bluuebunny/crossref_metadata_2025_split huggingface dataset:
Association between contact with a general practitioner and depressive symptoms during the COVID-19 pandemic and lockdown: a large community-based study in Hangzhou, China
Authors: Yang Fei , Lin Wenhui , Frost Eleanor , Min Yan , Xu Xiaochen , Wang Xiaoyan , Li Wei , Leng Yue , Zhao Xueyin , He Wei , Hsing Ann W , Zhu Shankuan 
Published: August 2021

ObjectivesTo determine the association of general practitioner (GP) contact with depressive symptoms during the COVID-19 pandemic and lockdown in China.DesignIn April 2020, a follow-up survey was conducted on the basis of a baseline survey conducted between October 2018 and May 2019.SettingThe survey was embedded in the Stanford Wellness Living Laboratory-China (WELL China) study, an ongoing prospective community-based cohort study during 2018–2019.ParticipantsThe survey was conducted by telephone interview among 4144 adult urban residents participating in the WELL China study at baseline. We collected information on sociodemographic characteristics, depressive symptoms and GP contact during the lockdown period (February to March 2020).Primary and secondary outcome measuresDepressive symptoms were measured using the WHO-Five Well-being Index, comprising five questionnaire items that briefly indicate psychological well-being. Logistic regression models were applied to assess the association between GP contact and depressive symptoms.ResultsIn total, 3356 participants responded to the survey; 203 were excluded owing to missing data on depressive symptoms, leaving 3153 participants in the present study. During lockdown, 449 participants had GP contact. GP contact was significantly negatively associated with prevalent depressive symptoms (OR, 0.67; 95% CI 0.51 to 0.89; p<0.01) and incident depressive symptoms (OR 0.68; 95% CI 0.51 to 0.93; p<0.05). Stratified analysis showed a significant negative association between depressive symptoms and GP contact in individuals who were 45–64 years old (p<0.01), had a middle or high education (p<0.01) and had self-reported non-communicable diseases (p<0.05).ConclusionsContact with GPs during the COVID-19 pandemic and lockdowns may have a negative association with depressive symptoms in community-dwelling populations. Given the possibility of further surges in COVID-19 infections, GPs’ contact in the community should be enhanced.
Pilot evaluation of risk assessment and enhanced protocols regarding contacts at an international professional golf event
Authors: Robinson Patrick G , Murray Andrew , Sheer Volker , Close Graeme , Kinane Denis F 
Published: August 2021

ObjectivesThe aim of this study was to assess whether a risk assessment and managed risk approach to contact tracing was practical and feasible at the Gran Canaria Lopesan Open 2021 and could inform further pilot work regarding disease transmission during elite sporting events.MethodsThis prospective cohort study included all international attendees. All participants required a minimum of one negative reverse transcriptase PCR (RT-PCR) test prior to travelling to each tournament. High-risk contacts were isolated for 10 days. Moderate-risk contacts received education regarding enhanced medical surveillance, had daily rapid antigen testing for 5 days, with RT-PCR day 5, mandated mask use and access to outside space for work purposes only. Low-risk contacts received rapid antigen testing every 48 hours and PCR testing on day 5.ResultsA total of 550 persons were accredited and were required to undergo RT-PCR testing before the event. Two of these tests were positive (0.36%). Of these, case 1 had 1 high, 23 moderate and 48 low-risk contacts. Case 2 did not have any significant travel history within 2 days of positive test and had one high-risk contact. There were no further positive tests on site in the wider cohort of attendees, from a total of 872 RT-PCR and 198 rapid antigen tests.ConclusionsThis pilot study showed it is practical, feasible and well accepted to provide enhanced (daily) virus testing and risk-mitigating measures at a professional golf event. Further study is required to assess the efficacy of these interventions; however, no transmission was found in this pilot study.
Gastrointestinal bleeding risk following concomitant treatment with oral glucocorticoids in patients on non-vitamin K oral anticoagulants
Authors: Holt Anders , Blanche Paul , Zareini Bochra , Rasmussen Peter Vibe , Strange Jarl Emanuel , Rajan Deepthi , Jensen Mads Hashiba , El-Sheikh Mohammed , Schjerning Anne-Marie , Schou Morten , Gislason Gunnar , Torp-Pedersen Christian , McGettigan Patricia , Lamberts Morten 
Published: August 2021

ObjectiveGastrointestinal bleeding (GIB) risk in relation to concomitant treatment with non-vitamin K oral anticoagulants (NOAC) and oral glucocorticoids is insufficiently explored. We aimed to investigate the short-term risk following coexposure.MethodsThis is a register-based, nationwide Danish study including patients with atrial fibrillation on NOACs during 2012–2018. Patients were defined as exposed to oral glucocorticoids if they claimed a prescription within 60 days prior to GIB. We investigated the associations between GIB and oral glucocorticoid exposure, reporting HRs via a nested case–control design and absolute risk via a cohort design. Matching terms were age, sex, calendar year, follow-up time and NOAC agent.Results98 376 patients on NOACs (median age: 75 years (IQR: 68–82), 44% female) were included, and 16% redeemed at least one oral glucocorticoid prescription within 3 years. HRs of GIB were increased comparing exposed with non-exposed patients (<20 mg daily dose, HR 1.54 (95% CI 1.29 to 1.84); ≥20 mg daily dose, HR 2.19 (95% CI 1.81 to 2.65)). 60-day standardised absolute risk of GIB following first claimed oral glucocorticoid prescription increased compared with non-exposed: 60-day absolute risk: 0.71% (95% CI 0.58% to 0.85%) vs 0.38% (95% CI 0.32% to 0.43%). The relative risk was elevated as well: risk ratio of 1.89 (95% CI 1.43 to 2.36).ConclusionsConcomitant treatment with NOACs and oral glucocorticoids was associated with a short-term rate and risk increase of GIB compared with patients only on NOACs. This could have implications for clinical management, necessitating closer monitoring or other risk mitigation strategies during episodes of cotreatment with oral glucocorticoids.
Prospective association between receipt of the economic impact payment and mental health outcomes
Authors: Tsai Jack , Huang Minda , Rajan Suja S , Elbogen Eric B 
Published: August 2021

BackgroundThe Coronavirus Aid, Relief, and Economic Security Act of 2020 provided ‘economic impact payments’ (EIPs) of $1200 to US adults with annual personal income of $75 000 or less. This study examined the prospective association between EIP receipt and mental health outcomes.MethodsA nationally representative sample of 3169 middle-income and low-income US adults completed a baseline assessment of their health and well-being in May–June 2020 and a 3-month follow-up assessment during the period of the COVID-19 pandemic when EIPs were distributed.ResultsControlling for sociodemographic characteristics, EIP recipients had higher odds of reporting a positive COVID-19 test, endorsing a history of post-traumatic stress disorder and reporting any illicit drug use in the past month than participants who did not receive EIP. Participants who did not receive EIP were more likely to report a history of anxiety disorder or alcohol use disorder and recent suicidal ideation than EIP recipients. There was no association between EIP receipt and financial distress, although over one-third to over half of EIP recipients were not employed at baseline. Between baseline and 3-month follow-up, receipt of EIP was significantly associated with reduced medical conditions and alcohol use problems, but increased depression, suicidal ideation and COVID-19 era-related stress.ConclusionThe EIP provided a brief income stimulus to many adults in need but was not associated with improvements in financial distress or mental health among middle-income and low-income recipients. Long-term income security and employment may be more important to improving and sustaining positive mental health outcomes.
Torus-Breakdown Near a Heteroclinic Attractor: A Case Study
Authors: Castro Luísa , Rodrigues Alexandre 
Published: August 2021

There are few explicit examples in the literature of vector fields exhibiting observable chaos that may be proved analytically. This paper reports numerical experiments performed for an explicit two-parameter family of [Formula: see text]-symmetric vector fields whose organizing center exhibits an attracting heteroclinic network linking two saddle-foci. Each vector field in the family is the restriction to [Formula: see text] of a polynomial vector field in [Formula: see text]. We investigate global bifurcations due to symmetry-breaking and we detect strange attractors via a mechanism called Torus-Breakdown. We explain how an attracting torus gets destroyed by following the changes in the unstable manifold of a saddle-focus. Although a complete understanding of the corresponding bifurcation diagram and the mechanisms underlying the dynamical changes is out of reach, we uncover complex patterns for the symmetric family under analysis, using a combination of theoretical tools and computer simulations. This article suggests a route to obtain rotational horseshoes and strange attractors; additionally, we make an attempt to elucidate some of the bifurcations involved in an Arnold tongue.
Rates and Patterns of Clonal Oncogenic Mutations in the Normal Human Brain
Authors: Ganz Javier , Maury Eduardo A. , Becerra Basheer , Bizzotto Sara , Doan Ryan N. , Kenny Connor J. , Shin Taehwan , Kim Junho , Zhou Zinan , Ligon Keith L. , Lee Eunjung Alice , Walsh Christopher A. 
Published: August 2021

AbstractAlthough oncogenic mutations have been found in nondiseased, proliferative nonneural tissues, their prevalence in the human brain is unknown. Targeted sequencing of genes implicated in brain tumors in 418 samples derived from 110 individuals of varying ages, without tumor diagnoses, detected oncogenic somatic single-nucleotide variants (sSNV) in 5.4% of the brains, including IDH1R132H. These mutations were largely present in subcortical white matter and enriched in glial cells and, surprisingly, were less common in older individuals. A depletion of high-allele frequency sSNVs representing macroscopic clones with age was replicated by analysis of bulk RNA sequencing data from 1,816 nondiseased brain samples ranging from fetal to old age. We also describe large clonal copy number variants and that sSNVs show mutational signatures resembling those found in gliomas, suggesting that mutational processes of the normal brain drive early glial oncogenesis. This study helps understand the origin and early evolution of brain tumors.Significance:In the nondiseased brain, clonal oncogenic mutations are enriched in white matter and are less common in older individuals. We revealed early steps in acquiring oncogenic variants, which are essential to understanding brain tumor origins and building new mutational baselines for diagnostics.This article is highlighted in the In This Issue feature, p. 1
Context-Dependent Immunomodulatory Effects of MEK Inhibition Are Enhanced with T-cell Agonist Therapy
Authors: Dennison Lauren , Ruggieri Amanda , Mohan Aditya , Leatherman James , Cruz Kayla , Woolman Skylar , Azad Nilofer , Lesinski Gregory B. , Jaffee Elizabeth M. , Yarchoan Mark 
Published: August 2021

AbstractMEK inhibition (MEKi) is proposed to enhance antitumor immunity but has demonstrated mixed results as an immunomodulatory strategy in human clinical trials. MEKi exerts direct immunomodulatory effects on tumor cells and tumor-infiltrating lymphocytes (TIL), but these effects have not been independently investigated. Here we modeled tumor-specific MEKi through CRISPR/Cas-mediated genome editing of tumor cells [MEK1 knockout (KO)] and pharmacologic MEKi with cobimetinib in a RAS-driven model of colorectal cancer. This approach allowed us to distinguish tumor-mediated and tumor-independent mechanisms of MEKi immunomodulation. MEK1 KO tumors demonstrated upregulation of JAK/STAT signaling, enhanced MHCI expression, CD8+ T-cell infiltration and T-cell activation, and impaired tumor growth that is immune dependent. Pharmacologic MEKi recapitulated tumor-intrinsic effects but simultaneously impaired T-cell activation in the tumor microenvironment. We confirmed a reduction in human peripheral-lymphocyte activation from a clinical trial of anti–PD-L1 (atezolizumab) with or without cobimetinib in biliary tract cancers. Impaired activation of TILs treated with pharmacologic MEKi was reversible and was rescued with the addition of a 4-1BB agonist. Collectively, these data underscore the ability of MEKi to induce context-dependent immunomodulatory effects and suggest that T cell–agonist therapy maximizes the beneficial effects of MEKi on the antitumor immune response.
Single-View Echocardiography by Nonexpert Practitioners to Detect Rheumatic Heart Disease: A Prospective Study of Diagnostic Accuracy
Authors: Francis Joshua R. , Whalley Gillian A. , Kaethner Alex , Fairhurst Helen , Hardefeldt Hilary , Reeves Benjamin , Auld Benjamin , Marangou James , Horton Ari , Wheaton Gavin , Robertson Terry , Ryan Chelsea , Brown Shannon , Smith Greg , dos Santos Januario , Flavio Ricardo , Embaum Karolina , da Graca Noronha Mario , Lopes Belo Sonia , Madeira Santos Carla , Georginha dos Santos Maria , Cabral Jose , do Rosario Ivonia , Harries Jessica , Francis Laura A. , Draper Anthony D.K. , James Christian L. , Davis Kimberly , Yan Jennifer , Mitchell Alice , da Silva Almeida Ines , Engelman Daniel , Roberts Kathryn V. , Ralph Anna P. , Remenyi Bo 
Published: August 2021

Background:
Echocardiographic screening can detect asymptomatic cases of rheumatic heart disease (RHD), facilitating access to treatment. Barriers to implementation of echocardiographic screening include the requirement for expensive equipment and expert practitioners. We aimed to evaluate the diagnostic accuracy of an abbreviated echocardiographic screening protocol (single parasternal-long-axis view with a sweep of the heart) performed by briefly trained, nonexpert practitioners using handheld ultrasound devices.

Methods:
Participants aged 5 to 20 years in Timor-Leste and the Northern Territory of Australia had 2 echocardiograms: one performed by an expert echocardiographer using a GE Vivid I or Vivid Q portable ultrasound device (reference test), and one performed by a nonexpert practitioner using a GE Vscan handheld ultrasound device (index test). The accuracy of the index test, compared with the reference test, for identifying cases with definite or borderline RHD was determined.

Results:
There were 3111 enrolled participants; 2573 had both an index test and reference test. Median age was 12 years (interquartile range, 10–15); 58.2% were female. Proportion with definite or borderline RHD was 5.52% (95% CI, 4.70–6.47); proportion with definite RHD was 3.23% (95% CI, 2.61–3.98).
Compared with the reference test, sensitivity of the index test for definite or borderline RHD was 70.4% (95% CI, 62.2–77.8), specificity was 78.1% (95% CI, 76.4–79.8).

Conclusions:
Nonexpert practitioners can be trained to perform single parasternal-long-axis view with a sweep of the heart echocardiography. However, the specificity and sensitivity are inadequate for echocardiographic screening. Improved training for nonexpert practitioners should be investigated.
Long‐Term Outcomes of Transcatheter Aortic Valve Replacement in Patients With End‐Stage Renal Disease
Authors: Ogami Takuya , Kurlansky Paul , Takayama Hiroo , Ning Yuming , Ali Ziad A. , Nazif Tamim M. , Vahl Torsten P. , Khalique Omar , Patel Amisha , Hamid Nadira , Ng Vivian G. , Hahn Rebecca T. , Avgerinos Dimitrios V. , Leon Martin B. , Kodali Susheel K. , George Isaac 
Published: August 2021

Background
Aortic stenosis is prevalent in end‐stage renal disease. Transcatheter aortic valve replacement (TAVR) is a plausible alternative for surgical aortic valve replacement. However, little is known regarding long‐term outcomes in patients with end‐stage renal disease who undergo TAVR.

Methods and Results

We identified all patients with end‐stage renal disease who underwent TAVR from 2011 through 2016 using the United States Renal Data System. The primary end point was 5‐year mortality after TAVR. Factors associated with 1‐ and 5‐year mortality were analyzed. A total of 3883 TAVRs were performed for patients with end‐stage renal disease. Mortality was 5.8%, 43.7%, and 88.8% at 30 days, 1 year, and 5 years, respectively. Case volumes increased rapidly from 17 in 2011 to 1495 in 2016. Thirty‐day mortality demonstrated a dramatic reduction from 11.1% in 2012 to 2.5% in 2016 (
P
=0.01). Age 75 or older (hazard ratio [HR], 1.14; 95% CI, 1.05–1.23 [
P
=0.002]), body mass index <25 (HR, 1.18; 95% CI, 1.08–1.28 [
P
<0.001]), chronic obstructive pulmonary disease (HR, 1.25; 95% CI, 1.1–1.35 [
P
<0.001]), diabetes mellitus as the cause of dialysis (HR, 1.22; 95% CI, 1.11–1.35 [
P
<0.001]), hypertension as the cause of dialysis (HR, 1.17; 95% CI, 1.06–1.29 [
P
=0.004]), and White race (HR, 1.17; 95% CI, 1.06–1.3 [
P
=0.002]) were independently associated with 5‐year mortality.

Conclusions
Short‐term outcomes of TAVR in patients with end‐stage renal disease have improved significantly. However, long‐term mortality of patients on dialysis remains high.
Geriatric Conditions Are Associated With Decreased Anticoagulation Use in Long‐Term Care Residents With Atrial Fibrillation
Authors: Zhang Ning , Patel Jay , Chen Zhiyong , Zhou Yanhua , Crawford Sybil , McManus David D. , Gurwitz Jerry , Shireman Theresa I. , Kapoor Alok 
Published: August 2021

Background

Anticoagulation is the mainstay for stroke prevention in patients with atrial fibrillation, but concerns about bleeding inhibit its use in residents of long‐term care facilities. Risk‐profiling algorithms using comorbid disease information (eg, CHADS
2
and ATRIA [Anticoagulation and Risk Factors in Atrial Fibrillation]) have been available for years. In the long‐term care setting, however, providers and residents may place more value on geriatric conditions such as mobility impairment, activities of daily living dependency, cognitive impairment, low body mass index, weight loss, and fall history.

Methods and Results

Using a retrospective cohort design, we measured the association between geriatric conditions and anticoagulation use and type. After merging nursing home assessments containing information about geriatric conditions (Minimum Data Set 2015) with Medicare Part A 2014 to 2015 claims and prescription claims (Medicare Part D) 2015 to 2016, we identified 228 741 residents with atrial fibrillation and elevated stroke risk (CHA
2
DS
2
‐VASc score ≥2) for our main analysis. Recent fall, activities of daily living dependency, moderate and severe cognitive impairment, low body mass index, and unintentional weight loss were all associated with lower anticoagulation use even after adjustment for multiple predictors of stroke and bleeding (odds ratios ranging from 0.51 to 0.91). Residents with recent fall, low body mass index, and unintentional weight loss were more likely to be using a direct oral anticoagulant, although the magnitude of this effect was smaller.

Conclusions
Geriatric conditions were associated with lower anticoagulation use. Preventing stroke in these residents with potential for further physical and cognitive impairment would appear to be of paramount significance, although the net benefit of anticoagulation in these individuals warrants further research.
The (Un)Suitability of Automatic Evaluation Metrics for Text Simplification
Authors: Alva-Manchego Fernando , Scarton Carolina , Specia Lucia 
Published: August 2021

Abstract
In order to simplify sentences, several rewriting operations can be performed, such as replacing complex words per simpler synonyms, deleting unnecessary information, and splitting long sentences. Despite this multi-operation nature, evaluation of automatic simplification systems relies on metrics that moderately correlate with human judgments on the simplicity achieved by executing specific operations (e.g., simplicity gain based on lexical replacements). In this article, we investigate how well existing metrics can assess sentence-level simplifications where multiple operations may have been applied and which, therefore, require more general simplicity judgments. For that, we first collect a new and more reliable data set for evaluating the correlation of metrics and human judgments of overall simplicity. Second, we conduct the first meta-evaluation of automatic metrics in Text Simplification, using our new data set (and other existing data) to analyze the variation of the correlation between metrics’ scores and human judgments across three dimensions: the perceived simplicity level, the system type, and the set of references used for computation. We show that these three aspects affect the correlations and, in particular, highlight the limitations of commonly used operation-specific metrics. Finally, based on our findings, we propose a set of recommendations for automatic evaluation of multi-operation simplifications, suggesting which metrics to compute and how to interpret their scores.
Prior Beliefs Modulate Projection
Authors: Degen Judith , Tonhauser Judith 
Published: August 2021

Abstract
Beliefs about the world affect language processing and interpretation in several empirical domains. In two experiments, we tested whether subjective prior beliefs about the probability of utterance content modulate projection, that is, listeners’ inferences about speaker commitment to that content. We find that prior beliefs predict projection at both the group and the participant level: the higher the prior belief in a content, the more speakers are taken to be committed to it. This result motivates the integration of formal analyses of projection with cognitive theories of language understanding.
Increased sea-level sensitivity to CO2 forcing across the Middle Pleistocene Transition from ice-albedo and ice-volume nonlinearities
Authors: Liautaud Parker , Huybers Peter 
Published: August 2021

AbstractProxy reconstructions indicate that sea level responded more sensitively to CO2 radiative forcing in the late Pleistocene than in the early Pleistocene, a transition that was proposed to arise from changes in ice-sheet dynamics. In this study we analyse the links between sea level, orbital variations, and CO2 using an energy-balance model having a simple ice sheet. Model parameters, including for age models, are inferred over the late Pleistocene using a hierarchical Bayesian method, and the inferred relationships are used to evaluate CO2 levels over the past 2 My in relation to sea level. Early-Pleistocene model CO2 averages 246 ppm (244 ppm - 249 ppm 95% c.i.) across 2-1 Ma and indicates that sea level was less sensitive to radiative forcing than in the late Pleistocene, consistent with foregoing δ11B-derived estimates. Weaker early-Pleistocene sea-level sensitivity originates from a weaker ice-albedo feedback and the fact that smaller ice sheets are thinner, absent changes over time in model equations or parameters. An alternative scenario involving thin and expansive early-Pleistocene ice sheets, in accord with some lines of geologic evidence, implies 15 ppm lower average CO2 or ~10-15 m higher average sea level during the early Pleistocene relative to the original scenario. Our results do not rule out dynamical transitions during the middle Pleistocene, but indicate that variations in the sea-level response to CO2 forcing over the past 2 My can be explained on the basis of nonlinearities associated with ice-albedo feedbacks and ice-sheet geometry that are consistently present across this interval.