bluuebunny/crossref_metadata_2025_split huggingface dataset:
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

Abstract
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

Abstract

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 &lt; .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 &lt; .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

Abstract

Introduction
A common criterion for being labeled a “never smoker” is having smoked &lt;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 &lt;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 &lt;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 &lt;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.
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

Abstract

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 &lt; 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

Abstract
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

Abstract

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.
Association between environmental air pollution and rheumatoid arthritis flares
Authors: Adami Giovanni , Viapiana Ombretta , Rossini Maurizio , Orsolini Giovanni , Bertoldo Eugenia , Giollo Alessandro , Gatti Davide , Fassio Angelo 
Published: January 2021

Abstract

Objectives
Environmental air pollution has been linked to the pathogenesis of RA. Nevertheless, evidence linking higher concentrations of air pollutants with the risk of RA reactivations is missing. The objective of the present study was to determine the association between RA flares and air pollution.

Methods
We collected longitudinal data of patients affected by RA and of the daily concentration of air pollutants in the Verona area. We designed a case-crossover study. We compared the exposure to pollutants in the 30-day and 60-day periods preceding an arthritic flare referent to the 30-day and 60-day preceding a low-disease activity visit.

Results
The study included 888 patients with RA with 3396 follow-up visits; 13 636 daily air pollution records were retrieved. We found an exposure–response relationship between the concentration of air pollutants and the risk of having abnormal CRP levels. Patients exposed to greater concentrations of air pollutants were at higher risk of having CRP levels ≥5 mg/l. Concentrations of CO, NO, NO2, NOx, PM10, PM2.5 and O3 were higher in the 60-day period preceding a flare.

Conclusions
We found a striking association between air pollution and RA disease severity and reactivations in a cohort of patients followed over a 5-year period. The exposure to high levels of air pollutants was associated with increased CRP levels and a higher risk of experiencing a flare of arthritis. This excessive risk was evident at very low levels of exposure.
Identification of novel avian and mammalian deltaviruses provides new insights into deltavirus evolution
Authors: Iwamoto Masashi , Shibata Yukino , Kawasaki Junna , Kojima Shohei , Li Yung-Tsung , Iwami Shingo , Muramatsu Masamichi , Wu Hui-Lin , Wada Kazuhiro , Tomonaga Keizo , Watashi Koichi , Horie Masayuki 
Published: January 2021

Abstract
Hepatitis delta virus (HDV) is a satellite virus that requires hepadnavirus envelope proteins for its transmission. Although recent studies identified HDV-related deltaviruses in certain animals, the evolution of deltaviruses, such as the origin of HDV and the mechanism of its coevolution with its helper viruses, is unknown, mainly because of the phylogenetic gaps among deltaviruses. Here, we identified novel deltaviruses of passerine birds, woodchucks, and white-tailed deer by extensive database searches and molecular surveillance. Phylogenetic and molecular epidemiological analyses suggest that HDV originated from mammalian deltaviruses and the past interspecies transmission of mammalian and passerine deltaviruses. Further, metaviromic and experimental analyses suggest that the satellite–helper relationship between HDV and hepadnavirus was established after the divergence of the HDV lineage from non-HDV mammalian deltaviruses. Our findings enhance our understanding of deltavirus evolution, diversity, and transmission, indicating the importance of further surveillance for deltaviruses.
Opportunities for Improved Potato Late Blight Management in the Republic of Ireland: Field Evaluation of the Modified Irish Rules Crop Disease Risk Prediction Model
Authors: Cucak Mladen , de Andrade Moral Rafael , Fealy Rowan , Lambkin Keith , Kildea Steven 
Published: January 2021

Potato late blight remains the most significant disease threat of potato cultivation globally, often requiring expensive, time-consuming, and environmentally unfriendly approaches to disease management. The goal of this research was to evaluate whether an estimation of potato late blight risk based on environmental factors can be reliably used to adjust the standard potato late blight management practices and the role of cultivar resistance under growing conditions and contemporary Phytophthora infestans populations in the Republic of Ireland. The modified Irish Rules model made it possible to reduce fungicide usage by 58.7% on average, compared with current standard practices used by growers and without adversely compromising disease control and yield, with similar results achieved by the half-dose program. Host resistance levels were found to be correlated with a delay in the initiation of the epidemics, final foliar disease levels, and reduction of fungicide usage. Disease levels on the highly resistant cultivars remained low, and a clear selection pattern toward the P. infestans genotypes EU_13_A2 and EU_6_A1 was observed. An increase in the frequency of strains belonging to genotypes EU_13_A2 and EU_6_A1 was also observed to occur in the latter part of the trial growing seasons. Because of the increasingly dynamic nature of the population structure, associated with the continued evolution of the P. infestans population and the arrival of EU_36_A2 in the Republic of Ireland, routine population monitoring is necessary to ensure that potato late blight control strategies remain effective.[Formula: see text] Copyright © 2021 The Author(s). This is an open access article distributed under the CC BY-NC-ND 4.0 International license .
The Relations Between Auditory Processing Scores and Cognitive, Listening and Reading Abilities
Authors: Seeto Mark , Tomlin Dani , Dillon Harvey 
Published: January 2021

Objectives:
To investigate associations between auditory processing abilities, cognitive abilities, listening ability, and reading ability in children.

Design:
This was a cross-sectional study involving 155 children (105 referred for auditory processing assessment and 50 with no reported listening concerns) aged between 7 and 13 years. Each child was assessed on auditory processing tests, cognitive tests, and a reading test. Additional data on reading ability were provided by the reading score from a national test. Questionnaires about the child’s listening ability were completed by a parent, a teacher, and the child.

Results:
Structural equation models relating auditory processing abilities, cognitive abilities, listening ability, and reading ability were developed. There was evidence that listening and reading abilities were associated with cognitive abilities when adjusting for auditory processing abilities, but little evidence that listening and reading abilities were associated with auditory processing abilities when adjusting for cognitive abilities.

Conclusions:
It should not be assumed that auditory processing tests and cognitive tests measure separate abilities. When investigating the association between auditory processing abilities and real-world abilities, it is important to adjust for cognitive abilities. Children with listening difficulties should undergo cognitive assessments in addition to auditory processing assessments.
Primary Septic Arthritis Among Children 6 to 48 Months of Age: Implications for PCR Acquisition and Empiric Antimicrobial Selection
Authors: Villani Mary C. , Hamilton Elizabeth C. , Klosterman Mary M. , Jo Chanhee , Kang Lisa H. , Copley Lawson A.B. 
Published: January 2021

Introduction:
Primary septic arthritis requires unique evaluation and treatment considerations for children in the 6- to 48-month age range because of the spectrum of identified pathogens and high rate of negative cultures. The purpose of this study is to evaluate primary septic arthritis in this age group in order to differentiate children with infection caused by Kingella kingae from those with other confirmed pathogens and those with no identified pathogen.

Methods:
Preschool children who underwent multidisciplinary evaluation and treatment for septic arthritis between 2009 and 2019 were retrospectively studied. Three cohorts were established for comparison of clinical and laboratory features of primary septic arthritis: (1) confirmed K. kingae, (2) confirmed other pathogen, and (3) presumed (without identified pathogen).

Results:
Among 139 children with septic arthritis, 40 (29%) were confirmed K. kingae, 29 (21%) other pathogen, and 70 (50%) presumed. Children with Kingella and those with presumed septic arthritis had significantly lower initial C-reactive protein (4.8 and 4.5 vs. 9.3 mg/dL) and fewer febrile hospital days (0.2 and 0.4 vs. 1.3 d) than children with other confirmed pathogens. Children with other pathogens had higher rates of bacteremia (38% vs. 0%) and positive joint fluid cultures (86% vs. 15%) than that of children with Kingella. The rate of polymerase chain reaction (PCR) acquisition was 38 of 40 (95.0%) Kingella cases, 18 of 29 (62.1%) other pathogen cases, and 33 of 70 (47.1%) presumed cases.

Conclusions:

K. kingae was the most commonly identified pathogen among 6-month to 4-year-old children. The Kingella and other identified pathogens in this study serve to guide empiric antimicrobial recommendations for this age range. Because of similarities between children with septic arthritis because of K. kingae and those with no identified pathogen, it is likely that an unrecognized burden of Kingella resides in culture negative cases, particularly if no PCR is sent. Systematic evaluation, including PCR acquisition, and a high index of suspicion for K. kingae are recommended to thoroughly evaluate septic arthritis in preschool children.

Level of Evidence:
Level III—Retrospective cohort comparison.