bluuebunny/crossref_metadata_2025_split huggingface dataset:
Development of a population pharmacokinetic/pharmacodynamic model for various oral paclitaxel formulations co-administered with ritonavir and thrombospondin-1 based on data from early phase clinical studies
Authors: van Eijk Maarten , Yu Huixin , Sawicki Emilia , de Weger Vincent A. , Nuijen Bastiaan , Dorlo Thomas P. C. , Beijnen Jos H. , Huitema Alwin D. R. 
Published: July 2022

Abstract
Purpose
Orally administered paclitaxel offers increased patient convenience while providing a method to prolong exposure without long continuous, or repeated, intravenous infusions. The oral bioavailability of paclitaxel is improved through co-administration with ritonavir and application of a suitable pharmaceutical formulation, which addresses the dissolution-limited absorption of paclitaxel. We aimed to characterize the pharmacokinetics of different paclitaxel formulations, co-administered with ritonavir, and to investigate a pharmacodynamic relationship between low-dose metronomic (LDM) treatment with oral paclitaxel and the anti-angiogenic marker thrombospondin-1 (TSP-1).

Methods
Fifty-eight patients treated with different oral paclitaxel formulations were included for pharmacokinetic analysis. Pharmacodynamic data was available for 36 patients. All population pharmacokinetic/pharmacodynamic modelling was performed using non-linear mixed-effects modelling.

Results
A pharmacokinetic model consisting of gut, liver, central, and peripheral compartments was developed for paclitaxel. The gastrointestinal absorption rate was modelled with a Weibull function. Relative gut bioavailabilities of the tablet and capsule formulations, as fractions of the gut bioavailability of the drinking solution, were estimated to be 0.97 (95%CI: 0.67–1.33) and 0.46 (95%CI: 0.34–0.61), respectively. The pharmacokinetic/pharmacodynamic relationship between paclitaxel and TSP-1 was modelled using a turnover model with paclitaxel plasma concentrations driving an increase in TSP-1 formation rate following an Emax relationship with an EC50 of 284 ng/mL (95%CI: 122–724).

Conclusion
The developed pharmacokinetic model adequately described the paclitaxel plasma concentrations for the different oral formulations co-administered with ritonavir. This model, and the established pharmacokinetic/pharmacodynamic relationship with TSP-1, may facilitate future development of oral paclitaxel.
The influence of Pacific-North American teleconnection on the North Pacific SST anomalies in Wintertime under the global warming
Authors: Chen Zheng , Gan Bolan , Huang Fei , Li Jianping , Wu Lixin , Fan Lei , Diao Yina 
Published: July 2022

AbstractThe impact of the enhancing Pacific-North American teleconnection (PNA) on the intensity of the first mode of SST anomalies (SSTa) in wintertime North Pacific [known as the Pacific decadal oscillation (PDO)-like SST pattern] under global warming is studied using reanalysis datasets and 12 selected CMIP5 models. The robust observational result of the PNA one month ahead of the PDO shows that the PNA has a great effect on the PDO-like SSTa. The intensities of PNA and PDO are defined with elimination of the ENSO signals to evaluate the direct impact of PNA on the PDO in the North Pacific under global warming. By comparing RCP8.5 and historical scenario of selected multi-models (PNA enhanced models), future projection illustrates that the PDO intensity will intensify 2.2 times its internal variability. Approximately 67% of the increase in PDO variations is contributed by the PNA-induced SSTa in the future warming scenario of multi-models ensemble mean. Models with stronger intensification of PNA variability tends to have larger magnitude of SSTa response in the North Pacific, which has more contributions to the enhancement of PDO intensity change in a warmer climate. This may shed some light on the projection of PDO variability and the relative role of PNA forcing under the global warming.
Childhood chronic condition and subsequent self-reported internalizing and externalizing problems in adolescence: a birth cohort study
Authors: Määttä Heidi , Honkanen Meri , Hurtig Tuula , Taanila Anja , Ebeling Hanna , Koivumaa-Honkanen Heli 
Published: July 2022

AbstractChronic conditions are common in childhood. We investigated the associations of childhood chronic conditions reported by parents with subsequent self-reported internalizing and externalizing problems in adolescence. A sample of 6290 children (3142 boys and 3148 girls) with data on chronic condition reported by parents both at 7 and at 16 years of age was obtained from the Northern Finland Birth Cohort 1986 (NFBC 1986), which is a longitudinal 1-year birth cohort (n = 9432) from an unselected, regionally defined population. Internalizing and externalizing problems were measured at 8 years of age with Rutter Children’s Behavioral Questionnaire by teachers and at 16 years of age with Youth Self-Report by adolescents. When studying the effects of history of chronic conditions on these problems at 16 years of age, childhood internalizing and externalizing problems and social relations were adjusted. A history of chronic condition predicted subsequent somatic complaints among all adolescents. Early-onset chronic conditions were related to subsequent externalizing (OR 1.35; 1.02–1.79) and attention problems (OR 1.33; 1.01–1.75) and later onset of chronic conditions with internalizing (OR 1.49; 1.22–1.82) and thought problems (OR 1.50; 1.18–1.92). The effect was specific for sex and the type of chronic condition.Conclusion: Childhood chronic conditions predicted internalizing and externalizing problems in adolescence. To prevent poor mental health trajectories, children with chronic conditions during their growth to adolescence need early support and long-term monitoring.

What is Known:• Childhood adversities increase the risk of mental disorders.• Internalizing and externalizing problems have been suggested for measuring childhood and adolescent psychopathologies.

What is New:• Having a chronic condition (CC) before the age of 7 or later but before the age of 16 had different outcomes in adolescence. The early onset predicted externalizing problems, whereas the late onset predicted internalizing problems and thought problems in adolescence. The risk of somatic complaints was increased regardless of CC onset time. These findings can reflect more restricted ability to mental processing in the younger children.
The role of magnetic resonance imaging in the diagnosis and prognostic evaluation of fetuses with congenital diaphragmatic hernia
Authors: Amodeo Ilaria , Borzani Irene , Raffaeli Genny , Persico Nicola , Amelio Giacomo Simeone , Gulden Silvia , Colnaghi Mariarosa , Villamor Eduardo , Mosca Fabio , Cavallaro Giacomo 
Published: July 2022

AbstractIn recent years, magnetic resonance imaging (MRI) has largely increased our knowledge and predictive accuracy of congenital diaphragmatic hernia (CDH) in the fetus. Thanks to its technical advantages, better anatomical definition, and superiority in fetal lung volume estimation, fetal MRI has been demonstrated to be superior to 2D and 3D ultrasound alone in CDH diagnosis and outcome prediction. This is of crucial importance for prenatal counseling, risk stratification, and decision-making approach. Furthermore, several quantitative and qualitative parameters can be evaluated simultaneously, which have been associated with survival, postnatal course severity, and long-term morbidity.Conclusion: Fetal MRI will further strengthen its role in the near future, but it is necessary to reach a consensus on indications, methodology, and data interpretation. In addition, it is required data integration from different imaging modalities and clinical courses, especially for predicting postnatal pulmonary hypertension. This would lead to a comprehensive prognostic assessment.

What is Known:• MRI plays a key role in evaluating the fetal lung in patients with CDH.• Prognostic assessment of CDH is challenging, and advanced imaging is crucial for a complete prenatal assessment and counseling.

What is New:• Fetal MRI has strengthened its role over ultrasound due to its technical advantages, better anatomical definition, superior fetal lung volume estimation, and outcome prediction.• Imaging and clinical data integration is the most desirable strategy and may provide new MRI applications and future research opportunities.
Febrile children with comorbidities at the emergency department — a multicentre observational study
Authors: Borensztajn Dorine M. , Hagedoorn Nienke N. , Carrol Enitan D. , von Both Ulrich , Emonts Marieke , van der Flier Michiel , de Groot Ronald , Herberg Jethro , Kohlmaier Benno , Levin Michael , Lim Emma , Maconochie Ian K. , Martinon-Torres Federico , Nijman Ruud G. , Pokorn Marko , Rivero-Calle Irene , Tsolia Maria , van der Velden Fabian J. S. , Vermont Clementien , Zavadska Dace , Zenz Werner , Zachariasse Joany M. , Moll Henriette A. 
Published: July 2022

Abstract
We aimed to describe characteristics and management of children with comorbidities attending European emergency departments (EDs) with fever. MOFICHE (Management and Outcome of Fever in children in Europe) is a prospective multicentre study (12 European EDs, 8 countries). Febrile children with comorbidities were compared to those without in terms of patient characteristics, markers of disease severity, management, and diagnosis. Comorbidity was defined as a chronic underlying condition that is expected to last > 1 year. We performed multivariable logistic regression analysis, displaying adjusted odds ratios (aOR), adjusting for patient characteristics. We included 38,110 patients, of whom 5906 (16%) had comorbidities. Most common comorbidities were pulmonary, neurologic, or prematurity. Patients with comorbidities more often were ill appearing (20 versus 16%, p < 0.001), had an ED-Paediatric Early Warning Score of > 15 (22 versus 12%, p < 0.001), or a C-reactive protein > 60 mg/l (aOR 1.4 (95%CI 1.3–1.6)). They more often required life-saving interventions (aOR 2.7, 95% CI 2.2–3.3), were treated with intravenous antibiotics (aOR 2.3, 95%CI 2.1–2.5), and were admitted to the ward (aOR 2.2, 95%CI 2.1–2.4) or paediatric intensive care unit (PICU) (aOR 5.5, 95% CI 3.8–7.9). They were more often diagnosed with serious bacterial infections (aOR 1.8, 95%CI 1.7–2.0), including sepsis/meningitis (aOR 4.6, 95%CI 3.2–6.7). Children most at risk for sepsis/meningitis were children with malignancy/immunodeficiency (aOR 14.5, 8.5–24.8), while children with psychomotor delay/neurological disease were most at risk for life-saving interventions (aOR 5.3, 4.1–6.9) or PICU admission (aOR 9.7, 6.1–15.5).Conclusions: Our data show how children with comorbidities are a population at risk, as they more often are diagnosed with bacterial infections and more often require PICU admission and life-saving interventions.

What is Known:• While children with comorbidity constitute a large part of ED frequent flyers, they are often excluded from studies.

What is New:• Children with comorbidities in general are more ill upon presentation than children without comorbidities.• Children with comorbidities form a heterogeneous group; specific subgroups have an increased risk for invasive bacterial infections, while others have an increased risk of invasive interventions such as PICU admission, regardless of the cause of the fever.
Partial regularity for $$\omega $$-minimizers of quasiconvex functionals
Authors: Li Zhuolin 
Published: July 2022

AbstractWe establish partial regularity for the$$\omega $$ω-minimizers of quasiconvex functionals of power growth. A first-order partial regularity result ofBV$$\omega $$ω-minimizers is obtained in the linear growth case under a Dini-type condition on$$\omega $$ω. Only assuming the smallness of$$\omega $$ωnear the origin, we show partial Hölder continuity in the subquadratic case by considering a normalised excess.
Feasibility of climate reanalysis data as a proxy for onsite weather measurements in outdoor thermal comfort surveys
Authors: Krüger Eduardo L. , Di Napoli Claudia 
Published: July 2022

Abstract Outdoor thermal comfort (OTC) surveys require synchronous monitoring of meteorological variables for direct comparisons against subjective thermal perception. The Universal Thermal Climate Index (UTCI) is a feasible index as it integrates meteorological conditions as a single value irrespective of urban morphological attributes or biological sex, age and body mass. ERA5-HEAT (Human thErmAl comforT) is a downloadable reanalysis dataset providing hourly grids of UTCI climate records at 0.25° × 0.25° spatial resolution from 1979 to present. We here evaluate for the first time whether it is possible to use ERA5-HEAT data as a proxy for the UTCI measured onsite during OTC surveys. A dataset comprising 1640 survey responses gathered over 14 OTC campaigns in Curitiba, Brazil (25°26′S, 49°16′W) was analysed. We assessed the bias obtained between the Dynamic Thermal Sensation, an index derived from the UTCI, and the thermal sensation reported by survey participants by considering locally measured meteorological variables and ERA5-HEAT reanalysis data. As ERA5-HEAT data are given on an hourly basis, prediction bias can be greatly reduced when accounting for survey responses close to the hour. In terms of seasons, the fall and winter seasons have diminished mean bias, though with larger spread than in summer. In terms of UTCI stress categories, prediction bias is lower for the thermal comfort range. When comparing reanalysis data against WMO station data as proxy candidates for survey field data, the former presented lower bias, less spread in terms of standard deviation and higher correlation to in situ data.
The efficacy of a self-help parenting program for parents of children with externalizing behavior: a randomized controlled trial
Authors: de Jong Suzanne R. C. , van den Hoofdakker Barbara J. , van der Veen-Mulders Lianne , Veenman Betty , Twisk Jos W. R. , Oosterlaan Jaap , Luman Marjolein 
Published: July 2022

AbstractParenting programs are effective for children with externalizing problems, but not always easily accessible for parents. In order to facilitate accessibility, we developed a self-help parenting program, consisting of a manual and online part. The efficacy of the program in reducing children’s externalizing problems was compared to waitlist in a randomized controlled trial. In addition, two versions of the program were exploratively compared, one with and one without biweekly telephonic support. Candidate moderators (child and parent factors) and parental satisfaction were also examined. We randomly assigned 110 families to one of the following three conditions: the support condition, the no support condition, or the waitlist condition. Intervention duration was 15 weeks. Outcomes were collected at baseline (T0), 8 weeks (T1), 15 weeks (T2), and 28 weeks (T3) and included daily telephonic measurements of parent-rated externalizing behavior and the Intensity scale of the parent-rated Eyberg Child Behavior Inventory (ECBI). Main analyses compared outcomes at T2, using longitudinal regressions with T0 as fixed factor. Results showed that children improved significantly more on both outcomes in the intervention condition compared to waitlist, with small to medium effect sizes. Parental satisfaction was high. Neither differences in efficacy nor in parental satisfaction were found between the support and no support condition. No moderators were detected. The newly developed self-help parenting program is effective in reducing children’s externalizing behavior problems and may help improve access to evidence-based care.
State politics and gender diversity in sport governance
Authors: Lesch Lara , Kerwin Shannon , Wicker Pamela 
Published: July 2022

AbstractThis study investigates the relationship between state politics and sport governance based on an institutional framework and the concept of spillover effects. Specifically, it examines whether spillover effects occur from state parliament and government composition to board gender diversity within sport governing bodies. Organizational-level data from German national and state sport governing bodies were collected (n = 930). They were combined with state-level data on the government composition by gender and political party (parliament, ministers) based on the location of each sport governing body’s headquarter. The results show that on average 20.1% of board members in sport governing bodies are women. Regression analyses indicate that the share of parliamentarians from the Social Democrats and the Green party is positively associated with the share of women in sport governance, while the share of Liberals in the parliament is negatively related. The share of women parliamentarians from the Social party and the share of women Conservative ministers are negatively related to women in sport governance. The findings indicate that women representation in sport governance is linked to state politics, suggesting that spillover effects occur from an organizations’ political environment.
Integration of Heterogeneous Biological Data in Multiscale Mechanistic Model Calibration: Application to Lung Adenocarcinoma
Authors: Palgen Jean-Louis , Perrillat-Mercerot Angélique , Ceres Nicoletta , Peyronnet Emmanuel , Coudron Matthieu , Tixier Eliott , Illigens Ben M. W. , Bosley Jim , L’Hostis Adèle , Monteiro Claudio 
Published: July 2022

AbstractMechanistic models are built using knowledge as the primary information source, with well-established biological and physical laws determining the causal relationships within the model. Once the causal structure of the model is determined, parameters must be defined in order to accurately reproduce relevant data. Determining parameters and their values is particularly challenging in the case of models of pathophysiology, for which data for calibration is sparse. Multiple data sources might be required, and data may not be in a uniform or desirable format. We describe a calibration strategy to address the challenges of scarcity and heterogeneity of calibration data. Our strategy focuses on parameters whose initial values cannot be easily derived from the literature, and our goal is to determine the values of these parameters via calibration with constraints set by relevant data. When combined with a covariance matrix adaptation evolution strategy (CMA-ES), this step-by-step approach can be applied to a wide range of biological models. We describe a stepwise, integrative and iterative approach to multiscale mechanistic model calibration, and provide an example of calibrating a pathophysiological lung adenocarcinoma model. Using the approach described here we illustrate the successful calibration of a complex knowledge-based mechanistic model using only the limited heterogeneous datasets publicly available in the literature.
Underlying mechanisms of change in cancer prevalence in older U.S. adults: contributions of incidence, survival, and ascertainment at early stages
Authors: Akushevich I. , Yashkin A. , Kovtun M. , Yashin A. I. , Kravchenko J. 
Published: July 2022

Abstract
Purpose
To quantitatively evaluate contributions of trends in incidence, relative survival, and stage at diagnosis to the dynamics in the prevalence of major cancers (lung, prostate, colon, breast, urinary bladder, ovaries, stomach, pancreas, esophagus, kidney, liver, and skin melanoma) among older U.S. adults age 65 +.

Methods
Trend partitioning was applied to the Surveillance, Epidemiology, and End Results Program data for 1973–2016.

Results
Growth of cancer prevalence in older adults decelerated or even decreased over time for all studied cancers due to decreasing incidence and improving survival for most of cancers, with a smaller contribution of the stage at cancer diagnosis. Changes in the prevalence of cancers of the lung, colon, stomach, and breast were predominantly due to decreasing incidence, increasing survival and more frequent diagnoses at earlier stages. Changes in prevalence of some other cancers demonstrated adverse trends such as decreasing survival in localized and regional stages (urinary bladder and ovarian) and growing impact of late-stage diagnoses (esophageal cancer).

Conclusion
While decelerating or decreasing prevalence of many cancers were due to a beneficial combination of decreasing incidence and increasing survival, there are cancers for which decelerating prevalence is due to lack of improvement in their stage-specific survival and/or increasing frequency of diagnosis at advanced stages. Overall, if the observed trends persist, it is likely that the burden associated with cancer prevalence in older U.S. adults will be lower comparing to projections based on constant increasing prevalence have previously estimated.
Self-discrepancy, Depression, Anxiety, and Psychological Well-Being: The Role of Affective Style and Self-efficacy
Authors: Schlechter Pascal , Hellmann Jens H. , Morina Nexhmedin 
Published: July 2022

Abstract
Background
Self-discrepancy theory posits that greater discrepancy between the actual and ideal self is related to dysphoria and greater discrepancy between the actual and ought self to anxiety. Despite both being transdiagnostically associated with psychopathology, differential effects of actual:ideal and actual:ought discrepancies have not been confirmed. There is further lack of knowledge about cognitive and affective factors implicated in the relationship between self-discrepancies and depression and anxiety. We therefore examined the relationship of actual:ideal/actual:ought discrepancies with depression, anxiety, and psychological well-being, and whether affective styles (concealing, adjusting, and tolerating) and self-efficacy emerge as mediators or moderators.

Methods
Self-discrepancies were measured as discrepancies in the Big Five taxonomy of personality. Participants (N = 596) responded to the 10-item Big Five Inventory and ideal/ought versions of these traits, and measures of affective styles, self-efficacy, depressive and anxiety symptoms, and well-being.

Results
Both self-discrepancies were positively associated with depression, anxiety, and negatively with well-being, self-efficacy, tolerating and adjusting. No differential effects of the two types of discrepancy emerged. The adjusting affective style and self-efficacy partly accounted for the relationships between self-discrepancies and the outcomes.

Conclusion
Knowledge about affective adjustment and self-efficacy in counteracting putative negative emotional effects of self-discrepancies may inform intervention efforts.
Revisiting and revising Tatarskii’s formulation for the temperature structure parameter ($$C_T^2$$) in atmospheric flows
Authors: Basu Sukanta , Holtslag Albert A. M. 
Published: July 2022

AbstractIn this paper, we revisit a well-known formulation of temperature structure parameter ($$C_T^2$$

C
T
2

), originally proposed by V. I. Tatarskii. We point out its limitations and propose a revised formulation based on turbulence variance and flux budget equations. Our formulation includes a novel physically-based outer length scale which can be estimated from routine meteorological data.
Bohmian Mechanics is Not Deterministic
Authors: Landsman Klaas 
Published: July 2022

AbstractI argue that Bohmian mechanics (or any similar pilot-wave theory) cannot reasonably be claimed to be a deterministic theory. If one assumes the “quantum equilibrium distribution” provided by the wave function of the universe, Bohmian mechanics requires an external random oracle in order to describe the (Kolmogorov–Levin–Chaitin) algorithmic randomness properties of typical outcome sequences of long runs of repeated identical experiments (which provably follow from the Born rule). This oracle lies beyond the scope of Bohmian mechanics (or any deterministic extension thereof), including the impossibility of explaining the randomness property in question from “random” initial conditions. Thus the advantages of Bohmian mechanics over other interpretations of quantum mechanics, if any, must lie at an ontological level, and in its potential to derive the quantum equilibrium distribution and hence the Born rule.