bluuebunny/crossref_metadata_2025_split huggingface dataset:
Normative cardiopulmonary exercise data for endurance athletes: the Cardiopulmonary Health and Endurance Exercise Registry (CHEER)
Authors: Petek Bradley J , Tso Jason V , Churchill Timothy W , Guseh J Sawalla , Loomer Garrett , DiCarli Milena , Lewis Gregory D , Weiner Rory B , Kim Jonathan H , Wasfy Meagan M , Baggish Aaron L 
Published: September 2021

Abstract

Aims
Accurate interpretation of cardiopulmonary exercise testing (CPET) relies on age, gender, and exercise modality-specific reference values. To date, clinically applicable CPET reference values derived from a source population of endurance athletes (EAs) have been lacking. The purpose of this study was to generate CPET reference values for use in the clinical assessment of EA.

Methods and Results
Prospective data accrued during the clinical care of healthy EA were used to derive CPET reference values and to develop novel equations for V˙O2peak. The performance of these equations was compared to the contemporary standard of care equations and assessed in a discrete EA validation cohort. A total of 272 EA (age = 42 ± 15 years, female = 31%, V˙O2peak = 3.6 ± 0.83 L/min) met inclusion criteria and comprised the derivation cohort. V˙O2peak prediction equations derived from general population cohorts described a modest amount of V˙O2peak variability [R2 = 0.58–0.70, root mean square error (RMSE) = 0.46–0.54 L/min] but were mis-calibrated (calibration-in-the-large = 0.45–1.18 L/min) among EA leading to significant V˙O2peak underestimation. Newly derived, externally validated V˙O2peak prediction equations for EA that included age, sex, and height for both treadmill (R2 = 0.74, RMSE = 0.42 L/min) and cycle ergometer CPET (Cycle: R2 = 0.69, RMSE = 0.42 L/min) demonstrated improved accuracy.

Conclusion
Commonly used V˙O2peak prediction equations derived from general population cohorts perform poorly among competitive EA. Newly derived CPET reference values including novel V˙O2peak prediction equations may improve the clinical utility of CPET in this rapidly growing patient population.
RNA polymerase mapping in plants identifies intergenic regulatory elements enriched in causal variants
Authors: Lozano Roberto , Booth Gregory T , Omar Bilan Yonis , Li Bo , Buckler Edward S , Lis John T , del Carpio Dunia Pino , Jannink Jean-Luc 
Published: September 2021

Abstract
Control of gene expression is fundamental at every level of cell function. Promoter-proximal pausing and divergent transcription at promoters and enhancers, which are prominent features in animals, have only been studied in a handful of research experiments in plants. PRO-Seq analysis in cassava (Manihot esculenta) identified peaks of transcriptionally engaged RNA polymerase at both the 5′ and 3′ end of genes, consistent with paused or slowly moving Polymerase. In addition, we identified divergent transcription at intergenic sites. A full genome search for bi-directional transcription using an algorithm for enhancer detection developed in mammals (dREG) identified many intergenic regulatory element (IRE) candidates. These sites showed distinct patterns of methylation and nucleotide conservation based on genomic evolutionary rate profiling (GERP). SNPs within these IRE candidates explained significantly more variation in fitness and root composition than SNPs in chromosomal segments randomly ascertained from the same intergenic distribution, strongly suggesting a functional importance of these sites. Maize GRO-Seq data showed RNA polymerase occupancy at IREs consistent with patterns in cassava. Furthermore, these IREs in maize significantly overlapped with sites previously identified on the basis of open chromatin, histone marks, and methylation, and were enriched for reported eQTL. Our results suggest that bidirectional transcription can identify intergenic genomic regions in plants that play an important role in transcription regulation and whose identification has the potential to aid crop improvement.
Widespread retention of ohnologs in key developmental gene families following whole-genome duplication in arachnopulmonates
Authors: Harper Amber , Baudouin Gonzalez Luis , Schönauer Anna , Janssen Ralf , Seiter Michael , Holzem Michaela , Arif Saad , McGregor Alistair P , Sumner-Rooney Lauren 
Published: September 2021

AbstractWhole-genome duplications (WGDs) have occurred multiple times during animal evolution, including in lineages leading to vertebrates, teleosts, horseshoe crabs, and arachnopulmonates. These dramatic events initially produce a wealth of new genetic material, generally followed by extensive gene loss. It appears, however, that developmental genes such as homeobox genes, signaling pathway components and microRNAs are frequently retained as duplicates (so-called ohnologs) following WGD. These not only provide the best evidence for WGD, but an opportunity to study its evolutionary consequences. Although these genes are well studied in the context of vertebrate WGD, similar comparisons across the extant arachnopulmonate orders are patchy. We sequenced embryonic transcriptomes from two spider species and two amblypygid species and surveyed three important gene families, Hox, Wnt, and frizzled, across these and 12 existing transcriptomic and genomic resources for chelicerates. We report extensive retention of putative ohnologs, further supporting the ancestral arachnopulmonate WGD. We also found evidence of consistent evolutionary trajectories in Hox and Wnt gene repertoires across three of the six arachnopulmonate orders, with interorder variation in the retention of specific paralogs. We identified variation between major clades in spiders and are better able to reconstruct the chronology of gene duplications and losses in spiders, amblypygids, and scorpions. These insights shed light on the evolution of the developmental toolkit in arachnopulmonates, highlight the importance of the comparative approach within lineages, and provide substantial new transcriptomic data for future study.
Grape Seed Flour Extends Longevity by Improving Multi-Organ Dysfunction and Age-Associated Oxidative Stress and Inflammation in Healthy Rat
Authors: Jebari Khawla , Charradi Kamel , Mahmoudi Mohamed , Kadri Safwen , Ben-Attia Mossadok , Mousslim Mohamed , El May Michèle Véronique , Limam Ferid , Aouani Ezzedine 
Published: September 2021

Abstract
According to the free-radical theory of aging, accumulation of reactive oxygen species (ROS) within mitochondria throughout life span leads to impairment of the main biological macromolecules as DNA, lipids, and proteins, which might be at the basis of premature aging. One way to test experimentally such a hypothesis consists in intervention studies using antioxidant nutrients aimed at limiting or inhibiting ROS production that should be able to reduce the aging rate and disease pathogenesis. Grape seed flour (GSF) contains a high level of phytochemicals among which bioactive polyphenols exhibit numerous biological properties and beneficial health effects as antioxidant, anti-inflammatory, anticarcinogenic, multi-organ (heart, liver, kidney, and brain among others) protective. The present study aimed at testing the ability of high dosing GSF (4 g/kg bw) used as a nutritional supplement to slow down aging and prolong life span of Wistar rats when administered from early life (1-month-old animals) till their natural death. Data clearly show that high-dose GSF extends organism longevity and health span by improving multi-organ damages, systemic fueling metabolism declines, and alleviated oxidative stress and inflammation in aging rats. Our data support the extending longevity effect of grape polyphenols especially when used as high dosing nutritional supplement or as natural medicine whose appropriate galenic form as solid lipid nanoformulation is currently under investigation.
Prevalence of Instrumental Activities of Daily Living Difficulties and Associated Cognitive Predictors Across Racial/Ethnic Groups: Findings From the KHANDLE Study
Authors: Chan Michelle L , Eng Chloe W , Gilsanz Paola , Whitmer Rachel A , Mungas Dan , Meyer Oanh , Farias Sarah Tomaszewski 
Published: September 2021

Abstract

Objective
Cognitive functioning is associated with instrumental activity of daily living (IADL) performance among older adults. The present study examines potential differences in the prevalence of IADL difficulty and association with cognition across diverse groups.

Method
Participants included 455 non-Hispanic Whites, 395 Blacks, 370 Asians, and 296 Latinos aged 65 years and older without a current dementia diagnosis from the Kaiser Healthy Aging and Diverse Life Experience cohort. Participants’ self-reported IADL functioning and cognition was measured across episodic memory and executive functioning.

Results
Older age, male gender, and being Black were associated with more IADL difficulties. Executive functioning showed a stronger association with IADLs than memory, and it was independent of health status, whereas memory was not. In joint models including both cognitive domains, executive functioning remained a significant predictor of IADL difficulty, but memory did not. Results for both cognitive domains were attenuated with self-rated health added to the joint model. These relationships did not significantly differ across racial/ethnic groups

Conclusions
Our study supports previous work suggesting that Black older adults are at increased risk for IADL disability. This is the first study we are aware of that examined the association between specific cognitive domains and IADL performance across multiple racial/ethnic groups. Findings indicate that cognitive functioning has similar associations with self-reported IADL disability across diverse groups, and that executive functioning plays a particularly important role in IADL disability among older adults without dementia; however, health status largely attenuates the relationship between IADL difficulty and cognition.
Behavior Change Factors and Retention in Dietary Interventions for Older Adults: A Scoping Review
Authors: Zaslavsky Oleg , Su Yan , Kim Boeun , Roopsawang Inthira , Wu Kuan-Ching , Renn Brenna N 
Published: September 2021

AbstractBackground and ObjectivesAlthough poor diet is a major driver of morbidity and mortality in people aged 60 and older, few dietary interventions are widely implemented for this population. We mapped behavior change theories, agents, and techniques in dietary interventions for adults aged 60 and older and explored relationships between these factors and ability to retain at least 80% of the study participants.Research Design and MethodsWe conducted a scoping review using MEDLINE, CINAHL, and Web of Science through April 2021 for dietary interventions in adults aged 60 and older. We collated, summarized, and calculated frequency distributions of behavior change theories, behavior change agents, and behavior change techniques (BCTs) using BCTv1 taxonomy with regard to participant retention across 43 studies.ResultsOnly 49% and 30% of the studies reported behavior theory and change agents, respectively. Of the studies reporting on theory and agents, the most common were social cognitive theory and the related mechanism of self-efficacy. The most common BCTv1 clusters were “shaping knowledge” and “goals and planning.” Several BCTv1 clusters such as “antecedents” and “reward and threat” and evidence for concordance between BCTs and change agents were more common in interventions with higher retention rates.Discussion and ImplicationsMechanistically concordant studies with BCTs that involve resource allocation and positive reinforcement through rewards may be advantageous for retention in dietary intervention for older adults. Future studies should continue developing theory and mechanism-oriented research. Furthermore, future studies should consider diversifying the portfolio of currently deployed BCTs and strengthening a concordance between BCTs and mechanisms of change.
Globalization, deglobalization and reglobalization: adapting liberal international order
Authors: Paul T V 
Published: September 2021

Abstract
Liberalism has been the most successful political ideology during the past two centuries in withstanding challenges and adapting to new environments. The liberal international order, set up after the Second World War and strengthened at the end of the Cold War, is going through a series of crises, propelled by deglobalization pressures, and the rise of illiberal and populist leaders, all challenging the three pillars of the liberal order: democracy, economic interdependence and international institutions. Two critical reasons for the decline of the liberal order are internal in terms of income distribution and institutional malaise. The article argues that the demise of the liberal order is not inevitable provided liberal states take remedial measures and adapt to the new environment as they did in 1919, 1930s, the second half of the 1940s, 1960s and 1991. Reformed globalization, or re-globalization is essential for facing the geopolitical challenges emanating from China and other illiberal states. The inability of other systems to offer both prosperity and freedom that the liberal order can provide is its main attractiveness. The connection between internal reforms in liberal states to address deepening inequalities and wealth distribution, a by-product of intensified globalization, and the prospects of liberal order's success is highlighted. The need for a refined welfare state taking into account the new realities to tackle the internal challenges is proposed.
Global health: an order struggling to keep up with globalization
Authors: Kornprobst Markus , Strobl Stephanie 
Published: September 2021

Abstract
Do global health institutions keep up with globalization forces? We contend that they seriously lag behind. While medical knowledge becomes more and more refined in showing how diseases spread globally, the political order meant to address this problem is barely global. It is global in terms of the promises it makes in declarations and even legally binding instruments (institutional foreground). But many entrenched political practices of interaction do not keep these promises (institutional background). We explain this with the dominance of a traditional diplomatic ‘feel of the game’ in which often narrowly defined national interests, positioning battles among states, and a subordination of global health under considerations of international security and economics prevail. Based on this diagnosis, we discuss three scenarios for the further evolution of the global health order: (1) the persistence of current institutions, (2) revisions of the institutional foreground and persistence of the background, and (3) a qualitative break that makes amendments to both. While the COVID-19 crisis provides openings for the third and, even more so, the second one, the current upheavals in the liberal constellation of orders makes the first scenario the most likely one.
States, interstitial organizations and the prospects for liberal international order
Authors: Bátora Jozef 
Published: September 2021

Abstract
This article proposes a complementary approach to analysing destabilization of the liberal international order (LIO) and argues that such challenges are related to endogenous institutional processes within the LIO. Faced with constraints of the core norms, rules and institutions of the LIO, states use interstitial organizations (INTOs)—new organizational forms recombining resources, rules, practices and structures from multiple institutional domains—allowing for innovative ways of delivering foreign policies. Using organization theory and new institutionalist approaches, the article outlines a three-dimensional analytical framework to the study of emergence of interstitial organizational forms and interstitial institutional change of international institutions. It applies this framework to the study of two types of INTOs—the European External Action Service (EEAS) and private military companies (PMCs)—both of which are shown to have transformational impacts on two core primary institutions of the modern state order, namely diplomacy and war. The article argues that reliance on INTOs can both enhance and constrain states' ability to promote the core principles of the LIO and concludes with a discussion of two possible paths of adaptation of this order.
A predictive model for identifying patients at risk of delayed transfer of care: a retrospective, cross-sectional study of routinely collected data
Authors: Davy Andrew , Hill Thomas , Jones Sarahjane , Dube Alisen , Lea Simon c , Watts Keiar l , Asaduzzaman M d 
Published: September 2021

Abstract

Background
Delays to the transfer of care from hospital to other settings represent a significant human and financial cost. This delay occurs when a patient is clinically ready to leave the inpatient setting but is unable to because other necessary care, support or accommodation is unavailable. The aim of this study was to interrogate administrative and clinical data routinely collected when a patient is admitted to hospital following attendance at the emergency department (ED), to identify factors related to delayed transfer of care (DTOC) when the patient is discharged. We then used these factors to develop a predictive model for identifying patients at risk for delayed discharge of care.

Objective
To identify risk factors related to the delayed transfer of care and develop a prediction model using routinely collected data.

Methods
This is a single centre, retrospective, cross-sectional study of patients admitted to an English National Health Service university hospital following attendance at the ED between January 2018 and December 2020. Clinical information (e.g. national early warning score (NEWS)), as well as administrative data that had significant associations with admissions that resulted in delayed transfers of care, were used to develop a predictive model using a mixed-effects logistic model. Detailed model diagnostics and statistical significance, including receiver operating characteristic analysis, were performed.

Results
Three-year (2018–20) data were used; a total of 92 444 admissions (70%) were used for model development and 39 877 (30%) admissions for model validation. Age, gender, ethnicity, NEWS, Glasgow admission prediction score, Index of Multiple Deprivation decile, arrival by ambulance and admission within the last year were found to have a statistically significant association with delayed transfers of care. The proposed eight-variable predictive model showed good discrimination with 79% sensitivity (95% confidence intervals (CIs): 79%, 81%), 69% specificity (95% CI: 68%, 69%) and 70% (95% CIs: 69%, 70%) overall accuracy of identifying patients who experienced a DTOC.

Conclusion
Several demographic, socio-economic and clinical factors were found to be significantly associated with whether a patient experiences a DTOC or not following an admission via the ED. An eight-variable model has been proposed, which is capable of identifying patients who experience delayed transfers of care with 70% accuracy. The eight-variable predictive tool calculates the probability of a patient experiencing a delayed transfer accurately at the time of admission.
Postmortem Analysis of Opioids and Metabolites in Skeletal Tissue
Authors: Vandenbosch Michiel , Pajk Stane , Van Den Bogaert Wouter , Wuestenbergs Joke , Van de Voorde Wim , Cuypers Eva 
Published: September 2021

Abstract
Every year, thousands of suspicious deaths are accounted for by an overdose of opioids. Occasionally all traditional matrices are unavailable due to decomposition. Skeletal tissue may pose a valid alternative. However, reference data on postmortem concentrations in bone tissue and bone marrow (BM) is sparse. Therefore, a liquid chromatography--tandem mass spectrometry method was developed and fully validated for the analysis of four opioids and two metabolites (tramadol, O-desmethyltramadol, morphine, fentanyl, norfentanyl, codeine) in bone tissue and BM. Sample preparation was performed using solid phase extraction (BM), methanolic extraction (bone) and a protein precipitation (whole blood). All validation parameters were successfully fulfilled. This method was applied to analyze 22 forensic cases involving opioids. All six opioids were proven to be detectable and quantifiable in all specimens sampled. When tramadol blood concentrations were correlated with bone concentrations, a linear trend could be detected. The same was seen between tramadol blood and BM concentration. A similar linear trend was seen when correlating codeine blood concentration with bone and BM concentration. Although some variability was detected, the same linear trend was seen for morphine. For fentanyl and norfentanyl, the sample size was too small to draw conclusions, regarding correlation. As far as the authors know this is the first-time fentanyl and norfentanyl are quantified in skeletal tissue. In conclusion, due to the absence of reference data for drugs in skeletal tissue, these findings are a step forward toward a more thorough understanding of drug concentration found in postmortem skeletal tissue.
Tramadol-Related Deaths: Genetic Analysis in Relation to Metabolic Ratios
Authors: Aly Sanaa M , Tartar Océane , Sabaouni Naoual , Hennart Benjamin , Gaulier Jean-michel , Allorge Delphine 
Published: September 2021

Abstract
Tramadol (TR) metabolism is mainly dependent on the enzymatic activity of CYP2D6, which is controlled by genetic polymorphisms. Individuals are classified as poor (PMs), intermediate (IMs), extensive (EMs) or ultrarapid metabolizers (UMs) according to their genotype or phenotype. The determination of the metabolic phenotype for CYP2D6 can be of utmost importance in forensic and clinical contexts that involve TR intake. The present study aimed to describe CYP2D6 genetic variants in cases of TR-related deaths and to assess which metabolic ratio(s) (MRs) would allow to determine CYP2D6 phenotype without having to perform genetic analyses. Forty-eight postmortem blood samples were selected from TR-related death cases previously analyzed in a forensic context in North of France between 2013 and 2019. Initial available data included blood concentrations of TR and its two main metabolites (M1 & M2) determined using an LC--MS-MS method. TR metabolism was expressed as various MRs comprising TR/M1, TR/M2 and M2/M1. After DNA extraction, sequencing was used for genetic variant detections that affect CYP2D6 activity/expression. In the present study, the allelic variants with the higher frequency were CYP2D6*1 (68%), followed by *4 (21%). The most frequent phenotype is EMs (59.6%), followed by IMs (23.4%), PMs (12.8%) and UMs (6.4%). There was no significant correlation between each calculated MR and the genotypically predicted phenotypes, except for M2/M1 which appears related to the PM phenotype. The observed distribution of CYP2D6 genetic variants in this TR-related death population was similar to that found in the general Caucasian population. The present study displayed that the blood M2/M1 ratio could be the best-correlated TR MR to the PM phenotype, and could thus be used in forensic contexts where genetic analyses are not possible or poorly informative. For the other phenotypes, especially the UM phenotype, genetic analysis appears to be the only reliable method to predict the CYP2D6 phenotype.