bluuebunny/crossref_metadata_2025 huggingface dataset:
Longer or shorter dual antiplatelet therapy in dialysis patients receiving a coronary drug-eluting stent? A rope game still ongoing
Authors: Burlacu Alexandru , Covic Adrian
Published: March 2020

In this issue of Clinical Kidney Journal, Park et al. presents the results of a nationwide population-based trial that included >5000 dialysis patients receiving a drug-eluting stent (DES). The main objective was to evaluate the effectiveness and the safety of prolonged dual antiplatelet therapy (DAPT). The primary outcome was a composite of mortality, non-fatal myocardial infarction, coronary revascularization and stroke, significantly lowered by a longer DAPT regimen at 12, 15 and 18 months, respectively. Longer DAPT tended to be correlated with higher bleeding events at all landmarks, with no statistical significance. An important element was that almost 75% of the index events were acute coronary syndromes. This study presents the first solid evidence for a significant benefit of prolonged DAPT in dialysis patients receiving a DES. We believe that end-stage renal disease is still in the middle of a rope game, being pulled to one side or another by other features, inclining towards a higher bleeding risk or towards higher ischaemic risk. The acute versus elective presentation seems to weigh in choosing the antiplatelet regimen. The ‘one-size-fits-all strategy’ is not suitable for this particular group. Probably in the future, practitioners will be provided with decision pathways generated by artificial intelligence algorithms yielding ‘truly individualized’ DAPT protocols for every single patient.
25-Hydroxyvitamin D and Risk of Osteoporotic Fractures: Mendelian Randomization Analysis in 2 Large Population-Based Cohorts
Authors: Çolak Yunus , Afzal Shoaib , Nordestgaard Børge G
Published: March 2020

Background

Whether low plasma 25-hydroxyvitamin D concentrations cause osteoporotic fractures is unclear. We tested the hypothesis that low plasma 25-hydroxyvitamin D concentrations are associated with increased risk of osteoporotic fractures using a Mendelian randomization analysis.

Methods

We genotyped 116 335 randomly chosen white Danish persons aged 20–100 years in 2 population-based cohort studies for plasma 25-hydroxyvitamin D decreasing genotypes in CYP2R1 (rs117913124 and rs12794714), DHCR7 (rs7944926 and rs11234027), GEMIN2 (rs2277458), and HAL (rs3819817); 35 833 had information on plasma 25-hydroxyvitamin D. We assessed risk of total, osteoporotic, and anatomically localized fractures from 1981 through 2017. Information on fractures and vital status was obtained from nationwide registries.

Results

During up to 36 years of follow-up, we observed 17 820 total fractures, 10 861 osteoporotic fractures, and 3472 fractures of hip or femur. Compared with individuals with 25-hydroxyvitamin D ≥ 50nmol/L, multivariable adjusted hazard ratios (95% CIs) for total fractures were 1.03 (0.97–1.09) for individuals with 25–49.9 nmol/L, 1.19 (1.10–1.28) for individuals with 12.5–24.9 nmol/L, and 1.39 (1.21–1.60) for individuals with 25-hydroxyvitamin D < 12.5 nmol/L. Corresponding hazard ratios were 1.07 (1.00–1.15), 1.25 (1.13–1.37), and 1.49 (1.25–1.77) for osteoporotic fractures and 1.09 (0.98–1.22), 1.37 (1.18–1.57), and 1.41 (1.09–1.81) for fractures of hip or femur, respectively. Hazard ratios per 1 increase in vitamin D allele score, corresponding to 3.0% (approximately 1.6 nmol/L) lower 25-hydroxyvitamin D concentrations, were 0.99 (0.98–1.00) for total fractures, 0.99 (0.97–1.00) for osteoporotic fractures, and 0.98 (0.95–1.00) for fractures of hip or femur.

Conclusions

Low plasma 25-hydroxyvitamin D concentrations were associated with osteoporotic fractures; however, Mendelian randomization analysis provided no evidence supporting a causal role for vitamin D in the risk for osteoporotic fractures.
ASFVdb: an integrative resource for genomic and proteomic analyses of African swine fever virus
Authors: Zhu Zhenglin , Meng Geng
Published: March 2020

The recent outbreaks of African swine fever (ASF) in China and Europe have threatened the swine industry globally. To control the transmission of ASF virus (ASFV), we developed the African swine fever virus database (ASFVdb), an online data visualization and analysis platform for comparative genomics and proteomics. On the basis of known ASFV genes, ASFVdb reannotates the genomes of every strain and newly annotates 5352 possible open reading frames (ORFs) of 45 strains. Moreover, ASFVdb performs a thorough analysis of the population genetics of all the published genomes of ASFV strains and performs functional and structural predictions for all genes. Users can obtain not only basic information for each gene but also its distribution in strains and conserved or high mutation regions, possible subcellular location and topology. In the genome browser, ASFVdb provides a sliding window for results of population genetic analysis, which facilitates genetic and evolutionary analyses at the genomic level. The web interface was constructed based on SWAV 1.0. ASFVdb is freely accessible at http://asfvdb.popgenetics.net.
Non-obstructive high-risk plaques increase the risk of future culprit lesions comparable to obstructive plaques without high-risk features: the ICONIC study
Authors: Ferraro Richard A , van Rosendael Alexander R , Lu Yao , Andreini Daniele , Al-Mallah Mouaz H , Cademartiri Filippo , Chinnaiyan Kavitha , Chow Benjamin J W , Conte Edoardo , Cury Ricardo C , Feuchtner Gudrun , de Araújo Gonçalves Pedro , Hadamitzky Martin , Kim Yong-Jin , Leipsic Jonathon , Maffei Erica , Marques Hugo , Plank Fabian , Pontone Gianluca , Raff Gilbert L , Villines Todd C , Lee Sang-Eun , Al’Aref Subhi J , Baskaran Lohendran , Cho Iksung , Danad Ibrahim , Gransar Heidi , Budoff Matthew J , Samady Habib , Stone Peter H , Virmani Renu , Narula Jagat , Berman Daniel S , Chang Hyuk-Jae , Bax Jeroen J , Min James K , Shaw Leslee J , Lin Fay Y
Published: March 2020

Aims

High-risk plaque (HRP) and non-obstructive coronary artery disease independently predict adverse events, but their importance to future culprit lesions has not been resolved. We sought to determine in patients prior to confirmed acute coronary syndrome (ACS) the association between lesion percent diameter stenosis (%DS), and the absolute number and prevalence of HRP. The secondary objective was to examine the relative importance of non-obstructive HRP in future culprit lesions.

Methods and results

Within the ICONIC study, a nested case–control study of patients undergoing coronary computed tomographic angiography (coronary CT), we included ACS cases with culprit lesions confirmed by invasive coronary angiography and coregistered to baseline coronary CT. Quantitative CT was used to evaluate obstructive (≥50%) and non-obstructive (<50%) diameter stenosis, with HRP defined as ≥2 features of spotty calcification, positive remodelling, or low-attenuation plaque at baseline. A total of 234 patients with downstream ACS over 54 (interquartile range 5–525.5) days exhibited 198/898 plaques with HRP on coronary CT. While HRP was less prevalent in non-obstructive (19.7%, 161/819) than obstructive lesions (46.8%, 37/79, P < 0.001), non-obstructive plaque comprised 81.3% (161/198) of HRP lesions overall. Among the 128 patients with identifiable culprit lesion precursors, the adjusted hazard ratio (HR) was 1.85 [95% confidence interval (CI) 1.26–2.72] for HRP, with no interaction between %DS and HRP (P = 0.82). Compared to non-obstructive HRP lesions, obstructive lesions without HRP exhibited a non-significant HR of 1.41 (95% CI 0.61–3.25, P = 0.42).

Conclusions

While HRP is more prevalent among obstructive lesions, non-obstructive HRP lesions outnumber those that are obstructive and confer risk clinically approaching that of obstructive lesions without HRP.
The Tribulations of Trials: Lessons Learnt Recruiting 777 Older Adults Into REtirement in ACTion (REACT), a Trial of a Community, Group-Based Active Aging Intervention Targeting Mobility Disability
Authors: Withall Janet , Greaves Colin J , Thompson Janice L , de Koning Jolanthe L , Bollen Jessica C , Moorlock Sarah J , Fox Kenneth R , Western Max J , Snowsill Tristan , Medina-Lara Antonieta , Cross Rosina , Ladlow Peter , Taylor Gordon , Zisi Vasiliki , Clynes James , Gray Selena , Agyapong-Badu Sandra , Guralnik Jack M , Rejeski W Jack , Stathi Afroditi
Published: March 2020

Background

Challenges of recruitment to randomized controlled trials (RCTs) and successful strategies to overcome them should be clearly reported to improve recruitment into future trials. REtirement in ACTion (REACT) is a United Kingdom-based multicenter RCT recruiting older adults at high risk of mobility disability to a 12-month group-based exercise and behavior maintenance program or to a minimal Healthy Aging control intervention.

Methods

The recruitment target was 768 adults, aged 65 years and older scoring 4–9 on the Short Physical Performance Battery (SPPB). Recruitment methods include the following: (a) invitations mailed by general practitioners (GPs); (b) invitations distributed via third-sector organizations; and (c) public relations (PR) campaign. Yields, efficiency, and costs were calculated.

Results

The study recruited 777 (33.9% men) community-dwelling, older adults (mean age 77.55 years (SD 6.79), mean SPPB score 7.37 (SD 1.56)), 95.11% white (n = 739) and broadly representative of UK quintiles of deprivation. Over a 20-month recruitment period, 25,559 invitations were issued. Eighty-eight percent of the participants were recruited via GP invitations, 5.4% via the PR campaign, 3% via word-of-mouth, and 2.5% via third-sector organizations. Mean recruitment cost per participant was £78.47, with an extra £26.54 per recruit paid to GPs to cover research costs.

Conclusions

REACT successfully recruited to target. Response rates were lower than initially predicted and recruitment timescales required adjustment. Written invitations from GPs were the most efficient method for recruiting older adults at risk of mobility disability. Targeted efforts could achieve more ethnically diverse cohorts. All trials should be required to provide recruitment data to enable evidence-based planning of future trials.
Blood DNA Methylation and Aging: A Cross-Sectional Analysis and Longitudinal Validation in the InCHIANTI Study
Authors: Tharakan Ravi , Ubaida-Mohien Ceereena , Moore Ann Zenobia , Hernandez Dena , Tanaka Toshiko , Ferrucci Luigi
Published: March 2020

Changes in DNA methylation have been found to be highly correlated with aging in humans, but causes or consequences of these changes are not understood. We characterized the DNA methylomes of several hundred people in the Invecchiare in Chianti study to identify DNA sites in which percent methylation was systematically different with age. Then, we tested the hypothesis that changes of percent methylation in the same DNA sites occur longitudinally for the same DNA sites in the same subjects. We identified six differentially methylated regions in which percent methylation showed robust longitudinal changes in the same direction. We then describe functions of the genes near these differentially methylated regions and their potential relationship with aging, noting that the genes appear to regulate metabolism or cell type specificity. The nature of transcription factor binding sites in the vicinity of these differentially methylated regions suggest that these age-associated methylation changes reflect modulation of two biological mechanisms: the polycomb repressive complex 2, a protein complex that trimethylates histone H3 on lysine 27, and the transcriptional repressor CCCTC-binding factor or CTCF, both of which are regulators of chromatin architecture. These findings are consistent with the idea that changes in methylation with aging are of adaptive nature.
Chronic Polypharmacy with Increasing Drug Burden Index Exacerbates Frailty and Impairs Physical Function, with Effects Attenuated by Deprescribing, in Aged Mice
Authors: Mach John , Gemikonakli Gizem , Logan Caitlin , Vander Wyk Brent , Allore Heather , Ekambareshwar Swathi , Kane Alice E , Howlett Susan E , de Cabo Rafael , Le Couteur David G , Hilmer Sarah N
Published: March 2020

Polypharmacy (use of ≥5 medications) and increasing Drug Burden Index (DBI) score (measure of person’s total exposure to anticholinergic/sedative medications) are associated with impaired physical function in observational studies of older adults. Deprescribing, the supervised withdrawal of medications for which harms outweigh benefits for an individual, may be a useful intervention. Current knowledge is limited to clinical observational studies that are unable to determine causality. Here, we establish a preclinical model that investigates the effects of chronic polypharmacy, increasing DBI, and deprescribing on global health outcomes in aging. In a longitudinal study, middle-aged (12 months) male C57BL/6J (B6) mice were administered control feed or feed and/or water containing polypharmacy or monotherapy with different DBI scores. At 21 months, each treatment group was subdivided (stratified by frailty at 21 months) to either continue on treatment for life or to have treatment withdrawn (deprescribed). Frailty and physical function were evaluated at 12, 15, 18, and 24 months, and were analyzed using a mixed modeling approach. Polypharmacy with increasing DBI and monotherapy with citalopram caused mice to become frailer, less mobile, and impaired their strength and functional activities. Critically, deprescribing in old age reversed a number of these outcomes. This is the first preclinical study to demonstrate that chronic polypharmacy with increasing DBI augments frailty and impairs function in old age, and that drug withdrawal in old age reversed these outcomes. It was not the number of drugs (polypharmacy) but the type and dose of drugs (DBI) that caused adverse geriatric outcomes.
Dissecting the Racial/Ethnic Disparity in Frailty in a Nationally Representative Cohort Study with Respect to Health, Income, and Measurement
Authors: Usher Therri , Buta Brian , Thorpe Roland J , Huang Jin , Samuel Laura J , Kasper Judith D , Bandeen-Roche Karen
Published: March 2020

Background

Racial/ethnic frailty prevalence disparities have been documented. Better elucidating how these operate may inform interventions to eliminate them. We aimed to determine whether physical frailty phenotype (PFP) prevalence disparities (i) are explained by health aspects, (ii) vary by income, or (iii) differ in degree across individual PFP criteria.

Methods

Data came from the 2011 National Health and Aging Trends Study baseline evaluation. The study sample (n = 7,439) included persons in all residential settings except nursing homes. Logistic regression was used to achieve aims (i)–(iii) listed above. In (i), health aspects considered were body mass index (BMI) status and number of chronic diseases. Analyses incorporated sampling weights and adjusted for sociodemographic factors.

Results

Comparisons are versus non-Hispanic whites: Non-Hispanic blacks (odds ratio [OR] = 1.46, 95% confidence interval [CI]: 1.21–1.76) and Hispanics (1.56, 1.20–2.03) continued to have higher odds of frailty after accounting for BMI status and number of chronic diseases. Non-Hispanic blacks had elevated odds of frailty in all income quartiles, including the highest (OR = 2.19, 1.24–3.397). Racial/ethnic disparities differed considerably across frailty criteria, ranging from a twofold increase in odds of slowness to a 25%–30% decrease in odds of self-reported exhaustion.

Conclusions

BMI and disease burden do not explain racial/ethnic frailty disparities. Black–white disparities are not restricted to low-income groups. Racial/ethnic differences vary considerably by NHATS PFP criteria. Our findings support the need to better understand mechanisms underlying elevated frailty burden in older non-Hispanic black and Hispanic Americans, how phenotypic measures capture frailty in racial/ethnic subgroups and, potentially, how to create assessments more comparable by race/ethnicity.
Early Retirement, Social Class, and Family Relationships in Cloutier’s Bonne retraite, Jocelyne (2018)
Authors: Mina-Riera Núria , Voyer Véronique
Published: March 2020

Background and Objectives

Aging women are continuously underrepresented in performing arts. An exception to this trend in Québec is Fabien Cloutier’s latest play Bonne retraite, Jocelyne (2018), whose protagonist is a middle-aged woman who has decided to take early retirement. This article aims at examining the interplay between the protagonist’s voluntary early retirement, gender, social class, and family relationships.

Research Design and Methods

This article mobilizes the theoretical framework of aging studies, which is underdeveloped in the French academic sphere. This qualitative case study connects gender issues and performative strategies in order to study a complex phenomenon within its context.

Results

We showed that Cloutier provides new representations of middle-aged women in his play, a corrective to the under-representation of such an age group of actors and actresses in Québec. Our results cast a new light on the combination of class privilege, gender, and ageism, as a most fruitful research orientation to be further developed in the future in order to pursue an in-depth analysis of early retirement.

Discussion and Implications

The play reveals that belonging to the upper-middle class is essential in order to be able, economically speaking, to retire early. Cloutier empowers Jocelyne both as an aging individual and as a woman by means of granting her the right to make her own decisions in life.
Introgression of Eastern Chinese and Southern Chinese haplotypes contributes to the improvement of fertility and immunity in European modern pigs
Authors: Chen Hao , Huang Min , Yang Bin , Wu Zhongping , Deng Zheng , Hou Yong , Ren Jun , Huang Lusheng
Published: March 2020

Background

Pigs were domesticated independently from European and Asian wild boars nearly 10,000 years ago. Chinese indigenous pigs have been historically introduced to improve Europe local pigs. However, the geographic origin and biological functions of introgressed Chinese genes in modern European pig breeds remain largely unknown.

Results

Here we explored whole-genome sequencing data from 266 Eurasian wild boars and domestic pigs to produce a fine-scale map of introgression between French Large White (FLW) and Chinese pigs. We show that FLW pigs had historical admixture with both Southern Chinese (SCN) and Eastern Chinese (ECN) pigs ~200–300 years ago. Moreover, a set of SCN haplotypes was shown to be beneficial for improving disease resistance and ECN haplotypes are favorable for improved reproductive performance in FLW pigs. In addition, we confirm human-mediated introgression events at the AHR locus, at which the haplotype of most likely ECN origin contributes to increased fertility of FLW pigs.

Conclusions

This study advances our understanding of the breeding history of global domestic pigs and highlights the importance of artificial introgression in the formation of phenotypic characteristics in domestic animals.
Quantification and Characterization of Phenolic Compounds from Northern Indian Propolis Extracts and Dietary Supplements
Authors: Avula Bharathi , Sagi Satyanarayanaraju , Masoodi Mubashir H , Bae Ji-Yeong , Wali Adil F , Khan Ikhlas A
Published: March 2020

Background

Propolis is a resinous substance produced by bees. Propolis extracts have been used for anti-inflammatory and antimicrobial activities. The use of propolis dietary supplements has been increasing in the United States and the rest of the world.

Objective

A simple, economic, and valid analytical method is needed for quality assessment of dietary supplements and extracts claiming to contain propolis.

Methods

A ultra-high performance liquid chromatography (UHPLC) quadropole time-of-flight-MS method was used to characterize the chemical composition of northern Indian propolis. Fourteen major phenolic compounds were quantified using a UHPLC-DAD method. An HPTLC method was used to develop chemical fingerprinting profiles for propolis extracts and dietary supplements. The seven propolis extracts and 14 dietary supplements purchased in the U.S. were analyzed using the UHPLC-DAD-QToF method.

Results

Fifty-seven compounds belonging to phenolic, coumarin, fatty acid, and terpene classes were identified in propolis extracts. Based on quantification results, the content of 14 phenolic compounds in propolis extracts varied from 19–32% in dietary supplements, a significant variation to the recommended daily intake (0.2–94 mg/day).

Conclusions/Highlights

The developed analytical methods can be used for quality assessment of propolis extracts and dietary supplements.
Multiple Respiratory Syncytial Virus Introductions Into a Neonatal Intensive Care Unit
Authors: Rose Erica Billig , Washington Erica J , Wang Lijuan , Benowitz Isaac , Thornburg Natalie J , Gerber Susan I , Peret Teresa C T , Langley Gayle E
Published: March 2020

Background

Outbreaks of respiratory syncytial virus (RSV) in neonatal intensive care units (NICUs) are of concern because of the risk of severe disease in young infants. We describe an outbreak of RSV in a NICU and use whole genome sequencing (WGS) to better understand the relatedness of viruses among patients.

Methods

An investigation was conducted to identify patients and describe their clinical course. Infection control measures were implemented to prevent further spread. Respiratory specimens from outbreak-related patients and the community were tested using WGS. Phylogenetic trees were constructed to understand relatedness of the viruses.

Results

Seven patients developed respiratory symptoms within an 11-day span in December 2017 and were diagnosed with RSV; 6 patients (86%) were preterm and 1 had chronic lung disease. Three patients required additional respiratory support after symptom onset, and none died. Six of 7 patients were part of the same cluster based on > 99.99% nucleotide agreement with each other and 3 unique single-nucleotide polymorphisms were identified in viruses sequenced from those patients. The seventh patient was admitted from the community with respiratory symptoms and had a genetically distinct virus that was not related to the other 6. Implementation of enhanced infection control measures likely limited the spread.

Conclusions

Using WGS, we found 2 distinct introductions of RSV into a NICU, highlighting the risk of healthcare-associated infections during RSV season. Early recognition and infection control measures likely limited spread, emphasizing the importance of considering RSV in the differential diagnosis of respiratory infections in healthcare settings.
Differentiating disc and black hole-driven jets with EHT images of variability in M87
Authors: Jeter Britton , Broderick Avery E , Gold Roman
Published: March 2020

Millimetre-wavelength very long baseline interferometric (mm-VLBI) observations of M87 by the Event Horizon Telescope (EHT) should provide a unique opportunity to observe and characterize the origins of jet variability already seen at longer wavelengths. Synchrotron spot models have been used to model variability near black holes; this work extends these by allowing spots to shear and deform in the jet velocity field. Depending on the position of the spot, shearing forces can significantly alter the structure of the spot, producing distinct signals in reconstructed images and light curves. The maximum intensity of the shearing spot can vary by as much as a factor of 5 depending on the spot azimuthal launch position, but the intensity decay time depends most significantly on the spot radial launch position. Spots launched by a black hole-driven jet exhibit distinct arc structures in reconstructed images, and exhibit brighter and shorter lived enhancements of the light curve. Spots launched by a wind-driven jet have exhibit much simpler structures in the image, and longer lived light-curve enhancements than spots launched by a black hole-driven jet.
Probing the size and charge of polycyclic aromatic hydrocarbons
Authors: Maragkoudakis A , Peeters E , Ricca A
Published: March 2020

We present a new method to accurately describe the ionization fraction and the size distribution of polycyclic aromatic hydrocarbons (PAHs) within astrophysical sources. To this purpose, we have computed the mid-infrared emission spectra of 308 PAH molecules of varying sizes, symmetries, and compactness, generated in a range of radiation fields. We show that the intensity ratio of the solo CH out-of-plane bending mode in PAH cations and anions (referred to as the ‘11.0’ μm band, falling in the 11.0–11.3 μm region for cations and anions) to their 3.3 μm emission scales with PAH size, similarly to the scaling of the 11.2/3.3 ratio with the number of carbon atoms (NC) for neutral molecules. Among the different PAH emission bands, it is the 3.3 μm band intensity that has the strongest correlation with NC, and drives the reported PAH intensity ratio correlations with NC for both neutral and ionized PAHs. The 6.2/7.7 intensity ratio, previously adopted to track PAH size, shows no evident scaling with NC in our large sample. We define a new diagnostic grid space to probe PAH charge and size, using the (11.2 + 11.0)/7.7 and (11.2 + 11.0)/3.3 PAH intensity ratios, respectively. We demonstrate the application of the (11.2 + 11.0)/7.7–(11.2 + 11.0)/3.3 diagnostic grid for galaxies M82 and NGC 253, for the planetary nebula NGC 7027, and the reflection nebulae NGC 2023 and NGC 7023. Finally, we provide quantitative relations for PAH size determination depending on the ionization fraction of the PAHs and the radiation field they are exposed to.
Neural physical engines for inferring the halo mass distribution function
Authors: Charnock Tom , Lavaux Guilhem , Wandelt Benjamin D , Sarma Boruah Supranta , Jasche Jens , Hudson Michael J
Published: March 2020

An ambitious goal in cosmology is to forward model the observed distribution of galaxies in the nearby Universe today from the initial conditions of large-scale structures. For practical reasons, the spatial resolution at which this can be done is necessarily limited. Consequently, one needs a mapping between the density of dark matter averaged over ∼Mpc scales and the distribution of dark matter haloes (used as a proxy for galaxies) in the same region. Here, we demonstrate a method for determining the halo mass distribution function by learning the tracer bias between density fields and halo catalogues using a neural bias model. The method is based on the Bayesian analysis of simple, physically motivated, neural network-like architectures, which we denote as neural physical engines, and neural density estimation. As a result, we are able to sample the initial phases of the dark matter density field while inferring the parameters describing the halo mass distribution function, providing a fully Bayesian interpretation of both the initial dark matter density distribution and the neural bias model. We successfully run an upgraded borg (Bayesian Origin Reconstruction from Galaxies) inference using our new likelihood and neural bias model with halo catalogues derived from full N-body simulations. In preliminary results, we notice there could potentially be orders of magnitude improvement in modelling compared to classical biasing techniques.
Binary–binary scattering in the secular limit
Authors: Hamers Adrian S , Samsing Johan
Published: March 2020

Binary–binary interactions are important in a number of astrophysical contexts including dense stellar systems such as globular clusters. Although less frequent than binary–single encounters, binary–binary interactions lead to a much richer range of possibilities such as the formation of stable triple systems. Here, we focus on the regime of distant binary–binary encounters, i.e. two binaries approaching each other on an unbound orbit with a periapsis distance Q much larger than the internal binary separations. This ‘secular’ regime gives rise to changes in the orbital eccentricities and orientations, which we study using analytic considerations and numerical integrations. We show that ‘direct’ interactions between the three orbits only occur starting at a high expansion order of the Hamiltonian (hexadecupole order), and that the backreaction of the outer orbit on the inner two orbits at lower expansion orders is weak. Therefore, to good approximation, one can obtain the changes of each orbit by using previously known analytic results for binary–single interactions, and replacing the mass of the third body with the total mass of the companion binary. Nevertheless, we find some dependence of the ‘binarity’ of the companion binary, and derive explicit analytic expressions for the secular changes that are consistent with numerical integrations. In particular, the eccentricity and inclination changes of orbit 1 due to orbit 2 scale as ϵSA, 1(a2/Q)2[m3m4/(m3 + m4)2], where ϵSA, 1 is the approximate quadrupole-order change, and a2 and (m3, m4) are the companion binary orbital semimajor axis and component masses, respectively. Our results are implemented in several python scripts that are freely available.
Aortic heterogeneity across segments and under high fat/salt/glucose conditions at the single-cell level
Authors: He Dongxu , Mao Aiqin , Zheng Chang-Bo , Kan Hao , Zhang Ka , Zhang Zhiming , Feng Lei , Ma Xin
Published: March 2020

The aorta, with ascending, arch, thoracic and abdominal segments, responds to the heartbeat, senses metabolites and distributes blood to all parts of the body. However, the heterogeneity across aortic segments and how metabolic pathologies change it are not known. Here, a total of 216 612 individual cells from the ascending aorta, aortic arch, and thoracic and abdominal segments of mouse aortas under normal conditions or with high blood glucose levels, high dietary salt, or high fat intake were profiled using single-cell RNA sequencing. We generated a compendium of 10 distinct cell types, mainly endothelial (EC), smooth muscle (SMC), stromal and immune cells. The distributions of the different cells and their intercommunication were influenced by the hemodynamic microenvironment across anatomical segments, and the spatial heterogeneity of ECs and SMCs may contribute to differential vascular dilation and constriction that were measured by wire myography. Importantly, the composition of aortic cells, their gene expression profiles and their regulatory intercellular networks broadly changed in response to high fat/salt/glucose conditions. Notably, the abdominal aorta showed the most dramatic changes in cellular composition, particularly involving ECs, fibroblasts and myeloid cells with cardiovascular risk factor-related regulons and gene expression networks. Our study elucidates the nature and range of aortic cell diversity, with implications for the treatment of metabolic pathologies.
Cytomegalovirus in Adult Allogeneic Blood and Marrow Transplant Patients Before or Around the Period of Neutrophil Recovery: A Single-Center, Retrospective, Descriptive Study
Authors: Martin Isabella , Valsamakis Alexandra , Gladstone Douglas , Jones Richard , Ambinder Richard , Avery Robin K
Published: March 2020

Background

Few reports exist on pre-engraftment cytomegalovirus (CMV) DNAemia in allogeneic blood or marrow transplant (allo BMT) recipients. We describe this clinical entity, its management, and the potential effect of 3 different quantitative CMV deoxyribonucleic acid (DNA) tests used during the 6-year study period.

Methods

We performed a retrospective, single-center study of allo BMT recipients from 2010 to 2015 who developed CMV DNAemia before neutrophil recovery (absolute neutrophil count [ANC] <1000 cells/mm3, “pre-engraftment CMV”) or who became neutropenic concomitant with detectable CMV DNA (“peri-engraftment CMV”). Clinical data were collected from the electronic medical record.

Results

Among 1151 adult allo BMT patients, 73 developed CMV DNAemia before engraftment or while neutropenic after initial engraftment. Most patients were eventually treated (valganciclovir or ganciclovir, N = 68; foscarnet, N = 1); 4 were not treated. First CMV detection occurred at median day +12 (range, 0–48), but treatment was not started until median day +33 (range, 4–105) at median ANC of 760 cells/mm3. Six patients had peak viral loads >5000 IU/mL; none had tissue-invasive disease. One developed ganciclovir resistance. No significant differences were observed upon stratification by quantitative CMV DNA test.

Conclusions

Cytomegalovirus DNA was detected in 6.3% of pre- and peri-engraftment allo-HSCT patients. Ganciclovir derivatives were commonly used for treatment despite risk of neutropenia. Treatment was typically deferred until CMV DNA and ANC rose. With rare exceptions, this treatment strategy did not appear to have adverse clinical consequences with respect to acute CMV. Different CMV DNA quantification tests used performed similarly from a clinical perspective despite different analytical performance characteristics.
Robotic-Assisted Stereotaxy for Deep Brain Stimulation Lead Implantation in Awake Patients
Authors: Faraji Amir H , Kokkinos Vasileios , Sweat James C , Crammond Donald J , Richardson R Mark
Published: March 2020

BACKGROUND

Robotic-assisted stereotaxy has been increasingly adopted for lead implantation in stereoelectroencephalography based on its efficiency, accuracy, and precision. Despite initially being developed for use in deep brain stimulation (DBS) surgery, adoption for this indication has not been widespread.

OBJECTIVE

To describe a recent robotic-assisted stereotaxy experience and workflow for DBS lead implantation in awake patients with and without microelectrode recording (MER), including considerations for intraoperative research using electrocorticography (ECoG).

METHODS

A retrospective review of 20 consecutive patients who underwent simultaneous bilateral DBS lead implantation using robotic-assisted stereotaxy was performed. Radial error was determined by comparing the preoperative target with the DBS lead position in the targeting plane on postoperative computed tomography. Information regarding any postoperative complications was obtained by chart review.

RESULTS

A novel method for robot coregistration was developed. We describe a standard workflow that allows for MER and/or ECoG research, and a streamlined workflow for cases in which MER is not required. The overall radial error for lead placement across all 20 patients was 1.14 ± 0.11 mm. A significant difference (P = .006) existed between the radial error of the first 10 patients (1.46 ± 0.19 mm) as compared with the second 10 patients (0.86 ± 0.09 mm). No complications were encountered.

CONCLUSION

Robotic-assisted stereotaxy has the potential to increase precision and reduce human error, compared to traditional frame-based DBS surgery, without negatively impacting patient safety or the ability to perform awake neurophysiology research.
Arabidopsis Sucrose Transporter AtSuc1 introns act as strong enhancers of expression
Authors: Lasin Praphapan , Weise Andreas , Reinders Anke , Ward John M
Published: March 2020

The expression of AtSUC1 is controlled by the promoter and intragenic sequences. AtSUC1 is expressed in roots, pollen and trichomes. However, AtSUC1 promoter-GUS transgenics only show expression in trichomes and pollen. Here, we show that the root expression of AtSUC1 is controlled by an interaction between the AtSUC1 promoter and two short introns. The deletion of either intron from whole-gene-GUS constructs results in no root expression, showing that both introns are required. The two introns in tandem, fused to GUS, produce high constitutive expression throughout the vegetative parts of the plant. When combined with the promoter, the expression driven by the introns is reduced and localized to the roots. In Arabidopsis seedlings, exogenously applied sucrose induces the expression of AtSUC1 in roots and causes anthocyanin accumulation. atsuc1 loss-of-function mutants are defective in sucrose-induced anthocyanin accumulation. We show that an AtSUC1 whole-gene-GUS construct expressing a nonfunctional AtSUC1 (D152N) mutant, that is transport inactive, is defective in sucrose-induced AtSUC1 expression when expressed in an atsuc1-null background. We also show that the transport-defective allele does not complement the loss of sucrose-induced anthocyanin accumulation in null atsuc1 mutants. The results indicate that sucrose uptake via AtSUC1 is required for sucrose-induced AtSUC1 expression and sucrose-induced anthocyanin accumulation and that the site for sucrose detection is intracellular.
Some Universal Solutions for a Class of Incompressible Elastic Body that is Not Green Elastic: The Case of Large Elastic Deformations
Authors: Bustamante R
Published: March 2020

Some universal solutions are studied for a new class of elastic bodies, wherein the Hencky strain tensor is assumed to be a function of the Kirchhoff stress tensor, considering in particular the case of assuming the bodies to be isotropic and incompressible. It is shown that the families of universal solutions found in the classical theory of nonlinear elasticity, are also universal solutions for this new type of constitutive equation.
What does cultural innovation stand for? Dimensions, processes, outcomes of a new innovation category
Authors: Pozzo Riccardo , Filippetti Andrea , Paolucci Mario , Virgili Vania
Published: March 2020

This article introduces the notion of cultural innovation, which requires adapting our approach to co-creation. The argument opens with a first conceptualization of cultural innovation as an additional and autonomous category of the complex processes of co-creation. The dimensions of cultural innovation are contrasted against other forms of innovation. In a second step, the article makes an unprecedented attempt in describing processes and outcomes of cultural innovation, while showing their operationalization in some empirical case studies. In the conclusion, the article considers policy implications resulting from the novel definition of cultural innovation as the outcome of complex processes that involve the reflection of knowledge flows across the social environment within communities of practices while fostering the inclusion of diversity in society. First and foremost, cultural innovation takes a critical stance against inequalities in the distribution of knowledge and builds innovation for improving the welfare of individuals and communities.
A Short-Read Genome Assembly Resource for Leveillula taurica Causing Powdery Mildew Disease of Sweet Pepper (Capsicum annuum)
Authors: Kusch Stefan , Németh Márk Z. , Vaghefi Niloofar , Ibrahim Heba M. M. , Panstruga Ralph , Kiss Levente
Published: March 2020

Powdery mildew of sweet pepper (Capsicum annuum) is an economically important disease. It is caused by Leveillula taurica, an obligate biotrophic ascomycete with a partly endophytic mycelium and haustoria, i.e., feeding structures formed in the mesophyll cells of infected host plant tissues. The molecular basis of its pathogenesis is largely unknown because genomic resources only exist for epiphytically growing powdery mildew fungi with haustoria formed exclusively in epidermal cells of their plant hosts. Here, we present the first reference genome assembly for an isolate of L. taurica isolated from sweet pepper in Hungary. The short read–based assembly consists of 23,599 contigs with a total length of 187.2 Mbp; the scaffold N50 is 13,899 kbp and N90 is 3,522 kbp; and the average GC content is 39.2%. We detected at least 92,881 transposable elements covering 55.5 Mbp (30.4%). BRAKER predicted 19,751 protein-coding gene models in this assembly. Our reference genome assembly of L. taurica is the first resource to study the molecular pathogenesis and evolution of a powdery mildew fungus with a partly endophytic lifestyle.
Correlation Between Brain Trauma Foundation Guidelines and Published Severe Traumatic Brain Injury Research
Authors: Lele Abhijit V. , To-adithep Puriwat , Chanthima Phuriphong , Lakireddy Viharika , Vavilala Monica S.
Published: March 2020

Four editions of the Brain Trauma Foundation’s (BTF) evidence-based guidelines have been published to guide clinical management after severe traumatic brain injury (TBI) and increase TBI research. We reviewed the association between published clinical severe TBI research and BTF guideline year of publication and guideline chapter topics. Using PubMed, we searched for peer-reviewed articles on severe TBI research published between 1975 and 2019. The frequency and study design of publications on chapter topics included in all 4 BTF guideline editions was collected and the relationship with published TBI research examined using linear regression and the coefficient of determination (r
2). A total of 845 relevant articles were identified, with an average of 19 articles published per year. There was an increase in the overall number of publications (r
2=0.72), with the largest increase occurring between the third and the fourth guideline editions (r
2=0.70, 31 articles/y). Across all 4 guideline editions, 54% (n=460) of publications were retrospective studies, 27.2% (n=230) prospective studies, 12% (n=101) randomized controlled trials, and 7.6% (n=64) meta-analyses/systematic reviews. Publication of retrospective study numbers increased the most (r
2=0.61), followed by prospective observational studies and meta-analyses/systematic reviews (r
2=0.47 each), and randomized controlled trials (r
2=0.39). The 3 most highly published guideline chapter topic areas were ventilator-associated pneumonia (r
2=0.70), hyperosmolar therapy (r
2=0.47), and decompressive craniectomy (r
2=0.41). In summary, the TBI research output increased over time and was associated with BTF guideline release. However, the increase in published TBI research was not consistent between serial editions of the BTF guidelines, and many studies did not incorporate high-quality prospective research designs.
Racial and Ethnic Disparities in Opioid Use Among US Adults With Back Pain
Authors: King Christian , Liu Xinliang
Published: March 2020

Study Design.

Retrospective cross-sectional study.

Objectives.

The aim of this study was to examine whether there are racial and ethnic disparities in opioid use for back pain treatment. In addition, we examine whether physical therapy reduces opioid use.

Summary of Background Data.

Back pain is a common health problem that affects most adults in their lifetime. Opioid and physical therapy are commonly used to treat back pain. While evidence indicates that there are substantial disparities in the receipt of opioids by race and ethnicity in opioid use in the United States, it remains unclear whether these disparities in opioid use exist in the treatment of back pain.

Methods.

Cross-sectional analysis of the 2010–2012 Medical Expenditures Panel Survey and logistic regression of a sample of about 4000 adults with back pain.

Results.

Logistic regression models showed statistically significant differences in opioids receipt by race among adult patients with back pain. Compared to White patients, Asian and Hispanic patients are less likely to be prescribed opioids. On the other hand, Black patients and patients of other race are more likely to receive an opioid prescription to treat their back pain even after accounting for socioeconomic status, health insurance status, and general health status. Additionally, patients who receive physical therapy treatment are less likely to be prescribed opioids.

Conclusion.

These findings suggest that there are racial disparities in the use of opioids and physical therapy may reduce opioid prescription use to treat back pain. These disparities may be contributing to disparities in back pain recovery and long-term health disparities in general.

Level of Evidence: 2
Talar Osteochondral Autograft Transplant
Authors: Jorgensen Anna , Edgar Cory , Geaney Lauren E.
Published: March 2020

Osteochondral lesions of the talus vary both in terms of patient symptoms and treatment options. Patient presentation is variable, commons symptoms include minor previous trauma with persistent pain, recurrent ankle swelling, and mechanical symptoms. Treatment often depends on the stability of the cartilage fragment and typically includes a course of conservative treatment. Surgical options include simple arthroscopy with loose body removal with or without microfracture, open reduction and internal fixation of the lesion, autologous chondrocyte implantation with structural allograft, or an osteochondral autograft transplant (OAT), typically using the knee as a donor site. Although a range of successful surgical treatments has been published, OATs demonstrates reliable functional outcomes and is a good option for large osteochondral lesions (>1.5 cm2), after a failed microfracture or in situations with cystic lesions. In this article, we aim to provide a comprehensive description of OAT of the talus.

Level of Evidence: Diagnostic Level V. See Instructions for Authors for a complete description of levels of evidence.
Challenges Frequently Encountered in the Secondary Use of Electronic Medical Record Data for Research
Authors: Edmondson Meghan E. , Reimer Andrew P.
Published: March 2020

The wide adoption of electronic medical records and subsequent availability of large amounts of clinical data provide a rich resource for researchers. However, the secondary use of clinical data for research purposes is not without limitations. In accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, we conducted a systematic review to identify current issues related to secondary use of electronic medical record data via MEDLINE and CINAHL databases. All articles published until June 2018 were included. Sixty articles remained after title and abstract review, and four domains of potential limitations were identified: (1) data quality issues, present in 91.7% of the articles reviewed; (2) data preprocessing challenges (53.3%); (3) privacy concerns (18.3%); and (4) potential for limited generalizability (21.7%). Researchers must be aware of the limitations inherent to the use of electronic medical record data for research and consider the potential effects of these limitations throughout the entire study process, from initial conceptualization to the identification of adequate sources that can provide data appropriate for answering the research questions, analysis, and reporting study results. Consideration should also be given to using existing data quality assessment frameworks to facilitate use of standardized data quality definitions and further efforts of standard data quality reporting in publications.
Sporotrichosis: A Clinicopathologic Study of 89 Consecutive Cases, Literature Review, and New Insights About Their Differential Diagnosis
Authors: Pereira Miguel A. , Freitas Roger J. , Nascimento Suelen B. , Pantaleão Luciana , Vilar Enoï G.
Published: March 2020

Background:

Sporotrichosis is the most common and least severe of deep mycoses. This disease has varied clinic presentation as well as several differential diagnosis.

Methods:

A cross-sectional and retrospective, individually based, observational study, based on records from the dermatopathology service of a university hospital in Brazil. A total of 175 patients were identified with clinical suspicion of sporotrichosis, from 2009 to 2017. Statistical analysis using prevalence ratios was conducted to characterize the clinicopathologic and epidemiological aspects.

Results:

The disease was suspected in 175 patients given the clinical presentation. Of these, 86 cases (49.14%) were sporotrichosis, 39 (22.29%) chronic granulomatous inflammatory processes of unidentified etiology, and 5 squamous cell carcinomas (2.86%). The majority of cases (52 or 60.46%) occurred in the upper limbs. A total of 40 samples presented a suppurative chronic granulomatous inflammatory process (46.51%). Only 5 samples (12.50%) showed positive staining (periodic-Schiff acid or GROCOTT).

Conclusions:

The sporotrichosis cases underwent both cumulative and linear growth, especially in the group above 60 years. Squamous cell carcinomas appeared several times as a misdiagnosis of sporotrichosis by dermatologists, so it should be considered as an important differential diagnose due to the current context of skin cancers.