bluuebunny/crossref_metadata_2025 huggingface dataset:
Development of SNP-Based Genomic Tools for the Canadian Bison Industry: Parentage Verification and Subspecies Composition
Authors: Yang Tianfu , Miller Michelle , Forgacs David , Derr James , Stothard Paul
Published: November 2020

Genomic technologies have been increasingly applied in livestock production due to their utility in production management and animal genetic improvement. The current project aimed to develop genomic resources for the Canadian bison industry, specifically a parentage verification tool and a subspecies composition tool. Both products stand to help with building and maintaining purebred and crossbred bison populations, and in turn bison conservation and production. The development of this genomic toolkit proceeded in two stages. In the single-nucleotide polymorphism (SNP) discovery and selection stage, raw sequence information from 41 bison samples was analyzed, and approximately 52.5 million candidate biallelic SNPs were discovered from 21 samples with high sequence quality. A set of 19,954 SNPs (2,928 for parentage verification and 17,026 for subspecies composition) were then selected for inclusion on an Axiom myDesign custom array. In the refinement and validation stage, 480 bison were genotyped using the custom SNP panel, and the resulting genotypes were analyzed to further filter SNPs and assess tool performance. In various tests using real and simulated genotypes, the two genomic tools showed excellent performance for their respective tasks. Final SNP sets consisting of 191 SNPs for parentage and 17,018 SNPs for subspecies composition are described. As the first SNP-based genomic toolkit designed for the Canadian bison industry, our results may provide a new opportunity in improving the competitiveness and profitability of the industry in a sustainable manner.
Modification of Experimental Design and Statistical Method for Mapping Imprinted QTLs Based on Immortalized F2 Population
Authors: Zheng Kehui , Yan Jiqiang , Deng Jiacong , Wu Weiren , Wen Yongxian
Published: November 2020

Genomic imprinting is an epigenetic phenomenon, which plays important roles in the growth and development of animals and plants. Immortalized F2(imF2) populations generated by random cross between recombinant inbred (RI) or doubled haploid (DH) lines have been proved to have significant advantages for mapping imprinted quantitative trait loci (iQTLs), and statistical methods for this purpose have been proposed. In this paper, we propose a special type of imF2population (R-imF2) for iQTL mapping, which is developed by random reciprocal cross between RI/DH lines. We also propose two modified iQTL mapping methods: two-step point mapping (PM-2) and two-step composite point mapping (CPM-2). Simulation studies indicated that: (i) R-imF2cannot improve the results of iQTL mapping, but the experimental design can probably reduce the workload of population construction; (ii) PM-2 can increase the precision of estimating the position and effects of a single iQTL; and (iii) CPM-2 can precisely map not only iQTLs, but also non-imprinted QTLs. The modified experimental design and statistical methods will facilitate and promote the study of iQTL mapping.
CD4 and CD8 T Cell Memory Interactions Alter Innate Immunity and Organ Injury in the CLP Sepsis Model
Authors: Taylor Matthew D. , Fernandes Tiago D. , Kelly Alexander P. , Abraham Mabel N. , Deutschman Clifford S.
Published: November 2020

The role of T cell memory in sepsis is poorly understood. Recent work has demonstrated that mice exposed to frequent antigenic stimulation, in contrast to laboratory mice, better recapitulate the human T cell repertoire. This difference may profoundly alter responses to inflammatory insults. We induced isolated T cell memory by inoculating C57Bl/6 mice with an anti-CD3ϵ activating antibody, a process we term “immune education.” These mice were subjected to the cecal ligation and puncture (CLP) model of sepsis and responses were compared to those of isotype-treated controls. CLP-induced increases in 1) CD4 T cell production and serum levels of IFNγ, 2) CD8 T cell granzyme B levels, and 3) innate cell function were all more pronounced in educated mice than in control mice. Immune education increased CLP-induced liver injury and decreased survival. The differences in responses to CLP were not recapitulated in mice with either isolated CD4 or isolated CD8 T cell memory. Relative to controls, CLP in educated CD8−/− mice (isolated CD4 memory) increased monocyte-derived dendritic cells. Combined CD4 and CD8 memory did not increase monocyte-derived dendritic cells; this combination recapitulated increases in neutrophil and inflammatory monocyte numbers in educated wild-type mice. Induction of T cell memory prior to CLP alters immune responses, organ function, and survival. Both CD4 and CD8 memory T cells play important and independent roles in this response. These findings have profound implications for the development of murine models of human inflammatory disorders such as infection and sepsis.
Interleukin (IL)-12 and IL-18 Synergize to Promote MAIT Cell IL-17A and IL-17F Production Independently of IL-23 Signaling
Authors: Cole Suzanne , Murray Janine , Simpson Catherine , Okoye Remi , Tyson Kerry , Griffiths Meryn , Baeten Dominique , Shaw Stevan , Maroof Asher
Published: November 2020

IL-23 is considered a critical regulator of IL-17 in Th17 cells; however, its requirement for inducing IL-17 production in other human immune subsets remains incompletely understood. Mucosal associated invariant T (MAIT) cells uniformly express retinoic acid receptor-related orphan receptor gamma t (RORγt) but only a minor population have been shown to produce IL-17A. Here we show that IL-17F is the dominant IL-17 isoform produced by MAIT cells, not IL-17A. For optimal MAIT cell derived IL-17A and IL-17F production, T cell receptor (TCR) triggering, IL-18 and monocyte derived IL-12 signaling is required. Unlike Th17 cells, this process is independent of IL-23 signaling. Using an in vitro skin cell activation assay, we demonstrate that dual neutralization of both IL-17A and IL-17F resulted in greater suppression of inflammatory proteins than inhibition of IL-17A alone. Finally, we extend our findings by showing that other innate-like lymphocytes such as group 3 innate lymphoid cells (ILC3) and gamma delta (γδ) T cells are also capable of IL-23 independent IL-17A and IL-17F production. These data indicate both IL-17F and IL-17A production from MAIT cells may contribute to tissue inflammation independently of IL-23, in part explaining the therapeutic disconnect between targeting IL-17 or IL-23 in certain inflammatory diseases.
Histology of Interstitial Lung Disease in Common Variable Immune Deficiency
Authors: Dhalla Fatima , Lochlainn Dylan J. Mac , Chapel Helen , Patel Smita Y.
Published: November 2020

Interstitial lung disease (ILD) is an important non-infectious complication in several primary immune deficiencies. In common variable immune deficiency (CVID) it is associated with complex clinical phenotypes and adverse outcomes. The histology of ILD in CVID is heterogeneous and mixed patterns are frequently observed within a single biopsy, including non-necrotising granulomatous inflammation, lymphoid interstitial pneumonitis, lymphoid hyperplasia, follicular bronchiolitis, organizing pneumonia, and interstitial fibrosis; ILD has to be differentiated from lymphoma. The term granulomatous-lymphocytic interstitial lung disease (GLILD), coined to describe the histopathological findings within the lungs of patients with CVID with or without multisystem granulomata, is somewhat controversial as pulmonary granulomata are not always present on histology and the nature of infiltrating lymphocytes is variable. In this mini review we summarize the literature on the histology of CVID-related ILD and discuss some of the factors that may contribute to the inter- and intra- patient variability in the histological patterns reported. Finally, we highlight areas for future development. In particular, there is a need for standardization of histological assessments and reporting, together with a better understanding of the immunopathogenesis of CVID-related ILD to resolve the apparent heterogeneity of ILD in this setting and guide the selection of rational targeted therapies in different patients.
Effects of Non-Coding RNA on Regulatory T Cells and Implications for Treatment of Immunological Diseases
Authors: Luo Yuanhanyu , Wang Honglin
Published: November 2020

Regulatory T cells (Tregs) are essential for regulating immune reactions and maintaining immune homeostasis. Non-coding RNAs (ncRNAs), including microRNAs and long non-coding RNAs, usually do not encode proteins but regulate intracellular biological processes at post-transcriptional levels. These ncRNAs have been demonstrated as key post-transcriptional regulators in the commitment of Tregs lineage and the plasticity of Tregs function. These ncRNAs can further be manipulated to benefit human immunological disorders caused by Tregs dysfunction. This review summarizes the effects of ncRNAs on Tregs and their potentials to be targets or approaches for the treatment of immunological diseases involving Tregs.
Extended Pelagic Life in a Bathybenthic Octopus
Authors: Villanueva Roger , Laptikhovsky Vladimir V. , Piertney Stuart B. , Fernández-Álvarez Fernando Ángel , Collins Martin A. , Ablett Jonathan D. , Escánez Alejandro
Published: November 2020

Planktonic stages of benthic octopuses can reach relatively large sizes in some species, usually in oceanic, epipelagic waters while living as part of the macroplankton. These young octopuses appear to delay settlement on the seabed for an undetermined period of time that is probably longer than for those octopus paralarvae living in coastal, neritic waters. The reason for this delay is unknown and existing information about their biology is very scarce. Here we report on the presence of juvenile and subadult forms of the bathybenthic octopusPteroctopus tetracirrhusin oceanic waters of the South and North Atlantic and its association with the pyrosomid speciesPyrosoma atlanticum, apparently used by the octopus as a refuge or shelter. The relatively large size of theP. tetracirrhusliving in oceanic waters as the individuals reported here, together with the morphological characteristics of this bathybenthic species including its gelatinous body, minute suckers embedded in swollen skin and the deep interbrachial web, indicates thatP. tetracirrhusmay be considered a model of a transitional octopus species that is colonizing the pelagic environment by avoiding descending to the bathyal benthos. This process seems to occur in the same way as in the supposed origin of the ctenoglossan holopelagic octopods of the families Amphitretidae, Bolitaenidae, and Vitreledonellidae, which have arisen via neoteny from the planktonic paralarval stages of benthic octopuses.
Advances in Microtechnology for Improved Cytotoxicity Assessment
Authors: Garcia-Hernando Maite , Benito-Lopez Fernando , Basabe-Desmonts Lourdes
Published: November 2020

In vitro cytotoxicity testing is essential in the pharmaceutical and environmental industry to study the effects of potential harmful compounds for human health. Classical assays present several disadvantages: they are commonly based on live-death labelling, are highly time consuming and/or require skilled personnel to be performed. The current trend is to reduce the number of required cells and the time during the analysis, while increasing the screening capability and the accuracy and sensitivity of the assays, aiming single cell resolution. Microfabrication and surface engineering are enabling novel approaches for cytotoxicity assessment, offering high sensitivity and the possibility of automation in order to minimize user intervention. This review aims to overview the different microtechnology approaches available in this field, focusing on the novel developments for high-throughput, dynamic and real time screening of cytotoxic compounds.
A Landscape of Opportunities for Microbial Ecology Research
Authors: Mony Cendrine , Vandenkoornhuyse Philippe , Bohannan Brendan J. M. , Peay Kabir , Leibold Mathew A
Published: November 2020

Microbes encompass tremendous biodiversity, provide support to all living forms, including humans, and play an important role in many ecosystem services. The rules that govern microorganism community assembly are increasingly revealed due to key advances in molecular and analytical methods but their understanding remain a key challenge in microbial ecology. The existence of biogeographic patterns within microbial communities has been established and explained in relation to landscape-scale processes, including selection, drift, dispersal and mutation. The effect of habitat patchiness on microorganisms’ assembly rules remains though incompletely understood. Here, we review how landscape ecology principles can be adapted to explore new perspectives on the mechanisms that determine microbial community structure. To provide a general overview, we characterize microbial landscapes, the spatial and temporal scales of the mechanisms that drive microbial assembly and the feedback between microorganisms and landscape structure. We provide evidence for the effects of landscape heterogeneity, landscape fragmentation and landscape dynamics on microbial community structure, and show that predictions made for macro-organisms at least partly also apply to microorganisms. We explain why emerging metacommunity approaches in microbial ecology should include explicit characterization of landscape structure in their development and interpretation. We also explain how biotic interactions, such as competition, prey-predator or mutualist relations may influence the microbial landscape and may be involved in the above-mentioned feedback process. However, we argue that the application of landscape ecology to the microbial world cannot simply involve transposing existing theoretical frameworks. This is due to the particularity of these organisms, in terms of size, generation time, and for some of them, tight interaction with hosts. These characteristics imply dealing with unusual and dependent space and time scales of effect. Evolutionary processes have also a strong importance in microorganisms’ response to their landscapes. Lastly, microorganisms’ activity and distribution induce feedback effects on the landscape that have to be taken into account. The transposition of the landscape ecology framework to microorganisms provides many challenging research directions for microbial ecology.
Impact of Fe(III) (Oxyhydr)oxides Mineralogy on Iron Solubilization and Associated Microbial Communities
Authors: Zhang Fengfeng , Battaglia-Brunet Fabienne , Hellal Jennifer , Joulian Catherine , Gautret Pascale , Motelica-Heino Mikael
Published: November 2020

Iron-reducing bacteria (IRB) are strongly involved in Fe cycling in surface environments. Transformation of Fe and associated trace elements is strongly linked to the reactivity of various iron minerals. Mechanisms of Fe (oxyhydr)oxides bio-reduction have been mostly elucidated with pure bacterial strains belonging to Geobacter or Shewanella genera, whereas studies involving mixed IRB populations remain scarce. The present study aimed to evaluate the iron reducing rates of IRB enriched consortia originating from complex environmental samples, when grown in presence of Fe (oxyhydr)oxides of different mineralogy. The abundances of Geobacter and Shewanella were assessed in order to acquire knowledge about the abundance of these two genera in relation to the effects of mixed IRB populations on kinetic control of mineralogical Fe (oxyhydr)oxides reductive dissolution. Laboratory experiments were carried out with two freshly synthetized Fe (oxyhydr)oxides presenting contrasting specific surfaces, and two defined Fe-oxides, i.e., goethite and hematite. Three IRB consortia were enriched from environmental samples from a riverbank subjected to cyclic redox oscillations related to flooding periods (Decize, France): an unsaturated surface soil, a flooded surface soil and an aquatic sediment, with a mixture of organic compounds provided as electron donors. The consortia could all reduce iron-nitrilotriacetate acid (Fe(III)-NTA) in 1–2 days. When grown on Fe (oxyhydr)oxides, Fe solubilization rates decreased as follows: fresh Fe (oxyhydr)oxides > goethite > hematite. Based on a bacterial rrs gene fingerprinting approach (CE-SSCP), bacterial community structure in presence of Fe(III)-minerals was similar to those of the site sample communities from which they originated but differed from that of the Fe(III)-NTA enrichments. Shewanella was more abundant than Geobacter in all cultures. Its abundance was higher in presence of the most efficiently reduced Fe (oxyhydr)oxide than with other Fe(III)-minerals. Geobacter as a proportion of the total community was highest in the presence of the least easily solubilized Fe (oxyhydr)oxides. This study highlights the influence of Fe mineralogy on the abundance of Geobacter and Shewanella in relation to Fe bio-reduction kinetics in presence of a complex mixture of electron donors.
Conjugation of Synthetic Polyproline Moietes to Lipid II Binding Fragments of Nisin Yields Active and Stable Antimicrobials
Authors: Deng Jingjing , Viel Jakob H. , Kubyshkin Vladimir , Budisa Nediljko , Kuipers Oscar P.
Published: November 2020

Coupling functional moieties to lantibiotics offers exciting opportunities to produce novel derivatives with desirable properties enabling new functions and applications. Here, five different synthetic hydrophobic polyproline peptides were conjugated to either nisin AB (the first two rings of nisin) or nisin ABC (the first three rings of nisin) by using click chemistry. The antimicrobial activity of nisin ABC + O6K3 against Enterococcus faecium decreased 8-fold compared to full-length nisin, but its activity was 16-fold better than nisin ABC, suggesting that modifying nisin ABC is a promising strategy to generate semi-synthetic nisin hybrids. In addition, the resulting nisin hybrids are not prone to degradation at the C-terminus, which has been observed for nisin as it can be degraded by nisinase or other proteolytic enzymes. This methodology allows for getting more insight into the possibility of creating semi-synthetic nisin hybrids that maintain antimicrobial activity, in particular when synthetic and non-proteinaceous moieties are used. The success of this approach in creating viable nisin hybrids encourages further exploring the use of different modules, e.g., glycans, lipids, active peptide moieties, and other antimicrobial moieties.
Alzheimer Cells on Their Way to Derailment Show Selective Changes in Protein Quality Control Network
Authors: Koopman Margreet B. , Rüdiger Stefan G. D.
Published: November 2020

Alzheimer’s Disease is driven by protein aggregation and is characterized by accumulation of Tau protein into neurofibrillary tangles. In healthy neurons the cellular protein quality control is successfully in charge of protein folding, which raises the question to which extent this control is disturbed in disease. Here, we describe that brain cells in Alzheimer’s Disease show very specific derailment of the protein quality control network. We performed a meta-analysis on the Alzheimer’s Disease Proteome database, which provides a quantitative assessment of disease-related proteome changes in six brain regions in comparison to age-matched controls. We noted that levels of all paralogs of the conserved Hsp90 chaperone family are reduced, while most other chaperones – or their regulatory co-chaperones - do not change in disease. The notable exception is a select group consisting of the stress inducible HSP70, its nucleotide exchange factor BAG3 – which links the Hsp70 system to autophagy - and neuronal small heat shock proteins, which are upregulated in disease. They are all members of a cascade controlled in the stress response, channeling proteins towards a pathway of chaperone assisted selective autophagy. Together, our analysis reveals that in an Alzheimer’s brain, with exception of Hsp90, the players of the protein quality control are still present in full strength, even in brain regions most severely affected in disease. The specific upregulation of small heat shock proteins and HSP70:BAG3, ubiquitous in all brain areas analyzed, may represent a last, unsuccessful attempt to advert cell death.
Comparison of Transparency and Shrinkage During Clearing of Insect Brains Using Media With Tunable Refractive Index
Authors: Bekkouche Bo M. B. , Fritz Helena K. M. , Rigosi Elisa , O'Carroll David C.
Published: November 2020

Improvement of imaging quality has the potential to visualize previously unseen building blocks of the brain and is therefore one of the great challenges in neuroscience. Rapid development of new tissue clearing techniques in recent years have attempted to solve imaging compromises in thick brain samples, particularly for high resolution optical microscopy, where the clearing medium needs to match the high refractive index of the objective immersion medium. These problems are exacerbated in insect tissue, where numerous (initially air-filled) tracheal tubes branching throughout the brain increase the scattering of light. To date, surprisingly few studies have systematically quantified the benefits of such clearing methods using objective transparency and tissue shrinkage measurements. In this study we compare a traditional and widely used insect clearing medium, methyl salicylate combined with permanent mounting in Permount (“MS/P”) with several more recently applied clearing media that offer tunable refractive index (n): 2,2′-thiodiethanol (TDE), “SeeDB2” (in variants SeeDB2S and SeeDB2G matched to oil and glycerol immersion, n = 1.52 and 1.47, respectively) and Rapiclear (also with n = 1.52 and 1.47). We measured transparency and tissue shrinkage by comparing freshly dissected brains with cleared brains from dipteran flies, with or without addition of vacuum or ethanol pre-treatments (dehydration and rehydration) to evacuate air from the tracheal system. The results show that ethanol pre-treatment is very effective for improving transparency, regardless of the subsequent clearing medium, while vacuum treatment offers little measurable benefit. Ethanol pre-treated SeeDB2G and Rapiclear brains show much less shrinkage than using the traditional MS/P method. Furthermore, at lower refractive index, closer to that of glycerol immersion, these recently developed media offer outstanding transparency compared to TDE and MS/P. Rapiclear protocols were less laborious compared to SeeDB2, but both offer sufficient transparency and refractive index tunability to permit super-resolution imaging of local volumes in whole mount brains from large insects, and even light-sheet microscopy. Although long-term permanency of Rapiclear stored samples remains to be established, our samples still showed good preservation of fluorescence after storage for more than a year at room temperature.
A Hybrid BCI Based on SSVEP and EOG for Robotic Arm Control
Authors: Zhu Yuanlu , Li Ying , Lu Jinling , Li Pengcheng
Published: November 2020

Brain-computer interface (BCI) for robotic arm control has been studied to improve the life quality of people with severe motor disabilities. There are still challenges for robotic arm control in accomplishing a complex task with a series of actions. An efficient switch and a timely cancel command are helpful in the application of robotic arm. Based on the above, we proposed an asynchronous hybrid BCI in this study. The basic control of a robotic arm with six degrees of freedom was a steady-state visual evoked potential (SSVEP) based BCI with fifteen target classes. We designed an EOG-based switch which used a triple blink to either activate or deactivate the flash of SSVEP-based BCI. Stopping flash in the idle state can help to reduce visual fatigue and false activation rate (FAR). Additionally, users were allowed to cancel the current command simply by a wink in the feedback phase to avoid executing the incorrect command. Fifteen subjects participated and completed the experiments. The cue-based experiment obtained an average accuracy of 92.09%, and the information transfer rates (ITR) resulted in 35.98 bits/min. The mean FAR of the switch was 0.01/min. Furthermore, all subjects succeeded in asynchronously operating the robotic arm to grasp, lift, and move a target object from the initial position to a specific location. The results indicated the feasibility of the combination of EOG and SSVEP signals and the flexibility of EOG signal in BCI to complete a complicated task of robotic arm control.
Differentiating Responders and Non-responders to rTMS Treatment for Disorder of Consciousness Using EEG After-Effects
Authors: He Renhong , Fan Jianzhong , Wang Huijuan , Zhong Yuhua , Ma Jianhua
Published: November 2020

Background: It is controversial whether repetitive transcranial magnetic stimulation (rTMS) has potential benefits in improving the awareness of patients with disorder of consciousness (DOC). We hypothesized that rTMS could improve consciousness only in DOC patients who have measurable brain responses to rTMS.

Objective: In this study, we aimed to investigate the EEG after-effects induced by rTMS in DOC patients and attempted to propose a prediction algorithm to discriminate between DOC patients who would respond to rTMS treatment from those who would not.

Methods: Twenty-five DOC patients were enrolled in this study. Over 4 weeks, each patient received 20 sessions of 20 Hz rTMS that was applied over the left dorsolateral prefrontal cortex (DLPFC). For each patient, resting-state EEG was recorded before and immediately after one session of rTMS to assess the neurophysiologic modification induced by rTMS. The coma recovery scale revised (CRS-R) was used to define responders with improved consciousness.

Results: Of the 25 DOC patients, 10 patients regained improved consciousness and were classified as responders. The responders were characterized by more preserved alpha power and a significant reduction of delta power induced by rTMS. The analysis of receiver operating characteristic (ROC) curves showed that the algorithm calculated from the relative alpha power and the relative delta power had a high accuracy in identifying DOC patients who were responders.

Conclusions: DOC patients who had more preserved alpha power and a significant reduction in the delta band that was induced by rTMS are likely to regain improved consciousness, which provides a tool to identify DOC patients who may benefit in terms of therapeutic consciousness.
Non-invasive Brain and Spinal Stimulation for Pain and Related Symptoms in Multiple Sclerosis: A Systematic Review
Authors: Zucchella Chiara , Mantovani Elisa , De Icco Roberto , Tassorelli Cristina , Sandrini Giorgio , Tamburin Stefano
Published: November 2020

Background: Neuropathic and nociceptive pain frequently affect patients with multiple sclerosis (MS), with a prevalence close to 90% and significant impact on general health and quality of life. Pharmacological strategies are widely used to treat pain in MS, but their effectiveness and side-effects are controversial. Among non-pharmacological treatments for pain, non-invasive brain and spinal stimulation (NIBSS) has shown promising preliminary results in MS.

Objective: Systematic review to investigate the effect of NIBSS for the management of pain in MS.

Methods: A literature search using Pubmed, Science Direct and Web of Science was conducted from databases inception to February 21, 2020 for studies assessing the analgesic effect of NIBSS on pain in MS.

Results: A total of 279 records were title- and abstract-screened, nine were assessed for full text and included. The NIBSS techniques explored were transcranial direct current stimulation (N = 5), transcranial magnetic stimulation (N = 2), transcranial random noise stimulation (N =1), transcutaneous spinal direct current stimulation (N = 1). The targets were the primary motor cortex (M1; N = 4), the left dorsolateral pre-frontal cortex (DLPFC; N = 3), the spinal cord (N = 1), unspecified brain target (N = 1). The study designs were randomized (N = 7), open label (N = 1), single case report (N = 1). Despite the differences in study design, target and NIBSS technique that impeded a meta-analysis, all the studies converge in showing a significant improvement of pain after active NIBSS with less consistent effects on other symptoms of the pain-related cluster (depression, fatigue, cognition) and quality of life.

Conclusions: Excitatory NIBSS over M1, left DLPFC and spinal cord appear to be the most effective protocols for pain in MS. Open questions include the use of neurophysiological or neuroimaging surrogate outcome measures, the stratification of patients according to the clinical profiles and underlying pathogenetic mechanisms and the combination of NIBSS to pharmacological treatment, neurorehabilitation, or psychotherapy to improve the clinical effect. The duration of the effect to NIBSS and the feasibility and efficacy of telemedicine NIBSS protocols are other open key questions.
Hepatitis B Virus Seropositivity Is a Poor Prognostic Factor of Pediatric Hepatocellular Carcinoma: a Population-Based Study in Hong Kong and Singapore
Authors: Liu Anthony P. Y. , Soh Shui-Yen , Cheng Frankie W. C. , Pang Herbert H. , Luk Chung-Wing , Li Chak-Ho , Ho Karin K. H. , Chan Edwin K. W. , Chan Albert C. Y. , Chung Patrick H. Y. , Kimpo Miriam S. , Ahamed Summaiyya H. , Loh Amos , Chiang Alan K. S.
Published: November 2020

Background

Hepatocellular carcinoma (HCC) is a rare hepatic malignancy in children. Hepatitis B virus (HBV) infection is a key predisposing factor in endemic regions but its impact on outcome has not been studied. We aim to evaluate the prognostic implication of HBV seropositivity and role of cancer surveillance in children with HCC from East Asian populations with national HBV vaccination.

Methods

Review of population-based databases for patients (< 18 years old) diagnosed with HCC from 1993 to 2017 in two Southeast Asian regions with universal HBV vaccination (instituted since 1988 and 1987 in Hong Kong and Singapore, respectively).

Results

Thirty-nine patients were identified (Hong Kong, 28; Singapore, 11). Thirty were male; median age at diagnosis was 10.8 years (range, 0.98–16.6). Abdominal pain was the commonest presentation while five patients were diagnosed through surveillance for underlying condition. Alpha-fetoprotein was raised in 36 patients (mean, 500,598 ng/ml). Nineteen had bilobar involvement, among the patients in whom pretreatment extent of disease (PRETEXT) staging could retrospectively be assigned, 3 had stage I, 13 had stage II, 4 had stage III, and 11 had stage IV disease. Seventeen had distant metastasis. HBsAg was positive in 19 of 38 patients. Two patients had fibrolamellar HCC. Upfront management involved tumor resection in 16 (liver transplantation, 2), systemic chemotherapy in 21, interventional procedures in 6 [transarterial chemoembolization (TACE), 5, radiofrequency ablation (RFA), 1], and radiotherapy in 4 (selective internal radiation, 3, external beam radiation, 1). Five-year event-free survival (EFS) and overall survival (OS) were 15.4 ± 6.0 and 26.1 ± 7.2%, respectively. Patient’s HBsAg positivity, metastatic disease and inability to undergo definitive resection represent poor prognostic factors in univariate and multivariable analyses. Patients diagnosed by surveillance had significantly better outcome.

Conclusion

Pediatric HCC has poor outcome. HBV status remains relevant in the era of universal HBV vaccination. HBV carrier has inferior outcome and use of surveillance may mitigate disease course.
Dihydroartemisinin Inhibits the Proliferation of Esophageal Squamous Cell Carcinoma Partially by Targeting AKT1 and p70S6K
Authors: Zhu Lili , Chen Xinhuan , Zhu Yanyan , Qin Jiace , Niu Tingting , Ding Yongwei , Xiao Yang , Jiang Yanan , Liu Kangdong , Lu Jing , Yang Wanjing , Qiao Yan , Jin Ge , Ma Junfen , Dong Ziming , Zhao Jimin
Published: November 2020

Dihydroartemisinin (DHA), a sesquiterpene lactone with endoperoxide bridge, is one of the derivatives of artemisinin. In addition to having good antimalarial properties, DHA exhibits anticancer effects including against malignant solid tumors. However, the mechanism by which DHA inhibits the progression of esophageal cancer, especially esophageal squamous cell carcinoma (ESCC), is unclear. In this study, DHA was found to inhibit the proliferation of ESCC, and the underlying molecular mechanisms were explored. DHA inhibited ESCC cells proliferation and anchorage-independent growth. Flow cytometry analysis revealed that DHA significantly blocked cell cycle in the G1 phase. The results of human phospho-kinase array revealed that DHA downregulated the levels of p70S6KT389 and p70S6KT421/S424. Furthermore, the levels of mTORS2448, p70S6KT389, p70S6KT421/S424 and RPS6S235/S236 were decreased after DHA treatment in KYSE30 and KYSE150 cells. We then explored the proteins targeted by DHA to inhibit the mTOR-p70S6K-RPS6 pathway. Results of the in vitro kinase assay revealed that DHA significantly inhibited phosphorylation of mTORS2448 by binding to AKT1 and p70S6K kinases. In vivo, DHA inhibited the tumor growth of ESCC patient-derived xenografts and weakened p-mTOR, p-p70S6K, and p-RPS6 expression in tumor tissues. Altogether, our results indicate that DHA has antiproliferative effects in ESCC cells and can downregulate mTOR cascade pathway partially by binding to AKT1 and p70S6K. Thus, DHA has considerable potential for the prevention or treatment of ESCC.
Hepatic Encephalopathy-Associated Cerebral Vasculopathy in Acute-on-Chronic Liver Failure: Alterations on Endothelial Factor Release and Influence on Cerebrovascular Function
Authors: Caracuel Laura , Sastre Esther , Callejo María , Rodrigues-Díez Raquel , García-Redondo Ana B. , Prieto Isabel , Nieto Carlos , Salaices Mercedes , Aller Ma Ángeles , Arias Jaime , Blanco-Rivero Javier
Published: November 2020

The acute-on-chronic liver failure (ACLF) is a syndrome characterized by liver decompensation, hepatic encephalopathy (HE) and high mortality. We aimed to determine the mechanisms implicated in the development of HE-associated cerebral vasculopathy in a microsurgical liver cholestasis (MHC) model of ACLF. Microsurgical liver cholestasis was induced by ligating and extracting the common bile duct and four bile ducts. Sham-operated and MHC rats were maintained for eight postoperative weeks Bradykinin-induced vasodilation was greater in middle cerebral arteries from MHC rats. Both Nω-Nitro-L-arginine methyl ester and indomethacin diminished bradykinin-induced vasodilation largely in arteries from MHC rats. Nitrite and prostaglandin (PG) F1αreleases were increased, whereas thromboxane (TX) B2was not modified in arteries from MHC. Expressions of endothelial nitric oxide synthase (eNOS), inducible NOS, and cyclooxygenase (COX) 2 were augmented, and neuronal NOS (nNOS), COX-1, PGI2synthase, and TXA2S were unmodified. Phosphorylation was augmented for eNOS and unmodified for nNOS. Altogether, these endothelial alterations might collaborate to increase brain blood flow in HE.
Hypercapnia Regulates Gene Expression and Tissue Function
Authors: Shigemura Masahiko , Welch Lynn C. , Sznajder Jacob I.
Published: November 2020

Carbon dioxide (CO2) is produced in eukaryotic cells primarily during aerobic respiration, resulting in higher CO2 levels in mammalian tissues than those in the atmosphere. CO2 like other gaseous molecules such as oxygen and nitric oxide, is sensed by cells and contributes to cellular and organismal physiology. In humans, elevation of CO2 levels in tissues and the bloodstream (hypercapnia) occurs during impaired alveolar gas exchange in patients with severe acute and chronic lung diseases. Advances in understanding of the biology of high CO2 effects reveal that the changes in CO2 levels are sensed in cells resulting in specific tissue responses. There is accumulating evidence on the transcriptional response to elevated CO2 levels that alters gene expression and activates signaling pathways with consequences for cellular and tissue functions. The nature of hypercapnia-responsive transcriptional regulation is an emerging area of research, as the responses to hypercapnia in different cell types, tissues, and species are not fully understood. Here, we review the current understanding of hypercapnia effects on gene transcription and consequent cellular and tissue functions.
Effects of Static Stretching With High-Intensity and Short-Duration or Low-Intensity and Long-Duration on Range of Motion and Muscle Stiffness
Authors: Fukaya Taizan , Kiyono Ryosuke , Sato Shigeru , Yahata Kaoru , Yasaka Koki , Onuma Remi , Nakamura Masatoshi
Published: November 2020

This study investigated the effects of static stretching (SS) delivered with the same load but using two protocols – high-intensity and short-duration and low-intensity and long-duration – on range of motion (ROM) and muscle stiffness. A total of 18 healthy students participated in the study. They randomly performed high-intensity and short-duration (120% and 100 s) or low-intensity and long-duration (50% and 240 s) SS. Outcomes were assessed on ROM, passive torque at dorsiflexion ROM, and shear elastic modulus of the medial gastrocnemius before and after static stretching. The results showed that ROM increased significantly at post-stretching compared to that at pre-stretching in both high-intensity and short-duration [+6.1° ± 4.6° (Δ25.7 ± 19.9%)] and low-intensity and long-duration [+3.6° ± 2.3° (Δ16.0 ± 11.8%)]. Also, the ROM was significantly higher at post-stretching in high-intensity and short-duration conditions than that in low-intensity and long-duration. The passive torque at dorsiflexion ROM was significantly increased in both high-intensity and short-duration [+5.8 ± 12.8 Nm (Δ22.9 ± 40.5%)] and low-intensity and long-duration [+2.1 ± 3.4 Nm (Δ6.9 ± 10.8%)] conditions, but no significant differences were observed between both conditions. The shear elastic modulus was significantly decreased in both high-intensity and short-duration [−8.8 ± 6.1 kPa (Δ − 38.8 ± 14.5%)] and low-intensity and long-duration [−8.0 ± 12.8 kPa (Δ − 22.2 ± 33.8%)] conditions. Moreover, the relative change in shear elastic modulus in the high-intensity and short-duration SS was significantly greater than that in low-intensity and long-duration SS. Our results suggest that a higher intensity of the static stretching should be conducted to increase ROM and decrease muscle stiffness, even for a short time.
Parallel Adaptation to Spatially Distinct Distortions
Authors: Sauer Yannick , Wahl Siegfried , Rifai Katharina
Published: November 2020

Optical distortions as a visual disturbance are inherent in many optical devices such as spectacles or virtual reality headsets. In such devices, distortions vary spatially across the visual field. In progressive addition lenses, for example, the left and right regions of the lens skew the peripheral parts of the wearers visual field in opposing directions. The human visual system adapts to homogeneous distortions and the respective aftereffects are transferred to non-retinotopic locations. This study investigates simultaneous adaptation to two opposing distortions at different retinotopic locations. Two oppositely skewed natural image sequences were presented to 10 subjects as adaptation stimuli at two distinct locations in the visual field. To do so, subjects were instructed to keep fixation on a target. Eye tracking was used for gaze control. Change of perceived motion direction was measured in a direction identification task. The point of subjective equality (PSE), that is, the angle at which a group of coherently moving dots was perceived as moving horizontal, was determined for both retinal locations. The shift of perceived motion direction was evaluated by comparing PSE before and after adaptation. A significant shift at both retinal locations in the direction of the skew distortion of the corresponding adaptation stimulus is demonstrated. Consequently, parallel adaptation to two opposing distortions in a retinotopic reference frame was confirmed by this study.
Toxoplasma gondii Effects on the Relationship of Kynurenine Pathway Metabolites to Acoustic Startle Latency in Schizophrenia vs. Control Subjects
Authors: Pearce Bradley D. , Massa Nicholas , Goldsmith David R. , Gandhi Zeal H. , Hankus Allison , Alrohaibani Alaaeddin , Goel Neha , Cuthbert Bruce , Fargotstein Molly , Barr Dana Boyd , Panuwet Parinya , Brown Victoria M. , Duncan Erica
Published: November 2020

Background:Chronic infection withToxoplasma gondii(TOXO) results in microcysts in the brain that are controlled by inflammatory activation and subsequent changes in the kynurenine pathway. TOXO seropositivity is associated with a heightened risk of schizophrenia (SCZ) and with cognitive impairments. Latency of the acoustic startle response, a putative index of neural processing speed, is slower in SCZ. SCZ subjects who are TOXO seropositive have slower latency than SCZ subjects who are TOXO seronegative. We assessed the relationship between kynurenine pathway metabolites and startle latency as a potential route by which chronic TOXO infection can lead to cognitive slowing in SCZ.

Methods:Fourty-seven SCZ subjects and 30 controls (CON) were tested on a standard acoustic startle paradigm. Kynurenine pathway metabolites were measured using liquid chromatography-tandem mass spectrometry were kynurenine (KYN), tryptophan (TRYP), 3-hydroxyanthranilic acid (3-OHAA), anthranilic acid (AA), and kynurenic acid (KYNA). TOXO status was determined by IgG ELISA.

Results:In univariate ANCOVAs on onset and peak latency with age and log transformed startle magnitude as covariates, both onset latency [F(1,61)= 5.76;p= 0.019] and peak latency [F(1,61)= 4.34;p= 0.041] were slower in SCZ than CON subjects. In stepwise backward linear regressions after stratification by Diagnosis, slower onset latency in SCZ subjects was predicted by higher TRYP (B = 0.42;p= 0.008) and 3-OHAA:AA (B = 3.68;p= 0.007), and lower KYN:TRYP (B = −185.42;p= 0.034). In regressions with peak latency as the dependent variable, slower peak latency was predicted by higher TRYP (B = 0.47;p= 0.013) and 3-OHAA:AA ratio (B = 4.35;p= 0.010), and by lower KYNA (B= −6.67;p= 0.036). In CON subjects neither onset nor peak latency was predicted by any KYN metabolites. In regressions stratified by TOXO status, in TOXO positive subjects, slower peak latency was predicted by lower concentrations of KYN (B = −8.08;p= 0.008), KYNA (B = −10.64;p= 0.003), and lower KYN:TRYP ratios (B = −347.01;p= 0.03). In TOXO negative subjects neither onset nor peak latency was predicted by any KYN metabolites.

Conclusions:KYN pathway markers predict slowing of startle latency in SCZ subjects and in those with chronic TOXO infection, but this is not seen in CON subjects nor TOXO seronegative subjects. These findings coupled with prior work indicating a relationship of slower latency with SCZ and TOXO infection suggest that alterations in KYN pathway markers may be a mechanism by which neural processing speed, as indexed by startle latency, is affected in these subjects.
Deficits in Prediction Ability Trigger Asymmetries in Behavior and Internal Representation
Authors: Philippsen Anja , Nagai Yukie
Published: November 2020

Predictive coding is an emerging theoretical framework for explaining human perception and behavior. The proposed underlying mechanism is that signals encoding sensory information are integrated with signals representing the brain's prior prediction. Imbalance or aberrant precision of the two signals has been suggested as a potential cause for developmental disorders. Computational models may help to understand how such aberrant tendencies in prediction affect development and behavior. In this study, we used a computational approach to test the hypothesis that parametric modifications of prediction ability generate a spectrum of network representations that might reflect the spectrum from typical development to potential disorders. Specifically, we trained recurrent neural networks to draw simple figure trajectories, and found that altering reliance on sensory and prior signals during learning affected the networks' performance and the emergent internal representation. Specifically, both overly strong or weak reliance on predictions impaired network representations, but drawing performance did not always reflect this impairment. Thus, aberrant predictive coding causes asymmetries in behavioral output and internal representations. We discuss the findings in the context of autism spectrum disorder, where we hypothesize that too weak or too strong a reliance on predictions may be the cause of the large diversity of symptoms associated with this disorder.
Leveraging Professional Sports Teams to Encourage Healthy Behavior: A Review of 4 Years of Calgary Flames Health Training Camp Events
Authors: Ori Elaine M. , Berry Tanya R. , McCormack Gavin R. , Brett Kelly R. , Lambros George A. , Ghali William A.
Published: November 2020

Professional sporting teams may be well-positioned to act as promoters of health behaviors given their fixture within a community, and association with physical activity, nutrition, and other healthy behaviors. Over 4 years, the Calgary Flames Sport and Entertainment Corporation in conjunction with local health promotion professionals, delivered a health promotion event to the public, The Calgary Flames Health Training Camp (FHTC) in Calgary, Alberta, Canada. The purpose of these annual events has been to inspire and encourage healthy behavior uptake and adherence. A description of the FHTC over each of 4 years (2015–2018), lessons learned, and some evaluative work done alongside the event on 2 of the 4 years. In 2017, self-report surveys were administered to event attendees to assess current health status including physical activity, socio-cognitive variables, health information preference, and intention to make healthful behavior change based on event attendance. Biometric data was collected including blood pressure, height, weight, and resting heart rate. Evaluations of the four consecutive events showed that the Calgary Flames Sport and Entertainment Corporation has an ability to attract substantial numbers of the general public to attend FHTC events. Self-report measures from 2017 suggest that already-active populations may be most interested in attending however, the events do appear to inspire attendees to consider behavioral changes for health. The events helped to identify individuals with health risks requiring medical attention but has not yet resulted in known behavior changes. Positive community health impacts may arise from collaboration between health promoters and professional sporting organizations.