bluuebunny/crossref_metadata_2025 huggingface dataset:
A Reference Genome Assembly of Simmental Cattle, Bos taurus taurus
Authors: Heaton Michael P , Smith Timothy P L , Bickhart Derek M , Vander Ley Brian L , Kuehn Larry A , Oppenheimer Jonas , Shafer Wade R , Schuetze Fred T , Stroud Brad , McClure Jennifer C , Barfield Jennifer P , Blackburn Harvey D , Kalbfleisch Theodore S , Davenport Kimberly M , Kuhn Kristen L , Green Richard E , Shapiro Beth , Rosen Benjamin D
Published: January 2021

Genomics research has relied principally on the establishment and curation of a reference genome for the species. However, it is increasingly recognized that a single reference genome cannot fully describe the extent of genetic variation within many widely distributed species. Pangenome representations are based on high-quality genome assemblies of multiple individuals and intended to represent the broadest possible diversity within a species. A Bovine Pangenome Consortium (BPC) has recently been established to begin assembling genomes from more than 600 recognized breeds of cattle, together with other related species to provide information on ancestral alleles and haplotypes. Previously reported de novo genome assemblies for Angus, Brahman, Hereford, and Highland breeds of cattle are part of the initial BPC effort. The present report describes a complete single haplotype assembly at chromosome-scale for a fullblood Simmental cow from an F1 bison–cattle hybrid fetus by trio binning. Simmental cattle, also known as Fleckvieh due to their red and white spots, originated in central Europe in the 1830s as a triple-purpose breed selected for draught, meat, and dairy production. There are over 50 million Simmental cattle in the world, known today for their fast growth and beef yields. This assembly (ARS_Simm1.0) is similar in length to the other bovine assemblies at 2.86 Gb, with a scaffold N50 of 102 Mb (max scaffold 156.8 Mb) and meets or exceeds the continuity of the best Bos taurus reference assemblies to date.
Mitochondrial DNA Profiling Reveals Two Lineages of Sun Bears in East and West Malaysia
Authors: Lai Wai-Ling , Chew Jactty , Gatherer Derek , Ngoprasert Dusit , Rahman Sadequr , Ayub Qasim , Kannan Adrian , Vaughan Eleanor , Wong Siew Te , Kulaimi Noor Azleen Mohd , Ratnayeke Shyamala
Published: January 2021

Sun bear populations are fragmented and at risk from habitat loss and exploitation for body parts. These threats are made worse by significant gaps in knowledge of sun bear population genetic diversity, population connectivity, and taxonomically significant management units. Using a complete sun bear mitochondrial genome, we developed a set of mitochondrial markers to assess haplotype variation and the evolutionary history of sun bears from Peninsular (West) Malaysia and Sabah (East Malaysia). Genetic samples from 28 sun bears from Peninsular Malaysia, 36 from Sabah, and 18 from Thailand were amplified with primers targeting a 1800 bp region of the mitochondrial genome including the complete mitochondrial control region and adjacent genes. Sequences were analyzed using phylogenetic methods. We identified 51 mitochondrial haplotypes among 82 sun bears. Phylogenetic and network analyses provided strong support for a deep split between Malaysian sun bears and sun bears in East Thailand and Yunnan province in China. The Malaysian lineage was further subdivided into two clades: Peninsular Malaysian and Malaysian Borneo (Sabah). Sun bears from Thailand occurred in both Sabah and Peninsular Malaysian clades. Our study supports recent findings that sun bears from Sundaland form a distinct clade from those in China and Indochina with Thailand possessing lineages from the three clades. Importantly, we demonstrate a more recent and clear genetic delineation between sun bears from the Malay Peninsula and Sabah indicating historical barriers to gene flow within the Sundaic region.
Economic burden of diabetes among medicare beneficiaries with cancer
Authors: McDaniel Cassidi C , Loh F Ellen , Rockwell Devan M , McDonald Courtney P , Chou Chiahung
Published: January 2021

Objectives

Older adults are commonly affected by cancer and diabetes, and an investigation of the economic burden faced by these older adults remains a research gap. Therefore, the objective was to assess the economic burden of diabetes among Medicare beneficiaries with cancer by analyzing annual costs from administrative claims data.

Methods

We conducted a retrospective, serial cross-sectional study using the Medicare Current Beneficiary Survey (MCBS) from 2006 to 2012. Eligible beneficiaries must be currently or previously diagnosed with cancer (of any type), ≥65 years of age, non-institutionalized and continuously enrolled annually in Medicare Parts A, B and D. Diagnoses of cancer and diabetes were determined through self-report or claims. The primary outcome was the total economic burden of diabetes per capita annually, operationalized as the difference in total direct costs between cancer patients with and without diabetes. Simple linear regression was used to analyze trends of costs across the years. Multivariable regression estimated the effect of diabetes and covariates on total annual spending among beneficiaries with cancer from 2006–2012.

Key findings

From 2006 to 2012, 4918 beneficiaries included in MCBS had cancer, with over 25% (1275) also having diabetes. From 2006 to 2012, the mean economic burden of diabetes was $7815 per capita annually. After adjusting for covariates, beginning in 2006, diagnosis of diabetes significantly predicted higher total annual spending among cancer beneficiaries in 2007 [coefficient (SE) = 0.5768 (0.1918), P = 0.003], 2011 [coefficient (SE) = 0.4303 (0.1817), P = 0.018] and 2012 [coefficient (SE) = 0.3605 (0.1758), P = 0.040].

Conclusions

Medicare beneficiaries with cancer experienced a higher economic burden from concurrent diabetes.
The Gaia DR2 halo white dwarf population: the luminosity function, mass distribution, and its star formation history
Authors: Torres Santiago , Rebassa-Mansergas Alberto , Camisassa María E , Raddi Roberto
Published: January 2021

We analyse the volume-limited nearly complete 100 pc sample of 95 halo white dwarf candidates identified by the second data release of Gaia. Based on a detailed population synthesis model, we apply a method that relies on Gaia astrometry and photometry to accurately derive the individual white dwarf parameters. This method is tested with 25 white dwarfs of our sample for which we took optical spectra and performed spectroscopic analysis. We build and analyse the halo white dwarf luminosity function, for which we find for the first time possible evidences of the cut-off, leading to an age estimate of ${\simeq}12\pm 0.5$ Gyr. The mass distribution of the sample peaks at $0.589\, \mathrm{ M}_{\odot }$, with $71{{\ \rm per\ cent}}$ of the white dwarf masses below $0.6\, \mathrm{ M}_{\odot }$ and just two massive white dwarfs of more than $0.8\, \mathrm{ M}_{\odot }$. From the age distribution, we find three white dwarfs with total ages above 12 Gyr, of which J1312−4728 is the oldest white dwarf known with an age of $12.41\pm 0.22\,$ Gyr. We prove that the star formation history is mainly characterized by a burst of star formation that occurred from 10 to 12 Gyr in the past, but extended up to 8 Gyr. We also find that the peak of the star formation history is centred at around 11 Gyr, which is compatible with the current age of the Gaia-Enceladus encounter. Finally, $13{{\ \rm per\ cent}}$ of our halo sample is contaminated by high-speed young objects (total age <7 Gyr). The origin of these white dwarfs is unclear but their age distribution may be compatible with the encounter with the Sagittarius galaxy.
hmcode-2020: improved modelling of non-linear cosmological power spectra with baryonic feedback
Authors: Mead A J , Brieden S , Tröster T , Heymans C
Published: January 2021

We present an updated version of the hmcode augmented halo model that can be used to make accurate predictions of the non-linear matter power spectrum over a wide range of cosmologies. Major improvements include modelling of baryon-acoustic oscillation (BAO) damping in the power spectrum and an updated treatment of massive neutrinos. We fit our model to simulated power spectra and show that we can match the results with an root mean square (RMS) error of 2.5 per cent across a range of cosmologies, scales $k \lt 10\, h\, \mathrm{Mpc}^{-1}$, and redshifts z < 2. The error rarely exceeds 5 per cent and never exceeds 16 per cent. The worst-case errors occur at z ≃ 2, or for cosmologies with unusual dark energy equations of state. This represents a significant improvement over previous versions of hmcode, and over other popular fitting functions, particularly for massive-neutrino cosmologies with high neutrino mass. We also present a simple halo model that can be used to model the impact of baryonic feedback on the power spectrum. This six-parameter physical model includes gas expulsion by active galactic nuclei (AGN) feedback and encapsulates star formation. By comparing this model to data from hydrodynamical simulations, we demonstrate that the power spectrum response to feedback is matched at the <1 per cent level for z < 1 and $k\lt 20\, h\, \mathrm{Mpc}^{-1}$. We also present a single-parameter variant of this model, parametrized in terms of feedback strength, which is only slightly less accurate. We make code available for our non-linear and baryon models at https://github.com/alexander-mead/HMcode and it is also available within camb and soon within class.
A synergy of the velocity gradients technique and the probability density functions for identifying gravitational collapse in self-absorbing media
Authors: Hu Yue , Lazarian A
Published: January 2021

The velocity gradients technique (VGT) and the probability density functions (PDFs) of mass density are tools to study turbulence, magnetic fields, and self-gravity in molecular clouds. However, self-absorption can significantly make the observed intensity different from the column density structures. In this work, we study the effects of self-absorption on the VGT and the intensity PDFs utilizing three synthetic emission lines of CO isotopologues 12CO (1–0), 13CO (1–0), and C18O (1–0). We confirm that the performance of VGT is insensitive to the radiative transfer effect. We numerically show the possibility of constructing 3D magnetic fields tomography through VGT. We find that the intensity PDFs change their shape from the pure lognormal to a distribution that exhibits a power-law tail depending on the optical depth for supersonic turbulence. We conclude the change of CO isotopologues’ intensity PDFs can be independent of self-gravity, which makes the intensity PDFs less reliable in identifying gravitational collapsing regions. We compute the intensity PDFs for a star-forming region NGC 1333 and find the change of intensity PDFs in observation agrees with our numerical results. The synergy of VGT and the column density PDFs confirms that the self-gravitating gas occupies a large volume in NGC 1333.
Modelling the delivery of dust from discs to ionized winds
Authors: Booth Richard A , Clarke Cathie J
Published: January 2021

A necessary first step for dust removal in protoplanetary disc winds is the delivery of dust from the disc to the wind. In the case of ionized winds, the disc and wind are sharply delineated by a narrow ionization front where the gas density and temperature vary by more than an order of magnitude. Using a novel method that is able to model the transport of dust across the ionization front in the presence of disc turbulence, we revisit the problem of dust delivery. Our results show that the delivery of dust to the wind is determined by the vertical gas flow through the disc induced by the mass-loss, rather than turbulent diffusion (unless the turbulence is strong, i.e. α ≳ 0.01). Using these results, we provide a simple relation between the maximum size of particle that can be delivered to the wind and the local mass-loss rate per unit area from the wind. This relation is independent of the physical origin of the wind and predicts typical sizes in the 0.01–$1\, \rm{\mu m}$ range for extreme-ultraviolet- or X-ray-driven winds. These values are a factor of ∼10 smaller than those obtained when considering only whether the wind is able to carry away the grains.
A fully general, non-perturbative treatment of impulsive heating
Authors: Banik Uddipan , van den Bosch Frank C
Published: January 2021

Impulsive encounters between astrophysical objects are usually treated using the distant tide approximation (DTA) for which the impact parameter, b, is assumed to be significantly larger than the characteristic radii of the subject, rS, and the perturber, rP. The perturber potential is then expanded as a multipole series and truncated at the quadrupole term. When the perturber is more extended than the subject, this standard approach can be extended to the case where rS ≪ b < rP. However, for encounters with b of order rS or smaller, the DTA typically overpredicts the impulse, Δv, and hence the internal energy change of the subject, ΔEint. This is unfortunate, as these close encounters are the most interesting, potentially leading to tidal capture, mass stripping, or tidal disruption. Another drawback of the DTA is that ΔEint is proportional to the moment of inertia, which diverges unless the subject is truncated or has a density profile that falls off faster than r−5. To overcome these shortcomings, this paper presents a fully general, non-perturbative treatment of impulsive encounters which is valid for any impact parameter, and not hampered by divergence issues, thereby negating the necessity to truncate the subject. We present analytical expressions for Δv for a variety of perturber profiles, apply our formalism to both straight-path encounters and eccentric orbits, and discuss the mass-loss due to tidal shocks in gravitational encounters between equal-mass galaxies.
Dark matter-deficient dwarf galaxies form via tidal stripping of dark matter in interactions with massive companions
Authors: Jackson R A , Kaviraj S , Martin G , Devriendt J E G , Slyz A , Silk J , Dubois Y , Yi S K , Pichon C , Volonteri M , Choi H , Kimm T , Kraljic K , Peirani S
Published: January 2021

In the standard ΛCDM (Lambda cold dark matter) paradigm, dwarf galaxies are expected to be dark matter-rich, as baryonic feedback is thought to quickly drive gas out of their shallow potential wells and quench star formation at early epochs. Recent observations of local dwarfs with extremely low dark matter content appear to contradict this picture, potentially bringing the validity of the standard model into question. We use NewHorizon, a high-resolution cosmological simulation, to demonstrate that sustained stripping of dark matter, in tidal interactions between a massive galaxy and a dwarf satellite, naturally produces dwarfs that are dark matter-deficient, even though their initial dark matter fractions are normal. The process of dark matter stripping is responsible for the large scatter in the halo-to-stellar mass relation in the dwarf regime. The degree of stripping is driven by the closeness of the orbit of the dwarf around its massive companion and, in extreme cases, produces dwarfs with halo-to-stellar mass ratios as low as unity, consistent with the findings of recent observational studies. ∼30 per cent of dwarfs show some deviation from normal dark matter fractions due to dark matter stripping, with 10 per cent showing high levels of dark matter deficiency (Mhalo/M⋆ < 10). Given their close orbits, a significant fraction of dark matter-deficient dwarfs merge with their massive companions (e.g. ∼70 per cent merge over time-scales of ∼3.5 Gyr), with the dark matter-deficient population being constantly replenished by new interactions between dwarfs and massive companions. The creation of these galaxies is therefore a natural by-product of galaxy evolution and their existence is not in tension with the standard paradigm.
Inclination dynamics of resonant planets under the influence of an inclined external companion
Authors: Rodet Laetitia , Lai Dong
Published: January 2021

Recent observations suggest that a large fraction of Kepler super-Earth systems have external giant planet companions (cold Jupiters), which can shape the architecture of the inner planets, in particular their mutual inclinations. The dynamical perturbation from cold Jupiters may account for the population of misaligned planets in the Kepler data. The effectiveness of this mechanism can be hindered by a strong planet–planet coupling in the inner system. In this paper, we study how mean-motion resonances (MMRs) affect this coupling and the expected misalignment. We derive approximate analytical expressions for the mutual inclination excitations in the inner planet system induced by an inclined companion, for various period ratios and perturber properties. In most cases, the mutual inclination is proportional to a dimensionless parameter that characterizes the strength of the perturber relative to the coupling in the inner system. We show that the MMR strengthens the inner coupling, reducing the mutual inclination induced by the perturber by a factor of a few. We find that the resonance is resilient to the perturbation, and derive a criterion for the libration of the resonant angle. Our results have applications for constraining unseen planetary perturbers, and for understanding the architecture of multiplanet systems.
Prospects for Galactic and stellar astrophysics with asteroseismology of giant stars in the TESS continuous viewing zones and beyond
Authors: Mackereth J Ted , Miglio Andrea , Elsworth Yvonne , Mosser Benoit , Mathur Savita , Garcia Rafael A , Nardiello Domenico , Hall Oliver J , Vrard Mathieu , Ball Warrick H , Basu Sarbani , Beaton Rachael L , Beck Paul G , Bergemann Maria , Bossini Diego , Casagrande Luca , Campante Tiago L , Chaplin William J , Chiappini Cristina , Girardi Léo , Jørgensen Andreas Christ Sølvsten , Khan Saniya , Montalbán Josefina , Nielsen Martin B , Pinsonneault Marc H , Rodrigues Thaíse S , Serenelli Aldo , Silva Aguirre Victor , Stello Dennis , Tayar Jamie , Teske Johanna , van Saders Jennifer L , Willett Emma
Published: January 2021

The NASA Transiting Exoplanet Survey Satellite (NASA-TESS) mission presents a treasure trove for understanding the stars it observes and the Milky Way, in which they reside. We present a first look at the prospects for Galactic and stellar astrophysics by performing initial asteroseismic analyses of bright (G < 11) red giant stars in the TESS southern continuous viewing zone (SCVZ). Using three independent pipelines, we detect νmax and Δν in 41 per cent of the 15 405 star parent sample (6388 stars), with consistency at a level of $\sim \! 2{{\ \rm per\ cent}}$ in νmax and $\sim \! 5{{\ \rm per\ cent}}$ in Δν. Based on this, we predict that seismology will be attainable for ∼3 × 105 giants across the whole sky and at least 104 giants with ≥1 yr of observations in the TESS-CVZs, subject to improvements in analysis and data reduction techniques. The best quality TESS-CVZ data, for 5574 stars where pipelines returned consistent results, provide high-quality power spectra across a number of stellar evolutionary states. This makes possible studies of, for example, the asymptotic giant branch bump. Furthermore, we demonstrate that mixed ℓ = 1 modes and rotational splitting are cleanly observed in the 1-yr data set. By combining TESS-CVZ data with TESS-HERMES, SkyMapper, APOGEE, and Gaia, we demonstrate its strong potential for Galactic archaeology studies, providing good age precision and accuracy that reproduces well the age of high [α/Fe] stars and relationships between mass and kinematics from previous studies based on e.g. Kepler. Better quality astrometry and simpler target selection than the Kepler sample makes this data ideal for studies of the local star formation history and evolution of the Galactic disc. These results provide a strong case for detailed spectroscopic follow-up in the CVZs to complement that which has been (or will be) collected by current surveys.
Undersurface Sequences
Authors: Reuven Ram
Published: January 2021

An undersurface sequence is a type of motivic parallelism that unifies parallel patterns into a single sequential unit. This article focuses on various undersurface sequences that leading Schenkerian scholars, including Schenker himself, integrated into their voice-leading graphs without explicitly pointing them out. The phenomenon is discussed according to different levels of distance from the surface, starting with sequences that lie very close to the surface and may allow for intuitive auditory perception, and ending with hidden sequences that lie deep in the middleground and are entirely analysis-dependent.
Nebula: ultra-efficient mapping-free structural variant genotyper
Authors: Khorsand Parsoa , Hormozdiari Fereydoun
Published: January 2021

Large scale catalogs of common genetic variants (including indels and structural variants) are being created using data from second and third generation whole-genome sequencing technologies. However, the genotyping of these variants in newly sequenced samples is a nontrivial task that requires extensive computational resources. Furthermore, current approaches are mostly limited to only specific types of variants and are generally prone to various errors and ambiguities when genotyping complex events. We are proposing an ultra-efficient approach for genotyping any type of structural variation that is not limited by the shortcomings and complexities of current mapping-based approaches. Our method Nebula utilizes the changes in the count of k-mers to predict the genotype of structural variants. We have shown that not only Nebula is an order of magnitude faster than mapping based approaches for genotyping structural variants, but also has comparable accuracy to state-of-the-art approaches. Furthermore, Nebula is a generic framework not limited to any specific type of event. Nebula is publicly available at https://github.com/Parsoa/Nebula.
PAUPARand PAX6 sequentially regulate human embryonic stem cell cortical differentiation
Authors: Xu Yanxin , Xi Jiajie , Wang Guiying , Guo Zhenming , Sun Qiaoyi , Lu Chenqi , Ma Li , Wu Yukang , Jia Wenwen , Zhu Songcheng , Guo Xudong , Bian Shan , Kang Jiuhong
Published: January 2021

Long noncoding RNAs (lncRNAs) play a wide range of roles in the epigenetic regulation of crucial biological processes, but the functions of lncRNAs in cortical development are poorly understood. Using human embryonic stem cell (hESC)-based 2D neural differentiation approach and 3D cerebral organoid system, we identified that the lncRNA PAUPAR, which is adjacent to PAX6, plays essential roles in cortical differentiation by interacting with PAX6 to regulate the expression of a large number of neural genes. Mechanistic studies showed that PAUPAR confers PAX6 proper binding sites on the target neural genes by directly binding the genomic regions of these genes. Moreover, PAX6 recruits the histone methyltransferase NSD1 through its C-terminal PST enrichment domain, then regulate H3K36 methylation and the expression of target genes. Collectively, our data reveal that the PAUPAR/PAX6/NSD1 complex plays a critical role in the epigenetic regulation of hESC cortical differentiation and highlight the importance of PAUPAR as an intrinsic regulator of cortical differentiation.
DeCompress: tissue compartment deconvolution of targeted mRNA expression panels using compressed sensing
Authors: Bhattacharya Arjun , Hamilton Alina M , Troester Melissa A , Love Michael I
Published: January 2021

Targeted mRNA expression panels, measuring up to 800 genes, are used in academic and clinical settings due to low cost and high sensitivity for archived samples. Most samples assayed on targeted panels originate from bulk tissue comprised of many cell types, and cell-type heterogeneity confounds biological signals. Reference-free methods are used when cell-type-specific expression references are unavailable, but limited feature spaces render implementation challenging in targeted panels. Here, we present DeCompress, a semi-reference-free deconvolution method for targeted panels. DeCompress leverages a reference RNA-seq or microarray dataset from similar tissue to expand the feature space of targeted panels using compressed sensing. Ensemble reference-free deconvolution is performed on this artificially expanded dataset to estimate cell-type proportions and gene signatures. In simulated mixtures, four public cell line mixtures, and a targeted panel (1199 samples; 406 genes) from the Carolina Breast Cancer Study, DeCompress recapitulates cell-type proportions with less error than reference-free methods and finds biologically relevant compartments. We integrate compartment estimates into cis-eQTL mapping in breast cancer, identifying a tumor-specific cis-eQTL for CCR3 (C–C Motif Chemokine Receptor 3) at a risk locus. DeCompress improves upon reference-free methods without requiring expression profiles from pure cell populations, with applications in genomic analyses and clinical settings.
BACH1 recruits NANOG and histone H3 lysine 4 methyltransferase MLL/SET1 complexes to regulate enhancer–promoter activity and maintains pluripotency
Authors: Niu Cong , Wang Siqing , Guo Jieyu , Wei Xiangxiang , Jia Mengping , Chen Zhaoxiong , Gong Wenxuan , Qin Yue , Wang Xinhong , Zhi Xiuling , Lu Meng , Chen Sifeng , Gu Mingxia , Zhang Jianyi , Han Jing-Dong J , Lan Fei , Meng Dan
Published: January 2021

Maintenance of stem-cell identity requires proper regulation of enhancer activity. Both transcription factors OCT4/SOX2/NANOG and histone methyltransferase complexes MLL/SET1 were shown to regulate enhancer activity, but how they are regulated in embryonic stem cells (ESCs) remains further studies. Here, we report a transcription factor BACH1, which directly interacts with OCT4/SOX2/NANOG (OSN) and MLL/SET1 methyltransferase complexes and maintains pluripotency in mouse ESCs (mESCs). BTB domain and bZIP domain of BACH1 are required for these interactions and pluripotency maintenance. Loss of BACH1 reduced the interaction between NANOG and MLL1/SET1 complexes, and decreased their occupancy on chromatin, and further decreased H3 lysine 4 trimethylation (H3K4me3) level on gene promoters and (super-) enhancers, leading to decreased enhancer activity and transcription activity, especially on stemness-related genes. Moreover, BACH1 recruited NANOG through chromatin looping and regulated remote NANOG binding, fine-tuning enhancer–promoter activity and gene expression. Collectively, these observations suggest that BACH1 maintains pluripotency in ESCs by recruiting NANOG and MLL/SET1 complexes to chromatin and maintaining the trimethylated state of H3K4 and enhancer–promoter activity, especially on stemness-related genes.
Adolescents and Young Adults Have Difficulty Understanding Nicotine Concentration Labels on Vaping Products Presented as mg/mL and Percent Nicotine
Authors: Morean Meghan E , Wackowski Olivia A , Eissenberg Thomas , Delnevo Cristine D , Krishnan-Sarin Suchitra
Published: January 2021

Introduction

E-cigarette e-liquid nicotine concentrations typically are labeled as mg/mL or percent nicotine. We examined whether these metrics accurately convey nicotine strength to young e-cigarette users and if youth can compare concentrations presented in mg/mL and percent nicotine.

Aims and Methods

Eight hundred and twenty-one adolescent and young adult e-cigarette users participated in the survey. Participants rated nicotine concentration strengths presented as mg/mL (0–60 mg/mL) and percent nicotine (0%–6%) from “no nicotine” to “very high nicotine.” Participants also viewed pairs of nicotine concentrations (eg, 18 mg/mL vs. 5%) and indicated which concentration was stronger or if the concentrations were equivalent.

Results

On average, participants correctly identified 5.92 (2.68) of 18 nicotine strengths, correctly identifying strengths labeled as mg/mL (3.47 [2.03]) more often than percent nicotine (2.45 [1.38], p < .001). Excluding nicotine-free, participants rated concentrations presented as mg/mL as stronger, more addictive, and more harmful than equivalent concentrations presented as percent nicotine. Participants seldom correctly identified that one concentration was stronger or that both were equivalent (7.58 [5.88] of 19 pairings), although they more often correctly identified the stronger concentration when it was presented in mg/mL (4.02 [SD = 3.01]) than in percent nicotine (2.53 [2.73], p < .001). The most consistent predictor of correct answers on these tasks was familiarity with using both products labeled as mg/mL and labeled as percent nicotine.

Conclusions

Young e-cigarette users had difficulty understanding nicotine concentrations labeled using the most common metrics, raising concerns about inadvertent exposure to high nicotine levels and suggesting that a more intuitive labeling approach is needed.

Implications

This study extends prior work showing that young e-cigarette users often are uncertain whether the e-liquids they use contain nicotine by demonstrating that adolescents and young adults have difficulty understanding nicotine concentrations labeled using the two most common metrics (mg/mL and percent nicotine). Errors generally underestimated nicotine strength, and users were not able to accurately compare nicotine concentrations presented as mg/mL and percent nicotine. Difficulty understanding labeling metrics persisted even after accounting for user characteristics like age and vaping experience, suggesting that a novel, easy to understand labeling system is needed to convey information about nicotine strength accurately.
Tobacco and Nicotine Use Among US Adult “Never Smokers” in Wave 4 (2016–2018) of the Population Assessment of Tobacco and Health Study
Authors: Klemperer Elias M , Hughes John R , Callas Peter W , West Julia C , Villanti Andrea C
Published: January 2021

Introduction

A common criterion for being labeled a “never smoker” is having smoked <100 lifetime cigarettes. This category is often used as an unexposed reference group to estimate the relative harm from cigarettes. We examined the amount of current and past cigarette and non-cigarette tobacco/nicotine use among adults who met this “never smoker” criterion.

Methods

We analyzed cross-sectional data from 17 179 adult “never smokers” (ie, reported <100 lifetime cigarettes) in Wave 4 (2016–2018) of the Population Assessment of Tobacco and Health (PATH) Study, a United States nationally representative sample. We used PATH-derived variables to describe “never smokers’” demographics as well as cigarette and non-cigarette tobacco/nicotine use.

Results

Approximately half of “never smokers” were young adults (49.3%). Most were white (68.6%) with some college or more (64.4%). Most “never smokers” had tried any cigarette or non-cigarette tobacco/nicotine in their lifetime (66.7%), 8.5% smoked cigarettes in the past 30 days, and 5.3% were current experimental (ie, some days or every day) cigarette smokers. By definition, “never smokers” reported smoking <100 lifetime cigarettes. One fifth (22.8%) had a lifetime history of established regular non-cigarette tobacco/nicotine use and 8.6% were current established regular non-cigarette tobacco/nicotine users. In total, 9.4% of “never smokers” were current experimental or established regular users of combustible tobacco.

Conclusions

The 100-cigarette lifetime threshold includes substantial amounts of current and past tobacco use and thus does not represent lack of exposure to cigarette or non-cigarette tobacco. “Never smoker” reference groups may produce underestimates of the relative harms from cigarettes.

Implications

The <100 lifetime cigarettes criterion may not capture what many would consider true “never smokers.” Relying on the current definition of “never smokers” as a reference group will include a substantial number of those currently and recently using combustible tobacco and thus produce data that may underestimate the relative harm from cigarettes. Prospective longitudinal research is needed to compare how the 100-cigarette lifetime threshold versus other definitions of regular cigarette smoking differ in predictive validity of clinically meaningful outcomes and health harms to determine the optimal criteria to define established cigarette smoking.
Charles V, Emperor
Authors: Boone Rebecca Ard
Published: January 2021

The figure of Charles V, Holy Roman Emperor (b. 1500–d. 1558), looms large over a wide swath of human experience in the 16th century. His empire impacted the direction of history in the Americas, Europe, and the Middle East. The military, diplomatic, and dynastic force of his empire weighed on cultural movements that included the Reformation, Renaissance, print revolution, witch trials, global trade, and colonization. The interplay of his narrow and shortsighted vision on one side and his military courage, administrative acumen, and devotion to duty as he understood it on the other has intrigued historians for nearly five hundred years. Every generation has found him relevant, but for different reasons. By all accounts he was talented in language acquisition. He also had the energy, intellect, and desire to understand the minutia of administrative and diplomatic business. His presence on the battlefield and documented courage helped him maintain the loyalty of his subjects. In short, he seems to have been a “good enough” emperor. Although he did not maintain political or religious unity in his empire, he defended the lands he inherited and maintained them under his family’s rule. His publicists devised an imperial program focused on his personal power as a ruler chosen by God to defend Christianity from internal and external forces of evil. The contemporary shift toward authoritarian rule in many countries today has given this program new relevance.
Artificial Intelligence and Learning
Authors: Lee Jaekyung , Lamb Richard , Kim Sunha
Published: January 2021

Rapid technological advances, particularly recent artificial intelligence (AI) revolutions such as digital assistants (e.g., Alexa, Siri), self-driving cars, and cobots and robots, have changed human lives and will continue to have even bigger impact on our future society. Some of those AI inventions already shocked people across the world by wielding their power of surpassing human intelligence and cognitive abilities; see, for example, the examples of Watson (IBM’s supercomputer) and AlphaGo (Google DeepMind’s AI program) beating the human champions of Jeopardy and Go games, respectively. Then many questions arise. How does AI affect human beings and the larger society? How should we educate our children in the AI age? What changes are necessary to help humans better adapt and flourish in the AI age? What are the key enablers of the AI revolution, such as big data and machine learning? What are the applications of AI in education and how do they work? Answering these critical questions requires interdisciplinary research. There is no shortage of research on AI per se, since it is a highly important and impactful research topic that cuts across many fields of science and technology. Nevertheless, there are no effective guidelines for educational researchers and practitioners that give quick summaries and references on this topic. Because the intersection of AI and education/learning is an emerging field of research, the literature is in flux and the jury is still out. Thus, our goal here is to give readers a quick introduction to this broad topic by drawing upon a limited selection of books, reports, and articles. This entry is organized into three major sections, where we present commentaries along with a list of annotated references on each of the following areas: (1) AI Impacts on the Society and Education; (2) AI Enablers: Big Data in Education and Machine Learning; and (3) Applications of AI in Education: Examples and Evidence.
South American Missions
Authors: Jones Cameron
Published: January 2021

While it is certainly true that more academic studies have focused on the North American missions, in terms of their historical impact South American missions were just as important to the frontiers of Spain and Portugal’s American empires. The massive size alone of the frontier region, stretching from the upper reaches of the Amazon basin to the headwaters of the Paraná as well as stretching across the lower Southern Cone, meant numerous missionary enterprises emerged in an attempt to evangelize the peoples who inhabited these regions. While small handfuls of Dominicans, Mercedarians, and Augustinians would engage in such efforts, most missions were established by the Jesuits or Franciscans. Certainly, for the Jesuits, or the Society of Jesus as they are properly known, American missions represented an extension of the Counter-Reformation for which they were created. Starting in the mid-16th century, this relatively new organization, founded in 1534, began in earnest to “reduce” the Indigenous peoples into their missions. These activities, however, abruptly ended when the Jesuits were expelled from both the Portuguese and Spanish empires in 1759 and 1767 respectfully. The much older Franciscan order had extensive experience in popular missions in Europe and was one of the first orders of regular clergy in the Americas. Franciscans, like the Jesuits, engaged in evangelizing activities throughout both North and South America from the colonial period to the present. The expulsion of the Jesuits, however, pushed them further to the forefront of missionizing efforts in the late colonial period. This acceleration of Franciscan missionary activity was aided by the establishment of the Apostolic Institute in 1682. The Institute created a pipeline of missionaries from Spain to come directly to frontier areas with funding from the crown. While this aided missionary efforts throughout South America, particularly in areas abandoned by the Jesuits, it embroiled the missionaries in the politics of the Bourbon reforms and their obsession with limited clerical power. Ultimately, while missionizing efforts continued into the Republican period, their association with the Spanish and Portuguese crowns led to widespread suppression and secularization following independence. The historiographical divide in the field tends to lie between usually older, Eurocentric histories by scholar-clerics which focus on the missionaries themselves, and newer studies carried out by more secular professional historians that examine how Indigenous populations were affected by the inherent imperialism of the missions, though exceptions abound.
Linguistic Profiling and Language-Based Discrimination
Authors: Baugh John
Published: January 2021

Linguistic profiling and other forms of linguistic discrimination were first attested in the Old Testament. The coinage of the word shibboleth traces its origin to the Book of Judges 12:6, where the inability to pronounce that word correctly would result in death; “They told him, ‘Please say shibboleth.’ If he said, ‘sibboleth,’ because he could not pronounce it correctly, they seized him and killed him at the fords of the Jordan.” Since then, other manifestations of human conflict and discrimination frequently exhibit linguistic demarcation in one form or another, and these shibboleths evolve over time. Warring factions may eventually make peace, as old rivalries come to be displaced or resolved. Advances in technology exacerbated these trends, as more-rapid modes of transportation increased contact and conflict among speakers of mutually unintelligible languages, accompanied by the development of increasingly efficient deadly weaponry that coincided with global expansionism along with sporadic conquests and the ensuing oppression of human enclaves throughout the world. The advent of global markets and multinational immigration has further accelerated circumstances where diverse human factions may use linguistic (dis)similarities as one of several means through which individuals formulate perceptual boundaries between groups that are familiar or unfamiliar. When compared to the historical longevity of discrimination based on language, linguistic evaluations of this phenomenon are relatively recent.
Thirty Years War, 1618–1648
Authors: Staiano-Daniels Lucian
Published: January 2021

Historians still debate what to call the conflict that convulsed Central Europe from 1618 to 1648. Although it is largely accepted that this is “The Thirty Years War,” and indeed some people called it that shortly after it was over, some historians use this phrase to denote other wars, beginning earlier or ending later. This Thirty Years War was one of the most destructive conflicts on earth. Although the fighting took place primarily in central Europe, this complex multifaceted struggle eventually sucked in people from Ireland to Muscovy west to east, and from Norway to Italy north to south. Compared to the population at the time, it may have been proportionally more deadly than any war in western or central Europe before or since. This is an excellent time for Thirty Years War research. Some tenacious misunderstandings about the way early-17th-century strategy and combat worked are being rooted out. Primary source research is being done. Sterile debates that occupied the entire 19th and early 20th centuries are now barely even remembered. A full bibliography would list hundreds of thousands of works over four hundred years; here are several.
Treatment Strategies for Generator Pocket Pain
Authors: Bao Jonathan , Khazen Olga , Olmsted Zachary T , Gechtman Guy , Shao Miriam M , DiMarzio Marisa , Topp Gregory , Sukul Vishad V , Staudt Michael D , Pilitsis Julie G
Published: January 2021

Objective

Generator site pain is a relatively common phenomenon in patients undergoing spinal cord stimulation (SCS) that complicates management and effective pain relief. This pain may be managed conservatively, with repositioning of the battery and, in some cases, with explant. Here we explore our experience with management of generator site pain (“pocket pain”) in a large single-center study.

Methods

All SCS permanent implants and implantable pulse generator (IPG) placements over 9 years were reviewed. Of 785 cases, we identified 43 patients with pocket pain (5.5%). Demographics and treatments of the pocket pain cohort were analyzed.

Results

The mean age (± SEM) of the pocket pain cohort was 46.86 ± 1.06, and there were 10/33 males/females. Females were overrepresented in pocket pain cohort (76.7%) when compared with the total SCS cohort (59.0%) (X2 = 5.93, P = 0.015). Diagnosis included failed back surgery syndrome (51.2%), complex regional pain syndrome (23.3%), and chronic neuropathic pain (25.5%). No patients improved with conservative therapy. All patients either went on to revision (n = 23) or explant (n = 20). Time from initial surgery to development of pocket pain was 7.5 months (range: 0.3–88) and from pocket pain to revision surgery was 4.5 months (range: 0.4–26). In addition, significantly more pocket pain patients (65.1%) had workers’ compensation (WC) insurance compared with patients without pocket pain (24.9%) (X2 = 33.3, P < 0.001).

Conclusion

In our institutional experience, pocket pain was inadequately managed with conservative treatments. Being female and having SCS filed under WC increased risk of pocket pain. Future work will explore the nuances in device placement based on body shape and manual activity responsibilities.
Quantitative nailfold capillaroscopy—update and possible next steps
Authors: Herrick Ariane L , Berks Michael , Taylor Chris J
Published: January 2021

We review the exciting potential (and challenges) of quantitative nailfold capillaroscopy, focusing on its role in systemic sclerosis. Quantifying abnormality, including automated analysis of nailfold images, overcomes the subjectivity of qualitative/descriptive image interpretation. First we consider the rationale for quantitative analysis, including the potential for precise discrimination between normal and abnormal capillaries and for reliable measurement of disease progression and treatment response. We discuss nailfold image acquisition and interpretation, and describe how early work on semi-quantitative and quantitative analysis paved the way for semi-automated and automated analysis. Measurement of red blood cell velocity is described briefly. Finally we give a personal view on ‘next steps’. From a clinical perspective, increased uptake of nailfold capillaroscopy by general rheumatologists could be achieved via low-cost hand-held devices with cloud-based automated analysis. From a research perspective, automated analysis could facilitate large-scale prospective studies using capillaroscopic parameters as possible biomarkers of systemic sclerosis-spectrum disorders.
Patients and clinicians define symptom levels and meaningful change for PROMIS pain interference and fatigue in RA using bookmarking
Authors: Bingham Clifton O , Butanis Alessandra L , Orbai Ana Maria , Jones Michelle , Ruffing Victoria , Lyddiatt Anne , Schrandt Mary Suzanne , Bykerk Vivian P , Cook Karon F , Bartlett Susan J
Published: January 2021

Objectives

Using patient-reported outcomes to inform clinical decision-making depends on knowing how to interpret scores. Patient-Reported Outcome Measurement Information System® (PROMIS®) instruments are increasingly used in rheumatology research and care, but there is little information available to guide interpretation of scores. We sought to identify thresholds and meaningful change for PROMIS Pain Interference and Fatigue scores from the perspective of RA patients and clinicians.

Methods

We developed patient vignettes using the PROMIS item banks representing a continuum of Pain Interference and Fatigue levels. During a series of face-to-face ‘bookmarking’ sessions, patients and clinicians identified thresholds for mild, moderate and severe levels of symptoms and identified change deemed meaningful for making treatment decisions.

Results

In general, patients selected higher cut points to demarcate thresholds than clinicians. Patients and clinicians generally identified changes of 5–10 points as representing meaningful change. The thresholds and meaningful change scores of patients were grounded in their lived experiences having RA, approach to self-management, and the impacts on function, roles and social participation.

Conclusion

Results offer new information about how both patients and clinicians view RA symptoms and functional impacts. Results suggest that patients and providers may use different strategies to define and interpret RA symptoms, and select different thresholds when describing symptoms as mild, moderate or severe. The magnitude of symptom change selected by patients and clinicians as being clinically meaningful in interpreting treatment efficacy and loss of response may be greater than levels determined by external anchor and statistical methods.