bluuebunny/crossref_metadata_2025 huggingface dataset:
Evaluating brain structure traits as endophenotypes using polygenicity and discoverability
Authors: Matoba Nana , Love Michael I. , Stein Jason L.
Published: July 2020

Human brain structure traits have been hypothesized to be broad endophenotypes for neuropsychiatric disorders, implying that brain structure traits are comparatively ‘closer to the underlying biology’. Genome-wide association studies from large sample sizes allow for the comparison of common variant genetic architectures between traits to test the evidence supporting this claim. Endophenotypes, compared to neuropsychiatric disorders, are hypothesized to have less polygenicity, with greater effect size of each susceptible SNP, requiring smaller sample sizes to discover them. Here, we compare polygenicity and discoverability of brain structure traits, neuropsychiatric disorders, and other traits (89 in total) to directly test this hypothesis. We found reduced polygenicity (FDR = 0.01) and increased discoverability of cortical brain structure traits, as compared to neuropsychiatric disorders (FDR = 3.68×10−9). We predict that ~8M samples will be required to explain the full heritability of cortical surface area by genome-wide significant SNPs, whereas sample sizes over 20M will be required to explain the full heritability of major depressive disorder. In conclusion, we find reduced polygenicity and increased discoverability of cortical structure compared to neuropsychiatric disorders, which is consistent with brain structure satisfying the higher power criterion of endophenotypes.
An immersive first-person navigation task for abstract knowledge acquisition
Authors: Kuhrt Doerte , St. John Natalie R. , Bellmund Jacob L. S. , Kaplan Raphael , Doeller Christian F.
Published: July 2020

Advances in virtual reality (VR) technology have greatly benefited spatial navigation research. By presenting space in a controlled manner, changing aspects of the environment one at a time or manipulating the gain from different sensory inputs, the mechanisms underlying spatial behaviour can be investigated. In parallel, a growing body of evidence suggests that the processes involved in spatial navigation extend to non-spatial domains. Here, we leverage VR technology advances to test whether participants can navigate abstract knowledge. We designed a two-dimensional quantity space - presented using a head-mounted display - to test if participants can navigate abstract knowledge using a first-person perspective navigation paradigm. To investigate the effect of physical movement, we divided participants into two groups: one walking and rotating on a motion platform, the other group using a gamepad to move through the abstract space. We found that both groups learned to navigate using a first-person perspective and formed accurate representations of the abstract space. Interestingly, navigation in the quantity space resembled behavioural patterns observed in navigation studies using environments with natural visuospatial cues. Notably, both groups demonstrated similar patterns of learning. Taken together, these results imply that both self-movement and remote exploration can be used to learn the relational mapping between abstract stimuli.
Blood-derived mitochondrial DNA copy number is associated with gene expression across multiple tissues and is predictive for incident neurodegenerative disease
Authors: Yang Stephanie Y. , Castellani Christina A. , Longchamps Ryan J. , Pillalamarri Vamsee K. , O’Rourke Brian , Guallar Eliseo , Arking Dan E.
Published: July 2020

Background

Mitochondrial DNA copy number (mtDNA-CN) can be used as a proxy for mitochondrial function and is associated with a number of aging-related diseases. However, it is unclear how mtDNA-CN measured in blood can reflect risk for diseases that primarily manifest in other tissues. Using the Genotype-Tissue Expression Project, we interrogated the relationships between mtDNA-CN measured in whole blood and gene expression from whole blood as well as 47 additional tissues.

Results

We evaluated associations between blood-derived mtDNA-CN and gene expression in whole blood for 418 individuals, correcting for known confounders and surrogate variables derived from RNA-sequencing. Using a permutation-derived cutoff (p<2.70e-6), mtDNA-CN was significantly associated with expression for 721 genes in whole blood, including nuclear genes that are required for mitochondrial DNA replication. Significantly enriched pathways included splicing (p=1.03e-8) and ubiquitin-mediated proteolysis (p=2.4e-10). Genes with target sequences for the mitochondrial transcription factor NRF1 were also enriched (p=1.76e-35).

In non-blood tissues, there were more significantly associated genes than expected in 30 out of 47 tested tissues, suggesting that global gene expression in those tissues is correlated with mtDNA-CN. Pathways that were associated in multiple tissues included RNA-binding, catalysis, and neurodegenerative disease. We evaluated the association between mtDNA-CN and incident neurodegenerative disease in an independent dataset, the UK Biobank, using a Cox proportional-hazards model. Higher mtDNA-CN was significantly associated with lower risk for incident neurodegenerative disease (HR=0.73, 95% CI= 0.66;0.90).

Conclusions

The observation that mtDNA-CN measured in whole blood is associated with gene expression in other tissues suggests that blood-derived mtDNA-CN can reflect metabolic health across multiple tissues. Key pathways in maintaining cellular homeostasis, including splicing, RNA binding, and catalytic genes were significantly associated with mtDNA-CN, reinforcing the importance of mitochondria in aging-related disease. As a specific example, genes involved in neurodegenerative disease were significantly enriched in multiple tissues. This finding, validated in a large independent cohort study showing an inverse association between mtDNA-CN and neurodegenerative disease, solidifies the link between blood-derived mtDNA-CN, altered gene expression in both blood and non-blood tissues, and aging-related disease.
Dynamical Ising model of spatially-coupled ecological oscillators
Authors: Nareddy Vahini Reddy , Machta Jonathan , Abbott Karen C. , Esmaeili Shadisadat , Hastings Alan
Published: July 2020

Long-range synchrony from short-range interactions is a familiar pattern in biological and physical systems, many of which share a common set of “universal” properties at the point of synchronization. Common biological systems of coupled oscillators have been shown to be members of the Ising universality class, meaning that the very simple Ising model replicates certain spatial statistics of these systems at stationarity. This observation is useful because it reveals which aspects of spatial pattern arise independently of the details governing local dynamics, resulting in both deeper understanding of and a simpler baseline model for biological synchrony. However, in many situations a system’s dynamics are of greater interest than their static spatial properties. Here, we ask whether a dynamical Ising model can replicate universal and non-universal features of ecological systems, using noisy coupled metapopulation models with two-cycle dynamics as a case study. The standard Ising model makes unrealistic dynamical predictions, but the Ising model with memory corrects this by using an additional parameter to reflect the tendency for local dynamics to maintain their phase of oscillation. By fitting the two parameters of the Ising model with memory to simulated ecological dynamics, we assess the correspondence between the Ising and ecological models in several of their features (location of the critical boundary in parameter space between synchronous and asynchronous dynamics, probability of local phase changes, and ability to predict future dynamics). We find that the Ising model with memory is reasonably good at representing these properties of ecological metapopulations. The correspondence between these models creates the potential for the simple and well-known Ising class of models to become a valuable tool for understanding complex biological systems.
Wnt-mediated interactions of tumor-initiating cells with a macrophage niche drive skin tumor formation
Authors: Fontenete Silvia , Christensen Johan , Martinez-Silgado Adriana , Zarzuela Eduardo , Muñoz Javier , Megias Diego , Castellana Donatello , Loewe Robert , Perez-Moreno Mirna
Published: July 2020

Skin tumor-initiating stem cells (tSCs) fuel skin squamous cell carcinoma (SCC) formation and development in a complex tumor microenvironment, but a role for immune cells in the tSC niche governing the process of tumor formation has remained elusive. Here, we define the existence of a tSC-macrophage niche, expressing high levels of Wnt ligands. Using conditional mouse genetic models to abrogate the secretion of Wnts, we show that both hair follicle SC- and macrophage-derived Wnts are essential for driving skin tumorigenesis, tSCs maintenance, and counteracting tumor regression. Loss of Wnts in either population uncouples the tSC-macrophage association. The proteomic signature of SCC cells reveals CD99 as a Wnt-dependent receptor for the macrophagecancer cell interaction. These results establish a role for a macrophage-tSC niche in governing SCC initiation and maintenance, uncovering potential candidates for immunoprevention against SCC.

One Sentence Summary

A macrophage-skin tumor-initiating cells bonding Wnt loop drives tumorigenesis.
A framework for studying behavioral evolution by reconstructing ancestral repertoires
Authors: Hernández Damián G. , Rivera Catalina , Cande Jessica , Zhou Baohua , Stern David L. , Berman Gordon J.
Published: July 2020

Although extensive behavioral changes often exist between closely related animal species, our understanding of the genetic basis underlying the evolution of behavior has remained limited. Here, we propose a new framework to study behavioral evolution by computational estimation of ancestral behavioral repertoires. We measured the behaviors of individuals from six species of fruit flies using unsupervised techniques and identified suites of stereotyped movements exhibited by each species. We then fit a Generalized Linear Mixed Model to estimate the suites of behaviors exhibited by ancestral species, as well as the intra- and inter-species behavioral covariances. We found that much of intraspecific behavioral variation is explained by differences between individuals in the status of their behavioral hidden states, what might be called their “mood.” Lastly, we propose a method to identify groups of behaviors that appear to have evolved together, illustrating how sets of behaviors, rather than individual behaviors, likely evolved. Our approach provides a new framework for identifying co-evolving behaviors and may provide new opportunities to study the genetic basis of behavioral evolution.
SEED-MEDIATED RNA INTERFERENCE OF ANDROGEN SIGNALING AND SURVIVAL NETWORKS INDUCES CELL DEATH IN PROSTATE CANCER CELLS
Authors: Corbin Joshua M. , Georgescu Constantin , Wren Jonathan D. , Xu Chao , Asch Adam S. , Ruiz-Echevarría Maria J.
Published: July 2020

Resistance to anti-androgen therapy in prostate cancer (PCa) is often driven by genetic and epigenetic aberrations in the androgen receptor (AR) and coregulators that maintain androgen signaling activity. We show that specific small RNAs downregulate expression of multiple essential and AR-coregulatory genes, leading to potent androgen signaling inhibition and PCa cell death. Expression of different sh-/siRNAs designed to target TMEFF2, preferentially reduce viability of PCa, but not benign, cells and growth of murine xenografts. Surprisingly this effect is independent of TMEFF2 expression. Transcriptomic and sh/siRNA seed sequence studies indicate that expression of these toxic shRNAs lead to downregulation of AR-coregulatory and essential genes thru mRNA 3’-UTR sequence complementarity to the seed sequence of the toxic shRNAs. These findings reveal a specialized form of the Death Induced by Survival gene Elimination (DISE) mechanism in PCa cells, that we have termed Androgen Network (AN)-DISE, and suggest a novel therapeutic strategy for PCa.
Does the phase of ongoing EEG oscillations predict auditory perception?
Authors: Tal I. , Leszczynski M. , Mesgarani N. , Schroeder C.E.
Published: July 2020

Effective processing of information from the environment requires the brain to selectively sample relevant inputs. The visual perceptual system has been shown to sample information rhythmically, oscillating rapidly between more and less input-favorable states. Evidence of parallel effects in auditory perception is inconclusive. Here, we combined a bilateral pitch-identification task with electroencephalography (EEG) to investigate whether the phase of ongoing EEG predicts auditory discrimination accuracy. We compared prestimulus phase distributions between correct and incorrect trials. Shortly before stimulus onset, each of these distributions showed significant phase concentration, but centered at different phase angles. The effects were strongest in theta and beta frequency bands. The divergence between phase distributions showed a linear relation with accuracy, accounting for at least 10% of inter-individual variance. Discrimination performance oscillated rhythmically at a rate predicted by the neural data. These findings indicate that auditory discrimination threshold oscillates over time along with the phase of ongoing EEG activity. Thus, it appears that auditory perception is discrete rather than continuous, with the phase of ongoing EEG oscillations shaping auditory perception by providing a temporal reference frame for information processing.
How many sirtuin genes are out there? evolution of sirtuin genes in vertebrates with a description of a new family member*
Authors: Opazo Juan C. , Vandewege Michael W. , Hoffmann Federico G. , Zavala Kattina , Meléndez Catalina , Luchsinger Charlotte , Cavieres Viviana A. , Vargas-Chacoff Luis , Morera Francisco J. , Burgos Patricia V. , Tapia-Rojas Cheril , Mardones Gonzalo A.
Published: July 2020

Studying the evolutionary history of gene families is a challenging and exciting task with a wide range of implications. In addition to exploring fundamental questions about the origin and evolution of genes, disentangling their evolution is also critical to those who do functional/structural studies to allow a deeper and more precise interpretation of their results in an evolutionary context. The sirtuin gene family is a group of genes that are involved in a variety of biological functions mostly related to aging. Their duplicative history is an open question, as well as the definition of the repertoire of sirtuin genes among vertebrates. Our results show a well-resolved phylogeny that represents an improvement in our understanding of the duplicative history of the sirtuin gene family. We identified a new sirtuin gene family member (SIRT3.2) that was apparently lost in the last common ancestor of amniotes but retained in all other groups of jawed vertebrates. According to our experimental analyses, elephant shark SIRT3.2 protein is located in mitochondria, the overexpression of which leads to an increase in cellular levels of ATP. Moreover,in vitroanalysis demonstrated it has deacetylase activity being modulated in a similar way to mammalian SIRT3. Our results indicate that there are at least eight sirtuin paralogs among vertebrates and that all of them can be traced back to the last common ancestor of the group that existed between 676 and 615 millions of years ago.
Tonically active neurons in the monkey dorsal striatum signal outcome feedback during trial-and-error search behavior
Authors: Inokawa Hitoshi , Matsumoto Naoyuki , Kimura Minoru , Yamada Hiroshi
Published: July 2020

An animal’s choice behavior is shaped by the outcome feedback from selected actions in a trial-and-error approach. Tonically active neurons (TANs), presumed cholinergic interneurons in the striatum, are thought to be involved in the learning and performance of reward-directed behaviors, but it remains unclear how TANs are involved in shaping reward-directed choice behaviors based on the outcome feedback. To this end, we recorded activity of TANs from the dorsal striatum of two macaque monkeys (Macaca fuscata; 1 male, 1 female) while they performed a multi-step choice task to obtain multiple rewards. In this task, the monkeys first searched for a rewarding target from among three alternatives in a trial-and-error manner and then earned additional rewards by repeatedly choosing the rewarded target. We found that a considerable proportion of TANs selectively responded to either the reward or the no-reward outcome feedback during the trial-and-error search, but these feedback responses were not observed during repeat trials. Moreover, the feedback responses of TANs were similarly observed in any search trials, without distinctions regarding the predicted probability of rewards and the location of chosen targets. Unambiguously, TANs detected reward and no-reward feedback specifically when the monkeys performed trial-and-error searches, in which the monkeys were learning the value of the targets and adjusting their subsequent choice behavior based on the reward and no-reward feedback. These results suggest that striatal cholinergic interneurons signal outcome feedback specifically during search behavior, in circumstances where the choice outcomes cannot be predicted with certainty by the animals.

Highlights

TANs signal reward and no-reward outcome feedback when monkeys made search behaviors

TANs respond regardless of predicted reward probability or chosen target location

TANs may signal feedback outcomes when rewards cannot be predicted with certainty
Employee turnover intentions and job performance from a planned change: the effects of an organizational learning culture and job satisfaction
Authors: Lin Chun-Yu , Huang Chung-Kai
Published: July 2020

Purpose

In the face of a changing and turbulent environment, an organizational learning culture (OLC) is crucial for the long-term operation of an organization. A learning culture provides the capacity to effectively integrate employees, and it also provides structure so that an organization can move forward via continuous learning and change. Few empirical results are available from Chinese companies enduring an organizational change. To bridge this research gap, this study investigated the relationships among an OLC, job satisfaction, turnover intentions and job performance during organizational change.

Design/methodology/approach

A quantitative approach with structural equation modeling (SEM) and bootstrapping estimation was used to test hypotheses developed from a sample of 434 employees in a restructured telecommunications company in Taiwan.

Findings

Employees who experienced a higher learning culture had lower levels of turnover intentions and exhibited better job performance. Job satisfaction had a negative impact on employee turnover intentions but a positive impact on job performance. Moreover, job satisfaction fully mediated the relationships between an OLC and employee turnover intentions and job performance. When encountering organizational planned changes, a vibrant learning culture gave employees a higher level of satisfaction in their jobs and workplace. Although unexpected challenges often appeared during the organizational changes, employees with a higher level of job satisfaction tended to fulfill their own job duties and showed fewer turnover intentions.

Originality/value

In investigating issues related to organizational change, this study provides managerial insights and addresses strategies for facilitating the adoption of an OLC into the design and implementation of a better workplace environment.
Where is Saudi Arabia's economy heading?
Authors: Rostan Pierre , Rostan Alexandra
Published: July 2020

Purpose

The purpose of the paper is to forecast economic indicators of the Saudi economy in the context of low oil prices which have taken a toll on the Saudi oil-dependent economy between 2014 and 2017. Trades and investments have plummeted, leading to significant budget deficits. In response, the government unveiled a plan called Saudi Vision 2030 in 2016 which has triggered structural economic reforms leading to an unprecedented strategy of transition from an oil-driven economy to a modern market economy.

Design/methodology/approach

This paper forecasts with spectral analysis economic indicators of the Saudi economy up to 2030 to provide a clearer picture of the future economy assuming that the effects of recent reforms have not yet been traced by most of the economic indicators.

Findings

2018–2030 forecasts are all bearish except West Texas Intermediate (WTI) oil price expected to average $64.40 during the period 2019–2030. Two additional exceptions are the Saudi population that should grow to 40 million in 2030 and the swelling gross domestic product (GDP) generated by the non-oil sector resulting from bold actions of the Saudi government who is willing to become less dependent on revenues generated by the oil sector.

Research limitations/implications

Government policymakers, economists and investors would have with spectral forecasts better insight and understanding of the Saudi economy dynamics at the early stage of major economic reforms implemented in the country. In 2020, the COVID-19 pandemic has brutally hurt the Saudi economy following a collapse in the global demand for oil and an oversupplied industry. The impact on the Saudi economy will depend on the optimal response brought by its government.

Social implications

Saudi Vision 2030 plan has already triggered a deep transformation of the Saudi society that is reviewed in this paper.

Originality/value

The forecast of Saudi economic indicators is a timely topic considering the challenges facing the economy and reforms being undertaken. Applying an original forecasting technique to economic indicators adds to the originality of the paper.
Journal of Intellectual Capital: a review of emerging themes and future trends
Authors: Bellucci Marco , Marzi Giacomo , Orlando Beatrice , Ciampi Francesco
Published: July 2020

Purpose

This article aims to provide a bibliometric and systematic literature analysis of studies published in the Journal of Intellectual Capital (JIC) from 2014 to 2018 in order to highlight emerging themes and future trends.

Design/methodology/approach

The analysis focused on 187 papers published on JIC over a period of five years. A scientometric approach to data mining enabled the detection of patterns in the dataset. Precisely, the investigation was conducted by integrating a bibliometric analysis on VOSviewer with a systematic literature review.

Findings

Four main streams of research on JIC emerged in the years of the analysis: reporting and disclosure of intellectual capital; intellectual capital research in universities, education and public sector; knowledge management; intellectual capital, financial performance, and market value.

Research limitations/implications

The study offers valid insights to the topics covered by the Journal of Intellectual Capital by identifying the main research gaps and trends, along with future research avenues.

Originality/value

Prior scholars mostly focused on systematic literature reviews, whilst the use of bibliometric methods generally seems to be a missing tile in the research domain. Also, none of the extant studies has focused on the Journal of Intellectual Capital with reference to the 2014–2018 period. The use of both bibliometric and systematic approaches to literature review delivered extremely fine-tuned results in terms of factors such as citations, contents and evolution of clusters over time.
Anticipating the end: exploring future-oriented sensemaking of change through metaphors
Authors: Bruskin Signe , Mikkelsen Elisabeth Naima
Published: July 2020

Purpose

The purpose of this paper is to explore whether there is a link between retrospective and prospective sensemaking by analyzing metaphors of past and potential future changes.

Design/methodology/approach

The article draws on interview data from employees, team managers and middle managers at an IT department of a Nordic bank.

Findings

The study found that organizational members' sensemaking of changes in the past were characterized by trivializing metaphors. In contrast, future-oriented sensemaking of potential changes were characterized by emotionally charged metaphors of uncertainty, war and the End, indicating that the organizational members anticipating a gloomier future.

Research limitations/implications

These findings might be limited to the organizational context of an IT department of a bank with IT professionals having an urge for control and sharing a history of a financial sector changing dramatically the last decade.

Originality/value

This article contributes to the emerging field of future-oriented sensemaking by showing what characterize past and future-oriented sensemaking of changes at a bank. Further, the paper contributes with an empirical study unpacking how organizational members anticipate an undesired future which might not be grounded in retrospective sensemaking.
The dark side of bright traits: How context cues misdirect facets of conscientiousness
Authors: Jeong Sophia Soyoung , Korsgaard M. Audrey , Morrell Daniel
Published: July 2020

Purpose

The authors test the proposition that there are dark sides to conscientiousness that are revealed when examining lower-level facets. The authors propose that potentially dysfunctional behavior is triggered by context cues that are relevant to duty versus achievement striving.

Design/methodology/approach

The authors conducted two laboratory experiments designed to test how context cues that are specific to duty and achievement striving influence the relationship between these facets and quality versus quantity dimensions of task performance.

Findings

In Study 1, the authors found that normative quality cues led to a stronger relationship between duty and discretionary quality performance. In Study 2, achievement striving was associated with lower levels of quality performance in the presence of competitive feedback cues.

Research limitations/implications

The findings illustrate that the dark side of duty and achievement striving emerges in two ways. First, when there is normative pressure for quality, dutiful individuals are apt to sacrifice efficiency. Second, when there is competitive feedback, achievement striving individuals focus on performance standards at the detriment of quality.

Practical implications

The findings point to the importance of precision and specificity when using personality measures for staffing. Equally important is the informational content of cues conveyed by the social, task and organizational context, in leveraging the impact of personality in the workplace.

Originality/value

This paper clarifies the dark side and bright side contradiction of conscientiousness, adding to the growing literature on unique and often competing consequences of duty and achievement striving. The authors also draw attention to the importance of the content of contextual cues, in trait activation of personality.
COVID-19 outbreak: implications on healthcare operations
Authors: Leite Higor , Lindsay Claire , Kumar Maneesh
Published: July 2020

Purpose

The COVID-19 pandemic is considered a major disruptive event of this decade, raising unforeseen socio-economic implications worldwide. This novel virus has increased the influx of patients in hospitals, and healthcare organisations are facing unprecedented constraints in their operations to deal with increased demand and pressed capacity. Thus, this article evaluates the impact of the COVID-19 pandemic on healthcare systems' demand, resources and capacity and provides research directions.

Design/methodology/approach

This is a viewpoint article and uses timely information on healthcare operations from both scholars and managers, published by diverse sources during the COVID-19 outbreak.

Findings

The authors discuss the focus on “flattening the curve of infection” as a measure to protect healthcare, delay the impact of increased demand and reorientate healthcare supply chain practices. Furthermore, the authors evaluate the role of lean practices on managing demand and capacity and improving quality across healthcare operations and supply chain. Finally, the authors suggest research directions on modern operational issues that emerged during this pandemic, such as discussions around the sustainability of lean post-pandemic, “just in time” practices, inventory trade-offs and lack of organisational responsiveness during untenable events.

Originality/value

In this article, the authors provide a contemporary assessment of the implications of the COVID-19 pandemic on healthcare operations, underscoring main economic and operational elements that can be affected, such as unforeseen demand, resources and capacity shortage. Therefore, the authors assess that healthcare organisations, practitioners and governments have to anticipate operational and economic impacts and, ultimately, to reassess their plans to deal with such adverse events.
Welfare‐Consequentialism: A Vaccine for Populism?
Authors: Semple Noel
Published: July 2020

This article is about two ideologies. Welfare‐consequentialism holds that government should adopt the policies that can rationally be expected to maximise aggregate welfare. Populism holds that society is divided into a pure people and a corrupt elite, and asserts that public policy should express the general will of the people. The responses of world governments to the coronavirus pandemic have clearly illustrated the contrast between these ideologies, and the danger that populist government poses to human wellbeing.

The article argues that welfare‐consequentialism offers a vaccine for populism. First, it rebuts populism’s claims about who government is for and what it should do. Second, the pessimism and distrust that make people crave populism can be satiated by successful welfare‐consequentialist government. Finally, welfare‐consequentialism’s sunny narrative of progress can be just as compelling to people as populism’s dark story has proven to be.
Recent trends in detecting, controlling, and detoxifying of patulin mycotoxin using biotechnology methods
Authors: Ngolong Ngea Guillaume Legrand , Yang Qiya , Castoria Raffaello , Zhang Xiaoyun , Routledge Michael N , Zhang Hongyin
Published: July 2020

Patulin (PAT) is a mycotoxin that can contaminate many foods and especially fruits and fruit‐based products. Therefore, accurate and effective testing is necessary to enable producers to comply with regulations and promote food safety. Traditional approaches involving the use of chemical compounds or physical treatments in food have provided practical methods that have been used to date. However, growing concerns about environmental and health problems associated with these approaches call for new alternatives. In contrast, recent advances in biotechnology have revolutionized the understanding of living organisms and brought more effective biological tools. This review, therefore, focuses on the study of biotechnology approaches for the detection, control, and mitigation of PAT in food. Future aspects of biotechnology development to overcome the food safety problem posed by PAT were also examined. We find that biotechnology advances offer novel, more effective, and environmental friendly approaches for the control and elimination of PAT in food compared to traditional methods. Biosensors represent the future of PAT detection and use biological tools such as aptamer, enzyme, and antibody. PAT prevention strategies include microbial biocontrol, the use of antifungal biomolecules, and the use of microorganisms in combination with antifungal molecules. PAT detoxification aims at the breakdown and removal of PAT in food by using enzymes, microorganisms, and various adsorbent biopolymers. Finally, biotechnology advances will be dependent on the understanding of fundamental biology of living organisms regarding PAT synthesis and resistance mechanisms.
Effects of age and sex on the relationship between body fat area and kidney events in patients with chronic kidney disease
Authors: Osako Kiyomi , Shibagaki Yugo , Inoue Eisuke , Sakurada Tsutomu
Published: July 2020

We examined the effects of age and sex on the relationship between body fat area and kidney events. We included 367 chronic kidney disease patients between 2011 and 2017. Patients' median age was 73.0 years; 262 (71.4%) patients were male. The median estimated glomerular filtration rate was 20.2 mL/min/1.73 m2. During the observation period, 187 patients developed kidney events. In males aged <75 years, high subcutaneous fat area was a risk factor for kidney events (hazard ratio: 1.06, 95% CI: 1.02‐1.11). In females aged <75 years, high visceral fat area reduced kidney events (hazard ratio: 0.83, 95% CI: 0.71‐0.97). In males and females ≥75 years, visceral fat area and subcutaneous fat area were not associated with kidney events. Body fat area was not a risk factor for chronic kidney disease progression in elderly patients. Opposite effects, in sex‐related body fat and kidney events, were shown in young patients.
Tryophagus putrescentiae induces inflammatory cytokine secretions from the human cell lines THP‐1 and EoL‐1 cells
Authors: Jeon Sang‐Jin , Kim Eun Joo , Oh Jihyun , Yun Chi‐Young
Published: July 2020

The present study aimed to identify the roles of the storage mite Tyrophagus putrescentiae (Tp) in relation to human skin diseases, such as atopic dermatitis. We examined the effects of T. putrescentiae extracts (TpE) on the secretion of inflammatory cytokines and their mRNA expression in human immune cells. Human monocytic THP‐1 and eosinophilic EoL‐1 cells were challenged with TpE and the inflammatory cytokines, interleukin‐6 (IL‐6), interleukin‐8 (IL‐8), and monocyte chemotactic protein‐1 (MCP‐1) secreted in culture supernatant were analyzed using an enzyme‐linked immunosorbent assay (ELISA). The mRNA levels in the cell cultures were also measured via reverse transcriptase‐polymerase chain reaction (RT‐PCR). In the THP‐1 cells, the TpE significantly induced the secretion of IL‐6, IL‐8, and MCP‐1 in a time‐ and dose‐dependent manner. It also stimulated increases in the expression levels of the IL‐6, IL‐8, and MCP‐1 mRNA. However, while the TpE induced IL‐8 and MCP‐1 mRNA levels in the EoL‐1 cells, it did not induce IL‐6 expression. Using Western blot analysis, we confirmed the activation of extracellular signal‐regulated kinase (ERK), a member of the mitogen‐activated protein kinases (MAPKs), in response to TpE challenge of the THP‐1 cells. Collectively, our results show that TpE challenge elicits inflammatory response in the human monocytic THP‐1 and eosinophilic EoL‐1 cells, and it induces increased production of the inflammatory cytokines IL‐6, IL‐8, and MCP‐1.
Information Risk and Debtholders’ Mispricing by Considering Audit Quality*
Authors: Jung Yong‐Ki , Kim Sun‐Hwa
Published: July 2020

We examine how audit quality perceptions impact debt mispricing in the presence of earnings management. The Big Four auditors (BFAs) and auditor tenure are used as proxies for perceptions of higher quality audits. Debt mispricing means that debtholders charge a lower (higher) cost of debt to a firm with low (high) accrual earnings management (AEM) and high (low) real earnings management (REM). We find that debt mispricing is accentuated (attenuated) by considering the BFA and auditor tenure because debtholders fixate on quality audits curving AEM. For low AEM and REM firms, debt investors place a premium on low AEM with the BFAs/long‐tenured auditors, worsening the mispricing. For high AEM and low REM firms, debt investors impose a “smaller discount” on high AEM with the BFAs/long‐tenured auditors. This study demonstrates that the accentuation (attenuation) of debt mispricing when considering the BFA and auditor tenure occurs mainly if the firm raised only private debt rather than both private and public debt.
Positive association between bitter taste threshold and preference of vegetables among adolescents
Authors: Hald Mathias , Hald Minna Onat , Stankovic Jelena , Niklassen Andreas Steenholt , Ovesen Therese
Published: July 2020

Aim

Better understanding of aspects of taste in adolescents is needed since it has bearings on food policies, food industry and pharmaceutical design. Furthermore, taste preferences likely play a role in overeating and anorexia. We aimed to validate a questionnaire about taste preferences and dietary habits along with measurements of sense of smell and taste.

Methods

We included adolescents from nearby schools in Aarhus, Denmark, from 2017 to 2019. Scoring preferences and habits on a Likert scale, they completed a food item questionnaire. Their chemosensation was tested by the Sniffin’ Sticks and Taste Drop Test.

Results

We included 100 adolescents: 53 males, 47 females; average age: 15.9 years (12‐17 years). Retest of the questionnaire showed good reliability (Cohen's kappa: 0.5953). Snacks scored the highest average liking (4.48), whereas starches had the highest frequency of consumption (3.64). Bitter taste threshold was positively associated with liking and familiarity with vegetables (P = .032; P = .012), respectively. Healthy self‐reported dietary habits were associated with a higher self‐reported consumption of vegetables and a decreased consumption of snacks.

Conclusion

Adolescents preferred unhealthy food items, but they also reported more frequent consumption of healthy than unhealthy food items. A higher threshold for the bitter taste, that is, being less sensitive to bitter taste, was associated with higher liking and familiarity of vegetables.
When anxiety becomes my propeller: Mental toughness moderates the relation between academic anxiety and academic avoidance
Authors: Hasty Leslie M. , Malanchini Margherita , Shakeshaft Nicholas , Schofield Kerry , Malanchini Maddalena , Wang Zhe
Published: July 2020

Background

High academic anxiety is associated with poor academic performance. One proposed mechanism of this association is that academic anxiety promotes learning avoidance behaviours, which in turn hinders students' opportunities to learn and grow. However, this proposition has not been thoroughly examined, particularly in afterschool learning settings. The present study aimed to address this gap.

Aims

First, we investigated whether individual differences in academic anxiety across three domains (mathematics, native language or L1, and second language learning or L2) predicted students' academic avoidance in the corresponding domain in high school. Second, given that individual differences in personality may result in employing different coping strategies to deal with academic anxiety, we examined how mental toughness (MT) moderated the relation between academic anxiety and academic avoidance.

Sample

Two waves of longitudinal data that were one semester apart were available for four hundred and forty‐four high school students.

Methods

Students self‐reported their MT, academic anxiety, and academic avoidance (i.e., time spent on studying a subject afterschool) in mathematics, L1, and L2.

Results

For students with higher MT, higher mathematics, L1, and L2 anxiety in the first semester predicted more time spent on learning the corresponding subject in the following semester, even after controlling for general anxiety, academic achievement, and initial academic avoidance.

Conclusions

These results challenge the proposition that all students with higher domain‐specific anxiety are more likely to avoid learning altogether in that domain. Rather, among students from the general school population who generally exhibit low to moderate levels of academic anxiety, higher academic anxiety is associated with more time investment in afterschool learning in mentally tough students.
Oncological outcome according to attainment of pentafecta after robot‐assisted radical cystectomy in patients with bladder cancer included in the multicentre KORARC database
Authors: Oh Jong Jin , Lee Sangchul , Ku Ja Hyeon , Kwon Tae Gyun , Kim Tae‐Hwan , Jeon Seung Hyun , Lee Sang Hyup , Nam Jong Kil , Kim Wan Seok , Jeong Byong Chang , Lee Ji Youl , Hong Sung Hoo , Rha Koon Ho , Han Woong Kyu , Ham Won Sik , Lee Young Goo , Lee Yong Seong , Park Sung Yul , Yoon Young Eun , Kang Sung Gu , Kang Seok Ho ,   Korean Robot Assisted Radical Cystectomy (KORARC) Study Group
Published: July 2020

Objectives

To investigate the oncological significance of a robot‐assisted radical cystectomy (RARC)‐related pentafecta in patients with bladder cancer.

Patients and Methods

Using the KORARC database, which includes data from 12 centres, data from 730 patients who underwent RARC between April 2007 and May 2019 were prospectively collected and retrospectively analysed. Pentafecta was achieved if patients met all of the following criteria: (i) negative soft tissue surgical margin; (ii) ≥16 lymph nodes removed; (iii) no major complications (Clavien–Dindo grade 3–5) within 90 days; (iv) no clinical recurrence within the first 12 months; and (v) no ureteroenteric stricture. Patients were divided into two groups according to pentafecta attainment, and a comparison of overall survival (OS) and cancer‐specific survival (CSS) using multivariate Cox proportional analysis was then carried out.

Results

Of the 730 patients included in this analysis, 208 (28.5%) attained the RARC pentafecta; the remaining 522 (71.5%) did not. The mean age of the patients was 64.67 years, 85.1% were men, 53.6% received a conduit, 37.7% received orthotopic neobladders and the total complication rate was 57.8%. Those who attained the pentafecta received more neobladders (P = 0.039), were more likely to be treated with the intracorporeal technique (P < 0.001), had longer operating times (P = 0.020) and had longer console time (P = 0.021) compared with those who did not attain the pentafecta. Over a mean of 31.1 months of follow‐up, the pentafecta attainment group had significantly higher OS and CSS rates compared with the non‐attainment group (10‐year OS 70.4% vs 58.1%, respectively [P = 0.016]; 10‐year CSS 87.8% vs 70.0%, respectively [P = 0.036]). Multivariate analysis showed that the RARC pentafecta was a significant predictor of overall mortality (hazard ratio 0.561; P = 0.038).

Conclusions

Patients who attained the RARC pentafecta had significantly better survival outcomes compared with those who did not. These criteria could be used to standardize assessment of the surgical quality of RARC. In the future, a similar study using an independent cohort is warranted to confirm our results.
Debate: Facing uncertainty with(out) a sense of control – cultural influence on adolescents’ response to the COVID‐19 pandemic
Authors: Zhu Nan , O Jiaqing , Lu Hui Jing , Chang Lei
Published: July 2020

The coronavirus disease 2019 (COVID‐19) pandemic has brought about healthcare, economic, and psychological crises around the world. The psychological impact on adolescents is likely going to be uneven across different societies, as cultures vary in terms of their dominant learning style that may influence how people cope with uncertainty and perceive their sense of control. We postulate that for adolescents in individualistic cultures where individual learning prevails, their sense of control might be undermined by societal disease‐control regulations that restrict personal freedoms, while adolescents’ sense of control might increase via participating in societal preventive efforts in collectivistic cultures where social learning is more prevalent. Individual differences regarding one’s sense of control would, in turn, have implications for adolescents’ short‐term adjustments to COVID‐19‐related challenges and their future development.
Lorlatinib in previously treated anaplastic lymphoma kinase‐rearranged non–small cell lung cancer: Japanese subgroup analysis of a global study
Authors: Seto Takashi , Hayashi Hidetoshi , Satouchi Miyako , Goto Yasushi , Niho Seiji , Nogami Naoyuki , Hida Toyoaki , Takahashi Toshiaki , Sakakibara‐Konishi Jun , Morise Masahiro , Nagasawa Takashi , Suzuki Mie , Ohkura Masayuki , Fukuhara Kei , Thurm Holger , Peltz Gerson , Nishio Makoto
Published: July 2020

Lorlatinib is a potent, brain‐penetrant, third‐generation anaplastic lymphoma kinase (ALK)/ROS proto‐oncogene 1 (ROS1) tyrosine kinase inhibitor (TKI) that is active against most known resistance mutations. This is an ongoing phase 1/2, multinational study (NCT01970865) investigating the efficacy, safety and pharmacokinetics of lorlatinib in ALK‐rearranged/ROS1‐rearranged advanced non–small cell lung cancer (NSCLC) with or without intracranial (IC) metastases. Because patterns of ALK TKI use in Japan differ from other regions, we present a subgroup analysis of Japanese patients. Patients were enrolled into six expansion (EXP) cohorts based on ALK/ROS1 mutation status and treatment history. The primary endpoint was the objective response rate (ORR) and the IC‐ORR based on independent central review. Secondary endpoints included pharmacokinetic evaluations. At data cutoff, 39 ALK‐rearranged/ROS1‐rearranged Japanese patients were enrolled across the six expansion cohorts; all received lorlatinib 100 mg once daily. Thirty‐one ALK‐rearranged patients previously treated with ≥1 ALK TKI (EXP2 to EXP5) were evaluable for ORR and 15 were evaluable for IC‐ORR. The ORR and the IC‐ORR for Japanese patients in EXP2‐5 were 54.8% (95% confidence interval [CI]: 36.0‐72.7) and 46.7% (95% CI: 21.3‐73.4), respectively. Among patients who had received prior alectinib only (EXP3B), the ORR was 42.9%; 95% CI: 9.9‐81.6). The most common treatment‐related adverse event (TRAE) was hypercholesterolemia (79.5%). Hypertriglyceridemia was the most common grade 3/4 TRAE (25.6%). Single‐dose and multiple‐dose pharmacokinetic profiles among Japanese patients were similar to those in non–Japanese patients. Lorlatinib showed clinically meaningful responses and IC responses among ALK‐rearranged Japanese patients with NSCLC who received ≥1 prior ALK TKI, including meaningful responses among those receiving prior alectinib only. Lorlatinib was generally well tolerated.
Relation of health‐related quality of life to near final height and body composition in adolescents with chronic endocrinopathies during transition period
Authors: Mittnacht Janna , Choukair Daniela , Breil Thomas , Klose Daniela , Inta Ioana , Bettendorf Markus
Published: July 2020

Introduction

We evaluated sequelae of disease and therapy in adolescents with chronic endocrinopathies using a medical and psychological workup to record health‐related quality of life (HRQoL), near final height (NFH) and body compositions during the transition period from paediatric to adult care.

Methods

Near final height, weight, body mass index (BMI), grip strength (GS), hip and waist circumference (HC; WC), skin folds (SF) and HRQoL T‐scores by KIDSCREEN and DISABKIDS were assessed in 134 patients (70 females and 64 males) from May 2010 to March 2016 diagnosed with congenital adrenal hyperplasia (CAH; n = 22), multiple pituitary hormone deficiency (MPHD; n = 17), growth hormone deficiency (GHD; n = 37), Turner syndrome (TS; n = 27), SGA‐short stature (SGA; n = 20) and Klinefelter syndrome (KS; n = 11).

Results

Median HRQoL T‐scores for KIDSCREEN (50.6‐56.5) and DISABKIDS (52.7‐58.9) ranged within references with considerable variations but without significant deficit in any diagnosis. Median‐corrected height SDS (CoH‐SDS: NFH‐SDS–TH [target height]‐SDS) was >−1, except in KS (SDS + 1.3) and in TS (SDS – 1.9; P < .0001) without correlations with HRQoL. Median BMI was below 25 kg/m2 in all patients except MPHD (26.5 kg/m2; SDS 1.5; P = .006). BMI correlated negatively in CAH females with self‐perception (rs = −.64, P = .0338), physical well‐being (rs = −.8; P = .0086), social exclusion rs = −.65; P = .031) and emotions (rs = −.7; P = .0169).

Conclusion

Health‐related quality of life and body compositions were similar to those of healthy adolescents. Lower scores in HRQoL dimensions as self‐perception, physical well‐being, social exclusion and emotions were detected and correlated negatively with BMI. Treatment strategies and psychological support should consider HRQoL and adapted in specific treatment guidelines.