bluuebunny/crossref_metadata_2025_split huggingface dataset:
Intravenous immunoglobulin induces IgG internalization by tolerogenic myeloid dendritic cells that secrete IL-10 and expand Fc-specific regulatory T cells
Authors: Hsieh Li-En , Song Jaeyoon , Tremoulet Adriana H , Burns Jane C , Franco Alessandra 
Published: May 2022

Abstract
Intravenous immunoglobulin (IVIG) is used as an immunomodulatory agent in many inflammatory conditions including Multisystem Inflammatory Syndrome-Children (MIS-C) and Kawasaki disease (KD). However, the exact mechanisms underlying its anti-inflammatory action are incompletely characterized. Here, we show that in KD, a pediatric acute vasculitis that affects the coronary arteries, IVIG induces a repertoire of natural Treg that recognize immunodominant peptides in the Fc heavy chain constant region. To address which antigen-presenting cell (APC) populations present Fc peptides to Treg, we studied the uptake of IgG by innate cells in subacute KD patients 2 weeks after IVIG and in children 1.6–14 years after KD. Healthy adults served as controls. IgG at high concentrations was internalized predominantly by two myeloid dendritic cell (DC) lineages, CD14+ cDC2 and ILT-4+ CD4+ tmDC mostly through Fcγ receptor (R) II and to a lesser extent FcγRIII. Following IgG internalization, these two DC lineages secreted IL-10 and presented processed Fc peptides to Treg. The validation of IVIG function in expanding Fc-specific Treg presented by CD14+ cDC2 and ILT-4+ CD4+ tmDC was addressed in a small cohort of patients with MIS-C. Taken together, these results suggest a novel immune regulatory function of IgG in activating tolerogenic innate cells and expanding Treg, which reveals an important anti-inflammatory mechanism of action of IVIG.
Evolving spectrum but persistent high mortality of COVID-19 among patients on kidney replacement therapy in the vaccine era: the Spanish COVID-19 KRT Registry
Authors: Quiroga Borja , Ortiz Alberto , Cabezas-Reina Carlos Jesús , Ruiz Fuentes María Carmen , Jiménez Verónica López , Larrondo Sofía Zárraga , Toapanta Néstor , Gómez María Molina , de Sequera Patricia , Sánchez-Álvarez Emilio ,   the Spanish COVID-19 KRT Registry collaborative group
Published: May 2022

ABSTRACT

Background
Kidney replacement therapy (KRT) conferred a high risk for coronavirus disease 2019 (COVID-19) related mortality early in the pandemic. We evaluate the presentation, treatment and outcomes of COVID-19 in patients on KRT over time during the pandemic.

Methods
This registry-based study involved 6080 dialysis and kidney transplant (KT) patients with COVID-19, representing roughly 10% of total Spanish KRT patients. Epidemiology, comorbidity, infection, vaccine status and treatment data were recorded, and predictors of hospital admission, intensive care unit (ICU) admission and mortality were evaluated.

Results
Vaccine introduction decreased the number of COVID-19 cases from 1747 to 280 per wave. Of 3856 (64%) COVID-19 KRT patients admitted to the hospital, 1481/3856 (38%) were admitted during the first of six waves. Independent predictors for admission included KT and the first wave. During follow-up, 1207 patients (21%) died, 500/1207 (41%) during the first wave. Among vaccinated patients, mortality was 19%, mostly affecting KT recipients. Overall, independent predictors for mortality were older age, disease severity (lymphopaenia, pneumonia) and ICU rejection. Among patient factors, older age, male sex, diabetes, KT and no angiotensin receptor blockers (ARB) were independent predictors of death. In KT recipients, individual immunosuppressants were independent predictors of death. Over time, patient characteristics evolved and in later pandemic waves, COVID-19 was mainly diagnosed in vaccinated KT recipients; in the few unvaccinated dialysis patients, ICU admissions increased and mortality decreased (28% for the first wave and 16–22% thereafter).

Conclusions
The clinical presentation and outcomes of COVID-19 during the first wave no longer represent COVID-19 in KRT patients, as the pandemic has become centred around vaccinated KT recipients. Vaccines lowered the incidence of diagnosed COVID-19 and mortality. However, mortality remains high despite increased access to ICU care.
Health surveillance indicators for diet and physical activity: what is available in European data sets for policy evaluation?
Authors: Stanley Isobel , Neumann-Podczaska Agnieszka , Wieczorowska-Tobis Katarzyna , Mensink Gert B M , Rosas Lina Garnica , Do Stefanie , Abu Omar Karim , Woods Catherine , Ahrens Wolfgang , Hebestreit Antje , Murrin Celine ,   the PEN Consortium
Published: May 2022

Abstract

Background
Policies targeting diet and physical activity have the potential to improve health and well-being at a population level. However, the impact of these policies in Europe is currently unknown. Based on existing data, as well as on a needs assessment, we derived a catalogue of indicators that can be employed to evaluate such policies. These indicators may also inform the further development and harmonization of surveillance systems.

Methods
Forty EU experts agreed on a list of key indicators and ranked their priority for future surveillance. We mapped these indicators onto variables provided by ongoing European surveillance systems. Using a Likert scale (well matched, somewhat matched, poorly matched, unmatched), we assessed the suitability of these variables as measures for the indicators.

Results
Key indicators included behaviour outcome indicators relating to diet (n = 72) and physical activity and sedentary behaviour (n = 67) as well as upstream determinants of these behaviours. It was possible to map 72% of diet indicators and 86% of physical activity and sedentary behaviour indicators onto at least one variable in an ongoing surveillance system.

Conclusions
Current monitoring and surveillance systems focus mainly on measuring ‘downstream’ indicators, while gaps exist in policy and environmental level data in dimensions such as inequality, funding and resources and governance.
Hybrid fitness effects modify fixation probabilities of introgressed alleles
Authors: Pfennig Aaron , Lachance Joseph 
Published: May 2022

Abstract
Hybridization is a common occurrence in natural populations, and introgression is a major source of genetic variation. Despite the evolutionary importance of adaptive introgression, classical population genetics theory does not take into account hybrid fitness effects. Specifically, heterosis (i.e. hybrid vigor) and Dobzhansky–Muller incompatibilities influence the fates of introgressed alleles. Here, we explicitly account for polygenic, unlinked hybrid fitness effects when tracking a rare introgressed marker allele. These hybrid fitness effects quickly decay over time due to repeated backcrossing, enabling a separation-of-timescales approach. Using diffusion and branching process theory in combination with computer simulations, we formalize the intuition behind how hybrid fitness effects affect introgressed alleles. We find that hybrid fitness effects can significantly hinder or boost the fixation probability of introgressed alleles, depending on the relative strength of heterosis and Dobzhansky–Muller incompatibilities effects. We show that the inclusion of a correction factor (α, representing the compounded effects of hybrid fitness effects over time) into classic population genetics theory yields accurate fixation probabilities. Despite having a strong impact on the probability of fixation, hybrid fitness effects only subtly change the distribution of fitness effects of introgressed alleles that reach fixation. Although strong Dobzhansky–Muller incompatibility effects may expedite the loss of introgressed alleles, fixation times are largely unchanged by hybrid fitness effects.
Evaluating the power and limitations of genome-wide association studies in Caenorhabditis elegans
Authors: Widmayer Samuel J , Evans Kathryn S , Zdraljevic Stefan , Andersen Erik C 
Published: May 2022

Abstract
Quantitative genetics in Caenorhabditis elegans seeks to identify naturally segregating genetic variants that underlie complex traits. Genome-wide association studies scan the genome for individual genetic variants that are significantly correlated with phenotypic variation in a population, or quantitative trait loci. Genome-wide association studies are a popular choice for quantitative genetic analyses because the quantitative trait loci that are discovered segregate in natural populations. Despite numerous successful mapping experiments, the empirical performance of genome-wide association study has not, to date, been formally evaluated in C. elegans. We developed an open-source genome-wide association study pipeline called NemaScan and used a simulation-based approach to provide benchmarks of mapping performance in collections of wild C. elegans strains. Simulated trait heritability and complexity determined the spectrum of quantitative trait loci detected by genome-wide association studies. Power to detect smaller-effect quantitative trait loci increased with the number of strains sampled from the C. elegans Natural Diversity Resource. Population structure was a major driver of variation in mapping performance, with populations shaped by recent selection exhibiting significantly lower false discovery rates than populations composed of more divergent strains. We also recapitulated previous genome-wide association studies of experimentally validated quantitative trait variants. Our simulation-based evaluation of performance provides the community with critical context to pursue quantitative genetic studies using the C. elegans Natural Diversity Resource to elucidate the genetic basis of complex traits in C. elegans natural populations.
Time-adjusted average Mayo endoscopic score predicts the risk of disease extent progression in distal ulcerative colitis patients
Authors: Wan Jian , Wang Xuan , Zhang Yujie , Xue Xianmin , Jia Hui , Wang Min , Liang Jie , Wu Kaichun 
Published: May 2022

Abstract

Background
Ulcerative colitis (UC) is a chronic lifelong disease. The disease extent of UC can progress over time. This study aimed to assess whether cumulative inflammatory burden (CIB) is associated with disease extension in distal UC (proctitis [E1] and left-sided colitis [E2]) patients, and to develop a quantified indicator of CIB.

Methods
In this retrospective study based on a prospective registry, distal UC patients receiving colonoscopies in Xijing Hospital (Xi’an, China) from January 2000 to May 2019 were studied. We developed a new score, namely the time-adjusted average Mayo endoscopic score (TA-MES), calculated as dividing the sum of the cumulative average MES over a period of surveillance time by the length of the endoscopic examination interval, to quantify the CIB. Cox regression was used to identify other potential risk factors.

Results
A total of 295 UC patients were followed for 1,487.02 patient-years. Among them, 140 patients (47.5%) experienced disease extension. Multivariate analysis showed that the TA-MES was significantly associated with disease extension in E1 (hazard ratio [HR], 2.90; 95% confidence interval [CI], 1.58–5.33, P = 0.001) and E2 (HR, 1.89; 95% CI, 1.16–3.09, P = 0.011) patients. Other risk factors included hemoglobin of &lt;90 g/L and appendiceal skip inflammation; the protective factors included age, E2 at diagnosis, former smoking, and 5-aminosalicylic acid dose. Otherwise, MES at diagnosis, maximal MES, and mean MES failed to estimate the risk of disease extension.

Conclusion
TA-MES is a good quantified indicator of CIB and is independently associated with increased disease extension in distal UC patients. Whether the dynamic multiple scoring system could be used as a risk factor in other chronic relapsing–remitting diseases is a direction for future research.
Ongoing transposition in cell culture reveals the phylogeny of diverse Drosophila S2 sublines
Authors: Han Shunhua , Dias Guilherme B , Basting Preston J , Nelson Michael G , Patel Sanjai , Marzo Mar , Bergman Casey M 
Published: May 2022

Abstract
Cultured cells are widely used in molecular biology despite poor understanding of how cell line genomes change in vitro over time. Previous work has shown that Drosophila cultured cells have a higher transposable element content than whole flies, but whether this increase in transposable element content resulted from an initial burst of transposition during cell line establishment or ongoing transposition in cell culture remains unclear. Here, we sequenced the genomes of 25 sublines of Drosophila S2 cells and show that transposable element insertions provide abundant markers for the phylogenetic reconstruction of diverse sublines in a model animal cell culture system. DNA copy number evolution across S2 sublines revealed dramatically different patterns of genome organization that support the overall evolutionary history reconstructed using transposable element insertions. Analysis of transposable element insertion site occupancy and ancestral states support a model of ongoing transposition dominated by episodic activity of a small number of retrotransposon families. Our work demonstrates that substantial genome evolution occurs during long-term Drosophila cell culture, which may impact the reproducibility of experiments that do not control for subline identity.
Participating in Cultural Life via Augmented Reality on Cultural Goods: What Role for Copyright?
Authors: Sappa Cristiana 
Published: May 2022

Abstract
Augmented Reality (AR) is a technology enabling the overlap of digital images with those from the real world. This technology can have a wide range of applications, including in the cultural heritage sector. AR initiatives can be implemented by cultural heritage institutes (CHIs) for educational and research purposes, but also by third parties as (complementary) commercial practices. When AR is applied to cultural goods, this can be referred to as the ‘exploitation’ of such goods. These goods often embed works of art which may fall under the protection of an Intellectual Property Right (IPR). This paper focuses on the importance of AR experiences when applied to cultural goods and explains why it is a suitable tool for a comprehensive and consistent achievement of the CHIs’ missions and, more broadly, for economic, cultural and social growth, as well as for a better implementation of the legal right of participation in cultural life. The analysis studies this from an IPR perspective and explains how copyright interferes with the development of AR applications. The work does not deal with the protection of AR outcomes as such. It discusses when and what challenges are raised for both moral rights and economic rights when data and images are communicated to the public via AR applications. Anyone that intends to develop AR needs to own economic rights. When rights are owned, if AR is developed by a public sector body or a CHI, rules on public sector information may also apply and facilitate the initiative. If the IPRs are not owned by the AR developer, the latter should request a license, probably via Collective Management Organizations, unless exceptions and limitations can provide for a solution. Thus, exceptions and limitations are one of the main focuses of this work.
Pharmacist’s role in immune-related adverse events management: real-world incidence and risk evaluation from immunotherapy
Authors: Meanwatthana J , Chantarasap P , Chuatrisorn I , Wiriya T , Jitawatanarat P 
Published: May 2022

Abstract

Objectives
The challenge of using immune checkpoint inhibitors (ICI) is the immune-related adverse events (irAEs). Nonetheless, there is scarce evidence regarding the irAEs in Thailand. The primary aims of this study are to assess the incidence as well as risk factors of irAEs among cancer patients in Wattanosoth hospital.

Methods
This was a cross-sectional retrospective chart review for the 3-year period (2017–2019). Data were collected after initiating the approved ICIs and patients were then followed for 12 months. The outcomes included incidences of irAEs, adverse events management, and tumor objective response. Bivariate analysis was performed for factors that might be associated with irAEs occurrences.

Results
Data from 91 patients was collected. There was a 49.5% overall irAEs incidence. The most frequent irAE to occur affected the endocrine system (29.85%). In addition, we identified that odds ratios of irAEs development increased in patients who had four or more ICI cycles or had a serum creatinine level higher than 1.2 mg/dl, (OR: 1.75; 95% CI 1.1611:2.6256, P = 0.0074) and (OR: 1.58; 95% CI: 1.0628:2.3574; P = 0.0238), respectively. The emergence of irAEs may be a sign of tumor objective responses (OR: 1.79; 95% CI 1.0035:3.1889; P = 0.0486).

Conclusion
This study demonstrates that irAEs are common in patients treated with ICIs. In addition, our study identifies that number of cycles and serum creatinine influence the development of irAEs. Hence, prompt recognition and an adequate monitoring plan should be cautiously taken into consideration.
Braided Quantum Groups and Their Bosonizations in the C*-Algebraic Framework
Authors: Roy Sutanu 
Published: May 2022

Abstract
We present a general theory of braided quantum groups in the ${\textrm {C}^*}$-algebraic framework using the language of multiplicative unitaries. Starting with a manageable multiplicative unitary in the representation category of the quantum codouble of a regular quantum group $\mathbb {G}$ we construct a braided ${\textrm {C}^*}$-quantum group over $\mathbb {G}$ as a ${\textrm {C}^*}$-bialgebra in the monoidal category of the $\mathbb {G}$-Yetter–Drinfeld ${\textrm {C}^*}$-algebras. Furthermore, we establish a one-to-one correspondence between braided ${\textrm {C}^*}$-quantum groups and ${\textrm {C}^*}$-quantum groups with a projection. Consequently, we generalise the bosonization construction for braided Hopf-algebras of Radford and Majid to braided ${\textrm {C}^*}$-quantum groups. Several examples are discussed. In particular, we show that the complex quantum plane admits a braided ${\textrm {C}^*}$-quantum group structure over the circle group ${\mathbb {T}}$ and identify its bosonization with the simplified quantum $\textrm {E}(2)$ group.
A Phase 1/2 Study of a Respiratory Syncytial Virus Prefusion F Vaccine With and Without Adjuvant in Healthy Older Adults
Authors: Baber James , Arya Mark , Moodley Yuben , Jaques Anna , Jiang Qin , Swanson Kena A , Cooper David , Maddur Mohan S , Loschko Jakob , Gurtman Alejandra , Jansen Kathrin U , Gruber William C , Dormitzer Philip R , Schmoele-Thoma Beate 
Published: May 2022

Abstract

Background
Respiratory syncytial virus (RSV) is an important cause of disease in older adults. We evaluated the safety and immunogenicity of a stabilized RSV prefusion F subunit (RSVpreF) vaccine candidate with/without adjuvant in adults aged 65–85 years.

Methods
Primary cohort participants were equally randomized to 1 of 7 RSVpreF formulations: 60 µg with either Al(OH)3 or CpG/Al(OH)3, 120 µg with either Al(OH)3 or CpG/Al(OH)3, 240 µg with either Al(OH)3 or CpG/Al(OH)3, 240 µg unadjuvanted, or placebo, administered concomitantly with high-dose seasonal inactivated influenza vaccine (SIIV). Participants in the month 0,2 cohort were randomized to RSVpreF 240 µg with CpG/Al(OH)3 or placebo, administered at months 0 and 2.

Results
All RSVpreF vaccine candidates elicited robust and persistent serum neutralizing responses when administered alone or with SIIV. There was no notable difference in neutralizing response between the formulations, including those containing CpG. In the month 0,2 cohort, there was no booster effect of dose 2. SIIV responses were similar or slightly lower with concomitant administration of RSVpreF. Most systemic and local reactions were mild and more frequent after RSVpreF than placebo.

Conclusions
RSVpreF formulations were well tolerated and elicited robust neutralizing responses in older adults; however, CpG/Al(OH)3 did not further enhance responses.
Clinical Trials Registration. NCT03572062.
When Do International Organizations Engage in Agency Slack? A Qualitative Comparative Analysis of United Nations Institutions
Authors: Heldt Eugénia C , Mello Patrick A , Novoselova Anna , Serrano Oswald Omar Ramon 
Published: May 2022

Abstract
The extensive delegation of power to international organizations (IOs) has been accompanied by occasional agency slack. While prior studies suggest that IOs’ propensity for agency slack may be rooted in their organizational characteristics, this has rarely been explored empirically. To address this lacuna, in this article we propose a conceptualization and measurement of agency slack and develop a framework of organizational characteristics. Our empirical analysis applies qualitative comparative analysis to assess the conditions under which agency slack occurs across sixteen United Nations institutions. We complement the cross-case analysis with two case illustrations. Our results document the empirical existence of two paths to agency slack, providing confirmatory evidence for our theoretical expectations. Path 1 combines staffing rules that are favorable for the agent with wide access to third parties. Path 2 entails the combination of favorable staffing rules with extensive delegation of authority and a vague organizational mandate.
All Peacekeeping is Local: Measuring Subnational Variation in Peacekeeping Effectiveness
Authors: Reeder Bryce W , Hendricks Michael , Goldring Edward 
Published: May 2022

AbstractUnderstanding whether peacekeepers reduce fatalities at the local level is an important question. We can have increased confidence in peacekeepers’ capabilities by testing whether deaths decrease in the locations where peacekeepers are present. However, commonly used modeling techniques cannot easily test peacekeepers’ local effectiveness. Coefficients from methods such as linear regression, logit, and count models provide average estimates of peacekeepers’ effects on violence. We argue that a solution lies in geographically weighted regression (GWR). GWR can more clearly reveal subnational spatial heterogeneity in peacekeepers’ (in)effectiveness at reducing violence. We conduct an illustrative test of our argument using data on the Democratic Republic of the Congo between 2001 and 2014 and replicate an existing study to show that GWR can also help resolve seemingly contradictory findings of whether peacekeepers are better at reducing violence by government or rebel actors. The article contains important implications for how scholars can more accurately measure peacekeeping effectiveness.