bluuebunny/crossref_metadata_2025_split huggingface dataset:
Troponin, A Predictor of Mortality in Methadone Exposure: An Observational Prospective Study
Authors: Sheibani Mehdi , Mirfallah Nassiri Akram Alsadat , Abedtash Amirhossein , McDonald Rebecca , Zamani Nasim , Hassanian‐Moghaddam Hossein 
Published: April 2021

Background
Methadone poisoning/overdose is a global public health problem. We aimed to determine whether methadone poisoning increased cardiac troponin and whether high‐sensitivity cardiac troponin I (hs‐cTnI) levels predicted the need for intensive care unit admission, intubation, and mortality.

Methods and Results

This observational, prospective single‐center study was done at Loghman‐Hakim Hospital (Tehran, Iran) from June 2018 until February 2019. Patients aged >14 years admitted with a diagnosis of methadone exposure were included. Patients were excluded if they had coexisting conditions associated with elevated hs‐cTnI levels. An ECG and hs‐cTnI levels were obtained on emergency department presentation. Patients were followed up on their need for intubation, intensive care unit admission, and in‐hospital mortality. Of 245 included patients (186 [75.9%] men; median age, 33 years), most referred to loss of consciousness (210 cases, 89%). Nineteen (7.7%) patients had hs‐cTnI levels of >0.1 ng/mL (positive), and 41 (16.7%) had borderline levels of 0.019 to 0.1 ng/mL. Twenty‐three (9.3%) cases were admitted to the intensive care unit, 21 (8.5%) needed intubation, and 5 (2%) died during hospitalization. An hs‐cTnI cutoff value of 0.019 ng/mL independently predicted mortality. For optimal concomitant sensitivity and specificity, receiver operating characteristic curve analysis was conducted and showed that hs‐cTnI had an independent significant association with mortality, with a cutoff value of 0.0365 ng/mL (odds ratio, 38.1; 95% CI, 2.3–641.9;
P
<0.001).

Conclusions
Methadone exposure/toxicity is a newly identified cause of elevated hs‐cTnI. Values >0.019 ng/mL, and particularly >0.0365 ng/mL, of hs‐cTnI predicted mortality in our sample. Future studies should measure troponin levels in methadone maintenance treatment clients to assess the risk of myocardial injury from long‐term exposure.
Hospitalization for Heart Failure Among Patients With Diabetes Mellitus and Reduced Kidney Function Treated With Metformin Versus Sulfonylureas: A Retrospective Cohort Study
Authors: Richardson Tadarro L. , Hackstadt Amber J. , Hung Adriana M. , Greevy Robert A. , Grijalva Carlos G. , Griffin Marie R. , Elasy Tom A. , Roumie Christianne L. 
Published: April 2021

Background
Metformin and sulfonylurea are commonly prescribed oral medications for type 2 diabetes mellitus. The association of metformin and sulfonylureas on heart failure outcomes in patients with reduced estimated glomerular filtration rate remains poorly understood.

Methods and Results

This retrospective cohort combined data from National Veterans Health Administration, Medicare, Medicaid, and the National Death Index. New users of metformin or sulfonylurea who reached an estimated glomerular filtration rate of 60 mL/min per 1.73 m
2
or serum creatinine of 1.5 mg/dL and continued metformin or sulfonylurea were included. The primary outcome was hospitalization for heart failure. Echocardiogram reports were obtained to determine each patient's ejection fraction (EF) (reduced EF <40%; midrange EF 40%–49%; ≥50%). The primary analysis estimated the cause‐specific hazard ratios for metformin versus sulfonylurea and estimated the cumulative incidence functions for heart failure hospitalization and competing events. The weighted cohort included 24 685 metformin users and 24 805 sulfonylurea users with reduced kidney function (median age 70 years, estimated glomerular filtration rate 55.8 mL/min per 1.73 m
2
). The prevalence of underlying heart failure (12.1%) and cardiovascular disease (31.7%) was similar between groups. There were 16.9 (95% CI, 15.8–18.1) versus 20.7 (95% CI, 19.5–22.0) heart failure hospitalizations per 1000 person‐years for metformin and sulfonylurea users, respectively, yielding a cause‐specific hazard of 0.85 (95% CI, 0.78–0.93). Among heart failure hospitalizations, 44.5% did not have echocardiogram information available; 29.3% were categorized as reduced EF, 8.9% as midrange EF, and 17.2% as preserved EF. Heart failure hospitalization with reduced EF (hazard ratio, 0.79; 95% CI, 0.67–0.93) and unknown EF (hazard ratio, 0.84; 95% CI 0.74–96) were significantly lower in metformin versus sulfonylurea users.

Conclusions
Among patients with type 2 diabetes mellitus who developed worsening kidney function, persistent metformin compared with sulfonylurea use was associated with reduced heart failure hospitalization.
Factors Associated With PCSK9 Inhibitor Initiation Among US Veterans
Authors: Derington Catherine G. , Colantonio Lisandro D. , Herrick Jennifer S. , Cook James , King Jordan B. , Rosenson Robert S. , Poudel Bharat , Monda Keri L. , Navar Ann Marie , Mues Katherine E. , Stevens Vanessa W. , Nelson Richard E. , Vanneman Megan E. , Muntner Paul , Bress Adam P. 
Published: April 2021

Background
Few adults at high risk for atherosclerotic cardiovascular disease events use a PCSK9i (proprotein convertase subtilisin/kexin type 9 inhibitor).

Methods and Results

Using data from the US Veterans Health Administration, we identified veterans who initiated a PCSK9i between January 2018 and December 2019, matched 1:4 to veterans who did not initiate this medication over this time period (case‐cohort study). Two cohorts of veterans were analyzed: (1) atherosclerotic cardiovascular disease, with a most recent low‐density lipoprotein cholesterol (LDL‐C) ≥70 mg/dL; and (2) severe hypercholesterolemia (ie, familial hypercholesterolemia or any prior LDL‐C ≥190 mg/dL, with most recent LDL‐C ≥100 mg/dL). Conditional logistic regression was used to analyze factors associated with PCSK9i initiation, adjusting for all factors, simultaneously. There were 2394 initiators and 9576 noninitiators in the atherosclerotic cardiovascular disease cohort (median LDL‐C, 141 and 96 mg/dL, respectively;
P
<0.001). Factors associated with a higher likelihood of PCSK9i initiation included age 65 to <75 versus <65 years, highest versus lowest quartile of median area‐level income, familial hypercholesterolemia, former statin use, and current ezetimibe use. PCSK9i initiation was lower among veterans of a race/ethnicity other than non‐Hispanic White. There were 245 initiators and 980 noninitiators in the severe hypercholesterolemia cohort (median LDL‐C, 183 and 151 mg/dL, respectively;
P
<0.001). Age ≥75 versus <65 years, history of chronic kidney disease, former statin use, and current ezetimibe use were associated with a higher likelihood of PCSK9i initiation.

Conclusions
Several patient‐level factors, including age, sex, and race/ethnicity, were significantly associated with PCSK9i initiation, suggesting an unmet treatment need in several patient groups.
The Jewish Contribution to Civilization Discourse: An Egyptian-Jewish Appropriation in the 1940s
Authors: Admiraal Lucia 
Published: April 2021

Abstract
The idea of the Jewish contribution to civilization is generally understood as a Western counter-discourse that, often expressed in response to anti-Semitism, aims to change attitudes towards Jews. My examination of the appropriation of this idea by the Egyptian-Jewish writer Alfred Yallouz in the early 1940s proposes that he embedded it in his national and regional politics of Jewish cultural reform. Here, it served the aim of promoting Jewish belonging to Arab society by addressing historical Jewish contributions to Arab culture, and connecting these to Arab-Jewish relations in the present.
Zur Übersetzungstechnik in den ‘Wachtendonckschen psalmen’
Authors: Quak Arend 
Published: April 2021

Abstract
The Old Dutch ‘Wachtendonck Psalms’ [10th C.] survive in fragmentary transcripts from the 16th and 17th centuries. The now-lost original manuscript contained an interlinear gloss that shows different levels of ability in translating the Latin text of the Psalms. Sometimes, the translation displays a good knowledge of Latin and at other times serious flaws can be observed. On the basis of this, this article suggests that there was more than one person involved in translating the Latin text.
Exeter Book Riddle 6, Lines 7–8
Authors: Afros Elena 
Published: April 2021

Abstract
One of the very few ‘rules’ that operate (almost) without exceptions in Old English prose and poetry is that in se-relatives, se is preceded by the preposition that governs it. In the entire Old English corpus, Mitchell (1985: §2244) finds only one counterexample in the Exeter Book Riddle 6, lines 7–8. In this relative clause, the preposition on governing the demonstrative þa that functions as both antecedent and relative is postposed. The present article suggests grouping the preposition on (7b) with the adverb feorran ‘far’ (8a) that immediately follows it and analysing the main verb of the relative clause as transitive. As a result, the relative clause follows the ‘rule’: the preposition on is no longer postposed, and the pronoun þa, which functions as a direct object in the principal and relative clauses, is assigned accusative by the main verbs of both clauses.
Runic alu and laukaz on Objects of the Germanic Migration Period
Authors: Sayers William 
Published: April 2021

Abstract
The identification of characters in some prophylactic runic inscriptions as representative not of their names or as loan words from other magic traditions but as abbreviations based on initial sounds of other early Germanic words not previously adduced in the interpretive context resolves problems associated with the signification and encoding practice of such Migration Age forms as alu, laukaz, and the stand-alone uses of the L- and N-runes.
<strong><em>Diderma aglomerospora</em> (Didymiaceae, Physarales, Myxomycetes), a new species from Brazil</strong>
Authors: BARBOSA DAVID ÍTALLO , MELO TIAGO ESPÓSITO O. , BREYNER FÁBIO ANDRÉ , CAVALCANTI LAISE DE HOLANDA 
Published: April 2021

Diderma aglomerospora is here proposed as a new species based on morphological analyses. The new species resembles D. badhamioides by possessing clustered spores but differs from it by the absence of a columella and narrower filaments of the capillitium. The type material was developed in moist chamber assembled with bark of live trees from a restinga forest environment in the Guadalupe Environmental Protection Area, Pernambuco, Northeast Brazil. Sporocarps are described and illustrated, and comments on characteristics of the microhabitat are provided.
A systematic review of randomized controlled trials examining workplace wellness interventions
Authors: Murphy Bridget , Parekh Niyati , Vieira Dorice L. , O’Connor Joyce A. 
Published: April 2021

Background: One of the influencing factors associated with weight gain is overeating as a maladaptive coping strategy to process or avoid the emotional impact of psychological stress. Psychological stress is chronically and pervasively associated with stress stemming from the workplace environment. Workplace wellness interventions have a unique opportunity to change environmental factors impacting psychological stress, which can improve individual food choice and weight management efforts. Aim: To synthesize evidence from randomized controlled trials on workplace wellness interventions that impact employee psychological stress and food choice or weight management. Methods: A systematic review was completed according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Selected studies were limited to English-language articles exploring randomized interventions at workplaces among adult employees and included measurements of psychometric stress and food choice (qualitative or quantitative) or biometric weight management. From the search, 10 studies were included in the final review. Results: Results were inconsistent across studies. There was no observable association between psychological stress reduction and food choice or weight management. Mid-length interventions (ranging from 6 to 9 months) had more consistent associations between intervention program implementation, reduced psychological stress, and improved food choice or weight management. Conclusions: The studies examining employee food choices and weight management efforts remained very heterogeneous, indicating that more research is needed in this specific area of employee wellness program planning and measurement. Consistent research methodology and assessment tools are needed to measure dietary intake.
Biomechanical Effects of Torquing on Upper Central Incisor with Thermoplastic Aligner: A Comparative Three-Dimensional Finite Element Study with and Without Auxillaries
Authors: Sandhya V , Arun AV , Reddy Vinay P , Mahendra S , Chandrashekar BS , Aravind  
Published: April 2021

Background and Objectives: This study was conducted to determine the effective method to torque the incisor with thermoplastic aligner using a three-dimensional (3D) finite element method. Materials and Methods: Three finite element models of maxilla and maxillary dentition were developed. In the first model, thermoplastic aligner without any auxiliaries was used. In the second and third models, thermoplastic aligner with horizontal ellipsoid composite attachment and power ridge were used, respectively. The software used for the study was ANSYS 14.5 FE. A force of 100 g was applied to torque the upper right central incisor. The resultant force transfer, stress distribution, and tooth displacement were evaluated. Results: The overall tooth displacement and stress distribution appeared high in the model with power ridge, whereas the root movement was more in the horizontal ellipsoid composite attachment model. The model without any auxillaries produced least root movement and stress distribution. Conclusion: Horizontal ellipsoid composite attachment achieved better torque of central incisor than the model with power ridge and model without any auxillaries.
Guest editorial: EU agencies in transnational criminal enforcement: From a coordinated approach to an integrated EU criminal justice
Authors: Öberg Jacob 
Published: April 2021

The articles in this special issue consider the institutional foundations of the Union’s criminal policy – a highly critical question for the future development of the Area of Freedom, Security and Justice. The ratification of the Lisbon Treaty and the subsequent legal and political developments have entailed an unprecedented reinforcement of the powers of the EU’s criminal justice agencies Europol, Eurojust and, recently, the establishment of a novel criminal justice body – the European Public Prosecutor’s Office. On the basis of the Treaty mandate, the EU legislator has adopted important reforms such as the EPPO Regulation, and new Europol and Eurojust regulations. In light of these developments, this special issue explores via a multi-disciplinary investigation the extent to which the increased competences of the EU and the stronger presence of EU criminal justice agencies have transformed EU criminal law from an ‘intergovernmental’ regime to a ‘supranational’ and ‘integrated’ framework. We expect that this special issue will enhance further debate on EU criminal justice agencies, encourage novel paths to bridge the boundaries between disciplinary epistemic communities in the study of EU criminal justice and more broadly contribute to an advanced understanding of the role of law in social and political integration.
Game Exposure, Player Characteristics, and Neuromuscular Performance Influence Injury Risk in Professional and Youth Field Hockey Players
Authors: Mason Joel , Wellmann Kai , Groll Andreas , Braumann Klaus-Michael , Junge Astrid , Hollander Karsten , Zech Astrid 
Published: April 2021

Background: Identifying factors that contribute to the occurrence of injury is an important step in designing training programs to minimize the risk of injury. However, despite high injury rates, variables contributing to injury in field hockey players remain relatively unexplored. Purpose: To identify factors that may predict injury in professional and youth field hockey players. Study Design: Cohort study; Level of evidence, 2. Method: Professional and youth hockey players completed preseason neuromuscular performance testing and were monitored for injuries, training, and game exposure throughout the subsequent 12-month indoor and outdoor hockey season. Least absolute shrinkage and selection operator analysis was conducted to identify injury risk factors. Receiver operating characteristic curves were then calculated to determine the individual predictive accuracy of the identified variables. Results: A total of 83 players (mean ± SD age, 20.7 ± 4.9 years; 34.9% female) with complete performance, injury, and exposure data were included for data analysis. Almost half of players (44.6%) sustained a time-loss injury during the season, and 73% of these injuries occurred in the lower limb. Playing more games and having an older age, asymmetrical and poor dynamic postural control, and better explosive performance were identified as jointly influencing the risk of injury. When considered individually, number of games played throughout the season was the most accurate predictor of injury risk (area under the curve [AUC] = 0.74; P < .001), while asymmetrical and poor dynamic postural control (AUCs = 0.61-0.65; P = .01-.04) and better explosive athletic performance (AUCs = 0.65-0.67; P < .01) were identified as moderate individual predictors of sustaining a general or lower limb injury. Conclusion: A number of modifiable factors were individually and jointly associated with an increased injury risk in field hockey players, providing initial evidence for the design of targeted and sport-specific training programs to mitigate the risk of injury.
Tumor-Intrinsic RIG-I Signaling Promotes Anti-CTLA-4 Checkpoint Inhibitor-Mediated Anticancer Immunity
Authors: Heidegger Simon , Wintges Alexander , Bek Sarah , Schmickl Martina , Ruland Jürgen , van den Brink Marcel R.M. , Peschel Christian , Haas Tobias , Poeck Hendrik 
Published: April 2021

Abstract
Strong inter-individual variation in clinical response to checkpoint inhibitors such as anti-CTLA-4 remains a major challenge. In a retrospective analysis, expression of viral defense genes in human melanomas including the cytosolic RNA receptor RIG-I (DDx58) has been associated with clinical benefit to CTLA-4 blockade. However, possible interconnections of these two distinct pathways remain unknown. Using CRISPR/Cas9 technology to generate B16 melanoma cells lines that lack nucleic acid receptors or downstream signaling molecules (RIG-I, STING, IRF3/7) together with available genetically deficient mouse models, we addressed the importance of nucleic acid receptor signaling in both tumor and host cells for the efficacy of anti-CTLA-4 immunotherapy. We here provide experimental proof that anti-CTLA-4 immunotherapy relies on tumor cell-intrinsic RIG-I but not STING signaling. Following anti-CTLA-4 treatment, tumor-intrinsic RIG-I signaling critically impacts on cross-presentation of tumor-associated antigen by CD103+ dendritic cells, the expansion of tumor antigen-specific CD8+ T cells and ultimately the accumulation of CD8+ T cells within tumor tissue. Consistently, therapeutic targeting of RIG-I with 5'-phosphorylated-RNA in both tumor and non-malignant cells potently augmented the efficacy of CTLA-4 checkpoint blockade. These processes were additionally dependent on host STING, MAVS and type I interferon signaling and were closely linked to RIG-I-mediated tumor cell death. In summary, our study identifies both tumor- and host-intrinsic RIG-I signaling as fundamental requirements for anti-CTLA-4-mediated antitumor immunity. Our data predict that targeting RIG-I may serve as a basis for the development of new combination strategies to increase the response rate of checkpoint inhibitor-based immunotherapy of malignancy including lymphoma, particularly in individuals that do not have a sufficient spontaneous antitumor T-cell immune response.

Disclosures
van den Brink: Jazz Pharmaceuticals: Consultancy; Seres: Research Funding; PureTech Health: Consultancy; Therakos Institute: Other: Speaking engagement.
Single Cell-Resolution Analysis of HSC Dysfunction in Mir-146a knockout Mice
Authors: Grants Jennifer , Wegrzyn Joanna , Knapp David , Hui Tony , O'Neill Kieran , Parker Jeremy , Deng Deborah , Boldin Mark , Hirst Martin , Eaves Connie J. , Karsan Aly 
Published: April 2021

Abstract
MicroRNA miR-146a is frequently depleted in myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML). Loss of miR-146a may be an initiating event in tumorigenesis, as miR-146a loss in mouse models is sufficient to cause features of MDS and eventual progression to AML. To define how miR-146a loss initiates tumorigenesis, we analyzed hematopoietic stem cell (HSC) function from miR-146a knockout (KO) mice prior to onset of an overt malignant phenotype. Tracking cell division kinetics, proliferation, and differentiation of single long-term HSC (LT-HSC; EPCR+CD45+CD48-CD150+) in culture, we found evidence that miR-146a KOreduces HSC quiescence and promotes differentiating cell divisions. Our data show that miR-146a KO HSC dysfunction may stem from loss of a CD150-bright EPCR-bright sub-population, which has previously been associated with robust HSC activity. In line with this, single cell DNA methylation profiling revealed a reduction in a primitive sub-population of LT-HSCs in miR-146a KO animals. In addition, single cell LT-HSC transplants revealed a myeloid repopulation bias. As reduced HSC cell cycle quiescence has been linked to impaired HSC self-renewal upon hematopoietic stress, such as serial transplantation, we assessed the frequency of serially transplantable HSCs by performing secondary transplants with limiting dilution. Serially transplantable HSC frequency was reduced in miR-146a KO compared to wild type, suggesting impaired HSC self-renewal. Transcriptome profiling of miR-146a KO hematopoietic stem and progenitor cells identified tumor necrosis factor (TNF) signaling activation as a potential driver of HSC dysfunction. LT-HSC cell cycle quiescence and the CD150-bright EPCR-bright LT-HSC sub-population were restored in miR-146a/TNF double KO mice, suggesting that aberrant TNF signaling activation drives HSC dysfunction upon loss of miR-146a. Gene expression levels in the TNF signaling network are inversely correlated with miR-146a levels in human AML, implying that TNF signaling may similarly disrupt HSC function in miR-146a- depleted myeloid malignancies. Overall, our findings suggest that miR-146a promotes HSC cell cycle quiescence and inhibits differentiation by antagonizing TNF signaling, in order to maintain a primitive sub-population of long-term self-renewing HSCs.

Disclosures
Eaves: Experimental Hematology: Other: Editor of journal; StemCell Technologies Inc: Other: Wife of owner.