bluuebunny/crossref_metadata_2025 huggingface dataset:
Use of dual-flow bioreactor to develop a simplified model of nervous-cardiovascular systems crosstalk: A preliminary assessment
Authors: Marchesi Nicoletta , Barbieri Annalisa , Fahmideh Foroogh , Govoni Stefano , Ghidoni Alice , Parati Gianfranco , Vanoli Emilio , Pascale Alessia , Calvillo Laura
Published: November 2020

Chronic conditions requiring long-term rehabilitation therapies, such as hypertension, stroke, or cancer, involve complex interactions between various systems/organs of the body and mutual influences, thus implicating a multiorgan approach. The dual-flow IVTech LiveBox2 bioreactor is a recently developed inter-connected dynamic cell culture model able to mimic organ crosstalk, since cells belonging to different organs can be connected and grown under flow conditions in a more physiological environment. This study aims to setup for the first time a 2-way connected culture of human neuroblastoma cells, SH-SY5Y, and Human Coronary Artery Smooth Muscle Cells, HCASMC through a dual-flow IVTech LiveBox2 bioreactor, in order to represent a simplified model of nervous-cardiovascular systems crosstalk, possibly relevant for the above-mentioned diseases. The system was tested by treating the cells with 10nM angiotensin II (AngII) inducing PKCβII/HuR/VEGF pathway activation, since AngII and PKCβII/HuR/VEGF pathway are relevant in cardiovascular and neuroscience research. Three different conditions were applied: 1- HCASMC and SH-SY5Y separately seeded in petri dishes (static condition); 2- the two cell lines separately seeded under flow (dynamic condition); 3- the two lines, seeded in dynamic conditions, connected, each maintaining its own medium, with a membrane as interface for biohumoral changes between the two mediums, and then treated. We detected that only in condition 3 there was a synergic AngII-dependent VEGF production in SH-SY5Y cells coupled to an AngII-dependent PKCβII/HuR/VEGF pathway activation in HCASMC, consistent with the observed physiological responsein vivo. HCASMC response to AngII seems therefore to be generated by/derived from the reciprocal cell crosstalk under the dynamic inter-connection ensured by the dual flow LiveBox 2 bioreactor. This system can represent a useful tool for studying the crosstalk between organs, helpful for instance in rehabilitation research or when investigating chronic diseases; further, it offers the advantageous opportunity of cultivating each cell line in its own medium, thus mimicking, at least in part, distinct tissuemilieu.
Gene expression profiling in human neutrophils after infection with Acinetobacter baumannii in vitro
Authors: Lázaro-Díez María , Chapartegui-González Itziar , Suberbiola Borja , Ocejo-Vinyals J. Gonzalo , López-Hoyos Marcos , Ramos-Vivas José
Published: November 2020

Acinetobacter baumannii is a Gram negative nosocomial pathogen that has acquired increasing worldwide notoriety due to its high antibiotic resistance range and mortality rates in hospitalized patients. Therefore, it is necessary to better understand key aspects of A. baumannii pathogenesis such as host-pathogen interactions. In this report, we analyzed both gene expression and cytokine production by human neutrophils infected with A. baumannii. Our assays reveal a proinflammatory response of neutrophils after A. baumannii infection, since intracellular transcription of effector proteins such as COX-2, transcription factors, and proinflammatory cytokines resulted significantly upregulated in neutrophils infected by A. baumannii, compared with unstimulated human neutrophils. Translation and release of CXCL-8, IL-1β and TNF-α by neutrophils was confirmed by protein quantification in culture supernatants. Results obtained in this report reinforce the importance of human neutrophils in controlling A. baumannii infections but also emphasize the proinflammatory nature of these host-pathogen interactions as a target for future immunomodulatory therapies.
Enhanced mitophagy in bronchial fibroblasts from severe asthmatic patients
Authors: Ramakrishnan Rakhee K. , Bajbouj Khuloud , Hachim Mahmood Y. , Mogas Andrea K. , Mahboub Bassam , Olivenstein Ronald , Hamoudi Rifat , Halwani Rabih , Hamid Qutayba
Published: November 2020

Background

Sub-epithelial fibrosis is a characteristic feature of airway remodeling in asthma which correlates with disease severity. Current asthma medications are ineffective in treating fibrosis. In this study, we aimed to investigate the mitochondrial phenotype in fibroblasts isolated from airway biopsies of non-asthmatic and severe asthmatic subjects by examining mitophagy as a mechanism contributing to fibroblast persistence and thereby, fibrosis in severe asthma.

Methods

Bioinformatics analysis of publicly available transcriptomic data was performed to identify the top enriched pathways in asthmatic fibroblasts. Endogenous expression of mitophagy markers in severe asthmatic and non-asthmatic fibroblasts was determined using qRT-PCR, western blot and immunofluorescence. Mitophagy flux was examined by using lysosomal protease inhibitors, E64d and pepstatin A. Mitochondrial membrane potential and metabolic activity were also evaluated using JC-1 assay and MTT assay, respectively.

Results

Bioinformatics analysis revealed the enrichment of Pink/Parkin-mediated mitophagy in asthmatic fibroblasts compared to healthy controls. In severe asthmatic fibroblasts, the differential expression of mitophagy genes, PINK1 and PRKN, was accompanied by the accumulation of PINK1, Parkin and other mitophagy proteins at baseline. The further accumulation of endogenous LC3BII, p62 and PINK1 in the presence of E64d and pepstatin A in severe asthmatic fibroblasts reinforced their enhanced mitophagy flux. Significantly reduced mitochondrial membrane potential and metabolic activity were also demonstrated at baseline confirming the impairment in mitochondrial function in severe asthmatic fibroblasts. Interestingly, these fibroblasts displayed neither an apoptotic nor senescent phenotype but a pro-fibrotic phenotype with an adaptive survival mechanism triggered by increased AMPKα phosphorylation and mitochondrial biogenesis.

Conclusions

Our results demonstrated a role for mitophagy in the pathogenesis of severe asthma where the enhanced turnover of damaged mitochondria may contribute to fibrosis in severe asthma by promoting the persistence and pro-fibrotic phenotype of fibroblasts.
Statistical tests under Dallal’s model: Asymptotic and exact methods
Authors: Li Zhiming , Ma Changxing , Ai Mingyao
Published: November 2020

This paper proposes asymptotic and exact methods for testing the equality of correlations for multiple bilateral data under Dallal’s model. Three asymptotic test statistics are derived for large samples. Since they are not applicable to small data, several conditional and unconditional exact methods are proposed based on these three statistics. Numerical studies are conducted to compare all these methods with regard to type I error rates (TIEs) and powers. The results show that the asymptotic score test is the most robust, and two exact tests have satisfactory TIEs and powers. Some real examples are provided to illustrate the effectiveness of these tests.
Unraveling the mechanism of recognition of the 3’ splice site of the adenovirus major late promoter intron by the alternative splicing factor PUF60
Authors: Hsiao Hsin-hao T. , Crichlow Gregg V. , Murphy James W. , Folta-Stogniew Ewa J. , Lolis Elias J. , Braddock Demetrios T.
Published: November 2020

Pre-mRNA splicing is critical for achieving required amounts of a transcript at a given time and for regulating production of encoded protein. A given pre-mRNA may be spliced in many ways, or not at all, giving rise to multiple gene products. Numerous splicing factors are recruited to pre-mRNA splice sites to ensure proper splicing. One such factor, the 60 kDa poly(U)-binding splicing factor (PUF60), is recruited to sites that are not always spliced, but rather function as alternative splice sites. In this study, we characterized the interaction of PUF60 with a splice site from the adenovirus major late promoter (the AdML 3' splice site, AdML3’). We found that the PUF60–AdML3’ dissociation constants are in the micromolar range, with the binding affinity predominantly provided by PUF60’s two central RNA recognition motifs (RRMs). A 1.95 Å crystal structure of the two PUF60 RRMs in complex with AdML3’ revealed a dimeric organization placing two stretches of nucleic acid tracts in opposing directionalities, which can cause looping of nucleic acid and explain how PUF60 affects pre-mRNA geometry to effect splicing. Solution characterization of this complex by light-scattering and UV/Vis spectroscopy suggested a potential 2:1 (PUF602:AdML3’) stoichiometry, consistent with the crystal structure. This work defines the sequence specificity of the alternative splicing factor PUF60 at the pre-mRNA 3’ splice site. Our observations suggest that control of pre-mRNA directionality is important in the early stage of spliceosome assembly, and advance our understanding of the molecular mechanism by which alternative and constitutive splicing factors differentiate among 3’ splice sites.
The Robson classification for caesarean section—A proposed method based on routinely collected health data
Authors: Triep Karen , Torbica Nenad , Raio Luigi , Surbek Daniel , Endrich Olga
Published: November 2020

Background

With an increasing rate of caesarean sections as well as rising numbers of multiple pregnancies, valid classifications for benchmarking are needed. The Robson classification provides a method to group cases with caesarean section in order to assess differences in outcome across regions and sites. In this study we set up a novel method of classification by using routinely collected health data. We hypothesize i that routinely collected health data can be used to apply complex medical classifications and ii that the Robson classification is capable of classifying mothers and their corresponding newborn into meaningful groups with regard to outcome.

Methods and findings

The study was conducted at the coding department and the department of obstetrics and gynecology Inselspital, University Hospital of Bern, Switzerland. The study population contained inpatient cases from 2014 until 2017. Administrative and health data were extracted from the Data Warehouse. Cases were classified by a Structured Query Language code according to the Robson criteria using data from the administrative system, the electronic health record and from the laboratory system. An automated query to classify the cases according to Robson could be implemented and successfully validated. A linkage of the mother’s class to the corresponding newborn could be established. The distribution of clinical indicators was described. It could be shown that the Robson classes are associated to outcome parameters and case related costs.

Conclusions

With this study it could be demonstrated, that a complex query on routinely collected health data would serve for medical classification and monitoring of quality and outcome. Risk-stratification might be conducted using this data set and should be the next step in order to evaluate the Robson criteria and outcome. This study will enhance the discussion to adopt an automated classification on routinely collected health data for quality assurance purposes.
Cardiovascular disease risk factors in Spain: A comparison of native and immigrant populations
Authors: Rodriguez-Alvarez Elena , Lanborena Nerea , Borrell Luisa N.
Published: November 2020

Cardiovascular disease (CDV) risk factors are highly prevalent among adults with low social class in Spain. However, little is known on how these factors are distributed in the immigrant population, a socio-economic disadvantaged population. Thus, this study aims to examine inequalities in CVD risk factors among immigrant and native populations. We conducted a cross-sectional study using data from the Spanish National Health Survey 2017 and used log-binomial regression to quantify the association of immigrant status on CVD risk factors among adults aged 25–64 years. The probabilities of having at least three CVD risk factors were higher for immigrants from Eastern Europe (PR: 1.25; 95% CI: 1.15–1.35) and lower for immigrants from Africa (PR: 0.79; 95% CI: 0.69–0.89) when compared with natives. The association of immigrant status and CVD risk factors varies with educational attainment (p-interaction = 0.001). Immigrants from Eastern Europe with low educational attainment have a higher probability of having at least three CVD risk factors compared with their native counterparts. In contrast, immigrants from Africa and Latin America with low educational attainment had a protective effect against having at least three CVD risk relative to natives. Health prevention and promotion strategies to reduce the burden of CVD taking should account for educational attainment given its differential effect among the immigrant population in Spain.
A new Bacillus thuringiensis protein for Western corn rootworm control
Authors: Yin Yong , Flasinski Stanislaw , Moar William , Bowen David , Chay Cathy , Milligan Jason , Kouadio Jean-Louis , Pan Aihong , Werner Brent , Buckman Karrie , Zhang Jun , Mueller Geoffrey , Preftakes Collin , Hibbard Bruce E. , Price Paula , Roberts James
Published: November 2020

The Western corn rootworm (WCR) Diabrotica virgifera virgifera LeConte is one of the most economically important insect pests in North America. Since 2003, transgenic maize expressing WCR-active proteins from Bacillus thuringiensis (Bt) have been widely adopted as the main approach to controlling WCR in the U.S. However, the emergence of field resistance to the Bt proteins in current commercial products has been documented in recent years, highlighting the need to develop additional tools for controlling this devasting pest. Here we report the discovery of Vpb4Da2 (initially assigned as Vip4Da2), a new insecticidal protein highly selective against WCR, through high-throughput genome sequencing of a Bt strain sourced from grain dust samples collected in the eastern and central regions of the US. Vpb4Da2 contains a sequence and domain signature distinct from families of other WCR-active proteins. Under field conditions, transgenic maize expressing Vpb4Da2 demonstrates commercial-level (at or below NIS 0.25) root protection against WCR, and reduces WCR beetle emergence by ≥ 97%. Our studies also conclude that Vpb4Da2 controls WCR populations that are resistant to WCR-active transgenic maize expressing Cry3Bb1, Cry34Ab1/Cry35Ab1 (reassigned as Gpp34Ab1/Tpp35Ab1), or DvSnf7 RNA. Based on these findings, Vpb4Da2 represents a valuable new tool for protecting maize against WCR.
Cloning, expression and purification of recombinant dermatopontin in Escherichia coli
Authors: Seetaraman Amritha Trikkur Madom , Mahajan Shubham , Subramaniam Kumar , Chandramohan Yamini , Dhanasekaran Anuradha
Published: November 2020

Dermatopontin (DPT) is an extracellular matrix (ECM) protein with diversified pharmaceutical applications. It plays important role in cell adhesion/migration, angiogenesis and ECM maintenance. The recombinant production of this protein will enable further exploration of its multifaceted functions. In this study, DPT protein has been expressed inEscherichia coli (E.coli)aiming at cost effective recombinant production. TheE.coliGJ1158 expression system was transformed with constructed recombinant vector (pRSETA-DPT) and protein was expressed as inclusion bodies on induction with NaCl. The inclusion bodies were solubilised in urea and renaturation of protein was done by on-column refolding procedure in Nickel activated Sepharose column. The refolded Histidine-tagged DPT protein was purified and eluted from column using imidazole and its purity was confirmed by analytical techniques. The biological activity of the protein was confirmed by collagen fibril assay, wound healing assay and Chorioallantoic Membrane (CAM) angiogenesis assay on comparison with standard DPT. The purified DPT was found to enhance the collagen fibrillogenesis process and improved the migration of human endothelial cells. About 73% enhanced wound closure was observed in purified DPT treated endothelial cells as compared to control. The purified DPT also could induce neovascularisation in the CAM model. At this stage, scaling up the production process for DPT with appropriate purity and reproducibility will have a promising commercial edge.
Bone marrow stromal cells induce an ALDH+ stem cell-like phenotype and enhance therapy resistance in AML through a TGF-β-p38-ALDH2 pathway
Authors: Yuan Bin , El Dana Fouad , Ly Stanley , Yan Yuanqing , Ruvolo Vivian , Shpall Elizabeth J. , Konopleva Marina , Andreeff Michael , Battula Venkata Lokesh
Published: November 2020

The bone marrow microenvironment (BME) in acute myeloid leukemia (AML) consists of various cell types that support the growth of AML cells and protect them from chemotherapy. Mesenchymal stromal cells (MSCs) in the BME have been shown to contribute immensely to leukemogenesis and chemotherapy resistance in AML cells. However, the mechanism of stroma-induced chemotherapy resistance is not known. Here, we hypothesized that stromal cells promote a stem-like phenotype in AML cells, thereby inducing tumorigenecity and therapy resistance. To test our hypothesis, we co-cultured AML cell lines and patient samples with BM-derived MSCs and determined aldehyde dehydrogenase (ALDH) activity and performed gene expression profiling by RNA sequencing. We found that the percentage of ALDH+ cells increased dramatically when AML cells were co-cultured with MSCs. However, among the 19 ALDH isoforms, ALDH2 and ALDH1L2 were the only two that were significantly upregulated in AML cells co-cultured with stromal cells compared to cells cultured alone. Mechanistic studies revealed that the transforming growth factor-β1 (TGF-β1)-regulated gene signature is activated in AML cells co-cultured with MSCs. Knockdown of TGF-β1 in BM-MSCs inhibited stroma-induced ALDH activity and ALDH2 expression in AML cells, whereas treatment with recombinant TGF-β1 induced the ALDH+ phenotype in AML cells. We also found that TGF-β1-induced ALDH2 expression in AML cells is mediated by the non-canonical pathway through the activation of p38. Interestingly, inhibition of ALDH2 with diadzin and CVT-10216 significantly inhibited MSC-induced ALDH activity in AML cells and sensitized them to chemotherapy, even in the presence of MSCs. Collectively, BM stroma induces ALDH2 activity in AML cells through the non-canonical TGF-β pathway. Inhibition of ALDH2 sensitizes AML cells to chemotherapy.
Optimal path test data generation based on hybrid negative selection algorithm and genetic algorithm
Authors: Mohi-Aldeen Shayma Mustafa , Mohamad Radziah , Deris Safaai
Published: November 2020

Path testing is the basic approach of white box testing and the main approach to solve it by discovering the particular input data of the searching space to encompass the paths in the software under test. Due to the increasing software complexity, exhaustive testing is impossible and computationally not feasible. The ultimate challenge is to generate suitable test data that maximize the coverage; many approaches have been developed by researchers to accomplish path coverage. The paper suggested a hybrid method (NSA-GA) based on Negative Selection Algorithm (NSA) and Genetic Algorithm (GA) to generate an optimal test data avoiding replication to cover all possible paths. The proposed method modifies the generation of detectors in the generation phase of NSA using GA, as well as, develops a fitness function based on the paths’ prioritization. Different benchmark programs with different data types have been used. The results show that the hybrid method improved the coverage percentage of the programs’ paths, even for complicated paths and its ability to minimize the generated number of test data and enhance the efficiency even with the increased input range of different data types used. This method improves the effectiveness and efficiency of test data generation and maximizes search space area, increasing percentage of path coverage while preventing redundant data.
Predicting takeover response to silent automated vehicle failures
Authors: Mole Callum , Pekkanen Jami , Sheppard William , Louw Tyron , Romano Richard , Merat Natasha , Markkula Gustav , Wilkie Richard
Published: November 2020

Current and foreseeable automated vehicles are not able to respond appropriately in all circumstances and require human monitoring. An experimental examination of steering automation failure shows that response latency, variability and corrective manoeuvring systematically depend on failure severity and the cognitive load of the driver. The results are formalised into a probabilistic predictive model of response latencies that accounts for failure severity, cognitive load and variability within and between drivers. The model predicts high rates of unsafe outcomes in plausible automation failure scenarios. These findings underline that understanding variability in failure responses is crucial for understanding outcomes in automation failures.
Disentangling comorbidity in chronic pain: A study in primary health care settings from India
Authors: Desai Geetha , T. S. Jaisoorya , G. Sunil Kumar , L. Manoj , G. R. Gokul , Bajaj Aakash , K. Thennarasu , Chaturvedi Santosh K.
Published: November 2020

Objectives

The study examined the prevalence, sociodemographic, and clinical correlates of chronic pain among primary care patients in the state of Kerala, India. It also examined the patterns and relationships of chronic physical and mental health conditions with chronic pain.

Methods

This study is a cross-sectional survey conducted among 7165 adult patients selected randomly by a multi-stage stratified design from 71 primary health centers. The questionnaires administered included Chronic pain screening questionnaire, self-reported Chronic physical health condition checklist, Patient Health Questionnaire-SADS, The Alcohol Use Disorders Identification Test, Fagerström Test for Nicotine Dependence, WHO Disability Assessment Schedule and WHOQOL- BREF for Quality/Satisfaction with Life. The prevalence and comorbid patterns of chronic pain were determined. Logistic regression analysis and generalized linear mixed-effects model was employed to examine the relationship of chronic pain to socio-demographic variables and examined physical and mental health conditions.

Results

A total of 1831 (27%) patients reported chronic pain. Among those with chronic pain, 28.3% reported no co-occurring chronic mental or physical illness, 35.3% reported one, and 36.3% reported multi-morbidity. In the multivariate analysis, patients with chronic pain when compared to those without had higher odds of being older, female, having lower education, not living with their family, greater disability, and poor satisfaction with life. Chronic pain was independently associated with both medical (hypertension, diabetes mellitus, tuberculosis, arthritis, and other medical illnesses) and mental health conditions (depressive disorders, anxiety disorders, and tobacco dependence). It showed a varying strength of association and additive effect with increasing number of co-occurring physical and mental illnesses.

Conclusions

Chronic pain is a common condition among primary care attendees associated with significant burden of medical and mental health comorbidity. The findings highlight the need to incorporate treatment models that will ensure appropriate management to improve outcomes within the resource constraints.
High prevalence of undiagnosed hypertension among men in North Central Nigeria: Results from the Healthy Beginning Initiative
Authors: Banigbe Bolanle Feyisayo , Itanyi Ijeoma Uchenna , Ofili Elizabeth Odilile , Ogidi Amaka Grace , Patel Dina , Ezeanolue Echezona Edozie
Published: November 2020

Background

The prevalence of hypertension in Nigeria is high and growing. The burden and risk factor distribution also vary by geographical zone. Information about prevalence, risk factors and disease status awareness are needed to guide evidence based public health response at the national and sub- national levels.

Purpose

This paper describes the prevalence of hypertension and its correlates, as well as hypertension status awareness among men in North Central, Nigeria.

Methods

A cross sectional survey was administered to male partners of pregnant women participating in the Healthy Beginning Initiative program from 2016–2018. Information on socio-demographic characteristics, risk factors, physical measurement and blood pressure readings were collected using a standardized protocol. Data was analyzed with simple and multiple logistic regression.

Results

The 6,538 men had a median age of 31 years [IQR: 26–37]. The prevalence of hypertension was 23.3% (95% CI: 22.3%-24.4%), while 46.7% had prehypertension. The odds of hypertension was associated with increasing age (OR:1.02, CI:1.01–1.03), being overweight (aOR:1.5,CI:1.3–1.8), being obese (aOR:2.6,CI:2.0–3.3), living in an urban area (aOR:1.6,CI:1.2–2.1), and alcohol use in the 30 days prior (aOR:1.2,CI:1.1–1.4). Overall, 4.5% (297/6,528) of participants had ever been told they have hypertension. Among the 23.3% (1,527/6,528) with hypertension, 7.1% (109/1,527) were aware of their disease status. Men aged 41–50 years (aOR: 1.8, CI: 1.0–3.3), and > 50 years (aOR: 2.2, CI: 1.1–4.3), had higher odds disease status awareness. Living in an urban area was associated with lower odds (aOR: 0.2, CI: 0.03–0.7) of hypertension status awareness.

Conclusion

This study showed that hypertension is already a significant public health burden in this population and that disease awareness level is very low. Alcohol use and obesity were associated with hypertension, highlighting some modifiable cardiovascular disease risk factors that are prevalent in the study population. Taken together, these findings can inform the design of interventions for primary and secondary cardiovascular disease prevention in Nigeria and similar settings.
The relationship between health mindsets and health protective behaviors: An exploratory investigation in a convenience sample of American Indian adults during the COVID-19 pandemic
Authors: John-Henderson Neha A. , Mueller Claudia M.
Published: November 2020

The Novel-coronavirus disease-2019 (COVID-2019) outbreak was declared a national emergency on March 13, 2020. To reduce the spread of the virus, Americans were asked to physically distance and to increase disinfecting behaviors such as hand washing. Previous research indicates that one’s mindset about health, or the degree to which they view health as fixed or modifiable, influences health behaviors. Current data indicates that American Indians (AIs) are at greater risk for COVID-19. As such, it is important to understand whether mindsets about health may affect behaviors which could prevent spread of the virus in AIs. In this exploratory investigation, a convenience sample of two hundred AI adults completed a questionnaire one month prior to the declaration of the COVID-19 pandemic as a national emergency. They provided demographic information and completed a measure of health mindsets. The second wave of data was collected approximately one month later, where we collected a measure of physical distancing behavior and a measure of disinfecting behaviors. In AI adults, health mindset predicted frequency of physical distancing behaviors and disinfecting behaviors, with individuals who viewed health as less fixed engaging in more physical distancing and disinfecting behaviors, while individuals who viewed health as more fixed reported less physical distancing and less disinfecting behaviors. In AIs, growth health mindsets predicted physical distancing and disinfecting behaviors, both of which are important in reducing the spread of COVID-19. Interventions which are designed to promote growth mindsets of health may promote health-protective behaviors in the context of the COVID-19 pandemic.
Dreaming during the Covid-19 pandemic: Computational assessment of dream reports reveals mental suffering related to fear of contagion
Authors: Mota Natália Bezerra , Weissheimer Janaina , Ribeiro Marina , de Paiva Mizziara , Avilla-Souza Juliana , Simabucuru Gabriela , Chaves Monica Frias , Cecchi Lucas , Cirne Jaime , Cecchi Guillermo , Rodrigues Cilene , Copelli Mauro , Ribeiro Sidarta
Published: November 2020

The current global threat brought on by the Covid-19 pandemic has led to widespread social isolation, posing new challenges in dealing with metal suffering related to social distancing, and in quickly learning new social habits intended to prevent contagion. Neuroscience and psychology agree that dreaming helps people to cope with negative emotions and to learn from experience, but can dreaming effectively reveal mental suffering and changes in social behavior? To address this question, we applied natural language processing tools to study 239 dream reports by 67 individuals, made either before the Covid-19 outbreak or during the months of March and April, 2020, when lockdown was imposed in Brazil following the WHO’s declaration of the pandemic. Pandemic dreams showed a higher proportion of anger and sadness words, and higher average semantic similarities to the terms “contamination” and “cleanness”. These features seem to be associated with mental suffering linked to social isolation, as they explained 40% of the variance in the PANSS negative subscale related to socialization (p = 0.0088). These results corroborate the hypothesis that pandemic dreams reflect mental suffering, fear of contagion, and important changes in daily habits that directly impact socialization.
Psychosocial job characteristics and mental health: Do associations differ by migrant status in an Australian working population sample?
Authors: Liu Xiaomin , Bowe Steven J. , Li Lin , Too Lay San , LaMontagne Anthony D.
Published: November 2020

Migrant workers may experience higher burdens of occupational injury and illness compared to native-born workers, which may be due to the differential exposure to occupational hazards, differential vulnerability to exposure-associated health impacts, or both. This study aims to assess if the relationships between psychosocial job characteristics and mental health vary by migrant status in Australia (differential vulnerability). A total of 8969 persons from wave 14 (2014–2015) of the Household Income and Labour Dynamics in Australia Survey were included in the analysis. Psychosocial job characteristics included skill discretion, decision authority and job insecurity. Mental health was assessed via a Mental Health Inventory-5 score (MHI-5), with a higher score indicating better mental health. Migrant status was defined by (i) country of birth (COB), (ii) the combination of COB and English/Non-English dominant language of COB and (iii) the combination of COB and years since arrival in Australia. Data were analysed using linear regression, adjusting for gender, age and educational attainment. Migrant status was analysed as an effect modifier of the relationships between psychosocial job characteristics and mental health. Skill discretion and decision authority were positively associated with the MHI-5 score while job insecurity was negatively associated with the MHI-5 score. We found no statistical evidence of migrant status acting as an effect modifier of the psychosocial job characteristic―MHI-5 relationships. With respect to psychosocial job characteristic―mental health relationships, these results suggest that differential exposure to job stressors is a more important mechanism than differential vulnerability for generating occupational health inequities between migrants and native-born workers in Australia.
Novel methods for epistasis detection in genome-wide association studies
Authors: Slim Lotfi , Chatelain Clément , Azencott Chloé-Agathe , Vert Jean-Philippe
Published: November 2020

More and more genome-wide association studies are being designed to uncover the full genetic basis of common diseases. Nonetheless, the resulting loci are often insufficient to fully recover the observed heritability. Epistasis, or gene-gene interaction, is one of many hypotheses put forward to explain this missing heritability. In the present work, we propose epiGWAS, a new approach for epistasis detection that identifies interactions between a target SNP and the rest of the genome. This contrasts with the classical strategy of epistasis detection through exhaustive pairwise SNP testing. We draw inspiration from causal inference in randomized clinical trials, which allows us to take into account linkage disequilibrium. EpiGWAS encompasses several methods, which we compare to state-of-the-art techniques for epistasis detection on simulated and real data. The promising results demonstrate empirically the benefits of EpiGWAS to identify pairwise interactions.
Effects of transcranial magnetic stimulation over the left posterior superior temporal gyrus on picture-word interference
Authors: Piai Vitória , Nieberlein Laura , Hartwigsen Gesa
Published: November 2020

Word-production theories argue that during language production, a concept activates multiple lexical candidates in left temporal cortex, and the intended word is selected from this set. Evidence for theories on spoken-word production comes, for example, from the picture-word interference task, where participants name pictures superimposed by congruent (e.g., picture: rabbit, distractor “rabbit”), categorically related (e.g., distractor “sheep”), or unrelated (e.g., distractor “fork”) words. Typically, whereas congruent distractors facilitate naming, related distractors slow down picture naming relative to unrelated distractors, resulting in semantic interference. However, the neural correlates of semantic interference are debated. Previous neuroimaging studies have shown that the left mid-to-posterior STG (pSTG) is involved in the interference associated with semantically related distractors. To probe the functional relevance of this area, we targeted the left pSTG with focal repetitive transcranial magnetic stimulation (rTMS) while subjects performed a picture-word interference task. Unexpectedly, pSTG stimulation did not affect the semantic interference effect but selectively increased the congruency effect (i.e., faster naming with congruent distractors). The facilitatory TMS effect selectively occurred in the more difficult list with an overall lower name agreement. Our study adds new evidence to the causal role of the left pSTG in the interaction between picture and distractor representations or processing streams, only partly supporting previous neuroimaging studies. Moreover, the observed unexpected condition-specific facilitatory rTMS effect argues for an interaction of the task- or stimulus-induced brain state with the modulatory TMS effect. These issues should be systematically addressed in future rTMS studies on language production.
Acid suppressants use and the risk of dementia: A population-based propensity score-matched cohort study
Authors: Wu Chia-Liang , Lei Wei-Yi , Wang Jaw-Shing , Lin Ching-En , Chen Chien-Lin , Wen Shu-Hui
Published: November 2020

In this population-based propensity score matched (PSM) cohort study, we aimed to investigate the risk of developing dementia with the use of acid suppressants, including proton pump inhibitors (PPIs) and histamine-2 receptor antagonists (H2 antagonists). Cohorts of PPI users (n = 2,778), H2 antagonist users (n = 6,165), and non-users (n = 86,238) were selected from a dataset covering the years 2000 to 2010 in Taiwan’s National Health Insurance Research Database. Patients in the three groups were PSM at a ratio of 1:1 within each comparison cohort (CC). Three CCs were created: (1) PPI users compared to non-users (CC1, n = 2,583 pairs); (2) H2 antagonist users compared to non-users (CC2, n = 5,955 pairs); and (3) PPI users compared to H2 antagonist users (CC3, n = 2,765 pairs). A multivariable robust Cox proportional hazard model was used to estimate the adjusted hazard ratio (aHR) and the 95% confidence interval (CI) for the risk of developing dementia. The multivariable analysis results show that the aHR of developing dementia during the follow-up period was 0.72 (CC1: 95% CI = 0.51–1.03, P = 0.07) for PPI users and 0.95 (CC2: 95% CI = 0.74–1.22, P = 0.69) for H2 antagonist users, when compared to non-users. Between the patients using acid suppressants, there was no difference between PPI and H2 antagonist users in the risk of developing dementia (CC3: aHR = 0.82, 95% CI = 0.58–1.17, P = 0.28). In conclusion, no association was observed between the use of acid suppressants and the risk of developing dementia in any of the three CCs. Further, randomized controlled trials are warranted to confirm this relationship.
Spatiotemporal changes caused by the intensive use of sea areas in the liaoning coastal economic zone of China
Authors: Ke Lina , Yin Shusheng , Wang Shuting , Wang Quanming
Published: November 2020

Oceans and their resources are experiencing immense pressure because of human exploitation. The intensive use of sea areas has become an important method in solving the contradiction between ocean supply and demand, thereby ensuring sustainable marine economy development, tapping potential sea-area utilization, reasonably allocating sea-area utilization structures, and increasing marine economic benefits. This paper explores the definition and connotation of intensive sea-area use and constructs an evaluation index system based on marine input intensity, marine utilization structure, marine economic benefit, and marine ecological environment. Multi-objective variable fuzzy set theory and fuzzy decision analysis methods were used to evaluate the intensive sea-area utilization in the Liaoning Coastal Economic Zone of China during 2004–2016. The spatial differentiation characteristics of intensive sea-area use were analysed using cluster analysis. The research result showed that: (1) Intensive utilization level of the Liaoning coastal economic zone has gradually increased, while it is still in a moderately weak level; (2) Sea area intensive utilization varied in degrees and fluctuates in the six cities under the jurisdiction of the Liaoning coastal economic zone; and (3) Marine input intensity, marine utilization structure, marine economic benefit, and marine sustainability indexes have increased in the cities, thereby exhibiting improvements in the Liaoning coastal economic zone.
Vesicular trafficking permits evasion of cGAS/STING surveillance during initial human papillomavirus infection
Authors: Uhlorn Brittany L. , Jackson Robert , Li Shuaizhi , Bratton Shauna M. , Van Doorslaer Koenraad , Campos Samuel K.
Published: November 2020

Oncogenic human papillomaviruses (HPVs) replicate in differentiating epithelium, causing 5% of cancers worldwide. Like most other DNA viruses, HPV infection initiates after trafficking viral genome (vDNA) to host cell nuclei. Cells possess innate surveillance pathways to detect microbial components or physiological stresses often associated with microbial infections. One of these pathways, cGAS/STING, induces IRF3-dependent antiviral interferon (IFN) responses upon detection of cytosolic DNA. Virion-associated vDNA can activate cGAS/STING during initial viral entry and uncoating/trafficking, and thus cGAS/STING is an obstacle to many DNA viruses. HPV has a unique vesicular trafficking pathway compared to many other DNA viruses. As the capsid uncoats within acidic endosomal compartments, minor capsid protein L2 protrudes across vesicular membranes to facilitate transport of vDNA to the Golgi. L2/vDNA resides within the Golgi lumen until G2/M, whereupon vesicular L2/vDNA traffics along spindle microtubules, tethering to chromosomes to access daughter cell nuclei. L2/vDNA-containing vesicles likely remain intact until G1, following nuclear envelope reformation. We hypothesize that this unique vesicular trafficking protects HPV from cGAS/STING surveillance. Here, we investigate cGAS/STING responses to HPV infection. DNA transfection resulted in acute cGAS/STING activation and downstream IFN responses. In contrast, HPV infection elicited minimal cGAS/STING and IFN responses. To determine the role of vesicular trafficking in cGAS/STING evasion, we forced premature viral penetration of vesicular membranes with membrane-perturbing cationic lipids. Such treatment renders a non-infectious trafficking-defective mutant HPV infectious, yet susceptible to cGAS/STING detection. Overall, HPV evades cGAS/STING by its unique subcellular trafficking, a property that may contribute to establishment of infection.
Ifit2 deficiency restricts microglial activation and leukocyte migration following murine coronavirus (m-CoV) CNS infection
Authors: Das Sarma Jayasri , Burrows Amy , Rayman Patricia , Hwang Mi-Hyun , Kundu Soumya , Sharma Nikhil , Bergmann Cornelia , Sen Ganes C.
Published: November 2020

The interferon-induced tetratricopeptide repeat protein (Ifit2) protects mice from lethal neurotropic viruses. Neurotropic coronavirus MHV-RSA59 infection of Ifit2-/- mice caused pronounced morbidity and mortality accompanied by rampant virus replication and spread throughout the brain. In spite of the higher virus load, induction of many cytokines and chemokines in the brains of infected Ifit2-/- mice were similar to that in wild-type mice. In contrast, infected Ifit2-/- mice revealed significantly impaired microglial activation as well as reduced recruitment of NK1.1 T cells and CD4 T cells to the brain, possibly contributing to the lack of viral clearance. These two deficiencies were associated with a lower level of microglial expression of CX3CR1, the receptor of the CX3CL1 (Fractalkine) chemokine, which plays a critical role in both microglial activation and leukocyte recruitment. The above results uncovered a new potential role of an interferon-induced protein in immune protection.
Human splice factors contribute to latent HIV infection in primary cell models and blood CD4+ T cells from ART-treated individuals
Authors: Moron-Lopez Sara , Telwatte Sushama , Sarabia Indra , Battivelli Emilie , Montano Mauricio , Macedo Amanda B. , Aran Dvir , Butte Atul J. , Jones R. Brad , Bosque Alberto , Verdin Eric , Greene Warner C. , Wong Joseph K. , Yukl Steven A.
Published: November 2020

It is unclear what mechanisms govern latent HIV infection in vivo or in primary cell models. To investigate these questions, we compared the HIV and cellular transcription profile in three primary cell models and peripheral CD4+ T cells from HIV-infected ART-suppressed individuals using RT-ddPCR and RNA-seq. All primary cell models recapitulated the block to HIV multiple splicing seen in cells from ART-suppressed individuals, suggesting that this may be a key feature of HIV latency in primary CD4+ T cells. Blocks to HIV transcriptional initiation and elongation were observed more variably among models. A common set of 234 cellular genes, including members of the minor spliceosome pathway, was differentially expressed between unstimulated and activated cells from primary cell models and ART-suppressed individuals, suggesting these genes may play a role in the blocks to HIV transcription and splicing underlying latent infection. These genes may represent new targets for therapies designed to reactivate or silence latently-infected cells.
Machine Learning techniques and Polygenic Risk Score application to prediction genetic diseases
Authors: Mena Mamani Nibeth
Published: November 2020

For the last 10 years and after important discoveries such as genomic understanding of the human being, there has been a considerable increase in the interest on research risk prediction models associated with genetic originated diseases through two principal approaches: Polygenic Risk Score and Machine Learning techniques. The aim of this work is the narrative review of the literature on Machine Learning techniques applied to obtaining the polygenic risk score, highlighting the most relevant research and applications at present. The application of these techniques has provided many benefits in the prediction of diseases, it is evident that the challenges of the use and optimization of these two approaches are still being discussed and investigated in order to have a greater precision in the prediction of genetic diseases.
The proliferation of virtual laboratories in educational fields
Authors: Vergara Diego , Extremera Jamil , Rubio Manuel Pablo , Dávila Lilian P.
Published: November 2020

Since its emergence in the 1960s, the use of virtual reality (VR) has grown progressively. This wide dissemination of VR has allowed its application in an increasing number of disciplines, including education. It is well known that virtual laboratories (VLs), which base their use in VR technology, are very useful tools in both university and professional training. In this article, the main advantages and disadvantages of the use of modern VLs in teaching are analyzed. In addition, the design and development process that must be followed to appropriately create these VLs is described in detail, as well as a small-scale study of the perception that university teachers have about the use of VR in education. Lastly, the reasons why the implementation of VR is not currently as broad as it would be expected, given its proven potential in different fields, are discussed.
Megalocytiviruses in ornamental fish: A review
Authors: Johan Che Azarulzaman Che , Zainathan Sandra Catherine
Published: November 2020

Iridoviruses, especially megalocytiviruses, are related to severe disease resulting in high economic losses in the aquaculture industry worldwide. The ornamental fish industry has been affected severely due to Megalocytivirus infections. Megalocytivirus is a DNA virus that has three genera; including red sea bream iridovirus, infectious spleen and kidney necrosis virus, and turbot reddish body iridovirus. Megalocytivirus causes non-specific clinical signs in ornamental fish. Cell culture, histology, immunofluorescence test, polymerase chain reaction (PCR) assay, and loop-mediated isothermal amplification assay have been used to diagnose megalocytiviruses. Risk factors such as temperature, transportation (export and import), and life stages of ornamental fish have been reported for the previous cases due to Megalocytivirus infections. In addition, other prevention and control methods also have been practiced in farms to prevent Megalocytivirus outbreaks. This is the first review of megalocytiviruses in ornamental fish since its first detection in 1989. This review discusses the occurrences of Megalocytivirus in ornamental fish, including the history, clinical signs, detection method, risk factors, and prevention measures.