bluuebunny/crossref_metadata_2025_split huggingface dataset:
Factors associated with work-related burnout in NHS staff during COVID-19: a cross-sectional mixed methods study
Authors: Gemine Rachel , Davies Gareth R , Tarrant Suzanne , Davies Richard M , James Meryl , Lewis Keir 
Published: January 2021

ObjectivesTo measure work-related burnout in all groups of health service staff during the COVID-19 pandemic and to identify factors associated with work-related burnout.DesignCross-sectional staff survey.SettingAll staff grades and types across primary and secondary care in a single National Health Service organisation.Participants257 staff members completed the survey, 251 had a work-related burnout score and 239 records were used in the regression analysis.Primary and secondary outcome measures(1) Work-related burnout as measured by the Copenhagen Burnout Inventory; (2) factors associated with work-related burnout identified through a multiple linear regression model; and (3) factors associated with work-related burnout identified through thematic analysis of free text responses.ResultsAfter adjusting for other covariates (including age, sex, job, being able to take breaks and COVID-19 knowledge), we observed meaningful changes in work-related burnout associated with having different COVID-19 roles (p=0.03), differences in the ability to rest and recover during breaks (p<0.01) and having personal protective equipment concerns (p=0.04). Thematic analysis of the free text comments also linked burnout to changes in workload and responsibility and to a lack of control through redeployment and working patterns. Reduction in non-COVID-19 services has resulted in some members of staff feeling underutilised, with feelings of inequality in workload.ConclusionsOur analyses support anecdotal reports of staff struggling with the additional pressures brought on by COVID-19. All three of the factors we found to be associated with work-related burnout are modifiable and hence their effects can be mitigated. When we next find ourselves in extraordinary times the ordinary considerations of rest and protection and monitoring of the impact of new roles will be more important than ever.
Cardiovascular risk factor mediation of the effects of education and Genetic Risk Score on cardiovascular disease: a prospective observational cohort study of the Framingham Heart Study
Authors: Powell Katie L , Stephens Sebastien R , Stephens Alexandre S 
Published: January 2021

ObjectivesLevel of education and genetic risk are key predictors of cardiovascular disease (CVD). While several studies have explored the causal mechanisms of education effects, it remains uncertain to what extent genetic risk is mediated by established CVD risk factors. This study sought to investigate this and explored the mediation of education and genetic effects on CVD by established cardiovascular risk factors in the Framingham Heart Study (FHS).DesignProspective observational cohort study.Participants7017 participants from the FHS.SettingCommunity-based cohort of adults in Framingham, Massachusetts, USA.Primary outcome measureIncident CVD. The total effects of education and genetic predisposition using a 63-variant genetic risk score (GRS) on CVD, as well as those mediated by established CVD risk factors, were assessed via mediation analysis based on the counterfactual framework using Cox proportional hazards regression models.ResultsOver a median follow-up time of 12.0 years, 1091 participants experienced a CVD event. Education and GRS displayed significant associations with CVD after adjustment for age and sex and the established risk factors smoking, total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), body mass index, systolic blood pressure (SBP) and diabetes. For education effects, smoking, HDL-C and SBP were estimated to mediate 18.8% (95% CI 9.5% to 43%), 11.5% (95% CI 5.7% to 29.0%) and 4.5% (95% CI 1.6% to 13.3%) of the total effect of graduate degree, respectively, with the collective of all risk factors combined mediating 38.5% (95% 24.1% to 64.9%). A much smaller proportion of the effects of GRS were mediated by established risk factors combined (17.6%, 95% CI 2.4% to 35.7%), with HDL-C and TC mediating 11.5% (95% CI 6.2% to 21.5%) and 3.1% (95% CI 0.2% to 8.3%), respectively.ConclusionsUnlike education inequalities, established risk factors mediated only a fraction of GRS effects on CVD. Further research is required to elucidate the underlying causal mechanisms of genetic contributions to CVD.
Diagnostic performance of melanocytic markers for immunocytochemical evaluation of lymph-node melanoma metastases on cytological samples
Authors: Ronchi Andrea , Zito Marino Federica , Toni Giorgio , Pagliuca Francesca , Russo Daniela , Signoriello Giuseppe , Moscarella Elvira , Brancaccio Gabriella , Argenziano Giuseppe , Franco Renato , Cozzolino Immacolata 
Published: January 2021

AimsThe diagnosis of metastatic cutaneous melanoma (CM) on lymph node fine needle aspiration samples may be challenging and usually requires confirmation by immunocytochemistry. However, the cytological material could be too scant to order a broad panel of markers. In this case, the pathologist is forced to choose the most advantageous antibodies. The most commonly used melanocytic markers include S100, Melan-A, HMB45 and SOX10 but their diagnostic yield on cytological samples has been poorly studied. The current work aimed to evaluate the diagnostic performance of melanocytic markers when applied to cell blocks obtained from fine needle aspiration cytology (FNAC) of lymph node metastases from CM.MethodsS100, Melan-A, HMB45 and SOX10 were tested on cell block sections of 38 lymphnode metastases from CM diagnosed by cytology. A combined score was built to evaluate each immunostaining, considering the intensity of the staining and the percentage of stained neoplastic cells.ResultsS100 and SOX10 revealed a higher sensitivity (100%) than Melan-A and HMB45 for the diagnosis of metastatic CM. Furthermore, SOX10 emerged as the melanocytic marker with the best staining performance.ConclusionSOX10 has a 100% detection rate and the most easily interpretable staining pattern compared with other melanocytic markers. Therefore, it is strongly recommended that SOX10 is included in the minimal immunocytochemical panel for the diagnostic evaluation of lymph node FNAC in patients with suspected CM metastasis.
Effects of cold water immersion on circulating inflammatory markers at the Kona Ironman World Championship
Authors: Bartley Jenna M , Stearns Rebecca L , Munoz Colleen , Nolan Julie K. , Radom-Aizik Shlomit , Maresh Carl M. , Casa Douglas J , Zaldivar Frank P. , Haddad Fadia , Ganio Matthew S. , Lee Elaine Choung-Hee 
Published: January 2021

Cold water immersion (CWI) purportedly reduces inflammation and improves muscle recovery post exercise, yet its effectiveness in specific contexts (ultraendurance) remains unclear. Thus, our aim was to study hematological profiles, systemic inflammation, and muscle damage responses to a specific post race CWI (vs. control) during recovery after the Ironman® World Championship, a culmination of ~100,000 athletes competing in global qualifying Ironman® events each year. Twenty-nine competitors were randomized into CWI or control (CON) group. Physiological parameters and blood samples were taken pre race (BASE), after intervention (POST), and 24 (+1DAY) and 48 hours (+2DAY) following the race. Muscle damage markers (plasma myoglobin, serum creatine kinase) were elevated at POST, +1DAY, and +2DAY, while inflammatory cytokines IL-6, IL-8, and IL-10 and total leukocyte counts were increased only at POST. CWI had no effect on these markers. Numbers of the most abundant circulating cell type, neutrophils, were elevated at POST more so in CWI (p<0.05, vs. CON). Despite that neutrophil counts may be a sensitive marker to detect subtle effects, CWI does not affect recovery markers 24- and 48-hours post race (vs. CON). Overall, we determine that our short CWI protocol was not sufficient to improve recovery. Novelty: • Ironman World Championship event increased circulating muscle damage markers, inflammatory markers, and hematological parameters, including circulating immune cell sub-populations that recover 24-48 hours after the race. • 12-min CWI post ultraendurance event affects the absolute numbers of neutrophils acutely, post race (vs. CON), but does not impact recovery 24- and 48-hours post race.
High-Density, Targeted Monitoring of Tyrosine Phosphorylation Reveals Activated Signaling Networks in Human Tumors
Authors: Stopfer Lauren E. , Flower Cameron T. , Gajadhar Aaron S. , Patel Bhavin , Gallien Sebastien , Lopez-Ferrer Daniel , White Forest M. 
Published: January 2021

Abstract

Tyrosine phosphorylation (pTyr) plays a pivotal role in signal transduction and is commonly dysregulated in cancer. As a result, profiling tumor pTyr levels may reveal therapeutic insights critical to combating disease. Existing discovery and targeted mass spectrometry–based methods used to monitor pTyr networks involve a tradeoff between broad coverage of the pTyr network, reproducibility in target identification across analyses, and accurate quantification. To address these limitations, we developed a targeted approach, termed “SureQuant pTyr,” coupling low input pTyr enrichment with a panel of isotopically labeled internal standard peptides to guide data acquisition of low-abundance tyrosine phosphopeptides. SureQuant pTyr allowed for reliable quantification of several hundred commonly dysregulated pTyr targets with high quantitative accuracy, improving the robustness and usability of targeted mass spectrometry assays. We established the clinical applicability of SureQuant pTyr by profiling pTyr signaling levels in human colorectal tumors using minimal sample input, characterizing patient-specific oncogenic-driving mechanisms. While in some cases pTyr profiles aligned with previously reported proteomic, genomic, and transcriptomic molecular characterizations, we highlighted instances of new insights gained using pTyr characterization and emphasized the complementary nature of pTyr measurements with traditional biomarkers for improving patient stratification and identifying therapeutic targets. The turn-key nature of this approach opens the door to rapid and reproducible pTyr profiling in research and clinical settings alike and enables pTyr-based measurements for applications in precision medicine.

Significance:
SureQuant pTyr is a mass spectrometry–based targeted method that enables sensitive and selective targeted quantitation of several hundred low-abundance tyrosine phosphorylated peptides commonly dysregulated in cancer, including oncogenic signaling networks.
Eugen Warming: um dinamarquês desvenda o cerrado brasileiro
Authors: Cavassan Osmar , Weiser Veridiana de Lara 
Published: January 2021

O botânico Johannes Eugenius Bülow Warming (1841-1924) atuou como professor de botânica nas Universidades de Copenhagen e Estocolmo, sendo também reitor em ambas e diretor do Jardim Botânico de Copenhagen. Visitou vários países em expedições científicas e foi conferencista em eventos, inclusive o Brasil. Figura de destaque na ecologia vegetal, Warming influenciou a geração de jovens botânicos e ecólogos que o sucederam, principalmente pela abordagem sistêmica ao cerrado. Alguns ecólogos atribuem a ele a expressão “fatores ecológicos”. O objetivo deste artigo é apresentar informações sobre a vida e obra de Warming destacando seus estudos sobre o cerrado e o seu papel na definição de linhas de pesquisa em ecologia vegetal. Warming, esteve no Brasil, mais precisamente em Lagoa Santa, Minas Gerais, de 1863 a 1866. Nesse período, coletou, descreveu e registrou em desenhos e fotografias a vegetação e representantes da flora do cerrado daquela região. Ele não se limitou aos aspectos estéticos, mas associou a vegetação e a flora do cerrado às características climáticas, edáficas e ocorrência de fogo. A importância de sua obra reside na maneira como ele procedeu em sua pesquisa. Publicou o primeiro estudo sobre o cerrado brasileiro na língua dinamarquesa, que foi traduzido para o português como Lagoa Santa: coribuição para a geografia phytobiologica por Johan Albert Constantin Löfgren (1854-1918) em 1908.
Chondroitin Sulfate
N
-acetylgalactosaminyltransferase-2 Impacts Foam Cell Formation and Atherosclerosis by Altering Macrophage Glycosaminoglycan Chain
Authors: Adhikara Imam Manggalya , Yagi Keiko , Mayasari Dyah Samti , Suzuki Yoko , Ikeda Koji , Ryanto Gusty Rizky Teguh , Sasaki Naoto , Rikitake Yoshiyuki , Nadanaka Satomi , Kitagawa Hiroshi , Miyata Okiko , Igarashi Michihiro , Hirata Ken-ichi , Emoto Noriaki 
Published: January 2021

Objective:

Chondroitin sulfate proteoglycans are the primary constituents of the macrophage glycosaminoglycan and extracellular microenvironment. To examine their potential role in atherogenesis, we investigated the biological importance of one of the chondroitin sulfate glycosaminoglycan biosynthesis gene, ChGn-2 (chondroitin sulfate
N
-acetylgalactosaminyltransferase-2), in macrophage foam cell formation.

Approach and Results:

ChGn-2-deficient mice showed decreased and shortened glycosaminoglycans. ChGn-2
−/−
/LDLr
−/−
(low-density lipoprotein receptor) mice generated less atherosclerotic plaque after being fed with Western diet despite exhibiting a metabolic phenotype similar to that of the ChGn-2
+/+
/LDLr
−/−
littermates. We demonstrated that in macrophages, ChGn-2 expression was upregulated in the presence of oxLDL (oxidized LDL), and glycosaminoglycan was substantially increased. Foam cell formation was significantly altered by ChGn-2 in both mouse peritoneal macrophages and the RAW264.7 macrophage cell line. Mechanistically, ChGn-2 enhanced oxLDL binding on the cell surface, and as a consequence, CD36—an important macrophage membrane scavenger receptor—was differentially regulated.

Conclusions:
ChGn-2 alteration on macrophages conceivably influences LDL accumulation and subsequently accelerates plaque formation. These results collectively suggest that ChGn-2 is a novel therapeutic target amenable to clinical translation in the future.

Graphic Abstract:
A graphic abstract is available for this article.
Differences in High‐ and Low‐Value Cardiovascular Testing by Health Insurance Provider
Authors: Kini Vinay , Mosley Bridget , Raghavan Sridharan , Khazanie Prateeti , Bradley Steven M. , Magid David J. , Ho P. Michael , Masoudi Frederick A. 
Published: January 2021

Background
Quality of care incentives and reimbursements for cardiovascular testing differ between insurance providers. We hypothesized that there are differences in the use of guideline‐concordant testing between Medicaid versus commercial insurance patients <65 years, and between Medicare Advantage versus Medicare fee‐for‐service patients ≥65 years.

Methods and Results

Using data from the Colorado All‐Payer Claims Database from 2015 to 2018, we identified patients eligible to receive a high‐value test recommended by guidelines: assessment of left ventricular function among patients hospitalized with acute myocardial infarction or incident heart failure, or a low‐value test that provides minimal patient benefit: stress testing prior to low‐risk surgery or routine stress testing within 2 years of percutaneous coronary intervention or coronary artery bypass graft surgery. Among 145 616 eligible patients, 37% had fee‐for‐service Medicare, 18% Medicare Advantage, 22% Medicaid, and 23% commercial insurance. Using multilevel logistic regression models adjusted for patient characteristics, Medicaid patients were less likely to receive high‐value testing for acute myocardial infarction (odds ratio [OR], 0.84 [0.73–0.98];
P
=0.03) and heart failure (OR, 0.59 [0.51–0.70];
P
<0.01) compared with commercially insured patients. Medicare Advantage patients were more likely to receive high‐value testing for acute myocardial infarction (OR, 1.35 [1.15–1.59];
P
<0.01) and less likely to receive low‐value testing after percutaneous coronary intervention/ coronary artery bypass graft (OR, 0.63 [0.55–0.72];
P
<0.01) compared with Medicare fee‐for‐service patients.

Conclusions
Guideline‐concordant testing was less likely to occur among patients with Medicaid compared with commercial insurance, and more likely to occur among patients with Medicare Advantage compared with fee‐for‐service Medicare. Insurance plan features may provide valuable targets to improve guideline‐concordant testing.
Bridging May Increase the Risk of Symptomatic Intracranial Hemorrhage in Thrombectomy Patients With Low Alberta Stroke Program Early Computed Tomography Score
Authors: Kaesmacher Johannes , Meinel Thomas R. , Nannoni Stefania , Olivé-Gadea Marta , Piechowiak Eike I. , Maegerlein Christian , Goeldlin Martina , Pierot Laurent , Seiffge David J. , Mendes Pereira Vitor , Heldner Mirjam R. , Grunder Lorenz , Costalat Vincent , Arnold Marcel , Dobrocky Tomas , Gralla Jan , Mordasini Pasquale , Fischer Urs , Panos Leonidas , Chaloulos-Iakovidis Panagiotis , Ribo Marc , Requena Manuel , Hajdu Steven D. , Benali Amel , Friedrich Benjamin , Schaafsma Joanna , Gawlitza Matthias 
Published: January 2021

Background and Purpose:
Whether intravenous thrombolysis (IVT) increases the risk for symptomatic intracranial hemorrhage (sICH) in patients treated with mechanical thrombectomy (MT) is a matter of debate. Purpose of this study was to evaluate the extent of early ischemia as a possible factor influencing the risk for sICH after IVT+MT versus direct MT.

Methods:
An explorative analysis of the BEYOND-SWIFT (Bernese-European Registry for Ischemic Stroke Patients Treated Outside Current Guidelines With Neurothrombectomy Devices Using the SOLITAIRE FR With the Intention for Thrombectomy) multicenter cohort was performed. We hypothesized that the sICH risk between IVT+MT versus direct MT differs across the strata of Alberta Stroke Program Early CT Scores (ASPECTS). For this purpose, all patients with ICA, M1, and M2 vessel occlusions and available noncontrast computed tomography or diffusion-weighed imaging ASPECTS (n=2002) were analyzed. We used logistic regression analysis in subgroups, as well as interaction terms, to address the risk of sICH in IVT+MT versus direct MT patients across the ASPECTS strata.

Results:

In 2002 patients (median age, 73.7 years; 50.7% women; median National Institutes of Health Stroke Scale score, 16), the overall rate of sICH was 6.5% (95% CI, 5.5%–7.7%). Risk of sICH differed across ASPECTS groups (9–10: 6.3%; 6–8: 5.6% and ≤5 9.8%;
P
=0.042). With decreasing ASPECTS, the risks of sICH in the IVT+MT versus the direct MT group increased from adjusted odds ratio of 0.61 ([95% CI, 0.24–1.60] ASPECTS 9–10), to 1.72 ([95% CI, 0.69–4.24] ASPECTS 6–8) and 6.31 ([95% CI, 1.87–21.29] ASPECTS ≤5), yielding a positive interaction term (1.91 [95% CI, 1.01–3.63]). Sensitivity analyses regarding diffusion-weighed imaging versus noncontrast computed tomography ASPECTS did not alter the primary observations.

Conclusions:
The extent of early ischemia may influence relative risks of sICH in IVT+MT versus direct MT patients, with an excess sICH risk in IVT+MT patients with low ASPECTS. If confirmed in post hoc analyses of randomized controlled trial data, IVT may be administered more carefully in patients with low ASPECTS eligible for and with direct access to MT.
Dabigatran or Aspirin After Embolic Stroke of Undetermined Source in Patients With Patent Foramen Ovale
Authors: Diener Hans-Christoph , Chutinet Aurauma , Easton J. Donald , Granger Christopher B. , Kleine Eva , Marquardt Lars , Meyerhoff Juliane , Zini Andrea , Sacco Ralph L. 
Published: January 2021

Background and Purpose:
Patent foramen ovale (PFO) may increase the risk of embolic stroke of undetermined source (ESUS). Guidelines suggest anticoagulation may be more effective than antiplatelets in preventing stroke in patients with ESUS and PFO when interventional closure is not performed.

Methods:
Patients with ESUS randomized to dabigatran (150/110 mg BID) or aspirin (100 mg QD) from the RE-SPECT ESUS study (Randomized, Double-Blind, Evaluation in Secondary Stroke Prevention Comparing the Efficacy and Safety of the Oral Thrombin Inhibitor Dabigatran Etexilate Versus Acetylsalicylic Acid in Patients With Embolic Stroke of Undetermined Source) were included. The rate of recurrent stroke (primary end point) and ischemic stroke was reported for patients with and without baseline PFO. A meta-analysis comparing the effects of anticoagulant and antiplatelet therapy on ischemic stroke in patients with PFO was updated to include RE-SPECT ESUS.

Results:

PFO was present in 680 of 5388 (12.6%) patients with documented PFO status. The risk of recurrent stroke with dabigatran versus aspirin was similar in patients with and without PFO (
P
for interaction, 0.8290). In patients with PFO, the meta-analysis found no statistically significant difference between anticoagulant and antiplatelet therapy (odds ratio, 0.70 [95% CI, 0.43–1.14]) for ischemic stroke.

Conclusions:
There is insufficient evidence to recommend anticoagulation over antiplatelet therapy for patients with ESUS and a PFO. More data are needed to guide antithrombotic therapy in this population.

Registration:

URL:
https://www.clinicaltrials.gov
. Unique identifier: NCT02239120.
Association of Lesion Location and Depressive Symptoms Poststroke
Authors: Klingbeil Julian , Brandt Max-Lennart , Wawrzyniak Max , Stockert Anika , Schneider Hans R. , Baum Petra , Hoffmann Karl-Titus , Saur Dorothee 
Published: January 2021

Background and Purpose:
Poststroke depression is a common stroke sequel, yet its neurobiological substrates are still unclear. We sought to determine whether specific lesion locations are associated with depressive symptoms after stroke.

Methods:
In a prospective study, 270 patients with first ever stroke were repeatedly tested with the depression subscale of the Hospital Anxiety and Depression Scale within the first 4 weeks and 6 months after stroke. Voxel-based lesion behavior mapping based on clinical imaging was performed to test for associations between symptoms of depression and lesion locations.

Results:
Frequency of poststroke depression (Hospital Anxiety and Depression Scale-D score >7) after 6 months was 19.6%. Higher Hospital Anxiety and Depression Scale-D scores for depression within the first 4 weeks were the only independent predictor for poststroke depression after 6 months in a multiple logistic regression also including age, sex, lesion volume, stroke severity, Barthel-Index, and the anxiety subscale of the Hospital Anxiety and Depression Scale. Nonparametric permutation-test based voxel-based lesion behavior mapping identified a cluster of voxels mostly within the left ventrolateral prefrontal cortex where lesions were significantly associated with more depressive symptoms after 6 months. No such association was observed within the right hemisphere despite better lesion coverage.

Conclusions:
Lesions in the left ventrolateral prefrontal cortex increase the risk of depressive symptoms 6 months poststroke. Lesions within the right hemisphere are unrelated to depressive symptoms. Recognition of left frontal lesions as a risk factor should help in the early diagnosis of poststroke depression through better risk stratification. The results are in line with evidence from functional imaging and noninvasive brain stimulation in patients without focal brain damage indicating that dysfunction in the left lateral prefrontal cortex contributes to depressive disorders.