bluuebunny/crossref_metadata_2025 huggingface dataset:
The impact of survey mode on US national estimates of adolescent drug prevalence: results from a randomized controlled study
Authors: Miech Richard A. , Couper Mick P. , Heeringa Steven G. , Patrick Megan E.
Published: September 2020

Background and Aims

Increasing numbers of school‐based drug surveys are transitioning data collection to electronic tablets from paper‐and‐pencil, which may produce a survey mode effect and consequent discontinuity in time trends for population estimates of drug prevalence. This study tested whether (a) overall, self‐reported drug use prevalence is higher on electronic tablets versus paper‐and‐pencil surveys, (b) socio‐demographics moderate survey mode effects and (c) levels of missing data are lower for electronic tablet versus paper‐and‐pencil modes.

Design

A randomized controlled experiment.

Setting

Results are nationally representative of students in the contiguous United States.

Participants

A total of 41 866 8th, 10th and 12th grade students who participated in the 2019 Monitoring the Future school‐based survey administration.

Intervention and comparator

Surveys were administered to students in a randomly selected half of schools with electronic tablets (intervention) and with paper‐and‐pencil format (comparator) for the other half.

Measurements

Primary outcome was the total number of positive drug use responses. Secondary outcomes were the percentage of respondents completing all drug questions, percentage of drug questions unanswered and mean number of missing drug items.

Findings

The relative risk (RR) for total number of positive drug use responses for electronic tablets versus paper‐and‐pencil surveys were small and their 95% confidence intervals (CI) included the value of one for reporting intervals of life‐time (RR = 1.03; 95% CI, 0.93–1.14), past 12 months (RR = 1.01; 95% CI, 0.91–1.11), past 30 days (RR = 1.05; 95% CI, 0.93–1.20) and for heavy use (RR = 1.10; 95% CI, 0.93–1.29). Multiplicative interaction tests indicated no moderation of these relative risks by race (white versus non‐white), population density, census region, public/private school, year of school participation, survey version or non‐complete drug responses. Levels of missing data were significantly lower for electronic tablets versus paper‐and‐pencil surveys.

Conclusions

Adolescent drug prevalence estimates in the United States differed little across electronic tablet versus paper‐and‐pencil survey modes, and showed little to no effect modification by socio‐demographics. Levels of missing data were lower for electronic tablets.
Morphology, ultrasonographic and computed tomography configuration of the dog pelvis and perineum
Authors: El‐gendy Samir , Alsafy Mohamed , Hanafy Basma , Karkoura Ashraf , Enany El‐said
Published: September 2020

The current study used topographic anatomy, distribution of arteries and nerves, sectional anatomy of the pelvis, computed tomography (CT) and ultrasonography examination to describe the canine pelvis and its organs. This study was conducted on twenty male and female baladi dogs, weighing 30–35 kg and aged between 1.5 and 2 years. The pelvis dorsal boundary appeared long and reached to the level of the third caudal vertebra. The vesicogenital pouch in the female extended further caudally than the rectogenital pouch while in the male the two pouches were at the same level and extended to the level of the first sacral vertebra. The plexus lumbosacralis formed from the ventral branches of the last three lumbar nerves and the first three sacral nerves. The obturator nerve arose from the ventral branches of the fifth and sixth lumbar nerves. We developed an anatomical atlas of the pelvis of both sexes of the dog using CT scans compared to anatomical sections. Our study is the first research on the pelvis in both sexes of the dog to compare sagittal CT scan data to sagittal anatomical sections. In the CT slices, the prostate appeared homogenous, relatively hypodense presenting with a soft tissue density. It appeared oval in the longitudinal sections and elliptical to round at the cross sections. It was situated on the floor of the pelvic cavity or the pelvic brim depending on its size. The present study is also the first to describe the fascia diaphragmatic pelvis.
Examining Managerial Misbehavior in Asian Banks through Loan Loss Provisions*☆
Authors: Saona Paolo , Azad Md. Abul Kalam
Published: September 2020

This paper reviews the impact of corporate ownership concentration, insider ownership, and the development of regulatory and financial systems on the opportunistic behavior of managers to alter financial reporting. By using the panel data technique with a sample of banks from 25 Asian countries, the major findings indicate that ownership concentration as well as insider ownership positively impact the banks’ accrual‐based earnings management. Results also reveal that an improvement in regulatory and financial systems restricts executives’ capacity to manage earnings. Islamic banking and IFRS adoption reduce the manipulation of earnings. Policy implications from the results are also discussed.
Determinants of support for the “Recycling Demonstration Project for the Soil Generated from Decontamination Activities” in postdisaster Fukushima, Japan
Authors: Mukai Tomoya , Nozawa Yuki , Ohta Takeshi , Miyagawa Ryu , Nakagawa Keiichi
Published: September 2020

Since 2018, the Japanese Ministry of the Environment (MoE) has worked on the “Recycling Demonstration Project for the Soil Generated from Decontamination Activities” (the Project), which aims to offer empirical evidence for the final disposal of radiation‐contaminated substances. To offer practical suggestions for the Project, this study aimed to explore determinants of its support. More specifically, building on previous studies on trust, this study proposed a hypothetical model in which support for the Project was determined by trust in the MoE, which in turn was determined by salient value similarity, ability, and motivation. Additionally, it was hypothesised that the relationships between trust and its different determinants differed: Salient value similarity showed a stronger relationship with trust in those who lived near the place where the Project is taking place whereas ability and motivation showed stronger relationships with trust in those who did not. Questionnaire‐based research was conducted in both Iitate village (n = 106), Fukushima, where the Project had been taking place, and Tokyo (n = 163), located approximately 220 km from Fukushima. Multilevel structural equation modelling supported the hypothesis. These results suggest that emphasising the similarity of values between the MoE and the public would help obtain the public’s support for the Project.
Unravelling how in vitro capacitation alters ram sperm chromatin before and after cryopreservation
Authors: Peris‐Frau Patricia , Álvarez‐Rodríguez Manuel , Martín‐Maestro Alicia , Iniesta‐Cuerda María , Sánchez‐Ajofrín Irene , Medina‐Chávez Daniela Alejandra , Garde José Julián , Villar Margarita , Rodríguez‐Martínez Heriberto , Soler Ana Josefa
Published: September 2020

Background

Sperm chromatin structure provides valuable information for the prediction of male fertility and can be altered during different procedures. Previous studies have shown that sperm chromatin condensation decreased during in vitro capacitation. Moreover, cryopreservation can affect sperm DNA integrity and chromatin compaction.

Objectives

This study aimed to investigate dynamic modifications produced in the chromatin structure of ram spermatozoa during in vitro capacitation before and after cryopreservation.

Materials and methods

Chromatin decondensation (AB+), DNA methylation, DNA fragmentation index (%DFI) and high DNA stainability (HDS) were evaluated in fresh and frozen‐thawed ram spermatozoa incubated under capacitating (CAP) conditions at 1, 5, 15, 30, 60, 120, 180 and 240 minutes and under non‐capacitating (NC) conditions at 0, 15 and 240 minutes.

Results

Incubation in NC conditions did not induce significant changes in chromatin condensation (P > .05; AB + and HDS). However, incubation of fresh and cryopreserved ram spermatozoa under CAP conditions significantly increased chromatin decondensation (P < .05), reaching the highest percentage of AB + and HDS from 180 to 240 minutes in fresh samples and from 5 to 30 minutes in cryopreserved samples. Both variables (HDS and AB+) were positively correlated with tyrosine phosphorylation, total motility, progressive motility, curvilinear velocity and amplitude of lateral head displacement, as well as between them under CAP conditions in fresh and cryopreserved spermatozoa. DNA methylation significantly increased in cryopreserved spermatozoa (P < .05), but only after extended incubation under CAP conditions (60‐240 minutes), while the %DFI, albeit higher in cryopreserved samples, remained constant under CAP and NC conditions in both types of sample (P > .05).

Discussion and conclusions

Our results suggest that sperm chromatin condensation decreased progressively during in vitro capacitation of ram spermatozoa, while sperm DNA integrity remained intact. Such changes in chromatin condensation appeared faster after sperm cryopreservation.
Non‐medical use of benzodiazepines and GABA analogues in Europe
Authors: Hockenhull Joanna , Amioka Elise , Black Joshua C. , Forber Alyssa , Haynes Colleen M. , Wood David M. , Dart Richard C. , Dargan Paul I.
Published: September 2020

Aims

We investigated the prevalence of non‐medical use (NMU) of benzodiazepines and GABA analogues in Europe.

Methods

Data were collected using the online Non‐Medical Use of Prescription Drugs (NMURx) survey from France, Germany, Italy, Spain and the UK.

Results

The study included 55 223 eligible surveys which, after post‐stratification weights were applied, represented approximately 260 million European adults. Lifetime NMU of benzodiazepines was highest in Spain (6.5%, 95% CI: 6.0–7.0) and lowest in Germany (1.7%, 1.5–2.0). Lifetime NMU of GABA analogues was highest in Germany (5.4%, 5.0–5.7) and lowest in France (2.2%, 1.9–2.5) and the UK (2.2%, 1.9–2.6) While no notable difference was observed for France or the UK, there was a higher prevalence of last 12‐month NMU of benzodiazepines compared to GABA analogues in Italy (2.4 times higher) and Spain (3.0 times higher) and a higher prevalence of NMU of GABA analogues compared to benzodiazepines in Germany (2.6 times higher).

Conclusion

This study shows that there is variation in NMU of benzodiazepines and GABA analogues among countries. Of particular interest is the high incidence of GABA analogue NMU in Germany and benzodiazepine NMU in Spain. Further research to identify factors and motivations responsible for the higher prevalence observed are essential to inform public health policies in those countries.
Towards intervention development to increase the uptake of COVID‐19 vaccination among those at high risk: Outlining evidence‐based and theoretically informed future intervention content
Authors: Williams Lynn , Gallant Allyson J. , Rasmussen Susan , Brown Nicholls Louise A. , Cogan Nicola , Deakin Karen , Young David , Flowers Paul
Published: September 2020

Objectives

Development of a vaccine against COVID‐19 will be key to controlling the pandemic. We need to understand the barriers and facilitators to receiving a future COVID‐19 vaccine so that we can provide recommendations for the design of interventions aimed at maximizing public acceptance.

Design

Cross‐sectional UK survey with older adults and patients with chronic respiratory disease.

Methods

During the UK’s early April 2020 ‘lockdown’ period, 527 participants (311 older adults, mean age = 70.4 years; 216 chronic respiratory participants, mean age = 43.8 years) completed an online questionnaire assessing willingness to receive a COVID‐19 vaccine, perceptions of COVID‐19, and intention to receive influenza and pneumococcal vaccinations. A free text response (n = 502) examined barriers and facilitators to uptake. The Behaviour Change Wheel informed the analysis of these responses, which were coded to the Theoretical Domains Framework (TDF). Behaviour change techniques (BCTs) were identified.

Results

Eighty‐six per cent of respondents want to receive a COVID‐19 vaccine. This was positively correlated with the perception that COVID‐19 will persist over time, and negatively associated with perceiving the media to have over‐exaggerated the risk. The majority of barriers and facilitators were mapped onto the ‘beliefs about consequences’ TDF domain, with themes relating to personal health, health consequences to others, concerns of vaccine safety, and severity of COVID‐19.

Conclusions

Willingness to receive a COVID‐19 vaccination is currently high among high‐risk individuals. Mass media interventions aimed at maximizing vaccine uptake should utilize the BCTs of information about health, emotional, social and environmental consequences, and salience of consequences.
Hungarian Roma and musical talent: Minority group members’ experiences of an apparently positive stereotype
Authors: Dobai Anna , Hopkins Nick
Published: September 2020

Minorities do not always welcome apparently positive stereotypes of their group. At first sight, this may appear churlish. However, we show that minority group members’ theorizing on the production and operation of apparently positive stereotypes helps explain such a negative reaction. Reporting interview data (N = 30) gathered with Hungarian Roma, we differentiated several bases for a negative response to the popular stereotype of Roma as possessing a distinctive musical talent. Although participants recognized the stereotype had instrumental value in easing everyday intergroup encounters, they also reported that the stereotype reflected the majority group’s power to define Roma identity; constrained recognition of qualities that they themselves valued; limited their abilities to act on terms that were their own; and could facilitate the reproduction of more negative Roma stereotypes. Taken together, these findings imply our participants saw this apparently positive stereotype as speaking volumes about the majority’s power to define Roma identity without reference to how they themselves defined their identity. We conclude with a discussion of the analytic value of the concept of ‘misrecognition’ in explaining negative responses to a positive stereotype. We also discuss the potential for such an apparently positive stereotype to facilitate improvements in intergroup relations.
Pseudoirreversible slow‐binding inhibition of trypanothione reductase by a protein–protein interaction disruptor
Authors: de Lucio Héctor , Toro Miguel A. , Camarasa María‐José , Velázquez Sonsoles , Gago Federico , Jiménez‐Ruiz Antonio
Published: September 2020

Background and Purpose

Peptide P4 was described as a dimerization disruptor of trypanothione reductase (TryR), a homodimeric enzyme essential for survival of trypanosomatids. Determination of the true inhibitory constant (Ki) for P4 was not achieved because reaction rates continuously decreased with time, even when substrate concentration was kept constant. The aim of this study was to find a suitable kinetic model that could allow characterization of the complex pattern of TryR inhibition caused by P4.

Experimental Approach

After showing the slow‐binding and pseudoirreversible activity of P4 against Leishmania infantum trypanothione reductase (Li‐TryR), analysis of the curvatures of the reaction progress curves at different inhibitor concentrations allowed us to define the apparent inhibitory constants (Kiapp) at five different substrate concentrations. Analysis of the changes in Kiapp values allowed precise definition of the type of inhibition.

Key Results

Li‐TryR inhibition by P4 requires two sequential steps that involve rapid generation of a reversible enzyme–inhibitor complex followed by a pseudoirreversible slow inactivation of the enzyme. Recovery of enzyme activity after inhibitor dissociation is barely detectable. P4 is a non‐competitive pseudoirreversible inhibitor of Li‐ TryR that displays an overall inhibition constant (Ki*) smaller than 0.02 μM.

Conclusion and Implications

Li‐TryRdimer disruption by peptide P4 is a pseudoirreversible time‐dependent process which is non‐competitive with respect to the oxidized trypanothione (TS2) substrate. Therefore, unlike reversible Li‐TryR competitive inhibitors, enzyme inhibition by P4 is not affected by the TS2 accumulation observed during oxidant processes such as the oxidative burst in host macrophages.
Cancer stem cells and their niche in the progression of squamous cell carcinoma
Authors: Oshimori Naoki
Published: September 2020

Most cancers harbor a small population of highly tumorigenic cells known as cancer stem cells (CSCs). Because of their stem cell‐like properties and resistance to conventional therapies, CSCs are considered to be a rational target for curable cancer treatment. However, despite recent advances in CSC research, CSC‐targeted therapies are not as successful as was initially hoped. The proliferative, invasive, and drug‐resistant properties of CSCs are regulated by the tumor microenvironment associated with them, the so‐called CSC niche. Thus, targeting tumor‐promoting cellular crosstalk between CSCs and their niches is an attractive avenue for developing durable therapies. Using mouse models of squamous cell carcinoma (SCC), we have demonstrated that tumor cells responding to transforming growth factor β (TGF‐β) function as drug‐resistant CSCs. The gene expression signature of TGF‐β–responding tumor cells has accelerated the identification of novel pathways that drive invasive tumor progression. Moreover, by focusing on the cytokine milieu and macrophages in the proximity of TGF‐β–responding tumor cells, we recently uncovered the molecular basis of a CSC–niche interaction that emerges during early tumor development. This review article summarizes the specialized tumor microenvironment associated with CSCs and discusses mechanisms by which malignant properties of CSCs are maintained and promoted.
Icaritin‐induced immunomodulatory efficacy in advanced hepatitis B virus‐related hepatocellular carcinoma: Immunodynamic biomarkers and overall survival
Authors: Qin Shu‐Kui , Li Qing , Ming Xu Jian , Liang Jun , Cheng Ying , Fan Ying , Jiang Jun , Ye Hao , Tao Huimin , Li Lian , Zheng Limin , Wei Zhaohui , Li Shu , Meng Kun , Ye Bin , Sun Yan
Published: September 2020

Advanced hepatitis B virus (HBV)‐related hepatocellular carcinoma HCC with poor prognosis is often associated with chronic inflammation, immune tolerance, and marked heterogeneity. The interleukin‐6 (IL‐6)/JAK/STAT3 signal pathways play multiple regulatory roles in modulating inflammation and immunity in cancers. Polarization of myeloid‐derived suppressor cells (MDSCs) is involved in HBV‐related immunosuppression and CD8+ T‐cell activation through ERK/IL‐6/STAT3. Icaritin is a small molecule that has displayed anticancer activities through IL‐6/JAK/STAT3 pathways in tumor cells and immune cells including CD8+ T cells, MDSCs, neutrophils, and macrophages. This study aimed to confirm icaritin immunomodulation in advanced HBV‐related HCC patients with poor prognosis. Immunomodulation of MDSCs was evaluated in BALB/c mice in vivo. Immunomodulation of serum cytokines and a panel of immune checkpoint proteins were assessed in HBV‐related, histologically confirmed HCC patients. Poor prognostic characteristics included HBV infection, bulky tumors, Child‐Pugh B classification, and metastasis. Clinical end‐points included safety, tumor response, and overall survival (OS). Icaritin treatment‐induced dynamics of serum cytokines IL‐6, IL‐8, IL‐10, and tumor necrosis factor‐α, and soluble immune checkpoint proteins TIM3, LAG3, CD28, CD80, and CTLA‐4 were assessed. No grade III/IV treatment‐related adverse events were observed. Time‐to‐progression was significantly associated with the prognostic factors. Improved survival was observed in the advanced HCC patients with dynamic changes of cytokines, immune checkpoint proteins, and immune cells. Median OS (329‐565 days) was significantly correlated with baseline hepatitis B surface antigen positivity, cytokines, tumor neoantigens, and Stenotrophomonas maltophilia infection. Composite biomarker scores of high‐level α‐fetoprotein and T helper type I (Th1)/Th2 cytokines associated with favorable survival warrant further clinical development of icaritin as an alternative immune‐modulatory regimen to treat advanced HCC patients with poor prognosis.
Ribosome assembly factor URB1 contributes to colorectal cancer proliferation through transcriptional activation of ATF4
Authors: Wang Tao , Li Lai‐Yuan , Chen Yi‐Feng , Fu Si‐Wu , Wu Zhi‐Wei , Du Bin‐Bin , Yang Xiong‐Fei , Zhang Wei‐Sheng , Hao Xiang‐Yong , Guo Tian‐Kang
Published: September 2020

Ribosome assembly factor URB1 is essential for ribosome biogenesis. However, its latent role in cancer remains unclear. Analysis of The Cancer Genome Atlas database and clinical tissue microarray staining showed that URB1 expression was upregulated in colorectal cancer (CRC) and prominently related to clinicopathological characteristics. Silencing of URB1 hampered human CRC cell proliferation and growth in vitro and in vivo. Microarray screening, ingenuity pathway analysis, and JASPAR assessment indicated that activating transcription factor 4 (ATF4) and X‐box binding protein 1 (XBP1) are potential downstream targets of URB1 and could transcriptionally interact through direct binding. Silencing of URB1 significantly decreased ATF4 and cyclin A2 (CCNA2) expression in vivo and in vitro. Restoration of ATF4 effectively reversed the malignant proliferation phenotype of URB1‐silenced CRC cells. Dual‐luciferase reporter and ChIP assays indicated that XBP1 transcriptionally activated ATF4 by binding with its promoter region. X‐box binding protein 1 colocalized with ATF4 in the nuclei of RKO cells, and ATF4 mRNA expression was positively regulated by XBP1. This study shows that URB1 contributes to oncogenesis and CRC growth through XBP1‐mediated transcriptional activation of ATF4. Therefore, URB1 could be a potential therapeutic target for CRC.
Gallotannins are non‐specific inhibitors of α‐amylase: Aggregates are the active species taking part in inhibition
Authors: Szabó Kármen , Hámori Csaba , Gyémánt Gyöngyi
Published: September 2020

The versatile biological activity of gallotannins has been investigated for a long time, including their use asα‐amylase inhibitors for the treatment of diabetes and its complications. The effectiveness of gallotannins on a wide range of enzymes refers to promiscuity. We proved that gallotannins are non‐specific promiscuousα‐amylase inhibitors, which exert their effect through their aggregates. A gallotannin of Aleppo oak origin fulfilled all the criteria for aggregators; significant changes could be observed in the IC50values in the presence of Triton™X‐100 detergent (from 2.3 to 110 μg/ml) and after enzyme–inhibitor preincubation (from 2.3 to 0.65 μg/ml). Increasing the enzyme concentration also led to the moderation of the inhibition by gallotannin. In addition, we observed that gallotannin molecules are those, which are involved in aggregation, and discrete protein molecules are adsorbed to the aggregates. This was revealed by the increasing particle size of gallotannin, which became three orders of magnitude higher after 150 min, whereas the size ofα‐amylase remained unchanged. Consequently, gallotannins should be used as anti‐diabetic drugs only if the necessity of higher dose due to their promiscuity is taken into account. Aggregation propensity should not be ignored in case of in vivo applications.
Design, synthesis and anti‐inflammatory study of novel N‐heterocyclic substituted Aloe‐emodin derivatives
Authors: Qiu Xiang , Pei Heying , Ni Hengfan , Su Zhengying , Li Yong , Yang Zhuang , Dou Caixia , Chen Lijuan , Wan Li
Published: September 2020

A novel series of Aloe‐emodin derivatives containing N‐heterocyclic moieties was designed and synthesized. The structure‐activity relationship studies (SARs) indicated that the replacement of hydroxyethyl and benzhydryl piperazine groups could improve efficacy. Compounds 12r and 14a–14c exhibited a higher inhibitory effect on LPS‐induced nitric oxide (NO) production in RAW264.7 macrophages than Aloe‐emodin did. Among them, 12r showed the most potent inhibition with an IC50 value of 5.66 ± 0.47 μM. Further toxicity and pharmacokinetic studies were carried out and 12r was found to be the most active structure with low toxicity risk and good metabolic properties. It could also decrease the levels of IL‐1β, TNF‐α, PGE2 and inhibit the activation of nuclear factor‐κB signalling pathway. Importantly, 12r showed oral bioavailability of up to 55.16% and attenuated the inflammatory symptoms in an ulcerative colitis mouse model in vivo. These results indicate that 12r is suitable for development as an anti‐inflammatory agent.
Behavioral Inhibition in Early Childhood and Adjustment in Late Adolescence in China
Authors: Chen Xinyin , Fu Rui , Li Dan , Chen Huichang , Wang Zhengyan , Wang Li
Published: September 2020

This study examined relations between behavioral inhibition in toddlerhood and social, school, and psychological adjustment in late adolescence in China. Data on behavioral inhibition were collected from a sample of 2‐year‐olds (initial N = 247). Follow‐up data were collected at 7 years for peer relationships and 19 years for adjustment across domains. The results showed that early inhibition positively predicted later social competence and school adjustment. Peer relationships in middle childhood served as a protective factor in the development of depression of inhibited children. The results indicate the distinct functional meaning of behavioral inhibition in the Chinese context from a developmental perspective.
Family Risk and Externalizing Problems in Chilean Children: Mediation by Harsh Parenting and Emotional Support
Authors: Ugarte Elisa , Narea Marigen , Aldoney Daniela , Weissman David G. , Hastings Paul D.
Published: September 2020

Latent class analysis and multigroup mediation were used with 8,860 families in Chile to identify risk groups varying in socioeconomic status, family structure, and maternal depression, to determine whether profiles differed in children’s development of externalizing problems (EP) from 35 to 61 months, and maternal parenting that predicted EP. Four groups were identified: one no‐risk profile and three risk profiles, impoverished and undereducated, depressed and impoverished, and father‐absent and impoverished. All classes differed in EP. Maternal emotional support and harsh parenting were differentially associated with the development of EP across the three risk groups, relative to the low‐risk group. Thus, specific constellations of adversities differentially predicted children’s EP and socialization processes mediating links between risk and EP. Implications are discussed.
Phenotypic and molecular spectrum of pyridoxamine‐5′‐phosphate oxidase deficiency: A scoping review of 87 cases of pyridoxamine‐5′‐phosphate oxidase deficiency
Authors: Alghamdi Malak , Bashiri Fahad A. , Abdelhakim Marwa , Adly Nouran , Jamjoom Dima Z. , Sumaily Khalid M. , Alghanem Bandar , Arold Stefan T.
Published: September 2020

Pyridoxamine‐5′‐phosphate oxidase (PNPO) deficiency is an autosomal recessive pyridoxal 5′‐phosphate (PLP)‐vitamin‐responsive epileptic encephalopathy. The emerging feature of PNPO deficiency is the occurrence of refractory seizures in the first year of life. Pre‐maturity and fetal distress, combined with neonatal seizures, are other associated key characteristics. The phenotype results from a dependency of PLP which regulates several enzymes in the body. We present the phenotypic and genotypic spectrum of (PNPO) deficiency based on a literature review (2002‐2020) of reports (n = 33) of patients with confirmed PNPO deficiency (n = 87). All patients who received PLP (n = 36) showed a clinical response, with a complete dramatic PLP response with seizure cessation observed in 61% of patients. In spite of effective seizure control with PLP, approximately 56% of patients affected with PLP‐dependent epilepsy suffer developmental delay/intellectual disability. There is no diagnostic biomarker, and molecular testing required for diagnosis. However, we noted that cerebrospinal fluid (CSF) PLP was low in 81%, CSF glycine was high in 80% and urinary vanillactic acid was high in 91% of the cases. We observed only a weak correlation between the severity of PNPO protein disruption and disease outcomes, indicating the importance of other factors, including seizure onset and time of therapy initiation. We found that pre‐maturity, the delay in initiation of PLP therapy and early onset of seizures correlate with a poor neurocognitive outcome. Given the amenability of PNPO to PLP therapy for seizure control, early diagnosis is essential.
Homozygous GLUL deletion is embryonically viable and leads to glutamine synthetase deficiency
Authors: Roifman Maian , Niles Kirsten M. , MacNeil Lauren , Blaser Susan , Noor Abdul , Godoy Ruth , van Mieghem Tim , Ryan Greg , Seaward Gareth , Sondheimer Neal , Mercimek‐Andrews Saadet , Schulze Andreas , Hewson Stacy , Ovadia Adi , Chitayat David , Morgen Eric K. , Hojilla Carlo , Kolomietz Elena , Watkins Nicholas , Häberle Johannes , Shannon Patrick
Published: September 2020

Glutamine synthetase (GS) is the enzyme responsible for the biosynthesis of glutamine, providing the only source of endogenous glutamine necessary for several critical metabolic and developmental pathways. GS deficiency, caused by pathogenic variants in the glutamate‐ammonia ligase (GLUL) gene, is a rare autosomal recessive inborn error of metabolism characterized by systemic glutamine deficiency, persistent moderate hyperammonemia, and clinically devastating seizures and multi‐organ failure shortly after birth. The four cases reported thus far were caused by homozygous GLUL missense variants. We report a case of GS deficiency caused by homozygous GLUL gene deletion, diagnosed prenatally and likely representing the most severe end of the spectrum. We expand the known phenotype of this rare condition with novel dysmorphic, radiographic and neuropathologic features identified on post‐mortem examination. The biallelic deletion identified in this case also included the RNASEL gene and was associated with immune dysfunction in the fetus. This case demonstrates that total absence of the GLUL gene in humans is viable beyond the embryonic period, despite the early embryonic lethality found in GLUL animal models.
Developing shared qualitative models for complex systems
Authors: Moon Katie , Browne Nicola K
Published: September 2020

Understanding complex systems is essential to ensure their conservation and effective management. Models commonly support understanding of complex ecological systems and, by extension, their conservation. Modeling, however, is largely a social process constrained by individuals’ mental models (i.e., a small‐scale internal model of how a part of the world works based on knowledge, experience, values, beliefs, and assumptions) and system complexity. To account for both system complexity and the diversity of knowledge of complex systems, we devised a novel way to develop a shared qualitative complex system model. We disaggregated a system (carbonate coral reefs) into smaller subsystem modules that each represented a functioning unit, about which an individual is likely to have more comprehensive knowledge. This modular approach allowed us to elicit an individual mental model of a defined subsystem for which the individuals had a higher level of confidence in their knowledge of the relationships between variables. The challenge then was to bring these subsystem models together to form a complete, shared model of the entire system, which we attempted through 4 phases: develop the system framework and subsystem modules; develop the individual mental model elicitation methods; elicit the mental models; and identify and isolate differences for exploration and identify similarities to cocreate a shared qualitative model. The shared qualitative model provides opportunities to develop a quantitative model to understand and predict complex system change.
Relative effects of recreational activities on a temperate terrestrial wildlife assemblage
Authors: Naidoo Robin , Burton A. Cole
Published: September 2020

Outdoor recreation is one of the fastest growing economic sectors in the world and provides many benefits to people. Assessing possible negative impacts of recreation is nevertheless important for sustainable management. Here, we used camera traps to assess relative effects of various recreational activities—as compared to each other and to environmental conditions—on a terrestrial wildlife assemblage in British Columbia, Canada. Across 13 species, only two negative associations between recreational activities and wildlife detections were observed at weekly scales: mountain biking on moose and grizzly bears. However, finer‐scale analysis showed that all species avoided humans on trails, with avoidance strongest for mountain biking and motorized vehicles. Our results imply that environmental factors generally shaped broad‐scale patterns of wildlife use, but highlight that recreational activities also have detectable impacts. These impacts can be monitored using the same camera‐trapping techniques that are commonly used to monitor wildlife assemblages.
Risk Assessment of Drug‐Induced Long QT Syndrome for Some COVID‐19 Repurposed Drugs
Authors: Michaud Veronique , Dow Pamela , Al Rihani Sweilem B. , Deodhar Malavika , Arwood Meghan , Cicali Brian , Turgeon Jacques
Published: September 2020

The risk‐benefit ratio associated with the use of repurposed drugs to treat severe acute respiratory syndrome‐coronavirus 2 (SARS‐CoV‐2)‐related infectious coronavirus disease 2019 (COVID‐19) is complicated because benefits are awaited, not proven. A thorough literature search was conducted to source information on the pharmacological properties of 5 drugs and 1 combination (azithromycin, chloroquine, favipiravir, hydroxychloroquine, remdesivir, and lopinavir/ritonavir) repurposed to treat COVID‐19. A risk assessment of drug‐induced long QT syndrome (LQTS) associated with COVID‐19 repurposed drugs was performed and compared with 23 well‐known torsadogenic and 10 low torsadogenic risk compounds. Computer calculations were performed using pharmacokinetic and pharmacodynamic data, including affinity to block the rapid component of the delayed rectifier cardiac potassium current (IKr) encoded by the human ether‐a‐go‐go gene (hERG), propensity to prolong cardiac repolarization (QT interval) and cause torsade de pointes (TdP). Seven different LQTS indices were calculated and compared. The US Food and Drug Administration (FDA) Adverse Event Reporting System (FAERS) database was queried with specific key words relating to arrhythmogenic events. Estimators of LQTS risk levels indicated a very high or moderate risk for all COVID‐19 repurposed drugs with the exception for azithromycin, although cases of TdP have been reported with this drug. There was excellent agreement among the various indices used to assess risk of drug‐induced LQTS for the 6 repurposed medications and 23 torsadogenic compounds. Based on our results, monitoring of the QT interval shall be performed when some COVID‐19 repurposed drugs are used, as such monitoring is possible for hospitalized patients or with the use of biodevices for outpatients.
Comparison of the quality of the microwave cell‐block method with the conventional cell‐block method in processing body fluid samples
Authors: Jayakumar Chippy , Sreerekha Jinkala , Gochhait Debasis , Perumal Prasanna Venkadesa , Kanungo Srikanta , Siddaraju Neelaiah , Gochhait Samanyoya , Ramatchandrin Lakshmi
Published: September 2020

Introduction

Conventional cell blocks (CCB) prepared from cytological specimens are very useful but the method is relatively time‐consuming. Suitable modifications in cell‐block techniques are beneficial for improving the turnaround time. We share our experience of a rapid microwave cell‐block (MCB) technique.

Aim and objectives

To study the quality of routine and immunohistochemical (IHC) staining of cell‐block sections from serous body fluids prepared by the MCB technique compared with the CCB technique.

Method

A total of 177 serous body fluid samples were processed by routine centrifugation technique, and the sediments were used for cell‐block preparations by both conventional and rapid microwave methods. Cell‐block sections were stained with haematoxylin and eosin stain. Haematoxylin and eosin staining quality was analysed using three parameters (cellularity, morphology and staining intensity). IHC for epithelial membrane antigen and calretinin were also performed, and the quality of staining was evaluated on 62/177 samples. Results were analysed using appropriate statistical tests.

Results

The time taken for processing cell blocks by the MCB method was 1 hour and 18 minutes compared to 13 hours and 45 minutes by CCB. The quality of sections by both methods showed good agreement for cellularity and intensity of staining, and moderate agreement for morphology. A 100% concordance was noted for distinguishing benign and malignant samples on morphology as well as with IHC stain results.

Conclusion

Although the techniques are comparable in terms of quality of routine and IHC staining, we recommend using the MCB technique due to its short turnaround time.
Association between asthma and cardiovascular disease
Authors: Wee Jee Hye , Park Min Woo , Min Chanyang , Byun Soo Hwan , Park Bumjung , Choi Hyo Geun
Published: September 2020

Background

Epidemiological studies on the association between asthma and cardiovascular disease have reported conflicting results. This cross‐sectional study evaluated the association between asthma and ischaemic heart disease (IHD)/stroke in Korean adults.

Materials and methods

Data from the Korean Genome and Epidemiology Study‐Health Examinees were used. Among 173 209 participants, 3162 asthmatic and 159 408 control participants were selected. Histories of asthma, IHD and stroke were obtained. Participants were categorized according to their current status of asthma management: 'well‐controlled', 'being treated', and 'not being treated'. Crude and adjusted (age, gender, body mass index, income, smoking, alcohol consumption, hypertension, diabetes, dyslipidaemia and nutritional intake) odds ratios (ORs) for IHD and stroke in asthmatic patients were analysed using a multiple logistic regression model.

Results

Participants with asthma reported a significantly higher prevalence of IHD (6.0% vs 3.0%) and stroke (2.3% vs 1.4%) than those without asthma (P < .001). Asthmatic participants had a higher OR (1.46, 95% confidence interval [CI] = 1.251‐1.71, P < .001) for IHD than those without asthma. The association between asthma and IHD was significant only in patients aged ≥53 years (men: adjusted OR = 1.31, 95% CI = 1.01‐1.70, P = .046; women: adjusted OR = 1.64, 95% CI = 1.32‐2.03, P < .001) according to age and sex and in the 'not being treated' asthma group (adjusted OR = 1.47, 95% CI = 1.14‐1.91, P = .003) according to the asthma management status. Stroke was not significantly associated with asthma (adjusted OR = 1.17, 95% CI = 0.92‐1.48, P = .203) in the adjusted model and all subgroup analyses.

Conclusion

Asthma was associated with IHD, mainly in older patients and untreated asthma patients, but not with stroke.
Roles of peer specialists and use of mental health services among youth with serious mental illness
Authors: Ojeda Victoria D. , Jones Nev , Munson Michelle R. , Berliant Emily , Gilmer Todd P.
Published: September 2020

Aim

To examine whether roles of peer specialists affect service use among Black, Latinx and White youth ages 16‐24 with serious mental illness (SMI) in Los Angeles and San Diego Counties.

Methods

Administrative data from 2015 to 2018 was used to summarize service use among 6329 transition age youth age 16‐24 with SMI who received services from 76 outpatient public mental health programs with peer specialists on staff. Roles of peer specialists were assessed via a program survey. Generalized linear models were used to assess the relationship between peer specialist characteristics and service use outcomes (ie, outpatient and inpatient).

Results

Having a transition age youth peer specialist on staff (vs older peer specialists) and having peer specialists that provide four or more services (vs fewer services) was associated with an increase in annual outpatient visits in both counties (P = <.001 each). In Los Angeles County, having three or more peer specialist trainings (vs fewer trainings) was associated with lower use of inpatient services (P < .001). In San Diego County, having a transition age youth peer specialist and peer specialists that provide four or more services was associated with lower use of inpatient services (P < .001 each).

Conclusions

Types of peer support and number of types of peer services were associated with mental health service utilization. Detailed examination of the roles of peer specialists is merited to identify the specific pathways that improve outcomes.
POEMS syndrome: A multisystem clonal disorder
Authors: Ali Tayyaba , Qazilbash Muzaffar H.
Published: September 2020

Polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, and skin changes (POEMS) syndrome is a rare condition defined by monoclonal plasma cell disorder, peripheral neuropathy, and other systemic symptoms. The pathophysiology of POEMS syndrome is unknown, but the overproduction of vascular endothelial growth factor (VEGF) appears to be an important contributory element. The diagnosis of POEMS syndrome requires the presence of both mandatory criteria (ie, polyneuropathy and a monoclonal plasma cell disorder), at least one major criterion (ie, osteosclerotic bone lesions, Castleman disease, or elevated serum or plasma levels of vascular endothelial growth factor), and at least one of the six minor criteria. POEMS syndrome lacks a standard treatment, but patients with limited sclerotic bone lesions are typically treated with radiation therapy. In contrast, those with widespread lesions receive chemotherapy and hematopoietic stem cell transplantation.
Arc/Arg3.1 function in long‐term synaptic plasticity: Emerging mechanisms and unresolved issues
Authors: Zhang Hongyu , Bramham Clive R.
Published: September 2020

Arc (activity‐regulated cytoskeleton‐associated protein) is posited as a critical regulator of long‐term synaptic plasticity at excitatory synapses, including long‐term potentiation, long‐term depression, inverse synaptic tagging and homoeostatic scaling, with pivotal roles in memory and postnatal cortical development. However, the mechanisms underlying the bidirectional regulation of synaptic strength are poorly understood. Here we review evidence from different plasticity paradigms, highlight outstanding issues and discuss stimulus‐specific mechanisms that dictate Arc function. We propose a model in which Arc bidirectionally controls synaptic strength by coordinate regulation of AMPA‐type glutamate receptor (AMPAR) trafficking and actin cytoskeletal dynamics in dendritic spines. Key to this model, Arc is proposed to function as an activity‐dependent regulator of AMPAR lateral membrane diffusion and trapping at synapses.
Cognitive‐motor interference in the wild: Assessing the effects of movement complexity on task switching using mobile EEG
Authors: Reiser Julian E. , Wascher Edmund , Rinkenauer Gerhard , Arnau Stefan
Published: September 2020

Adaptively changing between different tasks while in locomotion is a fundamental prerequisite of modern daily life. The cognitive processes underlying dual tasking have been investigated extensively using EEG. Due to technological restrictions, however, this was not possible for dual‐task scenarios including locomotion. With new technological opportunities, this became possible and cognitive‐motor interference can be studied, even in outside‐the‐lab environments. In the present study, participants carried out a cognitive‐motor interference task as they responded to cued, auditory task‐switch stimuli while performing locomotive tasks with increasing complexity (standing, walking, traversing an obstacle course). We observed increased subjective workload ratings as well as decreased behavioural performance for increased movement complexity and cognitive task difficulty. A higher movement load went along with a decrease of parietal P2, N2 and P3 amplitudes and frontal Theta power. A higher cognitive load, on the other hand, was reflected by decreased frontal CNV amplitudes. Additionally, a connectivity analysis using inter‐site phase coherence revealed that higher movement as well as cognitive task difficulty had an impairing effect on fronto‐parietal connectivity. In conclusion, subjective ratings, behavioural performance and electrophysiological results indicate that less cognitive resources were available to be deployed towards the execution of the cognitive task when in locomotion compared to standing still. Connectivity results also show a scarcity of attentional resources when switching a task during the highest movement complexity condition. Summarized, all findings indicate a central role of attentional control regarding cognitive‐motor dual tasking and an inherent limitation of cognitive resources.
Recurrence quantification analysis of dynamic brain networks
Authors: Lopes Marinho A. , Zhang Jiaxiang , Krzemiński Dominik , Hamandi Khalid , Chen Qi , Livi Lorenzo , Masuda Naoki
Published: September 2020

Evidence suggests that brain network dynamics are a key determinant of brain function and dysfunction. Here we propose a new framework to assess the dynamics of brain networks based on recurrence analysis. Our framework uses recurrence plots and recurrence quantification analysis to characterize dynamic networks. For resting‐state magnetoencephalographic dynamic functional networks (dFNs), we have found that functional networks recur more quickly in people with epilepsy than in healthy controls. This suggests that recurrence of dFNs may be used as a biomarker of epilepsy. For stereo electroencephalography data, we have found that dFNs involved in epileptic seizures emerge before seizure onset, and recurrence analysis allows us to detect seizures. We further observe distinct dFNs before and after seizures, which may inform neurostimulation strategies to prevent seizures. Our framework can also be used for understanding dFNs in healthy brain function and in other neurological disorders besides epilepsy.