bluuebunny/crossref_metadata_2025 huggingface dataset:
A Correlative Study Between IVIM-DWI Parameters and the Expression Levels of Ang-2 and TKT in Hepatocellular Carcinoma
Authors: Zheng Jing , Gong Xue Qin , Tao Yun Yun , Wang Ran , Yang Gang , Li Jing Dong , Ren Tian , Li Zu Mao , Yang Cui , Wang Wei Cheng , Yang Lin , Zhang Xiao Ming
Published: January 2021

Background

Noninvasive evaluation of the expression of angiopoietin-2 (Ang-2) and transketolase (TKT) in hepatocellular carcinoma (HCC) is of great significance for the clinical development of individualized treatment plans. However, the correlation between intravoxel incoherent motion diffusion weighted imaging (IVIM-DWI) and the expression of Ang-2 and TKT has not been reported. We sought to investigate the correlations between IVIM-DWI parameters and Ang-2 and TKT expression levels in HCCs.

Methods

Conventional non-enhanced magnetic resonance imaging (MRI) and IVIM-DWI and dynamic contrast MRI were performed for 61 patients with HCC before surgical treatment. Various IVIM-DWI parameters, such as apparent diffusion coefficient (ADC), slow apparent diffusion coefficient (D), fast apparent diffusion coefficient (D*) and fraction of fast apparent diffusion coefficient (f), were calculated using Function-MADC software. Expression levels of Ang-2 and TKT in HCC were detected via immunohistochemical staining and classified into two grades. Independent sample t tests were used to compare differences in parameters between the two groups. The Spearman rank correlation test was used to analyze the correlations between IVIM-DWI parameters and Ang-2 and TKT expression levels in HCCs.

Results

The D* and f values were significantly higher in the high Ang-2 group than in the low Ang-2 group; there were no obvious between-group differences in ADC and D. Ang-2 expression was positively correlated with D* and f but not with ADC and D. The ADC and D values were significantly lower in the high TKT group than in the low TKT group, whereas the between-group differences for D* and f were not significant. TKT expression was negatively correlated with ADC and D but not with D* and f.

Conclusions

IVIM-DWI can be used to evaluate Ang-2 and TKT expression in HCC.
MRD Tailored Therapy in AML: What We Have Learned So Far
Authors: Ngai Lok Lam , Kelder Angèle , Janssen Jeroen J. W. M. , Ossenkoppele Gert J. , Cloos Jacqueline
Published: January 2021

Acute myeloid leukemia (AML) is a heterogeneous clonal disease associated with a dismal survival, partly due to the frequent occurrence of relapse. Many patient- and leukemia-specific characteristics, such as age, cytogenetics, mutations, and measurable residual disease (MRD) after intensive chemotherapy, have shown to be valuable prognostic factors. MRD has become a rich field of research where many advances have been made regarding technical, biological, and clinical aspects, which will be the topic of this review. Since many laboratories involved in AML diagnostics have experience in immunophenotyping, multiparameter flow cytometry (MFC) based MRD is currently the most commonly used method. Although molecular, quantitative PCR based techniques may be more sensitive, their disadvantage is that they can only be applied in a subset of patients harboring the genetic aberration. Next-generation sequencing can assess and quantify mutations in many genes but currently does not offer highly sensitive MRD measurements on a routine basis. In order to provide reliable MRD results, MRD assay optimization and standardization is essential. Different techniques for MRD assessment are being evaluated, and combinations of the methods have shown promising results for improving its prognostic value. In this regard, the load of leukemic stem cells (LSC) has also been shown to add to the prognostic value of MFC-MRD. At this moment, MRD after intensive chemotherapy is most often used as a prognostic factor to help stratify patients, but also to select the most appropriate consolidation therapy. For example, to guide post-remission treatment for intermediate-risk patients where MRD positive patients receive allogeneic stem cell transplantation and MRD negative receive autologous stem cell transplantation. Other upcoming uses of MRD that are being investigated include: selecting the type of allogeneic stem cell transplantation therapy (donor, conditioning), monitoring after stem cell transplantation (to allow intervention), and determining drug efficacy for the use of a surrogate endpoint in clinical trials.
Driving Immune Responses in the Ovarian Tumor Microenvironment
Authors: Ning Franklin , Cole Christopher B. , Annunziata Christina M.
Published: January 2021

Ovarian cancer is the leading cause of death among gynecological neoplasms, with an estimated 14,000 deaths in 2019. First-line treatment options center around a taxane and platinum-based chemotherapy regimen. However, many patients often have recurrence due to late stage diagnoses and acquired chemo-resistance. Recent approvals for bevacizumab and poly (ADP-ribose) polymerase inhibitors have improved treatment options but effective treatments are still limited in the recurrent setting. Immunotherapy has seen significant success in hematological and solid malignancies. However, effectiveness has been limited in ovarian cancer. This may be due to a highly immunosuppressive tumor microenvironment and a lack of tumor-specific antigens. Certain immune cell subsets, such as regulatory T cells and tumor-associated macrophages, have been implicated in ovarian cancer. Consequently, therapies augmenting the immune response, such as immune checkpoint inhibitors and dendritic cell vaccines, may be unable to properly enact their effector functions. A better understanding of the various interactions among immune cell subsets in the peritoneal microenvironment is necessary to develop efficacious therapies. This review will discuss various cell subsets in the ovarian tumor microenvironment, current immunotherapy modalities to target or augment these immune subsets, and treatment challenges.
Can an Instrument Validated to Assess Parent–Child Interactions in the Laboratory Setting Be Applied to Home-Based Observations?
Authors: Lee Helen H. , Ochoa Nadia , Moragne-O'Neal Nia , Rosales Genesis F. , Pugach Oksana , Shadamoro Anuoluwapo , Martin Molly A.
Published: January 2021

Background: The Toothbrushing Observations Scale (TBOS) was developed in a laboratory setting to measure child and parent behaviors during toothbrushing. However, we required an instrument to assess home based behaviors. We assessed the feasibility of applying TBOS to observations of parents and their child (<3 years of age) in urban homes.

Methods: Sample consisted of 36 families recruited from university and community pediatric dental/medical clinics and a Women, Infants, and Children center in Chicago as part of a pilot study for a larger clinical trial. The average age of children in our sample was 20.7 months. Most of the parent participants were mothers (90%), and 75% of the parents identified as Hispanic. Parent–child dyads were video-recorded during home-based toothbrushing activities and footage was reviewed by two independent TBOS coders.

Results: The TBOS instrument consists of 12 parent and 18 child items. We were able to code five parent and ten child items.

Conclusion: The feasibility of applying the TBOS measure to our study population was somewhat limited by factors related to home-based observations and the young age of children in our study. Instruments need to be validated across natural settings, such as the home, to increase the quality and accuracy of human behavioral data.
Social Support and Loneliness Among Chinese Caregivers of Children With Chronic Kidney Disease During the COVID-19 Pandemic: A Propensity Score Matching Analysis
Authors: Shi Lin , Zhang Hengci , Yang Haiping , Wu Daoqi , Li Xiaoqin , Zhang Yunzhi , Chen Xuelan , Wang Mo
Published: January 2021

To evaluate social support and loneliness as well as their association among caregivers of children with chronic kidney disease (CKD) from China during the coronavirus disease 2019 (COVID-19) pandemic. We collected data for caregivers of children with CKD and caregivers of healthy children and matched the two groups using propensity score matching (PSM). We compared the differences in social support and loneliness between the two groups after matching and analyzed the relationship between social support and loneliness in the observation group. Before PSM, we analyzed the data for 247 caregivers of children with CKD and 315 caregivers of healthy children from 13 provinces. After PSM, the two groups each included 202 caregivers. The social support score of caregivers of children with CKD was lower than that of caregivers of healthy children (P < 0.002), while the loneliness score was higher for caregivers of children with CKD than for caregivers of healthy children (P < 0.008). The social support score was negatively correlated with the loneliness score (r = −0.598, P < 0.001). Caregivers of children with CKD experienced less social support and greater loneliness than caregivers of healthy children during the COVID-19 pandemic. Therefore, greater attention should be paid to providing social support for caregivers of CKD children and to improving the ability of these caregivers to cope with loneliness.
Sex-Associated Differences in Cytomegalovirus Prevention: Prophylactic Strategy is Potentially Associated With a Strong Kidney Function Impairment in Female Renal Transplant Patients
Authors: Blazquez-Navarro Arturo , Dang-Heine Chantip , Bauer Chris , Wittenbrink Nicole , Wolk Kerstin , Sabat Robert , Witzke Oliver , Westhoff Timm H. , Sawitzki Birgit , Reinke Petra , Thomusch Oliver , Hugo Christian , Babel Nina , Or-Guil Michal
Published: January 2021

Post-transplantation cytomegalovirus (CMV) syndrome can be prevented using the antiviral drug (val)ganciclovir. (Val)ganciclovir is typically administered following a prophylactic or a pre-emptive strategy. The prophylactic strategy entails early universal administration, the pre-emptive strategy, early treatment in case of infection. However, it is not clear which strategy is superior with respect to transplantation outcome; sex-specific effects of these prevention strategies are not known. We have retrospectively analyzed 540 patients from the multi-centre Harmony study along eight pre-defined visits: 308 were treated according to a prophylactic, 232 according to a pre-emptive strategy. As expected, we observed an association of prophylactic strategy with lower incidence of CMV syndrome, delayed onset and lower viral loads compared to the pre-emptive strategy. However, in female patients, the prophylactic strategy was associated with a strong impairment of glomerular filtration rate one year post-transplant (difference: −11.8 ± 4.3 ml min−1·1.73 m−2, p = 0.006). Additionally, we observed a tendency of higher incidence of acute rejection and severe BK virus reactivation in the prophylactic strategy group. While the prophylactic strategy was more effective for preventing CMV syndrome, our results suggest for the first time that the prophylactic strategy might lead to inferior transplantation outcomes in female patients, providing evidence for a strong association with sex. Further randomized controlled studies are necessary to confirm this potential negative effect.
Gut Microbiota Combined With Metabolomics Reveals the Repeated Dose Oral Toxicity of β-Cyclodextrin in Mice
Authors: Lv Shuangyu , Zhang Xiaomei , Feng Yu , Jiang Qiying , Niu Chenguang , Yang Yanjie , Wang Xinchun
Published: January 2021

Βeta-cyclodextrin (β-CD) with a hydrophobic cavity enables the formation of inclusion complexes with organic molecules. The formation of host–guest complexes makes the application of β-CD popular in many fields, but their interaction with organisms is poorly understood. In the present study, the effect of β-CD on gut microbiota (16S rRNA gene sequencing), serum metabolites (gas chromatography–mass spectrometry platform), and their correlation (Pearson correlation analysis) was investigated after 14 days repeated oral exposure in mice. β-CD did not significantly affect the α-diversity indexes, including Richness, Chao1, Shannon and Simpson indexes, but disturbed the structure of the gut bacteria according to the result of principal component analysis (PCA). After taxonomic assignment, 1 in 27 phyla, 2 in 48 classes, 3 in 107 orders, 6 in 192 families, and 8 in 332 genera were significantly different between control and β-CD treated groups. The serum metabolites were significantly changed after β-CD treatment according to the result of unsupervized PCA and supervised partial least squares-discriminant analysis (PLS-DA). A total of 112 differential metabolites (89 downregulated and 23 upregulated) were identified based on the VIP >1 from orthogonal PLS-DA and p <0.05 from Student’s t-test. The metabolic pathways, including ABC transporters, pyrimidine metabolism, purine metabolism, glucagon signaling pathway, insulin signaling pathway, and glycolysis/gluconeogenesis, were enriched by KEGG pathway analysis. Our study provides a general observation of gut microbiota, serum metabolites and their correlation after exposure to β-CD in mice, which will be helpful for future research and application of β-CD.
Are Anticholinergic Symptoms a Risk Factor for Falls in Older General Practice Patients With Polypharmacy? Study Protocol for the Development and Validation of a Prognostic Model
Authors: Dinh Truc Sophia , González-González Ana Isabel , Meid Andreas D. , Snell Kym I. E. , Rudolf Henrik , Brueckle Maria-Sophie , Blom Jeanet W. , Thiem Ulrich , Trampisch Hans-Joachim , Elders Petra J. M. , Donner-Banzhoff Norbert , Gerlach Ferdinand M. , Harder Sebastian , van den Akker Marjan , Glasziou Paul P. , Haefeli Walter E. , Muth Christiane
Published: January 2021

Background: Cumulative anticholinergic exposure, also known as anticholinergic burden, is associated with a variety of adverse outcomes. However, studies show that anticholinergic effects tend to be underestimated by prescribers, and anticholinergics are the most frequently prescribed potentially inappropriate medication in older patients. The grading systems and drugs included in existing scales to quantify anticholinergic burden differ considerably and do not adequately account for patients’ susceptibility to medications. Furthermore, their ability to link anticholinergic burden with adverse outcomes such as falls is unclear. This study aims to develop a prognostic model that predicts falls in older general practice patients, to assess the performance of several anticholinergic burden scales, and to quantify the added predictive value of anticholinergic symptoms in this context.

Methods: Data from two cluster-randomized controlled trials investigating medication optimization in older general practice patients in Germany will be used. One trial (RIME, n = 1,197) will be used for the model development and the other trial (PRIMUM, n = 502) will be used to externally validate the model. A priori, candidate predictors will be selected based on a literature search, predictor availability, and clinical reasoning. Candidate predictors will include socio-demographics (e.g. age, sex), morbidity (e.g. single conditions), medication (e.g. polypharmacy, anticholinergic burden as defined by scales), and well-being (e.g. quality of life, physical function). A prognostic model including sociodemographic and lifestyle-related factors, as well as variables on morbidity, medication, health status, and well-being, will be developed, whereby the prognostic value of extending the model to include additional patient-reported symptoms will be also assessed. Logistic regression will be used for the binary outcome, which will be defined as “no falls” vs. “≥1 fall” within six months of baseline, as reported in patient interviews.

Discussion: As the ability of different anticholinergic burden scales to predict falls in older patients is unclear, this study may provide insights into their relative importance as well as into the overall contribution of anticholinergic symptoms and other patient characteristics. The results may support general practitioners in their clinical decision-making and in prescribing fewer medications with anticholinergic properties.
Unlocking the Mystery of the Therapeutic Effects of Chinese Medicine on Cancer
Authors: Liu Shao-Hsiang , Chen Po-Sheng , Huang Chun-Chieh , Hung Yi-Tu , Lee Mei-Ying , Lin Wei-Hung , Lin Yuan-Chuan , Lee Alan Yueh-Luen
Published: January 2021

Over the past decade, the rise of cancer immunotherapy has coincided with a remarkable breakthrough in cancer therapy, which attracted increased interests in public. The scientific community clearly showed that the emergence of immunotherapy is an inevitable outcome of a holistic approach for cancer treatment. It is well established that traditional Chinese medicine (TCM) utilizes the principle of homeostasis and balance to adjust the healthy status of body. TCM treatment toward cancer has a long history, and the diagnosis and treatment of tumors were discussed in the ancient and classical literatures of Chinese medicine, such as the Yellow Emperor’s Inner Canon. Precious heritage has laid the foundation for the innovation and development of cancer treatment with TCM. The modern study indicated that TCM facilitates the treatment of cancer and enhances the survival rate and life expectancy of patients. However, the pharmacological mechanisms underlying these effects are not yet completely understood. In addition, physicians cannot always explain why the TCM treatment is effective and the mechanism of action cannot be explained in scientific terms. Here, we attempted to provide insights into the development of TCM in the treatment and interpret how TCM practitioners treat cancer through six general principles of TCM by using modern scientific language and terms based on newly discovered evidence.
Panax quinquefolius L. Saponins Protect Myocardial Ischemia Reperfusion No-Reflow Through Inhibiting the Activation of NLRP3 Inflammasome via TLR4/MyD88/NF-κB Signaling Pathway
Authors: Yu Ping , Li Yuangeng , Fu Wenwen , Li Xin , Liu Yanzhe , Wang Yaozhen , Yu Xiaofeng , Xu Huali , Sui Dayun
Published: January 2021

At present, many patients who undergo reperfusion immediately after percutaneous coronary intervention will undergo microvascular obstruction and reduction in myocardial blood flow. This phenomenon is called “no-reflow (NR),” and there is still no effective therapy for NR. Studies showed Panax quinquefolius L. saponins (PQS) have effect on MI/R injury, while the effect and mechanism of PQS on MI/R induced NR are not clear. In this study, we established a MI/R model to investigate whether PQS decrease NR phenomenon via suppression of inflammation. We found that PQS significantly alleviated the symptoms of NR by reducing ischemia, infarction, and NR area; improving cardiac function; preventing pathological morphology changes of myocardium; depressing leukocytes’ aggregation and adhesion; and suppressing the excessive inflammation. Further study demonstrated that PQS remarkably inhibited TLR4, MyD88, p-NF-κB, and NLRP3 inflammasome-associated protein, and these effects could be reversed by LPS. These results indicated that PQS may protect NR by inhibiting the activation of NLRP3 inflammasome via TLR4/MyD88/NF-κB signaling pathway in part, suggesting that PQS exist potential in preventing NR induced by MI/R.
Size of National Assemblies: The Classic Derivation of the Cube-Root Law is Conceptually Flawed
Authors: Margaritondo Giorgio
Published: January 2021

For half a century, the analysis of the size of national assemblies was dominated by the famous cube-root relation with the population. However, a revisitation of that historical work with a physicist’s approach reveals basic conceptual problems that fatally undermine its conclusions. Furthermore, the assembly size evaluation exceeds the accuracy of all power equations, which cannot be reliably used for political analysis.
Serum Renin Levels Increase With Age in Boys Resulting in Higher Renin Levels in Young Men Compared to Young Women, and Soluble Angiotensin-Converting Enzyme 2 Correlates With Renin and Body Mass Index
Authors: Jehpsson Lars , Sun Jiangming , Nilsson Peter M. , Edsfeldt Andreas , Swärd Per
Published: January 2021

Background: Age, sex, and body constitution may affect the shedding of membrane bound angiotensin-converting enzyme 2 (mACE2) and lead to a relative mACE2 deficiency. However, it is unclear if differences, reflected by serum renin levels, exist in the basal renin-angiotensin-system (RAS) between children and adults, boys, and girls as well as young women and young men. Furthermore, it remains to be investigated if renin and soluble ACE2 (sACE2) levels are correlated with body mass index (BMI) in children and young adults. The aim of this observational study was to assess age-and sex differences in serum renin, and the relationship between renin, soluble angiotensin-converting enzyme 2, and body mass index in a prospectively followed population-based cohort of children which were followed into young adulthood.

Study Design: We analyzed renin and sACE2 in serum in a prospectively followed population-based cohort at 9.9 (0.6) [mean (SD)] (n = 173), 11.7 (0.6) (n = 156), 14.8 (0.8) (n = 149), 18.8 (0.3) (n = 93), and 23.5 (0.7) (n = 152) years of age. Height (cm) and weight (kg) was measured and body mass index (BMI) was calculated as weight (kg)/height (m)2. Sex-related differences in renin levels were calculated using analysis of covariance, adjusted for age. Correlations were assessed by calculating the correlation coefficient (R2) using a multivariable linear mixed model.

Results: Both sexes had low renin levels up to 12 years of age. Thereafter renin levels increased more in boys than in girls. Males from the age of 15 had significantly higher levels than females (p < 0.001). There was a positive linear relationship between renin and sACE2 levels in male and female subjects (p < 0.001), and between sACE2 levels and BMI in males (p < 0.001).

Conclusion: Renin levels increase with age, are higher in men than in women since around puberty, and are correlated with sACE2 levels. Furthermore, sACE2 levels are correlated with body mass index in males. These findings indicate that high renin levels in males and females and a high BMI in males may activate pathways which increase the shedding of mACE2, with possible implications for the risk of severe coronavirus disease 2019.
Stricter Teacher, More Motivated Students? Comparing the Associations Between Teacher Behaviors and Motivational Beliefs of Western and East Asian Learners
Authors: Jiang Yushan , Lee Chi-Kin John , Wan Zhi Hong , Chen Junjun
Published: January 2021

Teacher behaviors are one of the most significant factors influencing student learning. Students from different cultures may have different interpretations of their teachers’ behaviors. This study compared the associations between teacher strictness, teacher feedback, and students’ motivational beliefs using data from six Western countries (the United States, the United Kingdom, Finland, Norway, Australia, and New Zealand) and six East Asian regions (Japan, Korea, mainland China, Hong Kong, Macau, and Taiwan) in the Program for International Student Assessment (PISA) 2015. A total of 89,869 15-year-old students were included in data analysis. The findings indicate that (i) teacher strictness was negatively associated with Western students’ motivation, but positively related to that of East Asian students; (ii) teacher feedback had significant positive associations with the motivational beliefs of both Western and East Asian students; and (iii) there was a positive relationship between teacher strictness and teacher feedback in East Asian context. These results highlight the need to consider cultural factors when interpreting students’ reactions to teacher behaviors.
Move and Be Moved: The Effect of Moving Specific Movement Elements on the Experience of Happiness
Authors: van Geest Jenneke , Samaritter Rosemarie , van Hooren Susan
Published: January 2021

Dynamic body feedback is used in dance movement therapy (DMT), with the aim to facilitate emotional expression and a change of emotional state through movement and dance for individuals with psychosocial or psychiatric complaints. It has been demonstrated that moving in a specific way can evoke and regulate related emotions. The current study aimed to investigate the effects of executing a unique set of kinetic movement elements on an individual mover’s experience of happiness. A specific sequence consisting of movement elements that recent studies have related to the feeling of happiness was created and used in a series of conditions. To achieve a more realistic reflection of DMT practice, the study incorporated the interpersonal dimension between the dance movement therapist (DMTh) and the client, and the impact of this interbodily feedback on the emotional state of the client. This quantitative study was conducted in a within-subject design. Five male and 20 female participants (mean age = 20.72) participated in three conditions: a solo executed movement sequence, a movement sequence executed with a DMTh who attuned and mirrored the movements, and a solo executed movement sequence not associated with feelings of happiness. Participants were only informed about the movements and not the feelings that may be provoked by these movements. The effects on individuals were measured using the Positive and Negative Affect Schedule and visual analog scales. Results showed that a specific movement sequence based on movement elements associated with happiness executed with a DMTh can significantly enhance the corresponding affective state. An additional finding of this study indicated that facilitating expressed emotion through movement elements that are not associated with happiness can enhance feelings such as empowerment, pride, and determination, which are experienced as part of positive affect. The results show the impact of specific full-body movement elements on the emotional state and the support outcome of DMT on emotion regulation.
A Bi-Dimensional Taxonomy of Social Responsivity in Middle Childhood: Prosociality and Reactive Aggression Predict Externalizing Behavior Over Time
Authors: Dobbelaar Simone , van Duijvenvoorde Anna C. K. , Achterberg Michelle , van der Meulen Mara , Crone Eveline A.
Published: January 2021

Developing social skills is essential to succeed in social relations. Two important social constructs in middle childhood, prosocial behavior and reactive aggression, are often regarded as separate behaviors with opposing developmental outcomes. However, there is increasing evidence for the co-occurrence of prosociality and aggression, as both might indicate responsivity to the social environment. Here, we tested whether a bi-dimensional taxonomy of prosociality and reactive aggression could predict internalizing and externalizing problems over time. We re-analyzed data of two well-validated experimental tasks for prosociality (the Prosocial Cyberball Game) and reactive aggression (the Social Network Aggression Task) in a developmental population sample (n= 496, 7–9 years old). Results revealed no associations between prosociality and reactive aggression, confirming the independence of those constructs. Interestingly, although prosociality and reactive aggression independently did not predict problem behavior, the interaction of both was negatively predictive of changes in externalizing problems over time. Specifically, only children who scored low on both prosociality and reactive aggression showed an increase in externalizing problems 1 year later, whereas levels of externalizing problems did not change for children who scored high on both types of behavior. Thus, our results suggest that at an individual level, reactive aggression in middle childhood might not always be maladaptive when combined with prosocial behavior, thereby confirming the importance of studying social competence across multiple dimensions.
A Corpus-Based Study on the Pragmatic Use of the ba Construction in Early Childhood Mandarin Chinese
Authors: Tsung Linda , Gong Yang Frank
Published: January 2021

This article reports on an inquiry that investigated the development of ba constructions in early childhood Mandarin. All cases of ba construction were extracted from the Early Childhood Mandarin Corpus collected from 168 preschoolers aged 2;6, 3;6, 4;6, and 5;6 (year; month; Li and Tse, 2011). Early Childhood Mandarin Corpus, University of Hong Kong. Data analysis indicated that: (1) Mandarin-speaking children produced a repertoire of 11 types of ba construction, and the children in the youngest age group (age 2;6) were able to produce six types of them; (2) children at 4 years old (age 4;6) experienced a critical developmental period of pragmatic use, and at 5 years old (age 5;6) they had attained cognitive and linguistic maturity in understanding the semantic and syntactic features of ba constructions; and (3) there was a significant age effect on the production of three types of ba construction, but no significant association between the children’s gender and their production of ba constructions. These findings offer fresh insights into understanding Chinese children’s innate capacity to understand the co-occurrence constraints concerning the syntactic, semantic and verb features inherent in ba construction, and their developmental ability to denote telic events by resorting to the appropriate ba sentence patterns.
Replicability. Politics and Poetics of Accountability, Validation and Legitimation
Authors: Gobo Giampietro
Published: January 2021

Replicability is a term that not only comes with different meanings in the literature of many domains but is often associated or confused with other terms such as ‘reproducibility,’ ‘repeatability,’ ‘reliability,’ ‘validity,’ and so on. To add to the confusion, it can even be used differently across diverse disciplines. Though all named concepts are important, what makes them barely advantageous is that they do not cover some peculiar aspects of the replicability and validation processes, i.e., appropriateness of conceptualization; trustworthiness of operational definition and operational acts; accuracy of researcher’s description, categorization and/or measurement; successfulness of observational (or field) relation. Moreover, in social sciences and organization studies, the concept of validity of data is highly questionable due to the quite frequent shortage of real statuses of the observed objects. The present paper aims to challenge the received view on the concept of ‘replicability,’ by proposing a “situational approach” based on the idea that replicability works under certain organizational and socio-technic conditions, and that it is heavily influenced by the way that different stakeholders (scientists, technicians, participants artifacts, and technologies) respond to them. Consequently, it is important to understand how and why replicability works in different contexts. Its main purpose, without denying the importance of current conventional perspectives on replicability and its siblings, is to widen and change them to include an organizational setting and a reflexive epistemology. This implies the pursuit of a third way of replicability, between the postmodernist negation of its possibility and its opposite, i.e., a naïve naturalism. A way asserting that replicability is a jigsaw puzzle or a mosaic, constituted by discursive practices (poetics) and organizational achievements guiding the politics of accountability, validation and legitimation. The domain here considered pertains to the social and organizational sciences. However, though going beyond the aim of this essay, many issues could be reframed and adapted to medical, natural and physical sciences, as some of the following examples can show.
Cause or Effect? The Role of Prognostic Uncertainty in the Fear of Cancer Recurrence
Authors: Han Paul K. J. , Gutheil Caitlin , Hutchinson Rebecca N. , LaChance Jason A.
Published: January 2021

Background

Fear of cancer recurrence (FCR) is an important cause of suffering for cancer survivors, and both empirical evidence and theoretical models suggest that prognostic uncertainty plays a causal role in its development. However, the relationship between prognostic uncertainty and FCR is incompletely understood.

Objective

To explore the relationship between prognostic uncertainty and FCR among patients with ovarian cancer (OC).

Design

A qualitative study was conducted utilizing individual in-depth interviews with a convenience sample of patients with epithelial ovarian cancer who had completed first-line treatment with surgery and/or chemotherapy. Semi-structured interviews explored participants’ (1) understanding of their prognosis; (2) experiences, preferences, and attitudes regarding prognostic information; and (3) strategies for coping with prognostic uncertainty. Inductive qualitative analysis and line-by-line software-assisted coding of interview transcripts was conducted to identify key themes and generate theoretical insights on the relationship between prognostic uncertainty and FCR.

Results

The study sample consisted of 21 participants, nearly all of whom reported experiencing significant FCR, which they traced to an awareness of the possibility of a bad outcome. Some participants valued and pursued prognostic information as a means of coping with this awareness, suggesting that prognostic uncertainty causes FCR. However, most participants acknowledged fundamental limits to both the certainty and value of prognostic information, and engaged in various strategies aimed not at reducing but constructing and maintaining prognostic uncertainty as a means of sustaining hope in the possibility of a good outcome. Participants’ comments suggested that prognostic uncertainty, fear, and hope are connected by complex, bi-directional causal pathways mediated by processes that allow patients to cope with, construct, and maintain their uncertainty. A provisional dual-process theoretical model was developed to capture these pathways.

Conclusion

Among patients with OC, prognostic uncertainty is both a cause and an effect of FCR—a fear-inducing stimulus and a hope-sustaining response constructed and maintained through various strategies. More work is needed to elucidate the relationships between prognostic uncertainty, fear, and hope, to validate and refine our theoretical model, and to develop interventions to help patients with OC and other serious illnesses to achieve an optimal balance between these states.
PET Hypometabolism of the Prefrontal-Cingulate Cortices in Internet Gaming Disorder
Authors: Kim Sun Ki , Jeong Hyeonseok , Im Jooyeon Jamie , Lee Sang Hoon , Chung Yong-An
Published: January 2021

Recently, excessive and uncontrolled use of online games has been recognized as a public concern. Although previous neuroimaging studies have reported structural and functional brain deficits in Internet gaming disorder (IGD), very few studies have investigated the regional cerebral metabolic rate of glucose (rCMRglu). This study investigated the differences in rCMRglu between individuals with IGD and healthy controls using 18F-fluoro-2-deoxyglucose positron emission tomography (18F-FDG PET). A total of 23 adults with IGD and 23 controls underwent brain 18F-FDG PET scans and completed self-report questionnaires. A whole-brain voxel-wise analysis of rCMRglu was conducted and associations between rCMRglu and severity of IGD were assessed. The IGD group showed higher impulsivity (p = 0.04) and lower self-control (p = 0.002) than the control group. In addition, the IGD group had lower FDG uptake in the left medial orbitofrontal gyrus, left middle cingulate cortex, left superior frontal gyrus, and right anterior cingulate cortex (p < 0.001). A significant negative association was found between the rCMRglu in the right anterior cingulate cortex and the number of fulfilled diagnostic criteria for IGD (β = −0.50, p = 0.02). Our results suggest that IGD may be associated with deficits of glucose metabolism in the prefrontal-cingulate cortices.
Structural Imaging-Based Biomarkers for Detecting Craving and Predicting Relapse in Subjects With Methamphetamine Dependence
Authors: Qi Chang , Fan Xiaobing , Foxley Sean , Wu Qiuxia , Tang Jinsong , Hao Wei , Xie An , Liu Jianbin , Feng Zhijuan , Liu Tieqiao , Liao Yanhui
Published: January 2021

Background: Craving is the predictor of relapse, and insula cortex (IC) is a critical neural substrate for craving and drug seeking. This study investigated whether IC abnormalities among MA users can detect craving state and predict relapse susceptibility.

Methods: A total of 142 subjects with a history of MA dependence completed structural MRI (sMRI) scans, and 30 subjects (10 subjects relapsed) completed 4-month follow-up scans. MA craving was measured by the Visual Analog Scale for Craving. Abnormalities of IC gray matter volume (GMV) between the subjects with and without craving were investigated by voxel-based morphometry (VBM). The receiver operating characteristic (ROC) analysis was performed for the region-of-interest (ROI) of IC GMV to assess the diagnostic accuracy.

Results: By comparing whole-brain volume maps, this study found that subjects without craving (n = 64) had a significantly extensive decrease in IC GMV (family-wise error correction, p < 0.05) than subjects with craving group (n = 78). The ROI of IC GMV had a significantly positive correlation with the craving scores reported by MA users. The ROC analysis showed a good discrimination (area under curve is 0.82/0.80 left/right) for IC GMV between the subjects with and without craving. By selecting Youden index cut-off point from whole model group, calculated sensitivity/specificity was equal to 78/70% and 70/75% for left and right IC, respectively. By applying the above optimal cut-off values to 30 follow-up subjects as validations, the results showed a similar sensitivity (73–80%) and specificity (73–80%) for detecting craving state as model group. For predicting relapse susceptibility, the sensitivity (50–55%) was low and the specificity (80–90%) was high.

Conclusions: Our study provides the first evidence that sMRI may be used to diagnosis the craving state in MA users based on optimal cut-off values, which could be served as MRI bio-markers and an objective measure of craving state.
Coronavirus Disease (COVID-19): Comprehensive Review of Clinical Presentation
Authors: Mehta Om Prakash , Bhandari Parshal , Raut Akshay , Kacimi Salah Eddine Oussama , Huy Nguyen Tien
Published: January 2021

COVID-19 is a rapidly growing pandemic with its first case identified during December 2019 in Wuhan, Hubei Province, China. Due to the rampant rise in the number of cases in China and globally, WHO declared COVID-19 as a pandemic on 11th March 2020. The disease is transmitted via respiratory droplets of infected patients during coughing or sneezing and affects primarily the lung parenchyma. The spectrum of clinical manifestations can be seen in COVID-19 patients ranging from asymptomatic infections to severe disease resulting in mortality. Although respiratory involvement is most common in COVID-19 patients, the virus can affect other organ systems as well. The systemic inflammation induced by the disease along with multisystem expression of Angiotensin Converting Enzyme 2 (ACE2), a receptor which allows viral entry into cells, explains the manifestation of extra-pulmonary symptoms affecting the gastrointestinal, cardiovascular, hematological, renal, musculoskeletal, and endocrine system. Here, we have reviewed the extensive literature available on COVID-19 about various clinical presentations based on the organ system involved as well as clinical presentation in specific population including children, pregnant women, and immunocompromised patients. We have also briefly discussed about the Multisystemic Inflammatory Syndrome occurring in children and adults with COVID-19. Understanding the various clinical presentations can help clinicians diagnose COVID-19 in an early stage and ensure appropriate measures to be undertaken in order to prevent further spread of the disease.
Financial Literacy, Financial Education, and Smoking Behavior: Evidence From Japan
Authors: Watanapongvanich Somtip , Khan Mostafa Saidur Rahim , Putthinun Pongpat , Ono Shunsuke , Kadoya Yoshihiko
Published: January 2021

In this study, we examine the relationship between financial literacy, financial education, and smoking behavior among the Japanese population. We hypothesize that financially literate and financially educated people, who have the ability to make more rational decisions, are less likely to smoke. Using the Preference Parameters Study of Osaka University, conducted in 2010 (N = 3,706), the probit regression results show that both financial literacy (with an emphasis on knowledge of investments) and financial education (with an emphasis on savings behavior) have a significant negative impact on smoking behavior. In addition, gender, age, education, marital status, household income and assets, risky behaviors, a myopic view of the future, risk preference, and level of happiness also significantly predict the likelihood of a person being a current smoker. This study provides empirical evidence that enhancing the rational decision-making ability of individuals through financial literacy and financial education may curtail smoking behavior.
Reviving Matrix for Nerve Reconstruction in Rabbit Model of Chronic Peripheral Nerve Injury With Massive Loss Defect
Authors: Rochkind Shimon , Almog Mara , Meilin Sigal , Nevo Zvi
Published: January 2021

Background and Aims:The aim of this study was to investigate the innovative guiding regenerative gel (GRG) and antigliotic GRG (AGRG) fillings for nerve conduits, prepared with Food and Drug Administration (FDA)-approved agents and expected to provide an alternative to autologous nerve graft and to enable reconnection of massive nerve gaps in a rabbit model of chronic peripheral nerve injury with massive loss defect that simulates the human condition of chronic injury with a large gap.

Methods:The components and dosimetry for GRG and AGRG formulations were investigatedin vitroon nerve cell culture andin vivoon 10-mm reconstructed sciatic nerves of 72 rats using different concentrations of agents and completed on a rabbit model of delayed (chronic) complete peripheral nerve injury with a 25-mm gap. Forty rabbits underwent delayed (9 weeks after complete injury of the tibial portion of the sciatic nerve) nerve tube reconstruction of a gap that is 25 mm long. GRG and AGRG groups were compared with autologous and empty tube reconstructed groups. Rats and rabbits underwent electrophysiological and histochemical assessments (19 weeks for rats and 40 weeks for rabbits).

Results:Application of AGRG showed a significant increase of about 78% in neurite length per cell and was shown to have the most promising effect on neuronal outgrowth, with total number of neurites increasing by 4-fold. The electrophysiological follow-up showed that AGRG treatment is most promising for the reconstruction of the tibial portion of the sciatic nerve with a critical gap of 25 mm. The beneficial effect of AGRG was found when compared with the autologous nerve graft reconstruction. Thirty-one weeks post the second surgery (delayed reconstruction), histochemical observation showed significant regeneration after using AGRG neurogel, compared with the empty tube, and succeeded in significantly regenerating the nerve, as well as the autologous nerve graft, which was almost similar to a healthy nerve.

Conclusion:We demonstrate that in the model of delayed peripheral nerve repair with massive loss defect, the application of AGRG led to a stronger nerve recovery and can be an alternative to autologous nerve graft.
Internal Threshold of Toxicological Concern (iTTC): Where We Are Today and What Is Possible in the Near Future
Authors: Ellison Corie A. , Api Anne Marie , Becker Richard A. , Efremenko Alina Y. , Gadhia Sanket , Hack C. Eric , Hewitt Nicola J. , Varcin Mustafa , Schepky Andreas
Published: January 2021

The Threshold of Toxicological Concern (TTC) is a risk assessment tool for evaluating low-level exposure to chemicals with limited toxicological data. A next step in the ongoing development of TTC is to extend this concept further so that it can be applied to internal exposures. This refinement of TTC based on plasma concentrations, referred to as internal TTC (iTTC), attempts to convert the chemical-specific external NOAELs (in mg/kg/day) in the TTC database to an estimated internal exposure. A multi-stakeholder collaboration formed, with the aim of establishing an iTTC suitable for human safety risk assessment. Here, we discuss the advances and future directions for the iTTC project, including: (1) results from the systematic literature search for metabolism and pharmacokinetic data for the 1,251 chemicals in the iTTC database; (2) selection of ~350 chemicals that will be included in the final iTTC; (3) an overview of the in vitro caco-2 and in vitro hepatic metabolism studies currently being generated for the iTTC chemicals; (4) demonstrate how PBPK modeling is being utilized to convert a chemical-specific external NOAEL to an internal exposure; (5) perspective on the next steps in the iTTC project.
Novel Diagnostic Tools for Identifying Cognitive Impairment in Dogs: Behavior, Biomarkers, and Pathology
Authors: Vikartovska Zuzana , Farbakova Jana , Smolek Tomas , Hanes Jozef , Zilka Norbert , Hornakova Lubica , Humenik Filip , Maloveska Marcela , Hudakova Nikola , Cizkova Dasa
Published: January 2021

Canine cognitive dysfunction syndrome (CCDS) is a progressive neurodegenerative disorder in senior dogs that is mainly associated with decreased ability to learn and respond to stimuli. It is commonly under-diagnosed because behavioral changes are often attributed to the natural process of aging. In the present study, we used for the first time a comprehensive approach enabling early diagnosis of canine patients with mild cognitive disorders (MiCI). We included CAnine DEmentia Scale (CADES) questionnaires, biochemical parameters, and biomarkers in blood serum, and correlated them with post-mortem histopathological changes. The CADES questionnaires enabled us to identify MiCI dogs developing changes mainly in domains corresponding to social interaction and spatial orientation, which seems to be crucial for delineating early cognitive disorders. Biochemical analyses in these dogs showed slightly elevated liver enzyme parameters (AST and ALT) and significantly decreased sodium and chloride levels in blood serum. Furthermore, we describe for the first time a significant increase of neurofilament light chain (NFL) in blood serum of MiCI dogs, compared to normal aging seniors and young controls, but no changes in TAU protein and amyloid-β (Aβ42) peptide levels. In canine brains with cognitive impairment, amyloid plaques of mainly diffuse and dense types were detected. Furthermore, activated microglia with amoeboid body and dystrophic processes occurred, in some cases with spheroidal and bulbous swellings. On the other hand, no TAU pathology or neurofibrillary tangles were detected. These results suggest that a combination of CADES questionnaire mainly with CNS injury biomarker (NFL) and with biochemical parameters (ALT, AST, Na, and Cl) in blood serum may predict CCDS in senior dogs.