater hydrozoan Craspedacusta sowerbii was introduced to habitats around the world and they spread into the surrounding water bodies thereafter. Despite an increase in reported observations, little is known about its genetics, physiology and ecology. The present study examined the organic content, elemental composition and energy content of jellyfish collected in Canada and the USA and compared these metrics with their marine counterparts and other co-occurring zooplankton. Specimens from the sampled lakes were sexed and molecularly characterized. Molecular, stoichiometric and energetic information is critical in determining distribution pathways and trophic connections. Molecular analyses showed two closely related sequences in North America, one shared by the Canadian and Japanese specimens, while another one is widely present across the Americas. Organic and all elemental contents were higher compared to marine jellyfish species. Estimated energy content of C. sowerbii was 20–27 kJ g DW−1, which is 2-fold higher than for marine hydrozoans and compared well with cladocerans, copepods and rotifers. Estimated C/P values indicated that cladocerans and copepods are suitable prey for C. sowerbii and that jellyfish may compete with juvenile fish to fulfill similar nutrient demands. Freshwater jellyfish were stoichiometrically and energetically different from marine hydrozoans, indicating higher importance in freshwater food webs than previously thought.
Phytochrome B mediates dim-light-reduced insect resistance by promoting the ethylene pathway in rice
Authors: Huang Jie , Qiu Ze-Yu , He Jun , Xu Hao-Sen , Wang Kan , Du Hua-Ying , Gao Dong , Zhao Wei-Ning , Sun Quan-Guang , Wang Yong-Sheng , Wen Pei-Zheng , Li Qi , Dong Xiao-Ou , Xie Xian-Zhi , Jiang Ling , Wang Hai-Yang , Liu Yu-Qiang , Wan Jian-Min
Published: November 2022

Increasing planting density is one of the most effective ways to improve crop yield. However, one major factor that limits crop planting density is the weakened immunity of plants to pathogens and insects caused by dim light (DL) under shade conditions. The molecular mechanism underlying how DL compromises plant immunity remains unclear. Here, we report that DL reduces rice (Oryza sativa) resistance against brown planthopper (BPH; Nilaparvata lugens) by elevating ethylene (ET) biosynthesis and signaling in a Phytochrome B (OsPHYB)-dependent manner. The DL-reduced BPH resistance is relieved in osphyB mutants, but aggravated in OsPHYB overexpressing plants. Further, we found that DL reduces the nuclear accumulation of OsphyB, thus alleviating Phytochrome Interacting Factor Like14 (OsPIL14) degradation, consequently leading to the up-regulation of 1-Aminocyclopropane-1-Carboxylate Oxidase1 (OsACO1) and an increase in ET levels. In addition, we found that nuclear OsphyB stabilizes Ethylene Insensitive Like2 (OsEIL2) by competitively interacting with EIN3 Binding F-Box Protein (OsEBF1) to enhance ET signaling in rice, which contrasts with previous findings that phyB blocks ET signaling by facilitating Ethylene Insensitive3 (EIN3) degradation in other plant species. Thus, enhanced ET biosynthesis and signaling reduces BPH resistance under DL conditions. Our findings provide insights into the molecular mechanism of the light-regulated ET pathway and host-insect interactions and potential strategies for sustainable insect management.
Structure-based engineering of minimal proline dehydrogenase domains for inhibitor discovery
Authors: Bogner Alexandra N , Ji Juan , Tanner John J
Published: November 2022

Proline dehydrogenase (PRODH) catalyzes the FAD-dependent oxidation of l-proline to Δ1-pyrroline-5-carboxylate and is a target for inhibitor discovery because of its importance in cancer cell metabolism. Because human PRODH is challenging to purify, the PRODH domains of the bacterial bifunctional enzyme proline utilization A (PutA) have been used for inhibitor development. These systems have limitations due to large polypeptide chain length, conformational flexibility and the presence of domains unrelated to PRODH activity. Herein, we report the engineering of minimal PRODH domains for inhibitor discovery. The best designs contain one-third of the 1233-residue PutA from Sinorhizobium meliloti and include a linker that replaces the PutA α-domain. The minimal PRODHs exhibit near wild-type enzymatic activity and are susceptible to known inhibitors and inactivators. Crystal structures of minimal PRODHs inhibited by S-(−)-tetrahydro-2-furoic acid and 2-(furan-2-yl)acetic acid were determined at 1.23 and 1.72 Å resolution. Minimal PRODHs should be useful in chemical probe discovery.
On weak compactness in projective tensor products
Authors: Rodríguez Josè
Published: November 2022

We study the property of being strongly weakly compactly generated (and some relatives) in projective tensor products of Banach spaces. Our main result is as follows. Let $1 \lt p,q \lt \infty$ be such that $1/p+1/q\geq 1$. Let X (resp., Y) be a Banach space with a countable unconditional finite-dimensional Schauder decomposition having a disjoint lower p-estimate (resp., q-estimate). If X and Y are strongly weakly compactly generated, then so is their projective tensor product $X {\widehat{\otimes}_\pi} Y$.
Therapeutic consequences in patients with both inflammatory rheumatic diseases and multiple sclerosis
Authors: Letarouilly Jean-Guillaume , Vermersch Patrick , Flipo René-Marc
Published: November 2022

Dealing with patients with both multiple sclerosis (MS) and inflammatory rheumatic disorders (IRDs) is not uncommon for a rheumatologist, as there is a statistical association between SpA and MS. As several CNS demyelinating events have been reported in patients treated with TNF inhibitor (TNFi), the pre-existing demyelinating disease was considered a contraindication for TNFi. However, this contraindication is mainly based on a randomized controlled trial in MS and not on large epidemiological studies. According to the last epidemiological studies, TNFi might not be an inducer of MS. Moreover, there are no clear recommendations on the use of the other DMARDs in patients suffering from an IRD and MS. In this review, we summarize the link between MS and IRDs and the impact of DMARDs on MS, especially TNFi. We also look at the impact of disease-modifying drugs for adults with MS and IRDs.
Cross-Modality Evidence for Reduced Choice History Biases in Psychosis-Prone Individuals
Authors: Eckert Anna-Lena , Gounitski Yael , Guggenmos Matthias , Sterzer Philipp
Published: November 2022

Objectives

Predictive processing posits that perception emerges from inferential processes within a hierarchical cortical system. Alterations of these processes may result in psychotic experiences, such as hallucinations and delusions. Central to the predictive processing account of psychosis is the notion of aberrant weights attributed to prior information and sensory input. Based on the notion that previous perceptual choices represent a relevant source of prior information, we here asked whether the propensity towards psychotic experiences may be related to altered choice history biases in perceptual decision-making.

Methods

We investigated the relationship between choice history biases in perceptual decision-making and psychosis proneness in the general population. Choice history biases and their adaptation to experimentally induced changes in stimulus serial dependencies were investigated in decision-making tasks with auditory (experiment 1) and visual (experiment 2) stimuli. We further explored a potential compensatory mechanism for reduced choice history biases by reliance on predictive cross-modal cues.

Results

In line with our preregistered hypothesis, psychosis proneness was associated with decreased choice history biases in both experiments. This association is generalized across conditions with and without stimulus serial dependencies. We did not find consistent evidence for a compensatory reliance on cue information in psychosis-prone individuals across experiments.

Conclusions

Our results show reduced choice history biases in psychosis proneness. A compensatory mechanism between implicit choice history effects and explicit cue information is not supported unequivocally by our data.
Comprehensive analysis of multivariable models for predicting severe dengue prognosis: systematic review and meta-analysis
Authors: Lee Hyelan , Hyun Seungjae , Park Sangshin
Published: November 2022

Dengue fever has often been confused with other febrile diseases, with deterioration occurring in the later state. Many predictive models for disease progression have been developed, but there is no definite statistical model for clinical use yet. We retrieved relevant articles through Global Health, EMBASE, MEDLINE and CINAHL Plus. The Prediction Model Risk of Bias Assessment Tool was adopted to assess potential bias and applicability. Statistical analysis was performed using Meta-DiSc software (version 1.4). Of 3184 research studies, 22 were included for the systematic review, of which 17 were selected for further meta-analysis. The pooled data of predictive accuracy was as follows: the sensitivity was 0.88 (95% CI 0.86 to 0.89), the specificity was 0.60 (95% CI 0.59 to 0.60), the positive likelihood ratio was 2.83 (95% CI 2.38 to 3.37), the negative likelihood ratio was 0.20 (95% CI 0.14 to 0.0.29) and the diagnostic OR was 16.31 (95% CI 10.25 to 25.94). The area under the summary receiver operating characteristic curve value was 0.86 (SE=0.02) with 0.79 (SE=0.02) of the Cochran Q test value. The overall predictive power of models in this study was relatively high. With careful adaption and standardization, the implementation of predictive models for severe dengue could be practical in actual clinical settings.
Carboplasty, a Minimally Invasive Procedure for Knee Osteoarthritis: Surgical Technique and Clinical Evidence
Authors: Madrazo-Ibarra Antonio , Kolin David A. , Hunter Tracey , Ogyaadu Joseph A. , Duah Henry O. , Tutu Henry O. , Bandoh Anthony , Nutsuklo Prudence , Boachie-Adjei Kwadwo , Carroll Kaitlin M. , Vad Amoli , Zhao Eric , Vad Vijay B.
Published: November 2022

Knee osteoarthritis affects ~16% of adults in the world and is considered one of the most incapacitating diseases. Despite the advances in scientific knowledge and biological treatments in the field of orthopedics, available nonsurgical treatments for knee osteoarthritis are limited and still ineffective in delaying or stopping the progression of arthritis. Biologics such as platelet-rich plasma, bone marrow aspirate, and progenitor cells have emerged as potential treatments for osteoarthritis; however, the results are still not as expected. Carboplasty is a new treatment that involves the application of bone marrow aspirate into the bone-cartilage interface and intra-articularly, with the intention of stopping the progression of osteoarthritis and delaying the need for total knee replacement. By applying bone marrow directly in the bone-cartilage interface, the communication between subchondral bone and articular cartilage may be reestablished, promoting the delivery of nutrients to the cartilage, and it is hoped that preserving, regenerating, and restoring knee cartilage. Thirteen patients with knee osteoarthritis underwent carboplasty. Patients showed a statistically significant improvement in the Veterans RAND 12 Item Health Survey, the visual analog scale for knee pain, the Western Ontario and McMaster University Osteoarthritis Index, and the Knee Injury and Osteoarthritis Outcome Score for Joint Replacement at 3 and 6 months postprocedure. No adverse events were reported during the follow-up. Carboplasty is promising and worthy of further research.
Ejection Fraction Improvement Does Not Reflect Changes in Quality of Life Following Cardiac Resynchronization Therapy
Authors: Rizzi Scott A. , Torre Michael , Bunch T. Jared , Fang James , Hess Rachel , Rodriguez-Correa Carlos , Spertus John A. , Stehlik Josef , Zhang Mingyuan , Zhang Yue , Steinberg Benjamin A.
Published: November 2022

Objective:

To determine if health-related quality of life (HRQoL) improvement after cardiac resynchronization therapy (CRT) correlates with improved left-ventricular ejection fraction (EF).

Background:

CRT was reported to improve EF and HRQoL in clinical trials of heart failure with reduced EF (HFrEF). It is unknown if improvements in HRQoL reflect EF response to CRT.

Methods:

We included HFrEF patients who underwent CRT and had both pre- and post-CRT HRQoL assessment. EF response was categorized as absent (0% change or decrease), modest (0%–19% increase), or significant (>20% increase). We examined the associations between EF response and generic (PROMIS) and HF-specific (KCCQ-12) HRQoL.

Results:

The group included 115 patients with mean age of 65 years and baseline EF of 31%; 39% were female (n = 45). Nineteen percent (n = 22) had significant, 57% (n = 66) modest, and 23% (n = 27) absent EF responses. AF burden across significant (8.9%), modest (4.8%), and absent EF responders (1.4%) was similar (P = 0.20). Significant improvements in KCCQ-12 (43.4–57.5, P = 0.003), current health visual analog scale (49.1–55.9, P = 0.042), PROMIS fatigue (58.9–55.1, P = 0.026), and PROMIS satisfaction (42.7–46.4, P = 0.020) resulted following CRT across all groups. There was no association between significant EF improvement and HRQoL by KCCQ-12 (nonresponse, 44.4%; modest response, 33.3%; and significant response, 22.2%) at 1 year (P = 0.52 across all groups).

Conclusion:

CRT was associated with a modest to significant EF response in a majority of patients. However, EF response did not significantly correlate with generic or HF-specific HRQoL measures. Further investigations are warranted into determinants of improved HRQoL following CRT.
New perspectives on the evolution of women's cooperation
Authors: Fox Stephanie A. , Scelza Brooke , Silk Joan , Kramer Karen L.
Published: November 2022

A holistic, evolutionary framework about human cooperation must incorporate information about women's cooperative behaviour. Yet, most empirical research on human cooperation has centered on men's behaviour or been derived from experimental studies conducted in western, industrialized populations. These bodies of data are unlikely to accurately represent human behavioural diversity. To address this gap and provide a more balanced view of human cooperation, this issue presents substantial new data and multi-disciplinary perspectives to document the complexity of women's cooperative behaviour. Research in this issue 1) challenges narratives about universal gender differences in cooperation, 2) reconsiders patrilocality and access to kin as constraints on women's cooperation, 3) reviews evidence for a connection between social support and women's health and 4) examines the phylogenetic roots of female cooperation. Here, we discuss the steps taken in this issue toward a more complete and evidence-based understanding of the role that cooperation plays in women's and girls' lives and in building human sociality.

This article is part of the theme issue ‘Cooperation among women: evolutionary and cross-cultural perspectives’.
Gender differences in cooperation across 20 societies: a meta-analysis
Authors: Spadaro Giuliana , Jin Shuxian , Balliet Daniel
Published: November 2022

Past research hypothesized that men and women differ in their tendency to cooperate with strangers in situations that involve a conflict of interests. However, recent empirical research has provided converging evidence that men and women cooperate to a similar extent, and that differences in cooperation can emerge in response to specific situational and societal contexts. Here we analyse six decades of empirical research on human cooperation using social dilemmas (1961–2017,k= 126) conducted across 20 industrialized societies, testing pre-registered hypotheses derived from evolutionary theory and social role theory. Overall, our findings revealed little-to-no evidence for an association between gender and cooperation using different meta-analytic approaches. We did not find within-study differences in cooperation between men and women (d= 0.011, 95% CI [−0.038, 0.060]). However, cooperation was slightly higher across studies with predominantly female samples (k= 972). In addition, contrary to our predictions, gender differences in cooperation did not emerge in response to the degree of conflicting interests in the situation, and societal levels of gender equality and economic development. We discuss the implications of these findings for our understanding of gender differences in cooperation.

This article is part of the theme issue ‘Cooperation among women: evolutionary and cross-cultural perspectives’.
Thriving together: the benefits of women's social ties for physical, psychological and relationship health
Authors: Bedrov Alisa , Gable Shelly L.
Published: November 2022

The relationship between social support and well-being is well established in social psychology, with evidence suggesting that these benefits are especially prominent among women. When faced with an environmental stressor, women are more likely to adopt a tend-and-befriend strategy rather than fight-or-flight. Furthermore, female friendships tend to be higher in self-disclosure and more frequently relied on for social support, which is associated with physical and psychological benefits. Women are also more effective at providing social support, further augmenting those benefits. We begin with an overview of the characteristics of women's social ties and how they can be especially useful in times of stress. We then transition to the benefits of female social networks even in the absence of negative events and incorporate research from health and social psychology to consider the positive implications of having strong social bonds and the negative implications of lacking such bonds. Additionally, we consider cross-cultural differences in tendencies to seek out social support and its subsequent benefits, as well as the need for more research with culturally diverse samples. It remains unclear the extent to which patterns of social support benefits for women vary cross-culturally.

This article is part of the theme issue ‘Cooperation among women: evolutionary and cross-cultural perspectives’.
Concentrating all helper protein functions on a single entity allows rescue of recombinant measles virus by transfection of just two plasmids
Authors: Auste Arne , Mühlebach Michael D.
Published: November 2022

The generation of recombinant measles virus (MeV) from manipulated genomes on plasmid DNA is quite a complex and inefficient process. As a member of the order Mononegavirales its single-stranded ssRNA genome in negative sense orientation is not infectious, but requires co-availability of the viral RNA-dependent RNA polymerase L, the polymerase co-factor phosphoprotein P, and the nucleocapsid protein N in defined relative amounts to establish infectious centres in transfected cell cultures that release replication-competent recombinant MeV particles. For this so-called rescue, different rescue systems were developed that rely on at least four different components. In this work, we establish a functional MeV rescue system just being composed of two components: the plasmid encoding the (modified) viral genome, and a one-helper-plasmid bundling all helper functions. In contrast to a rescue-system for Newcastle Disease Virus, another paramyxovirus, co-expression of all helper proteins by the same promoter failed. Instead, adaptation of the strength of the respective promoters to drive each helper gene´s expression to the relative expression found in MeV-infected cells or other rescue systems, which indeed adjusted respective mRNA and protein expression, yielded success, albeit not yet to the same efficacy as the four-component system. Thereby, our study paves the way for the development of easier and, after further optimization, more efficient rescue systems to generate recombinant MeV for e.g. the application as a vaccine platform or oncolytic virus, for example.
Prediction of Stroke Outcome in Mice Based on Non-Invasive MRI and Behavioral Testing
Authors: Knab Felix , Koch Stefan Paul , Major Sebastian , Farr Tracy D. , Mueller Susanne , Euskirchen Philipp , Eggers Moritz , Kuffner Melanie T.C. , Walter Josefine , Berchtold Daniel , Knauss Samuel , Dreier Jens P. , Meisel Andreas , Endres Matthias , Dirnagl Ulrich , Wenger Nikolaus , Hoffmann Christian J. , Boehm-Sturm Philipp , Harms Christoph
Published: November 2022

Background

Prediction of post-stroke outcome using the degree of subacute deficit or magnetic resonance imaging is well studied in humans. While mice are frequently used animals in preclinical stroke research, systematic analysis of outcome predictors is lacking.

Methods

We introduced heterogeneity into our study to broaden the applicability of our prediction tools. We analyzed the effect of 30, 45 and 60 minutes of arterial occlusion on the variance of stroke volumes. Next, we built a heterogeneous cohort of 215 mice using data from 15 studies that included 45 minutes of middle cerebral artery occlusion and various genotypes. Motor function was measured using the staircase test of skilled reaching. Phases of subacute and residual deficit were defined. Magnetic resonance images of stroke lesions were co-registered on the Allen Mouse Brain Atlas to characterize stroke topology. Different random forest prediction models that either used motor-functional deficit or imaging parameters were generated for the subacute and residual deficits.

Results

Variance of stroke volumes was increased by 45 minutes of arterial occlusion compared to 60 minutes and including various genotypes. We detected both a subacute and residual motor-functional deficit after stroke and different recovery trajectories. In mice with small cortical lesions, lesion volume was the best predictor of the subacute deficit. The residual deficit was most accurately predicted by the degree of the subacute deficit. When using imaging parameters for the prediction of the residual deficit, including information about the lesion topology increased prediction accuracy. A subset of anatomical regions within the ischemic lesion had particular impact on the prediction of long-term outcome.

Conclusions

We developed and validated a robust tool for the prediction of functional outcome after stroke in mice using a large heterogeneous cohort. Study design and imaging limitations are discussed. In the future, using outcome prediction can improve the design of preclinical studies and guide intervention decisions.
Childhood trauma moderates schizotypy-related brain morphology: Analyses of 1,182 healthy individuals from the ENIGMA Schizotypy working group
Authors: Quidé Yann , Watkeys Oliver J. , Tonini Emiliana , Grotegerd Dominik , Dannlowski Udo , Nenadić Igor , Kircher Tilo , Krug Axel , Hahn Tim , Meinert Susanne , Goltermann Janik , Gruber Marius , Stein Frederike , Brosch Katharina , Wroblewski Adrian , Thomas-Odenthal Florian , Usemann Paula , Straube Benjamin , Alexander Nina , Leehr Elisabeth J. , Bauer Jochen , Winter Nils R. , Fisch Lukas , Dohm Katharina , Rössler Wulf , Smigielski Lukasz , DeRosse Pamela , Moyett Ashley , Houenou Josselin , Leboyer Marion , Gilleen James , Thomopoulos Sophia I. , Thompson Paul M. , Aleman André , Modinos Gemma , Green Melissa J.
Published: November 2022

Schizotypy represents an index of psychosis-proneness in the general population often associated with childhood trauma exposure. Both schizotypy and childhood trauma are linked to structural brain alterations, and it is possible that trauma exposure moderates the extent of brain morphological differences associated with schizotypy. We addressed this question using data from a total of 1,182 healthy adults (age range: 18-65 years old, 647 females/535 males), pooled from nine sites worldwide, contributing to the Enhancing NeuroImaging Genetics through Meta-Analysis (ENIGMA) Schizotypy working group. All participants completed both the Schizotypal Personality Questionnaire Brief version (SPQ-B), and the Childhood Trauma Questionnaire (CTQ), and underwent a 3D T1-weighted brain MRI scan from which regional indices of subcortical grey matter volume and cortical thickness were determined. A series of multiple linear regressions revealed that differences in cortical thickness in four regions-of-interest were significantly associated with interactions between schizotypy and trauma; subsequent moderation analyses indicated that increasing levels of schizotypy were associated with thicker left caudal anterior cingulate gyrus, right middle temporal gyrus and insula, and thinner left caudal middle frontal gyrus, in people exposed to higher (but not low or average) levels of childhood trauma. This was found in the context of thicker bilateral medial orbitofrontal gyri, right rostral anterior cingulate gyrus, left temporal pole, left insula, and thinner left paracentral lobule directly associated with increasing levels of schizotypy. In addition, thinner left postcentral, superior parietal and lingual gyri, as well as thicker left caudal middle frontal gyrus and smaller left thalamus and right caudate were associated with increasing levels of childhood trauma exposure. These results suggest that alterations in brain regions critical for higher cognitive and integrative processes that are associated with schizotypy may be enhanced in individuals exposed to high levels of trauma.
Defining the Critical Educational Components of Informed Consent for Genetic Testing: Views of US-Based Genetic Counselors and Medical Geneticists
Authors: Hallquist Miranda L. G. , Borensztein Maia J. , Coughlin Curtis R. , Buchanan Adam H. , Faucett W. Andrew , Peay Holly L. , Smith Maureen E. , Tricou Eric P. , Uhlmann Wendy R. , Wain Karen E. ,   the CADRe workgroup, Ormond Kelly E.
Published: November 2022

The Clinical Genome Resource (ClinGen)ConsentandDisclosureRecommendation (CADRe) framework proposes that key components of informed consent for genetic testing can be covered with a targeted discussion for many conditions rather than a time-intensive traditional genetic counseling approach. We surveyed US genetics professionals (medical geneticists and genetic counselors) on their response to scenarios that proposed core informed consent concepts for clinical genetic testing developed in a prior expert consensus process. The anonymous online survey included responses to 3 (of 6 possible) different clinical scenarios that summarized the application of the core concepts. There was a binary (yes/no) question asking respondents whether they agreed the scenarios included the minimum necessary and critical educational concepts to allow an informed decision. Respondents then provided open-ended feedback on what concepts were missing or could be removed. At least one scenario was completed by 238 respondents. For all but one scenario, over 65% of respondents agreed that the identified concepts portrayed were sufficient for an informed decision; the exome scenario had the lowest agreement (58%). Qualitative analysis of the open-ended comments showed no consistently mentioned concepts to add or remove. The level of agreement with the example scenarios suggests that the minimum critical educational components for pre-test informed consent proposed in our prior work is a strong starting place for clinicians to provide targeted pre-test discussions. This may be helpful in providing consistency to the clinical practice of both genetics and non-genetics providers, and in future guideline development.
Pre- and asymptomatic viral shedding in high-risk contacts of monkeypox cases: a prospective cohort study
Authors: Brosius Isabel , Van Dijck Christophe , Coppens Jasmine , Vandenhove Leen , Bangwen Eugene , Vanroye Fien , Verschueren Jacob , Zange Sabine , Bugert Joachim , Michiels Johan , Bottieau Emmanuel , Soentjens Patrick , van Griensven Johan , Kenyon Chris , Ariën Kevin K. , Van Esbroeck Marjan , Vercauteren Koen , Liesenborghs Laurens ,   the ITM MPX consortium
Published: November 2022

Abstract

Epidemiological data suggest that clade IIb monkeypox virus (MPXV) is readily transmitted during sexual contact, even before symptom onset. However, presymptomatic shedding of MPXV remains to be demonstrated. Here, we prospectively followed up 25 individuals after high-risk exposure to MPXV. Daily anorectal, genital, and saliva samples and weekly blood and oropharyngeal samples were collected along with clinical information. During follow-up, 12/18 (66.0%) sexual and 1/7 (14.0%) non-sexual contacts showed evidence of MPXV infection by PCR, five of whom had low viral loads and no typical MPXV symptoms. In 5/6 (83.3%) patients with typical symptoms, viral DNA was detected as early as four days before symptom onset and in three of them, replication-competent virus was found. These findings emphasize the high risk of MPXV transmission during sexual contact and confirm the existence of presymptomatic viral shedding of MPXV. Sexual contacts of an MPXV-infected partner should abstain from sex irrespective of symptoms.
The potential impact of novel tuberculosis vaccine introduction on economic growth in low- and middle-income countries
Authors: Portnoy Allison , Arcand Jean-Louis , Clark Rebecca A. , Weerasuriya Chathika K. , Mukandavire Christinah , Bakker Roel , Patouillard Edith , Gebreselassie Nebiat , Zignol Matteo , Jit Mark , White Richard G. , Menzies Nicolas A.
Published: November 2022

Most individuals who develop tuberculosis (TB) are working-age adults living in low- and middle-income countries (LMICs). The resulting disability and death impacts economic productivity and burdens health systems. New TB vaccine candidates may reduce this burden. In this study, we estimated the impact of introducing novel TB vaccines on GDP growth in 105 LMICs, using a macroeconomic model to simulate country-level GDP trends between 2020 and 2080, in 2020 USD. We compared scenarios for introduction of infant and adolescent/adult vaccine candidates to a no-new-vaccine counterfactual. Compared to the no-new-vaccine counterfactual, both vaccination scenarios produced greater cumulative GDP in the modelled countries over the study period, equivalent to $1.6 (95% uncertainty interval: $0.8–3.0) trillion for the adolescent/adult vaccine, and $0.2 ($0.1–0.4) trillion for the infant vaccine. These GDP gains were substantially lagged relative to the time of vaccine introduction, and concentrated in countries with higher current TB incidence.
Alarming antibody evasion properties of rising SARS-CoV-2 BQ and XBB subvariants
Authors: Wang Qian , Iketani Sho , Li Zhiteng , Liu Liyuan , Guo Yicheng , Huang Yiming , Bowen Anthony D. , Liu Michael , Wang Maple , Yu Jian , Valdez Riccardo , Lauring Adam S. , Sheng Zizhang , Wang Harris H. , Gordon Aubree , Liu Lihong , Ho David D.
Published: November 2022

The SARS-CoV-2 Omicron variant continues to evolve, with new BQ and XBB subvariants now rapidly expanding in Europe/US and Asia, respectively. As these new subvariants have additional spike mutations, they may possess altered antibody evasion properties. Here, we report that neutralization of BQ.1, BQ.1.1, XBB, and XBB.1 by sera from vaccinees and infected persons was markedly impaired, including sera from individuals who were boosted with a WA1/BA.5 bivalent mRNA vaccine. Compared to the ancestral strain D614G, serum neutralizing titers against BQ and XBB subvariants were lower by 13-81-fold and 66-155-fold, respectively, far beyond what had been observed to date. A panel of monoclonal antibodies capable of neutralizing the original Omicron variant, including those with Emergency Use Authorization, were largely inactive against these new subvariants. The spike mutations that conferred antibody resistance were individually studied and structurally explained. Finally, the ACE2-binding affinities of the spike proteins of these novel subvariants were found to be similar to those of their predecessors. Taken together, our findings indicate that BQ and XBB subvariants present serious threats to the efficacy of current COVID-19 vaccines, render inactive all authorized monoclonal antibodies, and may have gained dominance in the population because of their advantage in evading antibodies.