bluuebunny/crossref_metadata_2025 huggingface dataset:
Development of a Virtual Chinese Pediatric Population Physiological Model Targeting Specific Metabolism and Kidney Elimination Pathways
Authors: Yao Xueting , Liu Xuanlin , Tu Siqi , Li Xiaobei , Lei Zihan , Hou Zhe , Yu Zhiheng , Cui Cheng , Dong Zhongqi , Salem Farzaneh , Li Haiyan , Liu Dongyang
Published: May 2021

Background: Physiologically based pharmacokinetic (PBPK) modeling and simulating may be a powerful tool in predicting drug behaviors in specific populations. It is a mathematical model that relates the pharmacokinetic (PK) profile of a compound with human anatomical characteristics, physiological characteristics, and biochemical parameters. Predictions using PBPK models offer a promising way to guide drug development and can be used to optimize clinical dosing regimens. However, PK data of new drugs in the pediatric population are too limited to guide clinical therapy, which may lead to frequent adverse events or insufficient efficacy for pediatric patients, particularly in neonates and infants.

Objective: The objective of this study was to establish a virtual Chinese pediatric population based on the physiological parameters of Chinese children that could be utilized in PBPK models.

Methods: A Chinese pediatric PBPK model was developed in Simcyp Simulator by collecting published Chinese pediatric physiological and anthropometric data to use as system parameters. This pediatric population model was then evaluated in the Chinese pediatric population by predicting the pharmacokinetic characteristics of four probe drugs: theophylline (major CYP1A2 substrate), fentanyl (major CYP3A4 substrate), vancomycin, and ceftazidime (renal-eliminated).

Results: The predicted maximum concentration (Cmax), area under the curve of concentration-time (AUC), and clearance (CL) for theophylline (CYP1A2 metabolism pathway) and fentanyl (CYP3A4 metabolism pathway) were within two folds of the observed data. For drugs mainly eliminated by renal clearance (vancomycin and ceftazidime) in the Chinese pediatric population, the ratio of prediction to observation for major PK parameters was within a 2-fold error range.

Conclusion: The model is a supplement to the previous Chinese population PBPK model. We anticipate the model to be a better representative of the pediatric Chinese population for drugs PK, offering greater clinical precision for medication given to the pediatric population, ultimately advancing clinical development of pediatric drugs. We can refine this model further by collecting more physiological parameters of Chinese children.
Zerumbone Suppresses the LPS-Induced Inflammatory Response and Represses Activation of the NLRP3 Inflammasome in Macrophages
Authors: Su Chia-Cheng , Wang Shu-Chi , Chen I-Chen , Chiu Fang-Yen , Liu Po-Len , Huang Chi-Han , Huang Kuan-Hua , Fang Shih-Hua , Cheng Wei-Chung , Huang Shu-Pin , Yeh Hsin-Chih , Liu Ching-Chih , Lee Po-Yen , Huang Ming-Yii , Li Chia-Yang
Published: May 2021

Zerumbone is a natural product isolated from the pinecone or shampoo ginger, Zingiber zerumbet (L.) Smith, which has a wide range of pharmacological activities, including anti-inflammatory effects. However, the effects of zerumbone on activation of the NLRP3 inflammasome in macrophages have not been examined. This study aimed to examine the effects of zerumbone on LPS-induced inflammatory responses and NLRP3 inflammasome activation using murine J774A.1 cells, murine peritoneal macrophages, and murine bone marrow-derived macrophages. Cells were treated with zerumbone following LPS or LPS/ATP treatment. Production of nitric oxide (NO) was measured by Griess reagent assay. The levels of IL-6, TNF-α, and IL-1β secretion were analyzed by ELISA. Western blotting analysis was performed to determine the expression of inducible NO synthase (iNOS), COX-2, MAPKs, and NLRP3 inflammasome-associated proteins. The activity of NF-κB was determined by a promoter reporter assay. The assembly of NLRP3 was examined by immunofluorescence staining and observed by confocal laser microscopy. Our experimental results indicated that zerumbone inhibited the production of NO, PGE2 and IL-6, suppressed the expression of iNOS and COX-2, repressed the phosphorylation of ERK, and decreased the activity of NF-κB in LPS-activated J774A.1 cells. In addition, zerumbone suppressed the production of IL-1β and inhibited the activity of NLRP3 inflammasome in LPS/ATP- and LPS/nigericin-activated J774A.1 cells. On the other hand, we also found that zerumbone repressed the production of NO and proinflammatory cytokines in LPS-activated murine peritoneal macrophages and bone marrow-derived macrophages. In conclusion, our experimental results demonstrate that zerumbone effectively attenuates the LPS-induced inflammatory response in macrophages both in vitro and ex vivo by suppressing the activation of the ERK-MAPK and NF-κB signaling pathways as well as blocking the activation of the NLRP3 inflammasome. These results imply that zerumbone may be beneficial for treating sepsis and inflammasome-related diseases.
Microbiome-Metabolomics Analysis Reveals the Protection Mechanism of α-Ketoacid on Adenine-Induced Chronic Kidney Disease in Rats
Authors: Mo Yenan , Sun Huang , Zhang Lei , Geng Wenjia , Wang Lixin , Zou Chuan , Wu Yuchi , Ji Chunlan , Liu Xusheng , Lu Zhaoyu
Published: May 2021

Objectives: As nitrogen-free precursors of corresponding essential amino, α-ketoacid have been widely prescribed to end-stage renal disease patients together with a low protein diet However, the impact of α-ketoacid on intestinal microbiota in chronic kidney disease (CKD) individuals is unknown. The study aims at investigating the variation in the intestinal microbiota and metabolic profile in response to α-ketoacid treatment in an adenine-induced CKD rat model.

Design: Rats in the treatment groups were given solution of compound α-ketoacid tablets. At the end of the study, blood, feces, colon tissues and kidney tissues were collected and processed for biochemical analyses, histological and western blot analyses, 16S rRNA sequence and untargeted metabolomic analyses.

Results:α-Ketoacid treatment reduced serum creatinine, blood urea nitrogen and 24 h urine protein, and alleviated tubular atrophy, glomerulosclerosis and interstitial fibrosis in adenine-induced CKD rats. Moreover, α-ketoacid significantly improved intestinal barrier and increased the abundance of Methanobrevibacter, Akkermansia, Blautia and Anaerositipes while reduced the abundance of Anaerovorax and Coprococcus_3 at the genus level. In addition, our results also demonstrated that α-ketoacid significantly reduced the concentrations of indoxyl sulfate, betaine, choline and cholesterol. Spearman’s correlation analysis revealed that the abundance of Coprococcus_3 was positively correlated with serum level of betaine, trimethylamine N-oxide, indoxyl sulfate, cholic acid and deoxycholic acid.

Conclusion:α-Ketoacid has a reno-protective effect against adenine-induced CKD, which may be mediated regulation of serum metabolic profiles via affecting intestinal microbial community.
Impact of DAA Treatment on Cardiovascular Disease Risk in Chronic HCV Infection: An Update
Authors: Roguljic Hrvoje , Nincevic Vjera , Bojanic Kristina , Kuna Lucija , Smolic Robert , Vcev Aleksandar , Primorac Dragan , Vceva Andrijana , Wu George Y. , Smolic Martina
Published: May 2021

Hepatitis C virus (HCV) infection is a systemic disease associated with multiple significant extrahepatic manifestations. Emerging studies indicate association between the HCV infection and a higher incidence of major adverse cardiovascular events such as: coronary artery disease, heart failure, stroke and peripheral artery disease, when compared to general population. Atherosclerosis is a common pathophysiologic mechanism of cardiovascular disease (CVD) development which is the leading cause of mortality in the Western world. Proposed mechanisms of HCV-induced atherosclerosis includes systemic inflammation due to the chronic infection with increased levels of pro-atherogenic cytokines and chemokines. Furthermore, it has been demonstrated that HCV exists and replicates within atheroschlerotic plaques, supporting the theory of direct pro-atherogenic effect of the virus. Direct acting antiviral agents (DAAs) represent a safe and highly effective treatment of HCV infection. Beside the improvement in liver-related outcomes, DAAs exhibit a beneficial effect on extra-hepatic manifestations of chronic HCV infection. Recently, it has been shown that patients with chronic HCV infection treated with DAA-based therapeutic regimes had a 43% reduction of CVD events incidence risk. Moreover, eradication of HCV with DAAs results in a significant positive effect on risk factors for cardiovascular disease, despite a general worsening of the lipid profile. This positive effects is mainly due to an improvement of endothelial function and glucose metabolism. Although DAA treatment is associated with a beneficial impact on cardiovascular events, further studies are needed to fully elucidate the mechanisms responsible.
Quantum Implications of Non-Extensive Statistics
Authors: Cabo Bizet Nana , Damián César , Obregón Octavio , Santos-Silva Roberto
Published: May 2021

Exploring the analogy between quantum mechanics and statistical mechanics, we formulate an integrated version of the Quantropy functional. With this prescription, we compute the propagator associated to Boltzmann–Gibbs statistics in the semiclassical approximation as K=F(T)exp(iScl/ℏ). We determine also propagators associated to different nonadditive statistics; those are the entropies depending only on the probability S± and Tsallis entropy Sq. For S±, we obtain a power series solution for the probability vs. the energy, which can be analytically continued to the complex plane and employed to obtain the propagators. Our work is motivated by the work of Nobre et al. where a modified q-Schrödinger equation is obtained that provides the wave function for the free particle as a q-exponential. The modified q-propagator obtained with our method leads to the same q-wave function for that case. The procedure presented in this work allows to calculate q-wave functions in problems with interactions determining nonlinear quantum implications of nonadditive statistics. In a similar manner, the corresponding generalized wave functions associated to S± can also be constructed. The corrections to the original propagator are explicitly determined in the case of a free particle and the harmonic oscillator for which the semiclassical approximation is exact, and also the case of a particle with an infinite potential barrier is discussed.
Quantum Control Landscapes Beyond the Dipole Approximation: Controllability, Singular Controls, and Resources
Authors: Russell Benjamin , Wu Re-Bing , Rabitz Herschel
Published: May 2021

We investigate the control landscapes of closed n-level quantum systems beyond the dipole approximation by including a polarizability term in the Hamiltonian. The latter term is quadratic in the control field. Theoretical analysis of singular controls is presented, which are candidates for producing landscape traps. The results for considering the presence of singular controls are compared to their counterparts in the dipole approximation (i.e., without polarizability). A numerical analysis of the existence of traps in control landscapes for generating unitary transformations beyond the dipole approximation is made upon including the polarizability term. An extensive exploration of these control landscapes is achieved by creating many random Hamiltonians which include terms linear and quadratic in a single control field. The discovered singular controls are all found not to be local optima. This result extends a great body of recent work on typical landscapes of quantum systems where the dipole approximation is made. We further investigate the relationship between the magnitude of the polarizability and the fluence of the control resulting from optimization. It is also shown that including a polarizability term in an otherwise uncontrollable dipole coupled system removes traps from the corresponding control landscape by restoring controllability. We numerically assess the effect of a polarizability term on a known example of a particular three-level Λ-system with a second order trap in its control landscape. It is found that the addition of the polarizability removes the trap from the landscape. The general practical control implications of these simulations are discussed.
Gravity Threshold and Dose Response Relationships: Health Benefits Using a Short Arm Human Centrifuge
Authors: Kourtidou-Papadeli Chrysoula , Frantzidis Christos A. , Gilou Sotiria , Plomariti Christina E. , Nday Christiane M. , Karnaras Dimitrios , Bakas Lefteris , Bamidis Panagiotis D. , Vernikos Joan
Published: May 2021

Purpose

Increasing the level of gravity passively on a centrifuge, should be equal to or even more beneficial not only to astronauts living in a microgravity environment but also to patients confined to bed. Gravity therapy (GT) may have beneficial effects on numerous conditions, such as immobility due to neuromuscular disorders, balance disorders, stroke, sports injuries. However, the appropriate configuration for administering the Gz load remains to be determined.

Methods

To address these issues, we studied graded G-loads from 0.5 to 2.0g in 24 young healthy, male and female participants, trained on a short arm human centrifuge (SAHC) combined with mild activity exercise within 40–59% MHR, provided by an onboard bicycle ergometer. Hemodynamic parameters, as cardiac output (CO), stroke volume (SV), mean arterial pressure (MAP), systolic blood pressure (SBP), diastolic blood pressure (DBP), and heart rate (HR) were analyzed, as well as blood gas analysis. A one-way repeated measures ANOVA and pairwise comparisons were conducted with a level of significancep< 0.05.

Results

Significant changes in heart rate variability (HRV) and its spectral components (Class, Fmax, and VHF) were found in all g loads when compared to standing (p< 0.001), except in 1.7 and 2.0g. There were significant changes in CO, cardiac index (CI), and cardiac power (CP) (p< 0.001), and in MAP (p= 0.003) at different artificial gravity (AG) levels. Dose-response curves were determined based on statistically significant changes in cardiovascular parameters, as well as in identifying the optimal G level for training, as well as the optimal G level for training. There were statistically significant gender differences in Cardiac Output/CO (p= 0.002) and Cardiac Power/CP (p= 0.016) during the AG training as compared to standing. More specifically, these cardiovascular parameters were significantly higher for male than female participants. Also, there was a statistically significant (p= 0.022) gender by experimental condition interaction, since the high-frequency parameter of the heart rate variability was attenuated during AG training as compared to standing but only for the female participants (p= 0.004).

Conclusion

The comprehensive cardiovascular evaluation of the response to a range of graded AG loads, as compared to standing, in male and female subjects provides the dose-response framework that enables us to explore and validate the usefulness of the centrifuge as a medical device. It further allows its use in precisely selecting personalized gravity therapy (GT) as needed for treatment or rehabilitation of individuals confined to bed.
Role of Reduced Sarco-Endoplasmic Reticulum Ca2+-ATPase Function on Sarcoplasmic Reticulum Ca2+ Alternans in the Intact Rabbit Heart
Authors: Wang Lianguo , Myles Rachel C. , Lee I-Ju , Bers Donald M. , Ripplinger Crystal M.
Published: May 2021

Sarcoplasmic reticulum (SR) Ca2+ cycling is tightly regulated by ryanodine receptor (RyR) Ca2+ release and sarco-endoplasmic reticulum Ca2+-ATPase (SERCA) Ca2+ uptake during each excitation–contraction coupling cycle. We previously showed that RyR refractoriness plays a key role in the onset of SR Ca2+ alternans in the intact rabbit heart, which contributes to arrhythmogenic action potential duration (APD) alternans. Recent studies have also implicated impaired SERCA function, a key feature of heart failure, in cardiac alternans and arrhythmias. However, the relationship between reduced SERCA function and SR Ca2+ alternans is not well understood. Simultaneous optical mapping of transmembrane potential (Vm) and SR Ca2+ was performed in isolated rabbit hearts (n = 10) using the voltage-sensitive dye RH237 and the low-affinity Ca2+ indicator Fluo-5N-AM. Alternans was induced by rapid ventricular pacing. SERCA was inhibited with cyclopiazonic acid (CPA; 1–10 μM). SERCA inhibition (1, 5, and 10 μM of CPA) resulted in dose-dependent slowing of SR Ca2+ reuptake, with the time constant (tau) increasing from 70.8 ± 3.5 ms at baseline to 85.5 ± 6.6, 129.9 ± 20.7, and 271.3 ± 37.6 ms, respectively (p < 0.05 vs. baseline for all doses). At fast pacing frequencies, CPA significantly increased the magnitude of SR Ca2+ and APD alternans, most strongly at 10 μM (pacing cycle length = 220 ms: SR Ca2+ alternans magnitude: 57.1 ± 4.7 vs. 13.4 ± 8.9 AU; APD alternans magnitude 3.8 ± 1.9 vs. 0.2 ± 0.19 AU; p < 0.05 10 μM of CPA vs. baseline for both). SERCA inhibition also promoted the emergence of spatially discordant alternans. Notably, at all CPA doses, alternation of SR Ca2+ release occurred prior to alternation of diastolic SR Ca2+ load as pacing frequency increased. Simultaneous optical mapping of SR Ca2+ and Vm in the intact rabbit heart revealed that SERCA inhibition exacerbates pacing-induced SR Ca2+ and APD alternans magnitude, particularly at fast pacing frequencies. Importantly, SR Ca2+ release alternans always occurred before the onset of SR Ca2+ load alternans. These findings suggest that even in settings of diminished SERCA function, relative refractoriness of RyR Ca2+ release governs the onset of intracellular Ca2+ alternans.
Amygdalar Corticotropin-Releasing Factor Signaling Is Required for Later-Life Behavioral Dysfunction Following Neonatal Pain
Authors: Davis Seth M. , Zuke Jared T. , Berchulski Mariah R. , Burman Michael A.
Published: May 2021

Neonatal pain such as that experienced by infants in the neonatal intensive care unit is known to produce later-life dysfunction including heightened pain sensitivity and anxiety, although the mechanisms remain unclear. Both chronic pain and stress in adult organisms are known to influence the corticotropin-releasing factor (CRF) system in the Central Nucleus of the Amygdala, making this system a likely candidate for changes following neonatal trauma. To examine this, neonatal rats were subjected to daily pain, non-painful handling or left undisturbed for the first week of life. Beginning on postnatal day, 24 male and female rats were subjected to a 4-day fear conditioning and sensory testing protocol. Some subjects received intra-amygdalar administration of either Vehicle, the CRF receptor 1 (CRF1) receptor antagonist Antalarmin, or the CRF receptor 2 (CRF2) receptor antagonist Astressin 2B prior to fear conditioning and somatosensory testing, while others had tissue collected following fear conditioning and CRF expression in the CeA and BLA was assessed using fluorescent in situ hybridization. CRF1 antagonism attenuated fear-induced hypersensitivity in neonatal pain and handled rats, while CRF2 antagonism produced a general antinociception. In addition, neonatal pain and handling produced a lateralized sex-dependent decrease in CRF expression, with males showing a diminished number of CRF-expressing cells in the right CeA and females showing a similar reduction in the number of CRF-expressing cells in the left BLA compared to undisturbed controls. These data show that the amygdalar CRF system is a likely target for alleviating dysfunction produced by early life trauma and that this system continues to play a major role in the lasting effects of such trauma into the juvenile stage of development.
Screening of Key Proteins Affecting Floral Initiation of Saffron Under Cold Stress Using iTRAQ-Based Proteomics
Authors: Chen Jing , Zhou Guifen , Dong Yan , Qian Xiaodong , Li Jing , Xu Xuting , Huang Huilian , Xu Limin , Li Liqin
Published: May 2021

Background

Saffron crocus (Crocus sativus) is an expensive and valuable species that presents preventive and curative effects. This study aimed to screen the key proteins affecting the floral initiation of saffron under cold stress and thus increasing yield by regulating the temperature.

Results

Protein expression profiles in flowering and non-flowering saffron buds were established using isobaric tags for relative or absolute quantitation (iTRAQ). A total of 5,624 proteins were identified, and 201 differentially abundant protein species (DAPs) were further obtained between the flowering and non-flowering groups. The most important functions of the upregulated DAPs were “sucrose metabolic process,” “lipid transport,” “glutathione metabolic process,” and “gene silencing by RNA.” Downregulated DAPs were significantly enriched in “starch biosynthetic process” and several oxidative stress response pathways. Three new flower-related proteins, CsFLK, CseIF4a, and CsHUA1, were identified in this study. The following eight key genes were validated by real-time qPCR in flowering and non-flowering top buds from five different growth phases: floral induction- and floral organ development-related genes CsFLK, CseIF4A, CsHUA1, and CsGSTU7; sucrose synthase activity-related genes CsSUS1 and CsSUS2; and starch synthase activity-related genes CsGBSS1 and CsPU1. These findings demonstrate the important roles played by sucrose/starch biosynthesis pathways in floral development at the mRNA level. During normal floral organ development, the sucrose contents in the top buds of saffron increased, and the starch contents decreased. In contrast, non-flowering buds showed significantly decreased sucrose contents under cold stress and no significant changes in starch contents compared with those in the dormancy stage.

Conclusion

In this report, the protein profiles of saffron under cold stress and a normal environment were revealed for the first time by iTRAQ. A possible “reactive oxygen species–antioxidant system–starch/sugar interconversion flowering pathway” was established to explain the phenomenon that saffron does not bloom due to low temperature treatment.
Can We Compare Solidarity Across Europe? What, Why, When, and How to Assess Exact and Approximate Equivalence of First- and Second-Order Factor Models
Authors: Lomazzi Vera
Published: May 2021

Although measurement invariance is widely considered a precondition for meaningful cross-sectional comparisons, substantive studies have often neglected evaluating this assumption, thereby risking drawing conclusions and making theoretical generalizations based on misleading results. This study offers a theoretical overview of the key issues concerning the measurement and the comparison of socio-political values and aims to answer the questions of what must be evaluated, why, when, and how to assess measurement equivalence. This paper discusses the implications of formative and reflective approaches to the measurement of socio-political values and introduces challenges in their comparison across different countries. From this perspective, exact and approximate approaches to equivalence are described as well as their empirical translation in statistical techniques, such as the multigroup confirmatory factor analysis (MGCFA) and the frequentist alignment method. To illustrate the application of these methods, the study investigates the construct of solidarity as measured by European Values Study (EVS) and using data collected in 34 countries in the last wave of the EVS (2017–2020). The concept is captured through a battery of nine items reflecting three dimensions of solidarity: social, local, and global. Two measurement models are hypothesized: a first-order factor model, in which the three independent dimensions of solidarity are correlated, and a second-order factor model, in which solidarity is conceived according to a hierarchical principle, and the construct of solidarity is reflected in the three sub-factors. In testing the equivalence of the first-order factor model, the results of the MGCFA indicated that metric invariance was achieved. The alignment method supported approximate equivalence only when the model was reduced to two factors, excluding global solidarity. The second-order factor model fit the data of only seven countries, in which this model could be used to study solidarity as a second-order concept. However, the comparison across countries resulted not appropriate at any level of invariance. Finally, the implications of these results for further substantive research are discussed.
Governing for Future Generations: How Political Trust Shapes Attitudes Towards Climate and Debt Policies
Authors: Fairbrother Malcolm , Arrhenius Gustaf , Bykvist Krister , Campbell Tim
Published: May 2021

Policy decisions, and public preferences about them, often entail judgements about costs people should be willing to pay for the benefit of future generations. Economic analyses discount policies’ future benefits based on expectations about increasing standards of living, while empirical studies in psychology have found future-oriented people are more motivated to protect the environment. In this article, using original surveys and survey experiments in four countries—Sweden, Spain, South Korea, and China—we show that support for future-oriented policies also strongly reflects people’s political trust. Focusing on policies for reducing either global warming or public debt, we find political trust operates on attitudes by shaping people’s (a) confidence in policies’ effectiveness and (b) willingness to sacrifice for others. The influence of political trust outweighs that of subjective concern, while discounting has so little impact that people who expect future generations to be richer are more, not less, willing to sacrifice.
Psychological Well-Being, Knowledge Management Behavior and Performance: The Moderating Role of Leader-Member Exchange
Authors: Kim Cheol Young
Published: May 2021

Knowledge is considered an essential resource and key to competitiveness. The behavior of sharing knowledge is an essential activity for the prosperity of the organization. For individuals, however, sharing knowledge can present a dilemma by giving up the exclusive right to certain knowledge that they own. This study identifies the psychological well-being as a leading factor in facilitating knowledge-sharing in dilemma situations. The author classified knowledge management behavior into sharing, hiding, and manipulating behavior, and studied them as mediators linking psychological well-being and performance. And to check the influence of the quality of the exchange relationship, leader-member exchange was used as a moderator. For the empirical analysis, 333 members from 12 organizations were surveyed by using different sources and times. Hierarchical regression analysis and bootstrapping analysis were conducted for verification of hypothesis. Results demonstrated that the psychological well-being influence directly on knowledge-sharing, -hiding, and -manipulating behaviors and indirectly on performance. In the multi-mediation test, only knowledge-sharing behavior mediated the relationship between psychological well-being and performance. And the moderating effect of leader-member exchange was significant only in the relationship between psychological well-being and knowledge-sharing behavior. This study contributes to the performance, knowledge management and positive psychology research fields, and suggests practical implications.
Executive Functions of Swedish Counterterror Intervention Unit Applicants and Police Officer Trainees Evaluated With Design Fluency Test
Authors: Vestberg Torbjörn , Tedeholm Peter G. , Ingvar Martin , Larsson Agneta C. , Petrovic Predrag
Published: May 2021

Executive functions (EF) represent higher order top-down mechanisms regulating information processing. While suboptimal EF have been studied in various patient groups, their impact on successful behavior is still not well described. Previously, it has been suggested that design fluency (DF)—a test including several simultaneous EF components mainly related to fluency, cognitive flexibility, and creativity—predicts successful behavior in a quickly changing environment where fast and dynamic adaptions are required, such as ball sports. We hypothesized that similar behaviors are of importance in the selection process of elite police force applicants. To test this hypothesis, we compared elite police force applicants (n = 45) with a control group of police officer trainees (n = 30). Although both groups were better than the norm, the elite police force applicants had a significantly better performance in DF total correct when adjusting for sex and age [F(1,71) = 18.98, p < 0.001]. To understand how this capacity was altered by stress and tiredness, we re-tested the elite police force applicants several days during an extreme field assessment lasting 10 days. The results suggested that there was a lower than expected improvement in DF total correct and a decline in the DF3-subtest that includes a larger component of cognitive flexibility than the other subtests (DF1 and DF2). Although there was a positive correlation between the baseline session and the re-test in DF3 [r(40) = 0.49, p = 0.001], the applicants having the highest scores in the baseline test also displayed the largest percentage decline in the re-test [r(40) = −0.46, p = 0.003]. In conclusion, our result suggests that higher order EF (HEF) that include cognitive flexibility and creativity are of importance in the application for becoming an elite police officer but relatively compromised in a stressful situation. Moreover, as the decline is different between the individuals, the results suggest that applicants should be tested during baseline conditions and during stressful conditions to describe their cognitive capacity fully.
Computational Language Assessments of Harmony in Life — Not Satisfaction With Life or Rating Scales — Correlate With Cooperative Behaviors
Authors: Kjell Oscar , Daukantaitė Daiva , Sikström Sverker
Published: May 2021

Different types of well-being are likely to be associated with different kinds of behaviors. The first objective of this study was, from a subjective well-being perspective, to examine whether harmony in life and satisfaction with life are related differently to cooperative behaviors depending on individuals’ social value orientation. The second objective was, from a methodological perspective, to examine whether language-based assessments calledcomputational language assessments(CLA), which enable respondents to answer with words that are analyzed using natural language processing, demonstrate stronger correlations with cooperation than traditional rating scales. Participants reported their harmony in life, satisfaction with life, and social value orientation before taking part in an online cooperative task. The results show that the CLA of overall harmony in life correlated with cooperation (all participants:r= 0.18,p< 0.05,n= 181) and that this was particularly true for prosocial participants (r= 0.35,p< 0.001,n= 96), whereas rating scales were not correlated (p> 0.05). No significant correlations (measured by the CLA or traditional rating scales) were found between satisfaction with life and cooperation. In conclusion, our study reveals an important behavioral difference between different types of subjective well-being. To our knowledge, this is the first study supporting the validity of self-reported CLA over traditional rating scales in relation to actual behaviors.
Continuous Magnitude Production of Loudness
Authors: Schlittenlacher Josef , Ellermeier Wolfgang
Published: May 2021

Continuous magnitude estimation and continuous cross-modality matching with line length can efficiently track the momentary loudness of time-varying sounds in behavioural experiments. These methods are known to be prone to systematic biases but may be checked for consistency using their counterpart, magnitude production. Thus, in Experiment 1, we performed such an evaluation for time-varying sounds. Twenty participants produced continuous cross-modality matches to assess the momentary loudness of fourteen songs by continuously adjusting the length of a line. In Experiment 2, the resulting temporal line length profile for each excerpt was played back like a video together with the given song and participants were asked to continuously adjust the volume to match the momentary line length. The recorded temporal line length profile, however, was manipulated for segments with durations between 7 to 12 s by eight factors between 0.5 and 2, corresponding to expected differences in adjusted level of −10, −6, −3, −1, 1, 3, 6, and 10 dB according to Stevens’s power law for loudness. The average adjustments 5 s after the onset of the change were −3.3, −2.4, −1.0, −0.2, 0.2, 1.4, 2.4, and 4.4 dB. Smaller adjustments than predicted by the power law are in line with magnitude-production results by Stevens and co-workers due to “regression effects.” Continuous cross-modality matches of line length turned out to be consistent with current loudness models, and by passing the consistency check with cross-modal productions, demonstrate that the method is suited to track the momentary loudness of time-varying sounds.
Alexithymia, Emotional Distress, and Perceived Quality of Life in Patients With Hashimoto’s Thyroiditis
Authors: Martino Gabriella , Caputo Andrea , Vicario Carmelo M. , Feldt-Rasmussen Ulla , Watt Torquil , Quattropani Maria C. , Benvenga Salvatore , Vita Roberto
Published: May 2021

Emotion-processing impairment represents a risk factor for the development of somatic illness, affecting negatively both health-related quality of life (HRQoL) and disease management in several chronic diseases. The present pilot study aims at (i) investigating the associations between alexithymia and depression, anxiety, and HRQoL in patients with Hashimoto’s thyroiditis (HT); (ii) examining the association between these three psychological conditions together with HRQoL, and thyroid autoantibodies status as well as thyroid echotexture in patients with HT; and (iii) comparing the intensity of all these clinical psychological features in patients with HT versus controls. Twenty-one patients with serologically or ultrasonographically verified HT and 16 controls with non-toxic goiter or postsurgical hypothyroidism were recruited for this study. Serum thyrotropin (TSH) and free thyroxine, as well as thyroid autoantibodies (thyroglobulin antibodies and thyroid peroxidase antibodies), were assayed. Alexithymia, depression, anxiety, and HRQoL were assessed with Toronto Alexithymia Scale; Beck Depression Inventory, second edition; Hamilton Anxiety Rating Scale; and Health Survey Short-Form 36, respectively. A negative relationship between the difficulty to describe feelings and the cognitive component of depression was found (r = -0.46, p = 0.04). Besides, patients with seronegative HT had lower somatic anxiety than patients with HT who tested positive (r = -0.68, p = 0.01 and r = -0.59, p = 0.04, respectively). Besides, no statistically significant difference was found between patients with HT and controls with regard to somatic anxiety. The present study suggests the relevance of alexithymia in patients suffering from HT, which may be intertwined with a possible state of underreported depression that is mainly expressed through physical complaints. Promoting the capability to describe and communicate feelings could contribute to psychological elaboration and coping with the disease and, consequently, to the improvement of self-management and perceived HRQoL.
The Personal Wellbeing Index in Spanish Palliative Care Professionals: A Cross-Sectional Study of Wellbeing
Authors: Pérez-Belmonte Sergio , Galiana Laura , Fernández Irene , Vidal-Blanco Gabriel , Sansó Noemí
Published: May 2021

Health professionals are especially exposed to stress, with consequences on professionals’ health and wellbeing. However, palliative care professionals’ wellbeing has been the subject of very little research. The aim of this work is to study the Personal Wellbeing Index (PWI) in a sample of Spanish palliative care professionals, as well as to study their levels of wellbeing and the relationships of wellbeing with variables such as gender, age, marital status, profession, and professional quality of life. A cross-sectional survey of Spanish palliative care professionals was conducted. The Spanish version of the PWI and the Short version of the Professional Quality of Life Scale were used. Here, 296 palliative care professionals attending patients at the end of life participated in the study. They showed medium to high levels of wellbeing. The PWI showed an adequate internal structure [χ2(20) = 116.130 (p < 0.001)]; Comparative Fit Index (CFI) = 0.970; standardized root mean square residual (SRMR) = 0.041; root mean square error of approximation (RMSEA) = 0.140 (0.116, 0.166)] and excellent estimates of reliability [α = 0.879 and Composite Reliability Index (CRI) = 0.923]. Wellbeing was higher for married compared to single and showed no relation with age, gender, and profession. Additionally, a structural equation model was estimated, in which a positive relation was found between wellbeing and compassion satisfaction and a negative one with burnout. The PWI is adequate to measure personal wellbeing in Spanish palliative care professionals.
Attention Span of Children With Mild Intellectual Disability: Does Music Therapy and Pictorial Illustration Play Any Significant Role?
Authors: Jacob Udeme Samuel , Pillay Jace , Oyefeso Esther Olufunke
Published: May 2021

This study investigated the effects of music therapy and pictorial illustration on the attention span of children with mild intellectual difficulties. A pre-test, post-test and control group quasi-experimental research design was used with a sample of children diagnosed with mild intellectual disability from three special schools in Ibadan, Nigeria. Fifty children were randomly selected and assigned to one of three groups: music therapy, pictorial illustration, or control (N = 50, male = 25, female = 25, mean age = 11.6 years). Twenty-four sessions of music therapy and pictorial illustration classes were held with the experimental group only. The Moss Attention Rating Scale was used before and after the intervention to collect data on participants’ attention span. Analysis of Covariance indicated that there was a significant statistical difference between pre-test and post-test results of the two groups. The estimated marginal means of post-attention span by treatment indicated that pictorial illustration had the highest post-attention span score, followed by music therapy, while post-attention span score for the control group was the least. Based on the findings, it is recommended that teachers, caregivers, and parents of children with mild intellectual disability adopt pictorial illustration and music therapy as teaching strategies to enhance their attention span.
Differential Metabolites in Chinese Autistic Children: A Multi-Center Study Based on Urinary 1H-NMR Metabolomics Analysis
Authors: Ma Yu , Zhou Hao , Li Chunpei , Zou Xiaobing , Luo Xuerong , Wu Lijie , Li Tingyu , Chen Xiang , Mao Meng , Huang Yi , Li Erzhen , An Yanpeng , Zhang Lili , Wang Tianqi , Xu Xiu , Yan Weili , Jiang Yonghui , Wang Yi
Published: May 2021

Background: Autism spectrum disorder (ASD) is a group of early-onset neurodevelopmental disorders. However, there is no valuable biomarker for the early diagnosis of ASD. Our large-scale and multi-center study aims to identify metabolic variations between ASD and healthy children and to investigate differential metabolites and associated pathogenic mechanisms.

Methods: One hundred and seventeen autistic children and 119 healthy children were recruited from research centers of 7 cities. Urine samples were assayed by 1H-NMR metabolomics analysis to detect metabolic variations. Multivariate statistical analysis, including principal component analysis (PCA), and orthogonal projection to latent structure discriminant analysis (OPLS-DA), as well as univariate analysis were used to assess differential metabolites between the ASD and control groups. The differential metabolites were further analyzed by receiver operating characteristics (ROC) curve analysis and metabolic pathways analysis.

Results: Compared with the control group, the ASD group showed higher levels of glycine, guanidinoacetic acid, creatine, hydroxyphenylacetylglycine, phenylacetylglycine, and formate and lower levels of 3-aminoisobutanoic acid, alanine, taurine, creatinine, hypoxanthine, and N-methylnicotinamide. ROC curve showed relatively significant diagnostic values for hypoxanthine [area under the curve (AUC) = 0.657, 95% CI 0.588 to 0.726], creatinine (AUC = 0.639, 95% CI 0.569 to 0.709), creatine (AUC = 0.623, 95% CI 0.552 to 0.694), N-methylnicotinamide (AUC = 0.595, 95% CI 0.523 to 0.668), and guanidinoacetic acid (AUC = 0.574, 95% CI 0.501 to 0.647) in the ASD group. Combining the metabolites creatine, creatinine and hypoxanthine, the AUC of the ROC curve reached 0.720 (95% CI 0.659 to 0.777). Significantly altered metabolite pathways associated with differential metabolites were glycine, serine and threonine metabolism, arginine and proline metabolism, and taurine and hypotaurine metabolism.

Conclusions: Urinary amino acid metabolites were significantly altered in children with ASD. Amino acid metabolic pathways might play important roles in the pathogenic mechanisms of ASD.
Galectin-3 Binding Protein, Depression, and Younger Age Were Independently Associated With Alexithymia in Adult Patients With Type 1 Diabetes
Authors: Melin Eva O. , Svensson Ralph , Dereke Jonatan , Hillman Magnus
Published: May 2021

Aims:Alexithymia has been linked to cardiovascular disease. The aim was to explore whether the immuno-inflammatory variables galectin-3 binding protein (Gal3BP), soluble (s)CD163 and galectin-3 were independently associated with alexithymia, while controlling for known risk factors for cardiovascular disease, such as depression, anxiety, impaired glycemic control, obesity, smoking, and physical inactivity in patients with type 1 diabetes (T1D).

Methods:Cross-sectional design. The participants were consecutively recruited from one diabetes out-patient clinic. Alexithymia, depression and anxiety were assessed by self-report instruments. Blood samples, anthropometrics, and blood pressure were collected, supplemented with data from electronic health records. High Gal3BP was defined as ≥3.3 μg/ml, high sCD163 as ≥0.6 μg/ml, high galectin-3 as ≥2.6 ng/ml, impaired glycemic control as HbA1c >70 mmol/mol (>8.6%) and abdominal obesity as waist circumference ≥ 1.02 m for men and ≥ 0.88 m for women.

Results:Two hundred and ninety two patients participated (men 56%, aged 18–59 years, alexithymia prevalence 15%). Patients with alexithymia had higher prevalence of depression (34 vs. 6%,p< 0.001), anxiety (61 vs. 30%,p< 0.001), high Gal3BP levels (39 vs. 17%,p= 0.004), high HbA1c levels (46 vs. 24%,p= 0.006), and abdominal obesity (29 vs. 15%,p= 0.045). Depression [adjusted odds ratio (AOR) 6.5, p< 0.001], high Gal3BP levels (AOR 2.4,p= 0.035), and age (AOR 0.96,p= 0.027) were independently associated with alexithymia. Abdominal obesity (AOR 4.0,p< 0.001), high Gal3BP levels (AOR 2.8,p= 0.002), and depression (AOR 2.9,p= 0.014) were associated with high HbA1c. Abdominal obesity and anxiety were associated [Crude odds ratio (COR) 2.4,p= 0.006].

Conclusions:T1D patients with alexithymia had higher prevalence of high Gal3BP levels, depression, impaired glycemic control, anxiety, and abdominal obesity, which are known risk factors for cardiovascular disease. Only high Gal3BP levels, depression, and younger age were independently associated with alexithymia in adult patients with T1D.
Causal Effects of Body Mass Index on Airflow Obstruction and Forced Mid-Expiratory Flow: A Mendelian Randomization Study Taking Interactions and Age-Specific Instruments Into Consideration Toward a Life Course Perspective
Authors: Probst-Hensch Nicole , Jeong Ayoung , Stolz Daiana , Pons Marco , Soccal Paola M. , Bettschart Robert , Jarvis Deborah , Holloway John W. , Kronenberg Florian , Imboden Medea , Schindler Christian , Lovison Gianfranco F.
Published: May 2021

Obesity has complex links to respiratory health. Mendelian randomization (MR) enables assessment of causality of body mass index (BMI) effects on airflow obstruction and mid-expiratory flow. In the adult SAPALDIA cohort, recruiting 9,651 population-representative samples aged 18–60 years at baseline (female 51%), BMI and the ratio of forced expiratory volume in 1 second (FEV1) to forced vital capacity (FVC) as well as forced mid-expiratory flow (FEF25–75%) were measured three times over 20 follow-up years. The causal effects of BMI in childhood and adulthood on FEV1/FVC and FEF25–75% were assessed in predictive (BMI averaged over 1st and 2nd, lung function (LF) averaged over 2nd and 3rd follow-up; N = 2,850) and long-term cross-sectional models (BMI and LF averaged over all follow-ups; N = 2,728) by Mendelian Randomization analyses with the use of weighted BMI allele score as an instrument variable and two-stage least squares (2SLS) method. Three different BMI allele scores were applied to specifically capture the part of BMI in adulthood that likely reflects tracking of genetically determined BMI in childhood. The main causal effects were derived from models containing BMI (instrumented by BMI genetic score), age, sex, height, and packyears smoked as covariates. BMI interactions were instrumented by the product of the instrument (BMI genetic score) and the relevant concomitant variable. Causal effects of BMI on FEV1/FVC and FEF25–75% were observed in both the predictive and long-term cross-sectional models. The causal BMI- LF effects were negative and attenuated with increasing age, and stronger if instrumented by gene scores associated with childhood BMI. This non-standard MR approach interrogating causal effects of multiplicative interaction suggests that the genetically rooted part of BMI patterns in childhood may be of particular relevance for the level of small airway function and airflow obstruction later in life. The methodological relevance of the results is first to point to the importance of a life course perspective in studies on the etiological role of BMI in respiratory health, and second to point out novel methodological aspects to be considered in future MR studies on the causal effects of obesity related phenotypes.