bluuebunny/crossref_metadata_2025_split huggingface dataset:
DOT1L complex regulates transcriptional initiation in human erythroleukemic cells
Authors: Wu Aiwei , Zhi Junhong , Tian Tian , Cihan Ali , Cevher Murat A. , Liu Ziling , David Yael , Muir Tom W. , Roeder Robert G. , Yu Ming 
Published: June 2021

Significance
DOT1L, the only H3K79 methyltransferase in human cells, forms a complex with AF10/AF17 and ENL/AF9, is dysregulated in mixed-lineage leukemia (MLLr), and is believed to regulate transcriptional elongation without direct evidence. Here, functional genomic, proteomic, and biochemical studies aimed at an understanding of the role of DOT1L in erythroleukemic cells show no major role in elongation but, surprisingly, reveal that DOT1L evidently has a role in transcriptional initiation by recruiting initiation factor TFIID and enhancing H2B mono-ubiquitination by restricting deubiquitination by the Spt-Ada-Gcn5-acetyltransferase (SAGA) complex. The results thus implicate the DOT1L complex in transcriptional initiation and raise the intriguing possibility that MLLr leukemic fusion proteins may also promote transcriptional initiation through modified DOT1L complexes.
Community benefits from !Xaus Lodge in the Kgalagadi Transfrontier Park, South Africa
Authors: Spenceley Anna 
Published: June 2021

Abstract
This case describes how !Xaus Lodge, a 24-bed community owned lodge in the remote Kgalagadi Transfrontier Park, provides employment and other economic opportunities to ‡Khomani San and Mier communities in South Africa. By partnering with the private operator Transfrontier Parks Destinations, the lodge has been able to access markets and generate positive returns for the state and rural community members.

Information
Snyman, S. and Spenceley, A. (2019) Private Sector Tourism in Conservation Areas in Africa. Chapter 4.3.3, Case study 25: !Xaus Lodge, South Africa. CAB International, pp. 116–119.
© CAB International 2021
Correct scaling of the correlation length from a theory for concentrated electrolytes
Authors: Ciach A , Patsahan O 
Published: June 2021

Abstract
Self-consistent theory for concentrated electrolytes is developed. Oscillatory decay of the charge–charge correlation function with the decay length that shows perfect agreement with the experimentally discovered and so far unexplained scaling is obtained. For the density–density correlations, monotonic asymptotic decay with the decay length comparable with the decay length of the charge correlations is found. We show that the correlation lengths in concentrated electrolytes depend crucially on the local variance of the charge density.
On a probabilistic model for martensitic avalanches incorporating mechanical compatibility
Authors: Della Porta Francesco , Rüland Angkana , Taylor Jamie M , Zillinger Christian 
Published: June 2021

AbstractBuilding on the work by Ballet al(2015MATEC Web of Conf.3302008), Cesana and Hambly (2018 A probabilistic model for interfaces in a martensitic phase transition arXiv:1810.04380), Torrentset al(2017Phys. Rev. E95013001), in this article we propose and study a simple, geometrically constrained, probabilistic algorithm geared towards capturing some aspects of the nucleation in shape-memory alloys. As a main novelty with respect to the algorithms by Ballet al(2015MATEC Web of Conf.3302008), Cesana and Hambly (2018 A probabilistic model for interfaces in a martensitic phase transition arXiv:1810.04380), Torrentset al(2017Phys. Rev. E95013001) we includemechanical compatibility. The mechanical compatibility here is guaranteed by usingconvex integration building blocksin the nucleation steps. We analytically investigate the algorithm’s convergence and the solutions’ regularity, viewing the latter as a measure for the fractality of the resulting microstructure. We complement our analysis with a numerical implementation of the scheme and compare it to the numerical results by Ballet al(2015MATEC Web of Conf.3302008), Cesana and Hambly (2018 A probabilistic model for interfaces in a martensitic phase transition arXiv:1810.04380), Torrentset al(2017Phys. Rev. E95013001).
Microwave diagnostics damage by parametric decay instabilities during electron cyclotron resonance heating in ASDEX Upgrade
Authors: Hansen S K , Jacobsen A S , Willensdorfer M , Nielsen S K , Stober J , Höfler K , Maraschek M , Fischer R , Dunne M 
Published: June 2021

Abstract
We present observations of microwave diagnostics damage in three discharges employing third-harmonic X-mode electron cylcotron resonance heating (ECRH) at the ASDEX Upgrade tokamak. In all cases, the diagnostics damage is explainable in terms of a parametric decay instability (PDI), where an X-mode ECRH wave decays to two trapped upper hybrid (UH) waves near half the ECRH frequency, followed by secondary instabilities, which generate strong microwave signals near multiples of half the ECRH frequency that cause the damage. Trapping of the UH waves near half the ECRH frequency is necessary to reduce the ECRH power required for exciting the PDIs to a level attainable at ASDEX Upgrade, and may occur when the second-harmonic UH resonance of the ECRH waves is present in a region of non-monotonic electron density, e.g. near the O-point of a magnetohydrodynamic mode or the plasma center. The diagnostics damage in the three discharges may be attributed to PDIs occurring near the O-point of a rotating mode, near the plasma center, and near the O-point of a locked mode, respectively. In the rotating mode case, the strong signals are shown to be quasi-periodic, with spikes occurring when the O-point of the mode passes through an ECRH beam, as expected. In the locked mode case, Thomson scattering profiles demonstrate the possibility of the primary PDI occurring based on experimental data for the first time under fusion-relevant conditions. Applying the framework used for ASDEX Upgrade to the X-mode ECRH scenarios planned for the early operation phase of ITER, the PDIs are found to be likely in connection with 170 GHz ECRH of half field scenarios and 104 GHz (or 110 GHz) ECRH of one third field scenarios. Finally, several strategies for mitigating diagnostics damage are proposed.
Bimodal polarons as a function of morphology in high efficiency polymer/acceptor blends for organic photovoltaics
Authors: Guo Junjun , Marin-Beloqui Jose M , Clarke Tracey M 
Published: June 2021

Abstract
The polymer PffBT4T-C9C13 (poly[(5,6-difluoro-2,1,3-benzothiadiazole-4,7-diyl)[3,3'''-bis(2-decyltetradecyl)[2,2':5',2'':5'',2'' -quaterthiophene]-5,5'''-diyl]]) produces organic solar cells of >11% efficiency with both fullerenes and non-fullerenes. We present a comprehensive morphology and spectroscopy study of this polymer and its blends, focusing on atomic force microscopy, x-ray diffraction, and transient absorption spectroscopy on microsecond timescales. Unusually, fullerene-induced ordering is observed, with the polymer/fullerene blend displaying a greater crystallinity compared to the pristine polymer. This was correlated with the appearance of bimodal polarons: fast-decaying polarons in the pristine amorphous polymer domains and trapped polarons localised in the fullerene-induced ordering (crystallline) domains. The lifetime of the trapped polaron was significantly enhanced upon thermal annealing, and the complex relationship observed between lifetime and film crystallinity suggest a contribution from trap states at the interfaces between ordered and disordered domains that lead to inhibited recombination. In contrast, blends incorporating the well-known analogue PffBT4T-2OD (with a shorter alkyl chain length) exhibit neither fullerene-induced ordering nor bimodal polarons. However, both PffBT4T-C9C13 and PffBT4T-2OD polymer blends show clear evidence of polymer triplet formation, which is the first time triplets have been identified in PffBT4T-based blends. In this study, we remark upon the complex relationship between morphology and the photophysics. This relationship will open the door to the synthesis of new molecules to control the blend morphology and thus optimise organic photovoltaic performance.
Socio-economic disparities and COVID-19 in the USA
Authors: Paul Ayan , Englert Philipp , Varga Melinda 
Published: June 2021

Abstract
COVID-19 is not a universal killer. We study the spread of COVID-19 at the county level for the United States up until the 15th of August, 2020. We show that the prevalence of the disease and the death rate are correlated with the local socio-economic conditions often going beyond local population density distributions, especially in rural areas. We correlate the COVID-19 prevalence and death rate with data from the US Census Bureau and point out how the spreading patterns of the disease show asymmetries in urban and rural areas separately and are preferentially affecting the counties where a large fraction of the population is non-white. Our findings can be used for more targeted policy building and deployment of resources for future occurrence of a pandemic due to SARS-CoV-2. Our methodology, based on interpretable machine learning and game theory, can be extended to study the spread of other diseases.
Health-Economic Value of Vaccination Against Group AStreptococcusin the United States
Authors: Andrejko Kristin , Whittles Lilith K , Lewnard Joseph A 
Published: June 2021

AbstractBackgroundVaccines are needed to reduce the burden of group A Streptococcus (GAS). We assessed the potential health-economic value of GAS vaccines achievable through prevention of invasive disease and acute upper respiratory infections in the United States.MethodsWe estimated annual incidence of invasive GAS disease and associated costs incurred from hospitalization and management of long-term sequelae, as well as productivity losses resulting from acute illness, long-term disability, and mortality. We also estimated healthcare and productivity costs associated with GAS pharyngitis, sinusitis, and acute otitis media. We estimated costs averted by prevention of invasive disease and acute upper respiratory infections for vaccines with differing efficacy profiles; our base case considered vaccines meeting the World Health Organization Preferred Product Profile (WHO-PPP) with a 6-year average duration of protection.ResultsCosts of invasive GAS disease and acute upper respiratory infections totaled $6.08 (95% confidence interval [CI], $5.33–$6.86) billion annually. Direct effects of vaccines meeting WHO-PPP characteristics and administered at ages 12 and 18 months would avert $609 (95% CI, $558–$663) million in costs annually, primarily by preventing noninvasive disease; with an additional dose at age 5 years, averted costs would total $869 (95% CI, $798–$945) million annually. Adult vaccination at age 65 years would avert $326 (95% CI, $271–$387) million in annual costs associated with invasive GAS disease. Indirect effects of vaccination programs reducing incidence of GAS diseases across all ages by 20% would avert roughly $1 billion in costs each year.ConclusionsThe economic burden of GAS is substantial. Our findings should inform prioritization of GAS vaccine development and evaluation.
Association between adiposity and cardiovascular outcomes: an umbrella review and meta-analysis of observational and Mendelian randomization studies
Authors: Kim Min Seo , Kim Won Jun , Khera Amit V , Kim Jong Yeob , Yon Dong Keon , Lee Seung Won , Shin Jae Il , Won Hong-Hee 
Published: June 2021

Abstract

Aims
The aim of this study was to investigate the causal relationship and evidence of an association between increased adiposity and the risk of incident cardiovascular disease (CVD) events or mortality.

Methods and results
Observational (informing association) and Mendelian randomization (MR) (informing causality) studies were assessed to gather mutually complementary insights and elucidate perplexing epidemiological relationships. Systematic reviews and meta-analyses of observational and MR studies that were published until January 2021 and evaluated the association between obesity-related indices and CVD risk were searched. Twelve systematic reviews with 53 meta-analyses results (including over 501 cohort studies) and 12 MR studies were included in the analysis. A body mass index (BMI) increase was associated with higher risks of coronary heart disease, heart failure, atrial fibrillation, all-cause stroke, haemorrhagic stroke, ischaemic stroke, hypertension, aortic valve stenosis, pulmonary embolism, and venous thrombo-embolism. The MR study results demonstrated a causal effect of obesity on all indices but stroke. The CVD risk increase for every 5 kg/m2 increase in BMI varied from 10% [relative risk (RR) 1.10; 95% confidence interval (CI) 1.01–1.21; certainty of evidence, low] for haemorrhagic stroke to 49% (RR 1.49; 95% CI 1.40–1.60; certainty of evidence, high) for hypertension. The all-cause and CVD-specific mortality risks increased with adiposity in cohorts, but the MR studies demonstrated no causal effect of adiposity on all-cause mortality.

Conclusion
High adiposity is associated with increased CVD risk despite divergent evidence gradients. Adiposity was a causal risk factor for CVD except all-cause mortality and stroke. Half (49%; 26/53) of the associations were supported by high-level evidence. The associations were consistent between sexes and across global regions. This study provides guidance on how to integrate evidence from observational (association) and genetics-driven (causation) studies accumulated to date, to enable a more reliable interpretation of epidemiological relationships.
Different circulating biomarkers in women and men with paroxysmal atrial fibrillation: results from the AF-RISK and RACE V studies
Authors: De With Ruben R , Artola Arita Vicente , Nguyen Bao-Oanh , Linz Dominik , Ten Cate Hugo , Spronk Henri , Schotten Ulrich , Jan van Zonneveld Anton , Erküner Ömer , Bayón M Agustina , Schmidt Anders S , Luermans Justin G L M , Crijns Harry J G M , Van Gelder Isabelle C , Rienstra Michiel 
Published: June 2021

Abstract

Aims
The clinical risk profile of atrial fibrillation (AF) patients is different in men and women. Our aim was to identify sex differences in blood biomarkers in patients with paroxysmal AF.

Methods and results
Sex differences in 92 blood biomarkers were measured in 364 patients included in our discovery cohort, the identification of a risk profile to guide atrial fibrillation therapy (AF-RISK) study, assessed by multivariable logistic regression and enrichment pathway analysis. Findings were subsequently confirmed in 213 patients included in our validation cohort, the Reappraisal of Atrial Fibrillation: Interaction between HyperCoagulability, Electrical remodelling, and Vascular Destabilisation in the Progression of AF (RACE V) study. In the discovery cohort, mean age was 59 ± 12 years, 41% were women. CHA2DS2-VASc-score was 1.6 ± 1.4. A total of 46% had hypertension, 10% diabetes, and 50% had heart failure, predominantly with preserved ejection fraction (47%). In women, activated leucocyte cell adhesion molecule (ALCAM) and fatty acid binding protein-4 (FABP-4) were higher. In men, matrix metalloproteinase-3 (MMP-3), C-C motif chemokine-16 (CCL-16), and myoglobin were higher. In the validation cohort, four out of five biomarkers could be confirmed: levels of ALCAM (P = 1.73 × 10–4) and FABP-4 (P = 2.46 × 10–7) and adhesion biological pathways [false discovery rate (FDR) = 1.23 × 10–8] were higher in women. In men, levels of MMP-3 (P = 4.31 × 10–8) and myoglobin (P = 2.10 × 10–4) and markers for extracellular matrix degradation biological pathways (FDR = 3.59 × 10–9) were higher.

Conclusion
In women with paroxysmal AF, inflammatory biomarkers were more often higher, while in men with paroxysmal AF, biomarkers for vascular remodelling were higher. Our data support the clinical notion that pathophysiological mechanisms in women and men with AF may differ.

Trial registration
Clinicaltrials.gov identifier NCT01510210 for AF-RISK; Clinicaltrials.gov NCT02726698 for RACE V.
Uridine diphosphate-N-acetylglucosamine-2-epimerase/N-acetylmannosamine kinasedeletion in mice leads to lethal intracerebral hemorrhage during embryonic development
Authors: Wedekind Henri , Kats Elina , Weiss Anna-Carina , Thiesler Hauke , Klaus Christine , Kispert Andreas , Horstkorte Rüdiger , Neumann Harald , Weinhold Birgit , Münster-Kühnel Anja , Abeln Markus 
Published: June 2021

AbstractAmong the enzymes of the biosynthesis of sialoglycoconjugates, uridine diphosphate-N-acetylglucosamine-2-epimerase/N-acetylmannosamine kinase (GNE), catalyzing the first essential step of the sialic acid (Sia) de novo biosynthesis, and cytidine monophosphate (CMP)-Sia synthase (CMAS), activating Sia to CMP-Sia, are particularly important. The knockout of either of these enzymes in mice is embryonically lethal. While the lethality of Cmas−/− mice has been attributed to a maternal complement attack against asialo fetal placental cells, the cause of lethality in Gne-deficient embryos has remained elusive. Here, we advanced the significance of sialylation for embryonic development through detailed histological analyses of Gne−/− embryos and placentae. We found that Gne−/− embryonic and extraembryonic tissues are hyposialylated rather than being completely deficient of sialoglycans, which holds true for Cmas−/− embryos. Residual sialylation of Gne−/− cells can be explained by scavenging free Sia from sialylated maternal serum glycoconjugates via the lysosomal salvage pathway. The placental architecture of Gne−/− mice was unaffected, but severe hemorrhages in the neuroepithelium with extensive bleeding into the cephalic ventricles were present at E12.5 in the mutants. At E13.5, the vast majority of Gne−/− embryos were asystolic. This phenotype persisted when Gne−/− mice were backcrossed to a complement component 3-deficient background, confirming distinct pathomechanisms of Cmas−/− and Gne−/− mice. We conclude that the low level of sialylation observed in Gne−/− mice is sufficient both for immune homeostasis at the fetal–maternal interface and for embryonic development until E12.5. However, formation of the neural microvasculature is the first critical process, depending on a higher degree of sialylation during development of the embryo proper.
Community engagement in deprived neighbourhoods during the COVID-19 crisis: perspectives for more resilient and healthier communities
Authors: den Broeder Lea , South Jane , Rothoff Auke , Bagnall Anne-Marie , Azarhoosh Firoez , van der Linden Gina , Bharadwa Meena , Wagemakers Annemarie 
Published: June 2021

SummaryThe current COVID-19 pandemic confines people to their homes, disrupting the fragile social fabric of deprived neighbourhoods and citizen’s participation options. In deprived neighbourhoods, community engagement is central in building community resilience, an important resource for health and a prerequisite for effective health promotion programmes. It provides access to vulnerable groups and helps understand experiences, assets, needs and problems of citizens. Most importantly, community activities, including social support, primary care or improving urban space, enhance health through empowerment, strengthened social networks, mutual respect and providing a sense of purpose and meaning. In the context of inequalities associated with COVID-19, these aspects are crucial for citizens of deprived neighbourhoods who often feel their needs and priorities are ignored. In this perspectives paper, illustrated by a varied overview of community actions in the UK and The Netherlands, we demonstrate how citizens, communities and organizations may build resilience and community power. Based on in-depth discussion among the authors we distilled six features of community actions: increase in mutual aid and neighbourhood ties, the central role of community-based organizations (CBOs), changing patterns of volunteering, use of digital media and health promotion opportunities. We argue that in order to enable and sustain resilient and confident, ‘disaster-proof’, communities, areas which merit investment include supporting active citizens, new (digital) ways of community engagement, transforming formal organizations, alignment with the (local) context and applying knowledge in the field of health promotion in new ways, focussing on learning and co-creation with citizen initiatives.
Antibiotic prescription policy for acute otitis media: do we follow the guidelines?
Authors: Marom Tal , Shefer Galit , Tshori Sagi , Mingelgrin Shira , Pitaro Jacob 
Published: June 2021

Abstract

Background
Acute otitis media (AOM) is a common cause for antibiotic prescription. Most guidelines endorse abstaining from immediate antibiotic treatment (‘watchful waiting’, WW) in mild–moderate episodes. We studied adherence rates to the latest AOM guidelines (2013), in terms of antibiotic type and prescription options.

Methods
In this population-based study, AOM episodes were identified in Clalit Health Services-insured children aged 0–10 years between 2011 and 2018, using a data-sharing platform. After identifying the index, prescription and issuing dates for antibiotics for each AOM episode, treatment was categorized as immediate (≤2 days after diagnosis) or WW (antibiotic not prescribed/issued; prescribed ≤2 days after diagnosis but issued on Days 2–7; or prescribed/issued on Days 2–7). Guideline adherence was measured according to age.

Results
Of the 491 106 episodes, 361 518 (73.6%) were treated with antibiotics. Following the 2013 guidelines, the ratio of episodes in children aged ≤6 months that were adherent (immediate treatment) was higher (OR = 1.22; 95% CI 1.15–1.29; P &lt; 0.001), whereas the adherent episode ratio for children aged 6–24 months and 2–10 years (WW) was lower (OR = 0.87; 95% CI 0.85–0.88 and OR = 0.94; 95% CI 0.92–0.96, respectively; P &lt; 0.001). Antibiotic prescription rates after 2013 for children aged ≤6 months were not different (OR = 1.03; 95% CI 0.96–1.1; P = 0.4), but were higher in children aged 6–24 months and 2–10 years (OR = 1.07; 95% CI 1.05–1.09; P &lt; 0.001 and OR = 1.02; 95% CI 1.01–1.04; P = 0.015, respectively). Amoxicillin was the most common antibiotic, administered in 75.6% of episodes. Azithromycin was most commonly associated with treatment failure (6.6%).

Conclusions
Improved adherence to the 2013 guidelines was observed only in children aged ≤6 months and over-treatment with antibiotics was still high.