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Jeffery Ho, Sabir Hussain,
Frontiers in Veterinary Science, Volume 8; doi:10.3389/fvets.2021.647308

Abstract:
This study aimed to determine if there has been an increase of global interest on pet adoption immediately after the WHO declaration of the pandemic and if the effect has been sustainable in 8 months on. We conducted a Google Trends search using keywords related to pet adoption. Relative search volume (RSV) was scored between 0 and 100 for the lowest and the highest, respectively. Top countries contributing to the dataset included Australia, the United States, Canada, New Zealand, the United Kingdom, Singapore, the Philippines, and Malaysia. From 2015 through 2020, the worldwide RSV for the categories of pet, dog and cat adoption peaked between April and May 2020, the early epidemic phase of the pandemic. These were significantly higher than the 5-year worldwide average RSV for all three categories (P = 0.001). Comparing to the same period in 2019, the RSV ratio (2020/2019) for both dog and cat adoption increased by up to 250%. Nonetheless, the RSV for dog adoption has been decreasing since July 2020 and returned to the 5-year average by December 2020. In contrast, the interest in cat adoption remained sustainably high, possibly reflecting the feline acclimation to indoor living. In conclusion, the global interest in pet adoptions surged in the early phase of the pandemic but not sustainable. With the launch of COVID-19 vaccines, there is a concern for separation anxiety and possible abandonment of these newly adopted pets when the owners would leave their homes for work in the future.
Salar Pashangzadeh, Morteza Motallebnezhad, Fatemeh Vafashoar, Azadeh Khalvandi,
Frontiers in Immunology, Volume 12; doi:10.3389/fimmu.2021.669382

Abstract:
MicroRNAs (miRNAs) are small noncoding conserved RNAs containing 19 to 24 nucleotides that are regulators of post-translational modifications and are involved in the majority of biological processes such as immune homeostasis, T helper cell differentiation, central and peripheral tolerance, and immune cell development. Autoimmune diseases are characterized by immune system dysregulation, which ultimately leads to destructive responses to self-antigens. A large body of literature suggests that autoimmune diseases and immune dysregulation are associated with different miRNA expression changes in the target cells and tissues of adaptive or innate immunity. miR-155 is identified as a critical modulator of immune responses. Recently conducted studies on the expression profile of miR-155 suggest that the altered expression and function of miR-155 can mediate vulnerability to autoimmune diseases and cause significant dysfunction of the immune system.
Beatriz Manriquez, Daniel Muller,
Frontiers in Microbiology, Volume 12; doi:10.3389/fmicb.2021.619122

Abstract:
In natural environments, microbial communities must constantly adapt to stressful environmental conditions. The genetic and phenotypic mechanisms underlying the adaptive response of microbial communities to new (and often complex) environments can be tackled with a combination of experimental evolution and next generation sequencing. This combination allows to analyse the real-time evolution of microbial populations in response to imposed environmental factors or during the interaction with a host, by screening for phenotypic and genotypic changes over a multitude of identical experimental cycles. Experimental evolution (EE) coupled with comparative genomics has indeed facilitated the monitoring of bacterial genetic evolution and the understanding of adaptive evolution processes. Basically, EE studies had long been done on single strains, allowing to reveal the dynamics and genetic targets of natural selection and to uncover the correlation between genetic and phenotypic adaptive changes. However, species are always evolving in relation with other species and have to adapt not only to the environment itself but also to the biotic environment dynamically shaped by the other species. Nowadays, there is a growing interest to apply EE on microbial communities evolving under natural environments. In this paper, we provide a non-exhaustive review of microbial EE studies done with systems of increasing complexity (from single species, to synthetic communities and natural communities) and with a particular focus on studies between plants and plant-associated microorganisms. We highlight some of the mechanisms controlling the functioning of microbial species and their adaptive responses to environment changes and emphasize the importance of considering bacterial communities and complex environments in EE studies.
Published: 7 May 2021
Frontiers in Medicine, Volume 8; doi:10.3389/fmed.2021.644760

Abstract:
Atopic dermatitis (AD) is among the most frequent inflammatory skin diseases in humans, affecting up to 20% of children and 10% of adults in higher income countries. Chronic pruritus is a disease-defining symptom of AD, representing the most burdensome symptom for patients. Severe chronic pruritus causes significant sleep disturbances and impaired quality of life, as well as increased anxiety, depression and suicidal behavior. Until recently, skin care, topical corticosteroids, and calcineurin-inhibitors were primarily used to treat mild to moderate AD, while phototherapy and immunosuppressive agents such as corticosteroids, cyclosporine, and methotrexate were used to treat patients with moderate to severe AD. The potential short- and long-term adverse events associated with these treatments or their insufficient therapeutic efficacy limited their use in controlling pruritus and eczema in AD patients over longer periods of time. As our understanding of AD pathophysiology has improved and new systemic and topical treatments have appeared on the market, targeting specific cytokines, receptors, or their intracellular signaling, a new era in atopic dermatitis and pruritus therapy has begun. This review highlights new developments in AD treatment, placing a specific focus on their anti-pruritic effects.
, Erika Gyengési, John W. Morley
Frontiers in Cellular Neuroscience, Volume 15; doi:10.3389/fncel.2021.686796

Abstract:
Editorial on the Research Topic Neuronal Pathways Affecting Glial Function The brain is a neuron-glia system, in which neuronal activity affects glia function and in return, glial cells impact neuronal activity. It is well-established that glia expresses a plethora of ionotropic and metabotropic receptors, and that under physiological conditions they can react to neuronal activity via different pathways, including enhancement of synaptic release of neurotransmitters (Buskila and Amitai, 2010), the release of neurotrophic factors (Liddelow et al., 2017) and Ca2+ dependent release of gliotransmitters (Pirttimaki et al., 2017). Moreover, damage associated molecular patterns (DAMP's) released from neurons during pathophysiological conditions can lead to glial reactivity and induction of neuroinflammation (Cunningham et al., 2019). However, the specific pathways and mechanisms by which neurons impact the functional activity of glial cells are still unclear. In this Research Topic we present a collection of articles discussing some of the pathways and mechanisms by which neurons impact the functional activity of glia during both physiological and pathological conditions. Stevenson et al. review the recent literature about neuron to glia communication pathways, focusing on studies concerning the impact of neurons on glial activity during neurodegenerative disorders. The authors specifically discuss the overall lack of glial support, due to the dysregulation of neuron to glia interactions, as a key contribution to the etiology and disease progression of neurodegeneration. Following an in depth description of the current standing, including processes by which neuronal signals are amplified via neuromodulation of glial activity and the glial processes that are affected during neurodegeneration, the authors discuss a new therapeutic strategy which place glia as the therapeutic target. Greferath et al. describes the glial changes in the retina during retinitis pigmentosa. Their findings indicate morphological changes between the dorsal and ventral regions of the retina, and point out the negative correlation between the presence of glia within the subretinal space and the thickness of debris which affects the loss of photoreceptors. They concluded that the breakdown in the outer limiting membrane in the ventral retina is critical for the extension of glial processes and migration of microglia into the subretinal space, that ultimately exacerbates photoreceptor death via release of cytokines (e.g., Ccl5) in this region of the retina. Pacholko et al. discuss the role astrocytes play in extending and amplifying neuromodulatory actions. Neuromodulators influence transitions between brain states, however these state changes are dynamic and occur over widespread regions of the CNS. Since a simple diffusion of neuromodulators alone is not sufficient to enable such a widespread effect, the authors hypothesize that astrocytes provide the means by which neuromodulators have their widespread influence. From their review of the literature the authors conclude that the interconnected astrocytic syncytium is essential for eliciting and extending neuromodulator effects by promoting synchronicity of neuronal populations associated with the different brain states. The cholinergic pathways in the CNS are involved in cognitive function and, under normal conditions, are supported by the intimate relationship between cholinergic neurons and glia. This relationship is essential to maintain protection against acute inflammatory and oxidative stresses. Cognitive decline in aging is in some cases associated with pathology, such as in Alzheimer's disease and Lewy Body dementia, but can also occur during physiological aging, and where there is a disruption in the central cholinergic pathways possibly associated with chronic neuroinflammation. Gamage et al. provide a summary of the role of glia, in particular microglia and astrocytes, in protecting against inflammatory and oxidative stress. They provide evidence implicating nicotinic acetylcholine receptors in that role, and that targeting these receptors could provide a therapeutic advantage in the treatment of age-related neurodegenerative diseases and chronic inflammation. Taking these results and reviews together, it is clear that our understanding of the role of glial cells, including microglia, astroglia and oligodendrocytes, has come a long way from being considered as merely a non-functional glue for neurons, to now being appreciated as a crucial player in supporting neuronal function. While decades of research is now trying to catch up on revealing the true depth and importance of their function and support during both physiological and pathological conditions, what we know today is most likely just still the tip of what could be a very large iceberg. By using modern experimental techniques and genetic manipulations, we will gain more insight into the functional relationship of glia and specific neuronal populations in the central nervous system during both healthy aging and disease conditions. This Research Topic is a good starting point and shows some of the reasons for the exciting promise of future research to reveal more about the function of glial cells. All authors conceived the project, revised the literature, wrote, and approved the manuscript. The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. Buskila, Y., and Amitai, Y. (2010). Astrocytic iNOS-dependent enhancement of synaptic release in mouse neocortex. J. Neurophysiol. 103, 1322–1328. doi: 10.1152/jn.00676.2009 PubMed Abstract | CrossRef Full Text | Google Scholar Cunningham, C., Dunne, A., and Lopez-Rodriguez, A. B. (2019). Astrocytes: heterogeneous and dynamic phenotypes in neurodegeneration and innate immunity. Neuroscientist 25, 455–474. doi:...
Jan Keiten-Schmitz, Linda Röder, Eran Hornstein, , Stefan Müller
Frontiers in Molecular Biosciences, Volume 8; doi:10.3389/fmolb.2021.673038

Abstract:
Spatial organization of cellular processes in membranous or membrane-less organelles (MLOs, alias molecular condensates) is a key concept for compartmentalizing biochemical pathways. Prime examples of MLOs are the nucleolus, PML nuclear bodies, nuclear splicing speckles or cytosolic stress granules. They all represent distinct sub-cellular structures typically enriched in intrinsically disordered proteins and/or RNA and are formed in a process driven by liquid-liquid phase separation. Several MLOs are critically involved in proteostasis and their formation, disassembly and composition are highly sensitive to proteotoxic insults. Changes in the dynamics of MLOs are a major driver of cell dysfunction and disease. There is growing evidence that post-translational modifications are critically involved in controlling the dynamics and composition of MLOs and recent evidence supports an important role of the ubiquitin-like SUMO system in regulating both the assembly and disassembly of these structures. Here we will review our current understanding of SUMO function in MLO dynamics under both normal and pathological conditions.
Tao Yan, Yuefeng Qiu, ,
Frontiers in Psychiatry, Volume 12; doi:10.3389/fpsyt.2021.658340

Abstract:
Mounting evidence demonstrates a close relationship between sleep disturbance and mood disorders, including major depression disorder (MDD) and bipolar disorder (BD). According to the classical two-process model of sleep regulation, circadian rhythms driven by the light–dark cycle, and sleep homeostasis modulated by the sleep–wake cycle are disrupted in mood disorders. However, the exact mechanism of interaction between sleep and mood disorders remains unclear. Recent discovery of the glymphatic system and its dynamic fluctuation with sleep provide a plausible explanation. The diurnal variation of the glymphatic circulation is dependent on the astrocytic activity and polarization of water channel protein aquaporin-4 (AQP4). Both animal and human studies have reported suppressed glymphatic transport, abnormal astrocytes, and depolarized AQP4 in mood disorders. In this study, the “glymphatic dysfunction” hypothesis which suggests that the dysfunctional glymphatic pathway serves as a bridge between sleep disturbance and mood disorders is proposed.
Farnoosh Emamian, Mostafa Mahdipour, Khadijeh Noori, Masoumeh Rostampour, S. Bentolhoda Mousavi, Habibolah Khazaie, Mohammadreza Khodaie-Ardakani, , Mojtaba Zarei
Frontiers in Psychiatry, Volume 12; doi:10.3389/fpsyt.2021.661286

Abstract:
Insomnia disorder (ID) is a common illness associated with mood and cognitive impairments. Subtyping ID is an ongoing debate in sleep medicine, but the underlying mechanisms of each subtype is poorly understood. Growing evidence suggests that subcortical brain structures play the key roles in pathophysiology of ID and its subtypes. Here, we aimed to investigate structural alteration of subcortical regions in patients with two common ID subtypes i.e., paradoxical and psychophysiological insomnia. Fifty-five patients and 49 healthy controls were recruited for this study and T1-weighted images and subjective and objective sleep parameters (i.e., Pittsburgh Sleep Quality Index and polysomnography) were collected from participants. Subcortical structures including the hippocampus, amygdala, caudate, putamen, globus pallidus, nucleus accumbens, and thalamus were automatically segmented in FSL. Volume and shape (using surface vertices) of each structure were compared between the groups, controlled for covariates, and corrected for multiple comparisons. In addition, correlations of sleep parameters and surface vertices or volumes were calculated. The caudate's volume was smaller in patients than controls. Compared with controls, we found regional shrinkage in the caudate, nucleus accumbens, posterior putamen, hippocampus, thalamus, and amygdala in paradoxical insomnia and shrinkage in the amygdala, caudate, hippocampus, and putamen in psychophysiological insomnia. Interestingly, comparing two patients groups, shape alteration in the caudate, putamen, and nucleus accumbens in paradoxical insomnia and shrinkage in the thalamus, amygdala, and hippocampus in psychophysiological insomnia were observed. Both subjective and objective sleep parameters were associated with these regional shape alterations in patients. Our results support the differential role of subcortical brain structures in pathophysiology of paradoxical and psychophysiological insomnia.
Shun Tasaka, , Noriyoshi Takahashi, Rei Umezawa, Takaya Yamamoto, Yojiro Ishikawa, Kazuya Takeda, Yu Suzuki, Noriyuki Kadoya
Published: 7 May 2021
Frontiers in Oncology, Volume 11; doi:10.3389/fonc.2021.665837

Abstract:
Background Xerostomia is one of the most common adverse events of radiotherapy in head and neck cancer patients. There have been many reports on functional changes of the parotid gland after radiation therapy, but there have been few reports on the volume of the parotid gland and its relationship with oral quality of life (QOL) and even fewer reports on longitudinal change of the parotid gland volume. The purpose of this study was to evaluate the long-term change of the parotid gland volume after intensity-modulated radiotherapy (IMRT) for nasopharyngeal carcinoma and the relationship between parotid irradiation dose and xerostomia symptoms. Methods We retrospectively analyzed 26 patients with nasopharyngeal cancer treated by IMRT. Longitudinal changes of parotid gland volumes after IMRT were evaluated on CT images. The parotid gland volumes in each period were converted to the ratio to parotid gland volumes before radiotherapy (relative parotid volume). Dunnett’s test was used to evaluate the longitudinal changes in relative parotid volumes at 0-6, 7-18, 19-30, 31-42, 43-54 and 55-66 months after IMRT. We assessed xerostomia 3 years or more after IMRT by measuring the degree of oral moisture using a moisture-checking device (Mucus, Life Co., Ltd.) and oral QOL evaluation by GOHAI (General Oral Health Assessment Index). Results The relative parotid volumes during radiotherapy and at 0-6, 7-18, 19-30, 31-42, 43-54 and 55-66 months after IMRT were 75.2 ± 14.3%, 67.2 ± 11.4%, 68.5 ± 15.9%, 72.4 ± 14.8%, 73.0 ± 13.8%, 76.2 ± 17.5%, and 77.1% ± 17.3%, respectively. The parotid volume had recovered significantly at 43-54 and 55-66 months after IMRT, especially in parotids receiving less than 40 Gy as the mean dose. The mean irradiated dose for bilateral parotids showed negative correlations with oral QOL score and oral moisture after a long period. Conclusions The parotid volume recovered gradually but had not reached a plateau even 3 years after radiotherapy, especially in parotids receiving less than 40 Gy as the mean dose.
, Jo Verschueren, Jean-Pierre Baeyens, Anne Benjaminse, Alli Gokeler, Ben Serrien, Ron Clijsen
Frontiers in Psychology, Volume 12; doi:10.3389/fpsyg.2021.533033

Abstract:
Background: Differential learning (DL) is a motor learning method characterized by high amounts of variability during practice and is claimed to provide the learner with a higher learning rate than other methods. However, some controversy surrounds DL theory, and to date, no overview exists that compares the effects of DL to other motor learning methods. Objective: To evaluate the effectiveness of DL in comparison to other motor learning methods in the acquisition and retention phase. Design: Systematic review and exploratory meta-analysis. Methods: PubMed (MEDLINE), Web of Science, and Google Scholar were searched until February 3, 2020. To be included, (1) studies had to be experiments where the DL group was compared to a control group engaged in a different motor learning method (lack of practice was not eligible), (2) studies had to describe the effects on one or more measures of performance in a skill or movement task, and (3) the study report had to be published as a full paper in a journal or as a book chapter. Results: Twenty-seven studies encompassing 31 experiments were included. Overall heterogeneity for the acquisition phase (post-pre; I 2 = 77%) as well as for the retention phase (retention-pre; I 2 = 79%) was large, and risk of bias was high. The meta-analysis showed an overall small effect size of 0.26 [0.10, 0.42] in the acquisition phase for participants in the DL group compared to other motor learning methods. In the retention phase, an overall medium effect size of 0.61 [0.30, 0.91] was observed for participants in the DL group compared to other motor learning methods. Discussion/Conclusion: Given the large amount of heterogeneity, limited number of studies, low sample sizes, low statistical power, possible publication bias, and high risk of bias in general, inferences about the effectiveness of DL would be premature. Even though DL shows potential to result in greater average improvements between pre- and post/retention test compared to non-variability-based motor learning methods, more high-quality research is needed before issuing such a statement. For robust comparisons on the relative effectiveness of DL to different variability-based motor learning methods, scarce and inconclusive evidence was found.
, Charlotte Melander, Ingrid Höjer
Published: 7 May 2021
Frontiers in Sociology, Volume 6; doi:10.3389/fsoc.2021.660638

Abstract:
This article draws from a broader research project Transnational childhoods, illuminating the agency and experiences of children and young people migrating from Poland and Romania to Sweden under the age of 18. Focusing on young people born in Poland and having social relationships post-migration as central theoretical component, the article explores the role that the Polish Catholic community in Sweden plays in the lives of young Polish migrants. It does so by grounding the analysis on 23 qualitative interviews, combined with network maps and life-lines, produced by the young Polish participants. The study identifies three important dimensions in the role of the Polish Catholic community. These are comprised of the community's role for young Poles' spiritual development and religious identity, for building new friendships and making sense of common migration and religious experiences, and guidance by specifically Polish Catholic priests in the young migrants' family relationships and in future life projects. The article concludes that while practicing religion and building significant social relationships within the Polish congregations the young migrants shape feelings of belonging and inclusion, however primarily within the limits of their own ethnic community. Further research is needed on the wider implications of primarily mono-ethnic relational practices for the young Poles' lives within the increasingly ethnically heterogeneous Swedish society.
, Martin Etzrodt, Sönke Bartling, Ray Walshe, Tomás Harrington, Neslihan Wittek, Sebastian Posth, Kevin Wittek, Andrei Ionita, Wolfgang Prinz, et al.
Frontiers in Blockchain, Volume 4; doi:10.3389/fbloc.2021.631648

Abstract:
Since its launch just over a decade ago by the cryptocurrency Bitcoin, the distributed ledger technology (DLT) blockchain has followed a breathtaking trajectory into manifold application spaces. This study aper analyses how key factors underpinning the success of this ground-breaking “Internet of value” technology, such as staking of collateral (“skin in the game”), competitive crowdsourcing, crowdfunding, and prediction markets, can be applied to substantially innovate the legacy organization of science, research, and technology development (RTD). Here, we elaborate a highly integrative, community-based strategy where a token-based crypto-economy supports finding best possible consensus, trust, and truth by adding unconventional elements known from reputation systems, betting, secondary markets, and social networking. These tokens support the holder’s formalized reputation and are used in liquid-democracy style governance and arbitration within projects or community-driven initiatives. This participatory research model serves as a solid basis for comprehensively leveraging collective intelligence by effectively incentivizing contributions from the crowd, such as intellectual property work, validation, assessment, infrastructure, education, assessment, governance, publication, and promotion of projects. On the analogy of its current blockbusters like peer-to-peer structured decentralized finance (“DeFi”), blockchain technology can seminally enhance the efficiency of science and RTD initiatives, even permitting to fully stage operations as a chiefless decentralized autonomous organization (DAOs).
Angela Gifford, Vivien Marmelat,
Frontiers in Psychology, Volume 12; doi:10.3389/fpsyg.2021.595816

Abstract:
The stressful nature of caring for an older adult with a chronic disease, such as Alzheimer’s disease (AD), can create barriers between the caregiver-care recipient, as they try to navigate their continuously changing social relationship. Interpersonal synchrony (i.e., matching or similarity of movement, emotions, hormones, or brain activity), is an innovative approach that could help to sustain caregiving relationship dynamics by promoting feelings of connection and empathy through shared behavior and experiences. This review investigates the current literature on interpersonal synchrony from an interdisciplinary perspective by examining interpersonal synchrony through psychological, neural, and hormonal measures across the adult lifespan. We then present a case for examining the degree to which interpersonal synchrony can be used to facilitate affiliation and well-being in the caregiver-care recipient relationship. We find that there is significant evidence in healthy adult populations that interpersonal synchrony can support affiliative feelings, prosocial behavior, and well-being. Characterizing the psychological, neural, and hormonal mechanisms of interpersonal synchrony is a first step towards laying the groundwork for the development of tools to support relational closeness and empathy in the caregiving context. Finally, we explore the strengths and limitations of using interpersonal synchrony to support relational well-being, and discuss possible avenues for future research.
, Wenqin Wang, Chuang Ma, Ray Ming
Published: 7 May 2021
Frontiers in Genetics, Volume 12; doi:10.3389/fgene.2021.687160

Abstract:
Editorial on the Research Topic Genomics-Enabled Crop Genetics In the genomics era, omics-based technologies have unprecedentedly promoted progress in plant biology, from plant growth and development, plant physiology to molecular genetic studies, and system and synthetic biology. While proteomics and metabolomics are becoming prevalent, genomics and transcriptomics are the most popular and widely used platforms for crop studies due to their rapidly decreased costs, improved sequencing quality, a broad spectrum of applications, and well-established bioinformatic tools. Genetic and functional genomic studies in crops, especially those in non-model crops, have been lagged far behind compared to those in model plant species for a couple of reasons. First, some crops can have a large, complex and polyploidy genome, such as wheat (Triticum aestivum) (International Wheat Genome Sequencing Consortium, 2018). Second, while a group of closely related crop species is often comparatively studied or used in breeding programs, they could have distinct genomes and/or ploidy levels, representing further technical challenges for molecular studies. For example, the peanuts include the cultivated peanut (Arachis hypogaes, AABB genome), the wild tetraploid peanut (Arachis monticola, AABB genome) and two wild diploid peanuts, Arachis duranensis (AA genome) and Arachis ipaensis (BB genome) (Bertioli et al., 2016, 2019; Chen et al., 2016, 2019; Lu et al., 2018; Yin et al., 2018, 2019; Zhuang et al., 2019). Another example is the cultivated bananas, which are interspecific or intraspecific hybrids between wild diploid Musa acuminata (AA genome) and Musa balbisiana (BB genome). They have various genotypes, including diploid (AA, BB, and AB), triploid (AAA, AAB, and ABB) and tetraploid (AAAB, AABB, ABBB) variants (D'Hont et al., 2012; Davey et al., 2013; Martin et al., 2016; Wang et al., 2019). Third, for many crops the genomic resources supporting functional studies and molecular breeding are not often available, including high-quality reference genome assemblies, high-density genetic maps, and genomics-characterized populations. Finally, in some crops (such as sorghum), genetic transformation is still challenging, and mutant resources are not well-established. When synergistically integrated with other omics approaches, genomic technologies can be compelling for crop genetics, representing a technological basis to help mitigate or circumvent the challenges mentioned above in crop studies. The papers included in this Research Topic, Genomics-Enabled Crop Genetics, illustrate this concept. The various studies collected in this Research Topic can be summarized into three major aspects: (1) the theme of “Genomic technologies promote germplasm characterization” includes contributions regarding molecular identification, characterization of crop species and accessions with genomics-based methods. (2) The subject of “Genomic technologies enhance crop population genetics” showcases the examples of population genetic studies facilitated by the genomic approaches. (3) The topic of “Genomic technologies enable functional mining of genomic components in crops,” on the other hand, presents the applications in multiple genomic and transcriptomic databases. These resources are comprehensively integrated to generate functional insights into the genomic components, e.g., genes, miRNAs and cis-regulatory elements. This Research Topic includes thirteen original research articles, one hypothesis and theory paper, one opinion paper and one review article, covering the following three aspects. Markers of simple sequence repeats (SSR) or chloroplast DNA are often used to study the phylogenetic relationship between accessions or species within a crop genus. Taking the advantages of RNA-seq that provides sequence information about functional genes in a cost-effective and high-throughput way, Karcı et al. performed transcriptome sequencing of pistachio (Pistacia vera), developed 233 genic SSR markers (gSSR) and studied the phylogenetic relationship using 55 gSSR markers from nine Pistacia species. This study exemplifies RNA-seq as a tool to contribute to the taxonomy of crop species and their relatives. Qiu et al. assembled the five fescue taxa's chloroplast genomes, including three subspecies of Festuca rubra, one Festuca brevipila, and one Festuca ovina, providing resources to screen fescue germplasm accessions and to refine species identification. With the plastid genome information, Qiu et al. reconstructed the phylogenetic relationship of the Festuca-Lolium complex. Synthetic or artificial polyploid hybrid materials within the Triticum genus or Triticum and its relative species represent essential wheat genetic improvement resources. Cytogenetic techniques can help provide insights into crop genomics, guiding further investigations on certain genomic issues. For example, to better characterize the tetraploid wheat-Aegilops ventricosa amphiploid materials, Zhang et al. observed the chromosomal behavior of the progeny plants (AABBDVDVNVNV) derived from crosses between T. turgidum (AABB) and Aegilops ventricosa (DVDVNVNV) using multicolor Fluorescence in situ hybridization (mc-FISH), providing insights into the genome stability of allopolyploidization in the wheat group. Genomic-based technologies have enhanced the traditional linkage mapping of quantitative trait loci (QTL) and enabled genome-wide association study (GWAS) by developing hundreds of thousands of markers (single nucleotide polymorphism, SNP, e.g., in most applications). In understudied crops, it is cost-effective to develop abundant SNP markers for QTL mapping by using reduced representation sequencing techniques, such as restriction-site associated DNA sequencing (RAD-seq) (Miller et al., 2007), genotyping-by-sequencing (GBS) (Elshire et al., 2011), and specific length amplified fragment sequencing (SLAF-seq) (Zhang et al.,...
Suliman Khan, Rabeea Siddique, Ding Huanfei, Muhammad Adnan Shereen, Ghulam Nabi, Qian Bai, Sehrish Manan, , , Hu Bowen
Frontiers in Bioengineering and Biotechnology, Volume 9; doi:10.3389/fbioe.2021.616555

Abstract:
Bone serves to maintain the shape of the human body due to its hard and solid nature. A loss or weakening of bone tissues, such as in case of traumatic injury, diseases (e.g., osteosarcoma), or old age, adversely affects the individual’s quality of life. Although bone has the innate ability to remodel and regenerate in case of small damage or a crack, a loss of a large volume of bone in case of a traumatic injury requires the restoration of bone function by adopting different biophysical approaches and chemotherapies as well as a surgical reconstruction. Compared to the biophysical and chemotherapeutic approaches, which may cause complications and bear side effects, the surgical reconstruction involves the implantation of external materials such as ceramics, metals, and different other materials as bone substitutes. Compared to the synthetic substitutes, the use of biomaterials could be an ideal choice for bone regeneration owing to their renewability, non-toxicity, and non-immunogenicity. Among the different types of biomaterials, nanocellulose-based materials are receiving tremendous attention in the medical field during recent years, which are used for scaffolding as well as regeneration. Nanocellulose not only serves as the matrix for the deposition of bioceramics, metallic nanoparticles, polymers, and different other materials to develop bone substitutes but also serves as the drug carrier for treating osteosarcomas. This review describes the natural sources and production of nanocellulose and discusses its important properties to justify its suitability in developing scaffolds for bone and cartilage regeneration and serve as the matrix for reinforcement of different materials and as a drug carrier for treating osteosarcomas. It discusses the potential health risks, immunogenicity, and biodegradation of nanocellulose in the human body.
Yuhua Wang, Haijie Guo
Published: 7 May 2021
Frontiers in Chemistry, Volume 9; doi:10.3389/fchem.2021.654347

Abstract:
Based on the actual application requirements of multicolor long persistent luminescence (LPL) materials, we highlight the recent developments in the last decade on human-eye-sensitive LPL materials and try to make a full list of known LPL compounds possessing wavelengths of 400–600 nm and a duration time longer than 10 h (>0.32 mcd/m2); these are more sensitive to the human eye's night vision and can be used throughout the night. We further emphasize our group research of novel LPL materials and the regulation of LPL color to enable a full palette. In the end, we try to summarize the challenges and perspectives of LPL materials for potential research directions based on our limited understandings. This review could offer new enlightenment for further exploration of new LPL materials in the visible light range and related applications.
, Zhongli Hu, TiePei Zhu, Zhitao Su, Xiaoyun Fang, Jijian Lin, Zhiqing Chen, Zhaoan Su, Panpan Ye, Jian Ma, et al.
Published: 7 May 2021
Frontiers in Medicine, Volume 8; doi:10.3389/fmed.2021.657772

Abstract:
Purpose: To establish quantitative profile of the morphologic changes among patients with active myopic choroidal neovascularization (mCNV) before and after anti-vascular endothelial growth factor (VEGF) therapy using optical coherence tomography angiography (OCTA) to assess the therapeutic response. Methods: Patients with active mCNV who received anti-VEGF injections between February 2017 to October 2020 and fit the study criteria were retrospectively reviewed. Quantitative analysis of their OCTA images were carried out to evaluate the morphologic features and vascular changes of mCNV lesions in response to anti-VEGF therapy. For further quantitative profiling, mCNV area, fractal dimension, vessel area, vessel density, vessel diameter, vessel length, vessel junction, junction density, and vessel tortuosity were obtained by means of advanced skeletonization postprocessing analyses. Results: Thirty-one eyes of 29 consecutive patients with OCTA-positive mCNV lesions (mean spherical equivalent: −12.55 ± 3.24 diopters) were included. The 31 cases were divided into two phenotypes at baseline: organized interlacing pattern (83.87%) and disorganized vascular loops pattern (16.13%). The values of mCNV area, fractal dimension, vessel area, vessel length, vessel junction, and junction density decreased remarkably 1 month after the initial anti-VEGF injection (p < 0.001). Although, vessel density, vessel diameter, and vessel tortuosity increased meanwhile, only vessel diameter displayed statistical significance (p = 0.027). Of note, relative ratio analysis showed that vessel junction was the most sensitive biomarker in response to anti-VEGF therapy, reflecting a mean decrease of 50.36%. Sensitivity lowered successively in biomarkers of vessel length, vessel area, junction density, mCNV area, and fractal dimension. In addition, percent change of mCNV area (r = 0.552, p = 0.002), fractal dimension (r = 0.446, p = 0.017), vessel area (r = 0.518, p = 0.005), and vessel length (r = 0.440, p = 0.019) were moderately associated with that of central retinal thickness. Conclusions: The study showed morphological as well as quantitative changes on OCTA responding to anti-VEGF treatment in mCNV patients, among which vessel junctions might be the most predictive biomarker. OCTA-based analysis, providing intuitive images and a large spectrum of quantitative data at the same time, could promote new insights into the therapeutic response assessment in mCNV patients.
, Daniel Boullosa, Rodrigo Ramirez-Campillo, Ajmol Ali,
Frontiers in Physiology, Volume 12; doi:10.3389/fphys.2021.669687

Abstract:
Editorial on the Research Topic Acute: Chronic Workload Ratio: Is There Scientific Evidence? The scientific monitoring of athletes is fundamental to determine and understand the individual biological responses to training (Halson, 2014). In elite sports, it is crucial to regularly monitor training and performance to detect biopositive or negative responses that can be used to effectively program training according to the needs of each athlete (Bourdon et al., 2017). Moreover, workload monitoring can also help to assess fatigue and indicate the need for recovery in different physically demanding situations to ultimately avoid injuries (Halson, 2014). As there is evidence that lower injury rates are associated with higher team sport performances (Eirale et al., 2013), sport scientists and medical staff should regularly and accurately evaluate athletes' injury risk using workload measures (Halson, 2014). Based on Banister et al. (1975) fitness and fatigue model, Gabbett et al. (2016) introduced the concept of the acute:chronic workload ratio (ACWR) with acute workload hypothetically representing the fatigue component and chronic workload the fitness component of Banister's model (Figure 1). ACWR allows individualized performance development and injury prevention using the relation between acute to chronic workload data. For this purpose, internal (e.g., heart rate, session-rate of perceived exertion [sRPE] × duration) and external (e.g., performance measures, tracking variables such as running speed and/or acceleration using Global Positioning Systems [GPS]) load measures should be collected to compute ACWR during training and competition (Malone et al., 2017). It has previously been recommended to determine the ratio between acute (training load accumulated during the last 7 days) and chronic (mean training load over the previous 3 to 6 weeks) workloads (Gabbett et al., 2016; Gabbett and Whiteley, 2017). The underlying rationale is that athletes' physical fitness develops adequately if the chronic load progressively increases to high levels while the acute load remains below, similar to, or slightly above the chronic workload (i.e., ACWR range between 0.8 and 1.3). Conversely, the athlete is considered not well-prepared and likely at an increased risk of sustaining acute or overuse injuries if the acute workload exceeds the chronic load (i.e., ACWR ≥ 1.5) (Malone et al., 2017; Windt and Gabbett, 2017). Figure 1. Conceptual model for developing athlete monitoring systems according to the fitness-fatigue model using the acute: chronic workload (ACWR) approach and internal/external workload measures. While the fitness component is comparable to chronic workload (e.g., 28 days rolling average workload), fatigue is comparable to acute workload (e.g., 7 days rolling average workload) (adapted from Coutts et al., 2018). Over the past 15 years, the ACWR approach has received a lot of attention from researchers and practitioners who are active in different sports such as Australian football, cricket, rugby, and soccer (Gabbett, 2016, 2020; Griffin et al., 2020). Figure 2 illustrates the exponential growth in the number of PubMed-listed publications per year on ACWR research using the search syntax (“acute to chronic work load ratio” OR ACWR). In 2016, the International Olympic Committee (IOC) published a consensus statement (Soligard et al., 2016) that suggests the use of the ACWR approach for injury prevention. In addition, Myers et al. (2020) reported level A evidence in support of the sRPE ACWR as an effective tool to prevent non-contact injuries in elite athletes. Despite evidence in favor of the ACWR approach, different authors have raised substantial criticism (Impellizzeri et al., 2020a,b; Wang et al., 2020). For instance, the validity of ACWR has been recently questioned due to the large heterogeneity of the internal (e.g., session RPE, heart rate) and the external load (e.g., GPS data, training time) variables that are used for ACWR calculation (Impellizzeri et al., 2020a,b; Wang et al., 2020). In addition, opponents of the ACWR approach argue that there is no rationale as to the exact time span for acute and chronic workload monitoring (Impellizzeri et al., 2020a,b). In the absence of a rationale, other authors have selected multiple time windows (Delecroix et al., 2018), but again the selected time span appears arbitrary. Another major criticism that has been postulated is that ACWR is a measure of training workload, most often assessed through spatio-temporal metrics from GPS data, but not a mechanical load parameter (Impellizzeri et al., 2020a,b). In a strict biomechanical sense, repetitive mechanical load, but not training load, is associated with an increased risk of tissue damage (Brüggemann and Niehoff, 2011). In other words, training load is not a surrogate of mechanical loading. Overall, the literature on ACWR research is controversial, which is why more research is needed. Figure 2. Number of PubMed listed publications per year related to the topic Acute: Chronic Workload Ratio (ACWR) between 1980 and 2020. The following search was applied in the electronic database PubMed (“acute to chronic work load ratio” OR ACWR). Accordingly, it was timely to elucidate strengths and weaknesses of the ACWR approach in the form of a Frontiers Research Topic entitled “Acute: Chronic Workload Ratio: Is there Scientific Evidence?.” Thus, the aims of this Research Topic were to provide knowledge on the underlying physiological mechanisms of ACWR and if there is a scientific evidence to support the use of this ratio as an approach for injury risk prediction in different sports. Overall, seven articles were published in this Research Topic. The contributing 45 authors are from different countries across the globe including Australia, Brazil, China, Czech-Republic, France, Germany, Iran, Slovakia, Spain, Switzerland, and the United States of...
Soma Farag, Claire Feeney, , Sonali Nagendran, Rajni Jain, Ahmad Aziz, Rashmi Akishar, Vassiliki Bravis, Karim Meeran
Frontiers in Endocrinology, Volume 12; doi:10.3389/fendo.2021.669871

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Background/Aims There is no universal consensus on the practical implementation and evaluation of the Amsterdam Declaration on Graves Orbitopathy in a Multidisciplinary Thyroid Eye Disease (MDTED) pathway. Recent recommendations from the UK TEAMeD-5 and BOPSS initiative highlight the importance of prevention, screening, and prompt referral of patients with moderate to severe and sight-threatening thyroid eye disease to multidisciplinary (MDTED) clinics and recommends annual auditing. We propose a practical service evaluation model with Key Performance Indicators (KPI) that are achievable and could be implemented across most TED pathways. Material and Methods We conducted a service evaluation from an integrated TED pathway in London with three MDTED clinics. Data was collected retrospectively from consecutive TED patients included: 1) Patient demographics, 2) Referral to first appointment time, 3) Documented smoking cessation and selenium supplementation advice, 4) Presenting disease activity and severity, 5) Investigations and treatments, including radio-iodine, 6) Time from decision to treatment initiation, 7) Initial and subsequent thyroid status. Results The median age was 49.0 yrs, 77.5% (183/236) were female and 49.5% (101/204) Afro-Caribbean or Asian. At their first clinic attendance, 47.6% (110/231) were biochemically euthyroid and 76.7% (79/103) at discharge. All 23.1% (52/225) current smokers received smoking cessation advice and 64.8% (153/236) received selenium supplementation advice. Intravenous methylprednisolone was given to 33.9% (80/236) patients and 12.7% (30/236) received second-line immunosuppression. All 7.2% (17/236) patients with sight-threatening disease received treatment within two weeks of diagnosis. Conclusions This study forms a waymark for other units using TEAMeD-5 and BOPSS audit criteria. Dedicated electronic patient records with ongoing data capture, including quality of life assessments, and diagnostic coding would significantly aid future auditing, improve patient care, and facilitate a national audit of TED management. A future survey when the TED standards have become embedded would be instructive to see whether this has improved TED care.
Young Ji Kim, Sun-Woo Yoon, Jin Ho Jang, Dae Gwin Jeong, Beom Jun Lee, Hye Kwon Kim
Frontiers in Veterinary Science, Volume 8; doi:10.3389/fvets.2021.650866

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Feline parvovirus (FPV) is a small, non-enveloped, single-stranded DNA virus that infects cats. We recently isolated a feline parvovirus Fe–P2 strain from a dead stray cat in Iksan, 2017. Its partial genomic sequence (4,643 bases) was obtained, and phylogenetic analysis based on the VP2 nucleotide sequence showed that the FPV Fe-P2 strain was closely related to the FPV isolate Gigucheon in cat, 2017 (MN400978). In addition, we performed a serum neutralization (SN) test with the FPV isolates in various mammalian sera. These were from raccoon dog, water deer, Eurasian otter, Korean hare, leopard cat, and Asian badger, which were kindly provided by Chungnam Wild Animal Rescue Center. Notably, serological evidence of its infection was found in Asian badger, Meles leucurus (2/2) and leopard cat, Prionailurus bengalensis (5/8) through SN tests, whereas there was no evidence in raccoon dog, water deer, Eurasian otter, and Korean hare based on the collected sera in this study. These findings might provide partial evidence for the possible circulation of FPV or its related viruses among wild leopard cat and Asian badger in Korea. There should be additional study to confirm this through direct detection of FPVs in the related animal samples.
Chuchu Feng, , , Xiaomin Peng, Haixia Guo, Liping Zhan, Xilin Xiong, Wenjun Weng, Jiaqiang Li, Jianpei Fang
Published: 7 May 2021
Frontiers in Oncology, Volume 11; doi:10.3389/fonc.2021.631682

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In this study, the immune microenvironment in Langerhans cell histiocytosis (LCH) was characterized to determine if immune indices are predictive of severity. Serum samples from 54 treatment-naïve patients were analyzed quantitatively for inflammatory cytokines and immunoglobulins before and after the induction of chemotherapy. The initial serum sIL-2R, TNF-α, and IL-10 of untreated LCH patients with risk organ involvement (RO+) were significantly higher than those with single-system (SS) involvement. LCH patients with hematologic involvement exhibited a significantly higher sIL-2R, TNF-α, IL-10, and IL-1β expression, as compared to the group without involvement. sIL-2R, TNF-α, and IL-10 were increased in patients with liver or spleen involvement. Th cells have decreased in the liver+ and spleen+ group, and Ts cells were significantly decreased in non-response group after induction chemotherapy. The serum level of immune indices represents, to some extent, the severity of the disease. Pertinent laboratory inspections can be used to improve risk stratification and guide immunotherapy.
Corrigendum
, Wolfgang Müller, Jonathan Erez
Frontiers in Earth Science, Volume 9; doi:10.3389/feart.2021.681294

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A Corrigendum on Intrashell Variability of Trace Elements in Benthic Foraminifera Grown Under High CO2 Levels by Levi, A., Müller, W., and Erez, J. (2019). Front. Earth Sci. 7:247. doi: 10.3389/feart.2019.00247 In our original article an error occurred during its preparation. While the subject and the content of our paper is very different to that of Not et al. (2018), we used their introduction initially to obtain recent references on the effects of pCO2. By act of technical mistake, their introduction was copied into our manuscript during the initial writing process and then was not removed. We are deeply sorry for this mistake and would like to convey our sincere apologies to C. Not, B. Thibodeau, and Y. Yokoyama and to the journal for our oversight. We completely rewrote the introduction. We confirm that our experimental data and subsequent interpretation are original and genuine and only the introductory text was affected, which is now remedied. (Not, C., Thibodeau, B., and Yokoyama, Y. (2018). Incorporation of Mg, Sr, Ba, U, and B in high-Mg calcite benthic foraminifers cultured under controlled pCO2. Geochem. Geophys. Geosyst. 19, 83–98. doi: 10.1002/2017GC007225) A correction has been made to the introduction: “Foraminifera shells are well-known archives for paleoceanography and paleoclimate reconstructions. In addition to the use of foraminifera for biostratigraphy and paleoecology (e.g., CLIMAP project, 1976; Crowley, 2000), stable isotopes (δ18O and δ13C), trace elements and their isotopes (Cd/Ca, Mg/Ca, U/Ca, δ11B, and more) are successfully used for studying past ocean chemistry and paleocirculation (e.g., Emiliani and Shackleton, 1974; Sanyal et al., 1996; Lea, 1999; Nürnberg, 2000; Barker and Elderfield, 2002; Lear et al., 2002; Katz et al., 2010; Allen et al., 2016; Foster and Rae, 2016). Recently it has been proposed that Na/Ca could be used to reconstruct past ocean calcium concentrations (Hauzer et al., 2018). However, different species of foraminifera at the same location show different shell chemistries and isotopic compositions, which are attributed to “vital effects” representing deviations from expected thermodynamic equilibrium (e.g., Erez, 1978). These deviations are mostly associated with the calcification process that is biologically controlled and thus may affect the incorporation of trace and minor elements and their isotopes into the calcite shells (e.g., Erez, 1978, 2003; Elderfield et al., 1996; Bentov and Erez, 2006; Zeebe et al., 2008; de Nooijer et al., 2014; Gussone et al., 2016). One of the main factors that control foraminiferal calcification is the carbonate system in seawater (e.g., ter Kuile et al., 1989; Spero et al., 1997; Erez, 2003). It is therefore expected that the increase in atmospheric CO2 (pCO2), causing ocean acidification, may reduce foraminiferal calcification as well as affect their shell chemistry (e.g., Erez, 2003; Kuroyanagi et al., 2009; Dias et al., 2010; Fujita et al., 2011; Vogel and Uthicke, 2012; McIntyre-Wressnig et al., 2013). For example Mg/Ca in planktic foraminifera shows species-specific sensitivity to the carbonate system (e.g., Russell et al., 2004; Kisakürek et al., 2008; Allen et al., 2016; Evans et al., 2016, 2018; Holland et al., 2017; Gray and Evans, 2019). An additional complication in the study of foraminiferal proxies is the intra-shell compositional variability (or banding) within individual specimens of both planktic and benthic foraminifera. This has been demonstrated in both trace elements and stable isotopes (e.g., Erez, 2003; Eggins et al., 2004; Rollion-Bard et al., 2008; Hathorne et al., 2009; Branson et al., 2015; Spero et al., 2015; Jonkers et al., 2016; Fehrenbacher et al., 2017; van Dijk et al., 2017, 2019; Geerken et al., 2019; Davis et al., 2020). Intensive experimental work (Eggins et al., 2004; Spero et al., 2015; Jonkers et al., 2016; Fehrenbacher et al., 2017) on planktic foraminifera demonstrated that Mg-rich bands are deposited during the night hours while low-Mg bands are precipitated during the daytime, perhaps connected with mitochondrial activity. Erez (2003) proposed that in large benthic foraminifera banding occurs when a new chamber is created in a two-step process: the first layer of organic-rich matrix (primary calcite) is associated with high concentrations of trace elements, while the secondary thick layer, often termed lamination, covers the existing exposed chambers and is composed of low trace element calcite (secondary calcite). The alteration between high and low elemental bands may thus be attributed to the process of sequential chamber formation (Erez, 2003; Bentov and Erez, 2005, 2006). While this may explain the daily banding in planktic foraminifera that add a chamber every day, the banding phenomena overall are not well-understood. Furthermore, the effect of ocean acidification on the element banding is not known. In this study, we measured the intra-shell variability of trace elements (B, Mg, Na, K, Sr, Ba, and U) in the two benthic foraminifera species Amphistegina lobifera and A. lessonii, cultured at four DIC concentrations (2,340, 2,420, 2,440, and 2,570 μM). These correspond to four pCO2 levels of 430, 560, 740, and 1,390 μatm. These two species are commonly found in coral-reef environments of the Gulf of Eilat, and as such they are an important component of the carbonate sediments in this marine environment (Reiss and Hottinger, 1984). The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way. The original article has been updated. Allen, K. A., Hönisch, B., Eggins, S. M., Haynes, L. L., Rosenthal, Y., and Yu, J. (2016). Trace element proxies for surface ocean conditions: a synthesis of culture calibrations with planktic foraminifera. Geochim. Cosmochim. Acta 193, 197–221. doi: 10.1016/j.gca.2016.08.015 CrossRef...
, Seizo Tanaka
Frontiers in Built Environment, Volume 7; doi:10.3389/fbuil.2021.669601

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Based on the experience of the 2011 Great East Japan Earthquake and the following tsunami, this study aims to develop effective analytical tools that can comprehensively be applied to buildings under multi-phase hazardous loads such as seismic motion, fluid force, and debris impact. Simulations by two kinds of analytical tools were conducted. First, a structural collapse analysis of a steel frame building under successive applications of varying loads was performed using the ASI (Adaptively Shifted Integration)-Gauss code, which simulates behaviors of structures by simple modeling. The steel frame building model was first excited under an acceleration record observed in Kesennuma-shi during the earthquake, and fluid forces due to a tsunami wave were applied. Then, the collapse behavior of the building was investigated by implementing a sophisticated contact algorithm in the numerical code to express a collision between debris and a building. It became evident that the damage to the building intensifies if a head-on collision occurs under a tsunami flow with a lower inundation height, and the damage to the building becomes larger if sideway collisions occur under a tsunami flow with a higher inundation height and higher velocity. The second simulation was conducted by using the stabilized finite element method based on the volume of fluid method, to estimate a drag coefficient of an actual tsunami evacuation building with openings. The practicability of an estimated wave force using the drag coefficient was confirmed by comparing with the wave force obtained from the fluid analysis. Finally, a sequential structural analysis, with a debris collision phase at the end, was conducted using the ASI-Gauss code to simulate the washout behavior of the building.
Zhen Yuan, Xufang Shen, , Jieming Jiang, Binwei Liu, Lei Zhang, Yumeng Wu, Ying Liu, Qi Liu
Frontiers in Endocrinology, Volume 12; doi:10.3389/fendo.2021.674954

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To examine the effect and mechanism of thyroid hormone on gonadal sex differentiation, Takifugu rubripes larvae were treated with goitrogen (methimazole, MET, 1000 μg/g), and thyroxine (T4, 2nM) from 25 to 80 days after hatching (dah). Gonadal histology and sex ratios of fish were then determined at 80 dah. MET treatment induced masculinization, but T4 treatment did not induce feminization in T. rubripes larvae. Transcriptomic analysis of gonads at 80 dah was then conducted. Among the large number of differentially expressed genes between the groups, the expression of foxl2, cyp19a1a, and dmrt1 was altered. The expression of foxl2, cyp19a1a, dmrt1 and gsdf at 25, 40, 55 days after treatment (dat) was further analyzed by qPCR. MET treatment suppressed the expression of foxl2 and cyp19a1a, and induced the expression of dmrt1 in genetic females (p < 0.05). Additionally, T4 treatment induced an increase in the expression of cyp19a1a in genetic XY gonads only at 25 dat. However, the increase in cyp19a1a expression did not continue to 40 and 55 dat. This may explain why feminization of larvae was not found in the T4-treated group. Thus, the present study provides the first evidence that MET treatment causes masculinization in teleost fish. The effects of MET-induced masculinization in T. rubripes may act primarily via suppression of the expression of foxl2 and cyp19a1a, and stimulation of the expression of dmrt1. Moreover, the effects of higher concentrations of T4 or different concentrations of T3, on sex differentiation require further testing.
Vanessa Bednarz, Miguel Leal, Eric Béraud, Joana Ferreira Marques,
Frontiers for Young Minds, Volume 9; doi:10.3389/frym.2021.574637

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Coral reefs are one of the most endangered habitats due to climate change, but not enough attention has been paid to how plastic pollution affects coral reef health. Plastics are massively produced worldwide for many purposes and they degrade very slowly, breaking down into tiny, invisible particles of 5 mm or less, called microplastics. When these tiny particles reach coral reefs, they harm corals by constantly rubbing on them through the action of waves and currents. Corals may also ingest microplastics and get a false sense of “fullness,” which results in the coral not feeding on nutritious food. Within the coral, microplastics may block the gut and cause internal damage. Also, microplastics, which are already made of chemicals, can pick up pollutants and harmful microorganisms from the seawater and transfer them to the coral. A reduction of microplastics pollution is therefore urgent.
Corrigendum
Pooja Ghatalia, Chad H. Smith, Arthur Winer, Jiangtao Gou, Lesli A. Kiedrowski, Michael Slifker, Patricia D. Saltzberg, Nicole Bubes, Fern M. Anari, Vineela Kasireddy, et al.
Published: 7 May 2021
Frontiers in Oncology, Volume 11; doi:10.3389/fonc.2021.674782

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A Corrigendum onClinical Utilization Pattern of Liquid Biopsies (LB) to Detect Actionable Driver Mutations, Guide Treatment Decisions and Monitor Disease Burden During Treatment of 33 Metastatic Colorectal Cancer (mCRC) Patients (pts) at a Fox Chase Cancer Center GI Oncology Subspecialty Clinic By Ghatalia P, Smith CH, Winer A, Gou J, Kiedrowski LA, Slifker M, Saltzberg PD, Bubes N, Anari FM, Kasireddy V, Varshavsky A, Liu Y, Ross EA and El-Deiry WS (2019). Front. Oncol. 8:652. doi: 10.3389/fonc.2018.00652 In the original article, there was a mistake in Figure 3 as published. Incorrect CT scans were provided for two patients, while another patient’s CT scan was erroneously duplicated. The error was previously missed by the authors and the reviewers. The corrected Figure 3 appears below. The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way. The original article has been updated. Figure 3 Correlations between tumor burden as assessed by radiographic imaging (CT scans) or CEA (tumor marker) and liquid biopsy mutation parameters (alts or number of alterations/number of mutated genes and maxpct or maximal allele frequency of mutated allele). (Top Left) Maxpct, CEA, and alts follow a downward trend as disease on CT scan improves. Center: With growth of mediastinal mass on CT, note rise in maxpct, CEA, and alts. (Top Right) As lung disease worsens on CT, maxpct, CEA, and alts increase. (Bottom Left) Despite increasing tumor on CT scan and rising CEA, maxpct did not rise. Liquid biopsy did contain APC and TP53 mutations, indicating presence of ctDNA. (Bottom Right) Liver metastases decreased between 1/2017 and 7/2017 and then increased in 11/2017. Allele freq. low (2–4%) probably due to low disease burden on CT. Keywords: liquid biopsy, precision oncology, molecular target, tumor heterogeneity, drug resistance, tumor burden, cfDNA Citation: Ghatalia P, Smith CH, Winer A, Gou J, Kiedrowski LA, Slifker M, Saltzberg PD, Bubes N, Anari FM, Kasireddy V, Varshavsky A, Liu Y, Ross EA and El-Deiry WS (2021) Corrigendum: Clinical Utilization Pattern of Liquid Biopsies (LB) to Detect Actionable Driver Mutations, Guide Treatment Decisions and Monitor Disease Burden During Treatment of 33 Metastatic Colorectal Cancer (mCRC) Patients (pts) at a Fox Chase Cancer Center GI Oncology Subspecialty Clinic. Front. Oncol. 11:674782. doi: 10.3389/fonc.2021.674782 Received: 18 March 2021; Accepted: 18 March 2021;Published: 07 May 2021. Approved by: Frontiers Editorial Office, Frontiers Media SA, Switzerland Copyright © 2021 Ghatalia, Smith, Winer, Gou, Kiedrowski, Slifker, Saltzberg, Bubes, Anari, Kasireddy, Varshavsky, Liu, Ross and El-Deiry. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. *Correspondence: Wafik S. El-Deiry, [email protected]
, Lea Bressan, Maria J. Wierbos, Henrik Becker, Andy Emmonds, Martin Obee, Victor L. Knoop, Monica Menendez, Kay W. Axhausen
Frontiers in Future Transportation, Volume 2; doi:10.3389/ffutr.2021.665006

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Interactions among different modes or vehicle classes in urban road networks affect the network performance in different and complex ways. Thus, an answer to the question of “how many cars are too many for a city?” is not trivial. However, multi-modal macroscopic fundamental diagrams (MFD) offer a novel opportunity to answer this question. So far, no methodology exists to estimate multi-modal MFDs resulting from arbitrary multi-modal interactions. In this paper, we propose a methodology to capture additional delays in the shape of the MFD and derive an approach for estimating multi-modal MFDs thereof. The influence on the MFD shape is established using the two-fluid theory of urban traffic by defining pairwise copula functions between travel times of each mode. In contrast to many existing approaches, the presented approach retains individual mode's speed information. We show the applicability of the approach with a tri-modal case of bicycles, buses, and cars with empirical data from Amsterdam (The Netherlands) and London (United Kingdom). Although the approach is not limited to this specific tri-modal case, we use the example to discuss the initial policy question by deriving optimal modal splits for a given accumulation of travelers. Last, we compare the new approach to existing estimation methods for bi-modal MFDs describing car and bus traffic.
, Jason A. Efstathiou
Published: 7 May 2021
Frontiers in Oncology, Volume 11; doi:10.3389/fonc.2021.675311

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Radiation therapy plays a crucial role for the management of genitourinary malignancies, with technological advancements that have led to improvements in outcomes and decrease in treatment toxicities. However, better risk-stratification and identification of patients for appropriate treatments is necessary. Recent advancements in imaging and novel genomic techniques can provide additional individualized tumor and patient information to further inform and guide treatment decisions for genitourinary cancer patients. In addition, the development and use of targeted molecular therapies based on tumor biology can result in individualized treatment recommendations. In this review, we discuss the advances in precision oncology techniques along with current applications for personalized genitourinary cancer management. We also highlight the opportunities and challenges when applying precision medicine principles to the field of radiation oncology. The identification, development and validation of biomarkers has the potential to personalize radiation therapy for genitourinary malignancies so that we may improve treatment outcomes, decrease radiation-specific toxicities, and lead to better long-term quality of life for GU cancer survivors.
Julie A. Klaric, Stas Wüst,
Frontiers in Molecular Biosciences, Volume 8; doi:10.3389/fmolb.2021.668821

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DNA double-strand breaks (DSBs) are highly cytotoxic DNA lesions. To protect genomic stability and ensure cell homeostasis, cells mount a complex signaling-based response that not only coordinates the repair of the broken DNA strand but also activates cell cycle checkpoints and, if necessary, induces cell death. The last decade has seen a flurry of studies that have identified RNA-binding proteins (RBPs) as novel regulators of the DSB response. While many of these RBPs have well-characterized roles in gene expression, it is becoming increasingly clear that they also have non-canonical functions in the DSB response that go well beyond transcription, splicing and mRNA processing. Here, we review the current understanding of how RBPs are integrated into the cellular response to DSBs and describe how these proteins directly participate in signal transduction, amplification and repair at damaged chromatin. In addition, we discuss the implications of an RBP-mediated DSB response for genome instability and age-associated diseases such as cancer and neurodegeneration.
, Romuald Lepers, Pantelis Theodoros Nikolaidis, Caio Victor Sousa
Frontiers in Physiology, Volume 12; doi:10.3389/fphys.2021.686858

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Editorial on the Research Topic The Elderly Athlete Age-related declines in physical activity levels and exercise training can accelerate the reductions in physical function and performance in older adults. Because elderly athletes (masters athletes) maintain high levels of physical activity, they may serve as an example of an optimal healthy human aging. Indeed, the master athlete has been proposed as an ideal model to determine successful aging due to his or her chronic participation in high-intensity exercise (Lazarus and Harridge, 2017; Tanaka et al., 2019). The last decades had a remarkable increase in endurance and ultra-endurance events, reflecting a significant participation increase of master athletes. Master athletes compete not only for the glory of participation but also for the achievement of high performance. In recent years, several astonishing reports show the outstanding achievements of master athletes (Lepers and Stapley, 2016). For example, master athletes compete in distance running (i.e., 100, 200, 400, 800, 1,500, 5,000, 10,000 m, and marathon) until the age group 95–99 years (Schneider et al., 2019). The number of master marathoners older than 75 years has increased in the last 25 years (Ahmadyar et al., 2016), and master marathoners can finish a marathon at the age of 90 years and older (Knechtle et al., 2014a; Mueller et al., 2014). In some instances, male master marathoners older than 90 years can complete a 6-h-run (Knechtle and Nikolaidis, 2018) or even a 12-h-run (Knechtle et al., 2018). Recently, it has been reported that master runners older than 80- or 90 years finished a 100-km ultra-marathon (Stohr et al., 2021). It is even possible to achieve a World Record after the 100th year of age. A study by Lepers et al. (2016) investigated all best performances achieved by centenarians for swimming, cycling, and running. They found 60 performances belonging to 19 individuals, with 10 in athletics, 8 in swimming, and one in cycling. Apart from running, swimming seems to be an ideal sports discipline for centenarians. An analysis of participation and performance of male and female age group backstroke swimmers competing in 50, 100, and 200 m pool swimming at the FINA World Masters Championships held between 1986 and 2014 showed that swimmers in age group 100–104 compete in this discipline (Unterweger et al., 2016). The Canadian Jaring Timmerman, the world's oldest masters swimmer, set four world records in the age group 100–104 years and stands solely responsible for creating the age group 105–109 years in masters swimming (Swam). In this context, a total of seven articles were published- six studies investigated elderly athletes—in the Research Topic “The Elderly Athlete” (www.frontiersin.org/research-topics/14067/the-elderly-athlete#overview). These studies investigated different aspects such as muscle strength (Taveira et al.), cardiac characteristics (Wooten et al.; Hoffmann et al.), physical fitness, and lifestyle (Wooten et al.). A study comparing trunk muscle strength and postural control of older adults (age ≥ 65 years old) found thatolder adult runners presented a higher isokinetic torque of extensor trunk muscles postural control than non-runners (Taveira et al.). Two studies explored cardiac aspects of master athletes. A first study investigated sex differences in cardiac structure, function, and left ventricular systolic global longitudinal strain among female and male masters athletes of 55–60 years old, showing cardiac sex differences regarding selected cardiac dimensions (Wooten et al.). A second study compared left ventricular dimensions and function in elite master athletes aged 60 years involved in throwing events requiring strength to those interested in endurance events and sprinting. Left ventricular diastolic function was not different in throwers but superior in endurance athletes and sprinters than age-matched historical controls (Hoffmann et al.). Physical fitness seems to affect also later in life. A study investigating 240 master athletes participating in the World Masters Athletics Championships showed that the lifestyles of master athletes contributed to improved general life satisfaction (Wooten et al.). Another study investigated the age-related decline in running performance of sub-3-h marathoners for five consecutive calendar decades longitudinally. The authors found that it is possible with consistent training and racing regimensto limit the age-related decline in marathon performance to < 7% per decade at least until 60 years of age (Lepers et al.). Although athletes of the age of 60–65 years belong by definition to the category of master athletes, athletes at the age of 50 years are at their peak for very long (48-h run) ultra-marathons (Knechtle et al., 2014b). Runners older than 70 years finishedthe “Leadville 100-Mile Endurance Race” in Colorado, USA (Charles Williams at the age of 70 years), the “Badwater 135-Mile Ultramarathon Race” which is considered as the “Toughest Footrace In The World” in California, USA (Jack Deness, 75 years), the “UTMB” (Ultra-Trail du Mont-Blanc) in Chamonix, France (Christoph Geiger, 73 years) or the Western States 100-Mile Endurance Run in California, USA (Nick Bassett, 73 years) (Runner, 2019). Finally, we thank all authors, reviewers, and editors for their contribution to the present Research Topic. We hope that this Research Topic will stimulate further research in this area. Future scientific studies need to investigate the motivation, preparation, and physiology of master athletes 70 years and older up to the centenarians. To date scientific evidence in the field comes mainly from studies conducted in men only. Research is nevertheless warranted to determine potential sex differences in the effects of lifelong exercise on the age-related decline in performance. The aspect of sex...
Xue-Hui Zhang, Chen-Chen Feng, Li-Jian Pei, Ya-Nan Zhang, Liu Chen, Xu-Qiang Wei, Jia Zhou, Yue Yong,
Frontiers in Neuroscience, Volume 15; doi:10.3389/fnins.2021.657507

Abstract:
Neuropathic pain (NeuP) is an important clinical problem accompanying negative mood symptoms. Neuroinflammation in the amygdala is critically involved in NeuP, and the dopamine (DA) system acts as an important endogenous anti-inflammatory pathway. Electroacupuncture (EA) can improve the clinical outcomes in NeuP, but the underlying mechanisms have not been fully elucidated. This study was designed to assess the effectiveness of EA on pain and pain-related depressive-like and anxiety-like behaviors and explore the role of the DA system in the effects of EA. Male Sprague-Dawley rats were subjected to the chronic constrictive injury (CCI) model to induce NeuP. EA treatment was carried out for 30 min once every other day for 3 weeks. The results showed that CCI caused mechanical hyperalgesia and depressive and anxiety-like behaviors in rats and neuroinflammation in the amygdala, such as an increased protein level of TNFα and IL-1β and activation of astrocytes. EA treatment significantly improved mechanical allodynia and the emotional dysfunction induced by CCI. The effects of EA were accompanied by markedly decreased expression of TNFα, IL-1β, and glial fibrillary acid protein (GFAP) in the amygdala. Moreover, EA treatment reversed CCI-induced down-regulation of DA concentration, tyrosine hydroxylase (TH) expression, and DRD1 and DRD2 receptors. These results suggest that EA-ameliorated NeuP may possibly be associated with the DA system to inhibit the neuroinflammation in the amygdala.
Tushar Suhasaria,
Frontiers in Astronomy and Space Sciences, Volume 8; doi:10.3389/fspas.2021.655883

Abstract:
Refractory dust grains have an important role to play in the chemistry of star and planet-forming regions. Their surfaces interact with interstellar gas and act as a catalyst for the formation of simple and complex molecules in space. Several mechanisms have been invoked to explain how molecular hydrogen is formed in reactions on dust grain surfaces in different regions of space. In this article, we give an overview of our understanding of the laboratory experiments, conducted over the last 20 years, that deal with H2 formation on interstellar grain analogs in space simulated conditions.
Marcin Sarewicz, Sebastian Pintscher, Łukasz Bujnowicz, Małgorzata Wolska,
Published: 7 May 2021
Frontiers in Chemistry, Volume 9; doi:10.3389/fchem.2021.658877

Abstract:
Cytochrome bc 1 (mitochondrial complex III) catalyzes electron transfer from quinols to cytochrome c and couples this reaction with proton translocation across lipid membrane; thus, it contributes to the generation of protonmotive force used for the synthesis of ATP. The energetic efficiency of the enzyme relies on a bifurcation reaction taking place at the Qo site which upon oxidation of ubiquinol directs one electron to the Rieske 2Fe2S cluster and the other to heme b L. The molecular mechanism of this reaction remains unclear. A semiquinone spin-coupled to the reduced 2Fe2S cluster (SQo-2Fe2S) was identified as a state associated with the operation of the Qo site. To get insights into the mechanism of the formation of this state, we first constructed a mutant in which one of the histidine ligands of the iron ion of heme b L Rhodobacter capsulatus cytochrome bc 1 was replaced by asparagine (H198N). This converted the low-spin, low-potential heme into the high-spin, high-potential species which is unable to support enzymatic turnover. We performed a comparative analysis of redox titrations of antimycin-supplemented bacterial photosynthetic membranes containing native enzyme and the mutant. The titrations revealed that H198N failed to generate detectable amounts of SQo-2Fe2S under neither equilibrium (in dark) nor nonequilibrium (in light), whereas the native enzyme generated clearly detectable SQo-2Fe2S in light. This provided further support for the mechanism in which the back electron transfer from heme b L to a ubiquinone bound at the Qo site is mainly responsible for the formation of semiquinone trapped in the SQo-2Fe2S state in R. capusulatus cytochrome bc 1.
Haihui Jiang, Kefu Yu, Yong Cui, Xiaohui Ren, Mingxiao Li, Chuanwei Yang, Xuzhe Zhao, Qinghui Zhu,
Frontiers in Immunology, Volume 12; doi:10.3389/fimmu.2021.632547

Abstract:
Background World Health Organization (WHO) grade IV glioma remains one of the most lethal tumors with a dismal prognosis and inevitable recurrence. We evaluated the safety and efficacy of immunotherapy with radiotherapy in this population of patients. Methods This study was a single-arm, open-label, phase I trial based on patients with recurrent WHO grade IV glioma. Patients were treated with intracranial and systemic immunoadjuvants in combination with low-dose reirradiation. The primary endpoint of the present trial was safety. Secondary endpoints were overall survival (OS) and progression-free survival (PFS). This trial is registered at ClinicalTrials.gov, NCT03392545. Results Thirty patients were enrolled. The most common adverse events (AEs) were fever (66.7%), vomiting (33.3%), headache (30.0%), and fatigue (23.3%). Only a single patient experienced grade 3 fever, and no grade 4 AEs or deaths related to treatment were observed. Of the 30 patients, 1 (3.3%) had a complete response, 5 (16.7%) had a partial response, 9 (30.0%) had stable disease, and 15 (50.0%) had progressive disease, resulting in an objective response rate of 20.0%. The median PFS of the entire cohort was 88.0 (61.0-254.0) days, and the median OS was 362.0 (197.0-601.0) days. Patients could be divided into responders and non-responders, and these groups exhibited a significant difference in terms of survival time, T lymphocyte subsets, frequency of cell division cycle 27 (CDC27) mutation status, and CD15 and CD68 expression (P<0.05). Conclusion The combination of immunotherapy and radiotherapy is well tolerated and may provide clinical benefit for patients with recurrent WHO grade IV glioma. A prospective phase II study is needed to further validate the efficacy of our therapeutic regimen.
Taiqiang Li, Shimao Wu, Wenke Yang, Marc-André Selosse,
Frontiers in Plant Science, Volume 12; doi:10.3389/fpls.2021.647114

Abstract:
Orchid distribution and population dynamics are influenced by a variety of ecological factors and the formation of holobionts, which play key roles in colonization and ecological community construction. Seed germination, seedling establishment, reproduction, and survival of orchid species are strongly dependent on orchid mycorrhizal fungi (OMF), with mycorrhizal cheating increasingly observed in photosynthetic orchids. Therefore, changes in the composition and abundance of OMF can have profound effects on orchid distribution and fitness. Network analysis is an important tool for the study of interactions between plants, microbes, and the environment, because of the insights that it can provide into the interactions and coexistence patterns among species. Here, we provide a comprehensive overview, systematically describing the current research status of the effects of OMF on orchid distribution and dynamics, phylogenetic signals in orchid–OMF interactions, and OMF networks. We argue that orchid–OMF associations exhibit complementary and specific effects that are highly adapted to their environment. Such specificity of associations may affect the niche breadth of orchid species and act as a stabilizing force in plant–microbe coevolution. We postulate that network analysis is required to elucidate the functions of fungal partners beyond their effects on germination and growth. Such studies may lend insight into the microbial ecology of orchids and provide a scientific basis for the protection of orchids under natural conditions in an efficient and cost-effective manner.
Peipei Zhou, Lin Zhou, Yingying Shi, Zhuolun Li, Liwei Liu, Lihua Zuo, Jun Zhang, Shuhong Liang, Jian Kang, Shuzhang Du, et al.
Frontiers in Molecular Biosciences, Volume 8; doi:10.3389/fmolb.2021.630291

Abstract:
The incidence of cerebral ischemic stroke characterized by high mortality is increasing every year. Danshen Chuanxiongqin Injection (DSCXQ), a traditional Chinese medicine (TCM) preparation, is often applied to treat cerebral apoplexy and its related sequelae. However, there is a lack of systematic research on how DSCXQ mediates its protective effects against cerebral ischemia stroke. Metabolomic analysis based on UHPLC-Q-Orbitrap HRMS was employed to explore the potential mechanisms of DSCXQ on ischemic stroke induced by transient middle cerebral artery occlusion (MCAO). Pattern analysis and metabolomic profiling, combined by multivariate analysis disclosed that 55 differential metabolites were identified between Sham group and Model group, involving sphingolipid metabolism, glycerophospholipid metabolism, phenylalanine, tyrosine and tryptophan biosynthesis, primary bile acid biosynthesis, pantothenate and CoA synthesis and valine, leucine and isoleucine biosynthesis pathways. DSCXQ could reverse brain metabolic deviations in stroke by significantly upregulating the levels of L-tryptophan, Lyso (18:0/0:0), LPC (18:2), Indole-3-methyl acetate, and downregulating the levels of sphinganine 1-phosphate, L-threonic acid, glutaconic acid and N6,N6,N6-Trimethyl-L-lysine. In our study, we focused on the neuroprotective effects of DSCXQ against neuroinflammatory responses and neuronal apoptosis on a stroke model based on sphingolipid metabolism. The expressions of Sphk1, S1PR1, CD62P, Bcl-2, Bax, and cleaved Caspase-3 in brain tissue were evaluated. The neurological deficit, cerebral infarct size and behavioral abnormality were estimated. Results showed that DSCXQ intervention significantly reduced cerebral infarct size, ameliorated behavioral abnormality, inhibited the expression of Sphk1, S1PR1, CD62P, Bax, Cleaved Caspase-3, while increased the level of Bcl-2, and prevented neuronal apoptosis. The limitations are that our study mainly focused on the verification of sphingolipid metabolism pathway in stroke, and while other metabolic pathways left unverified. Our study indicates that SphK1-SIP axis may potentiate neuroinflammatory responses and mediate brain damage through neuronal apoptosis, and DSCXQ could suppress the activity of SphK1-SIP axis to protect brain tissue in cerebral ischemia. In conclusion, this study facilitates our understanding of metabolic changes in ischemia stroke and the underlying mechanisms related to the clinical application of DSCXQ.
Zhiwang Zhang, Qichao Liao, Yu Sun, Tingli Pan, Siqi Liu, Weiwei Miao, Yixing Li, Lei Zhou, Gaoxiao Xu
Published: 7 May 2021
Frontiers in Nutrition, Volume 8; doi:10.3389/fnut.2021.667622

Abstract:
Meat is an essential food, and pork is the largest consumer meat product in China and the world. Intramuscular fat has always been the basis for people to select and judge meat products. Therefore, we selected the Duroc, a western lean pig breed, and the Luchuan, a Chinese obese pig breed, as models, and used the longissimus dorsi muscle for lipidomics testing and transcriptomics sequencing. The purpose of the study was to determine the differences in intramuscular fat between the two breeds and identify the reasons for the differences. We found that the intramuscular fat content of Luchuan pigs was significantly higher than that of Duroc pigs. The triglycerides and diglycerides related to flavor were higher in Luchuan pigs compared to Duroc pigs. This phenotype may be caused by the difference in the expression of key genes in the glycerolipid metabolism signaling pathway.
Frontiers in Political Science, Volume 3; doi:10.3389/fpos.2021.637344

Abstract:
In light of recent crises, not least the COVID-19 pandemic, citizen trust in the political system has been highlighted as one of the central features ensuring citizen compliance and the functioning of democracy. Given its many desirable consequences, one of the key questions is how to increase political trust among ordinary citizens. This paper investigates the role of democratic quality in determining citizens’ trust in the political system. While we know that citizens’ evaluations of democratic performance are a strong predictor of political trust, previous research has shown that trust is not always higher in political systems with higher democratic quality, indicating that democratic performance evaluations do not always correspond to actual democratic quality. Several moderating factors may account for this disconnect between democratic quality and citizens’ evaluations of democratic performance and, ultimately, political trust. For one, citizens may receive different information about the political system; second, they may process this information in different ways; and third, they may have different standards of what democratic quality ought to be. Using survey data from three rounds of the World Values Survey (2005–2020) and aggregate data on democratic quality and other macro determinants of political trust from the V-Dem project and World Development Indicators for 50 democracies around the world, this contribution empirically investigates the complex relationship between democratic quality, democratic performance evaluations, and political trust in multi-level moderated mediation models. Its findings demonstrate that democratic quality affects political trust indirectly through citizens’ democratic performance evaluations and that this indirect effect is stronger for citizens with higher political interest, higher education, and especially those with more liberal conceptions of democracy.
Ming Xin, , Hock Eng Khoo, Li Li, Xuemei He, Ping Yi, Yayuan Tang,
Frontiers in Plant Science, Volume 12; doi:10.3389/fpls.2021.666805

Abstract:
This study aimed to evaluate the changes in aromatic components and other chemical properties of Tainong mango during fruit development, ripening, and storage. As the volatiles of Tainong mango and their related molecular mechanisms remain unclear, volatile profile, metabonomics, and transcriptome analyses were applied to investigate the molecular determinants of the synthesis of aroma components in mango during fruit development and storage. Total acids, total sugar, total carotenoids, enzyme activities of the mango pulp samples were also determined. Volatile components of the mango pulp samples were identified using a gas chromatography-mass spectrometric method. Ribonucleic acid (RNA) sequences of the samples were analyzed by real-time polymerase chain reaction. The results showed that 181 volatiles were isolated and identified in the fruit at seven stages. Compared to the other stages, mango collected on day 8 and day 12 had higher concentrations of 17 volatile components, especially (E,Z)-2,6-nonadienal, 53384 transcripts were also detected through RNA sequencing. The differentially expressed genes analyses included catalytic activity, transferase activity, adenosine diphosphate binding, transcription factor activity, and oxidoreductase activity. α-Pinene content and expression of the differentially expressed genes involved in terpenoid metabolism and enzyme activities in the terpenoid metabolic pathways gradually increased during the maturity of the fruit, and had maximum values at day 8 of storage. Moreover, the integrative analyses revealed potential molecular insights of mango development and aroma formation in the fruit.
Cleide Angolano, Elzbieta Kaczmarek, Sanah Essayagh, Soizic Daniel, Lynn Y. Choi, Brian Tung, Gabriel Sauvage, Andy Lee, Franciele C. Kipper, Maria B. Arvelo, et al.
Frontiers in Cardiovascular Medicine, Volume 8; doi:10.3389/fcvm.2021.651230

Abstract:
Rationale: Decreased expression and activity of endothelial nitric oxide synthase (eNOS) in response to inflammatory and metabolic insults is the hallmark of endothelial cell (EC) dysfunction that preludes the development of atherosclerosis and hypertension. We previously reported the atheroprotective properties of the ubiquitin-editing and anti-inflammatory protein A20, also known as TNFAIP3, in part through interrupting nuclear factor-kappa B (NF-κB) and interferon signaling in EC and protecting these cells from apoptosis. However, A20's effect on eNOS expression and function remains unknown. In this study, we evaluated the impact of A20 overexpression or knockdown on eNOS expression in EC, at baseline and after tumor necrosis factor (TNF) treatment, used to mimic inflammation. Methods and Results: A20 overexpression in human coronary artery EC (HCAEC) significantly increased basal eNOS mRNA (qPCR) and protein (western blot) levels and prevented their downregulation by TNF. Conversely, siRNA-induced A20 knockdown decreased eNOS mRNA levels, identifying A20 as a physiologic regulator of eNOS expression. By reporter assays, using deletion and point mutants of the human eNOS promoter, and knockdown of eNOS transcriptional regulators, we demonstrated that A20-mediated increase of eNOS was transcriptional and relied on increased expression of the transcription factor Krüppel-like factor (KLF2), and upstream of KLF2, on activation of extracellular signal-regulated kinase 5 (ERK5). Accordingly, ERK5 knockdown or inhibition significantly abrogated A20's ability to increase KLF2 and eNOS expression. In addition, A20 overexpression in HCAEC increased eNOS phosphorylation at Ser-1177, which is key for the function of this enzyme. Conclusions: This is the first report demonstrating that overexpression of A20 in EC increases eNOS transcription in an ERK5/KLF2-dependent manner and promotes eNOS activating phosphorylation. This effect withstands eNOS downregulation by TNF, preventing EC dysfunction in the face of inflammation. This novel function of A20 further qualifies its therapeutic promise to prevent/treat atherosclerosis.
Onur Can Karabulut, Betül Asiye Karpuzcu, Erdem Türk, Ahmad Hassan Ibrahim,
Frontiers in Molecular Biosciences, Volume 8; doi:10.3389/fmolb.2021.647424

Abstract:
Adenoviruses (AdVs) constitute a diverse family with many pathogenic types that infect a broad range of hosts. Understanding the pathogenesis of adenoviral infections is not only clinically relevant but also important to elucidate the potential use of AdVs as vectors in therapeutic applications. For an adenoviral infection to occur, attachment of the viral ligand to a cellular receptor on the host organism is a prerequisite and, in this sense, it is a criterion to decide whether an adenoviral infection can potentially happen. The interaction between any virus and its corresponding host organism is a specific kind of protein-protein interaction (PPI) and several experimental techniques, including high-throughput methods are being used in exploring such interactions. As a result, there has been accumulating data on virus-host interactions including a significant portion reported at publicly available bioinformatics resources. There is not, however, a computational model to integrate and interpret the existing data to draw out concise decisions, such as whether an infection happens or not. In this study, accepting the cellular entry of AdV as a decisive parameter for infectivity, we have developed a machine learning, more precisely support vector machine (SVM), based methodology to predict whether adenoviral infection can take place in a given host. For this purpose, we used the sequence data of the known receptors of AdVs, we identified sets of adenoviral ligands and their respective host species, and eventually, we have constructed a comprehensive adenovirus–host interaction dataset. Then, we committed interaction predictions through publicly available virus-host PPI tools and constructed an AdV infection predictor model using SVM with RBF kernel, with the overall sensitivity, specificity, and AUC of 0.88 ± 0.011, 0.83 ± 0.064, and 0.86 ± 0.030, respectively. ML-AdVInfect is the first of its kind as an effective predictor to screen the infection capacity along with anticipating any cross-species shifts. We anticipate our approach led to ML-AdVInfect can be adapted in making predictions for other viral infections.
Runzhen Zhao, Zhenlei Su, Andrey A. Komissarov, Shan-Lu Liu, Guohua Yi, Steven Idell, Michael A. Matthay,
Frontiers in Immunology, Volume 12; doi:10.3389/fimmu.2021.691249

Abstract:
Background Dynamic D-dimer level is a key biomarker for the severity and mortality of COVID-19 (coronavirus disease 2019). How aberrant fibrinolysis influences the clinical progression of COVID-19 presents a clinicopathological dilemma challenging intensivists. Methods We performed meta-analysis and meta regression to analyze the associations of plasma D-dimer with 106 clinical variables to identify a panoramic view of the derangements of fibrinolysis in 14,862 patients of 42 studies. There were no limitations of age, gender, race, and country. Raw data of each group were extracted separately by two investigators. Individual data of case series, median and interquartile range, and ranges of median or mean were converted to SDM (standard deviation of mean). Findings The weighted mean difference of D-dimer was 0.97 µg/mL (95% CI 0.65, 1.29) between mild and severe groups, as shown by meta-analysis. Publication bias was significant. Meta-regression identified 58 of 106 clinical variables were associated with plasma D-dimer levels. Of these, 11 readouts were negatively related to the level of plasma D-dimer. Further, age and gender were confounding factors. There were 22 variables independently correlated with the D-dimer level, including respiratory rate, dyspnea plasma K+, glucose, SpO2, BUN (blood urea nitrogen), bilirubin, ALT (alanine aminotransferase), AST (aspartate aminotransferase), systolic blood pressure, and CK (creatine kinase). Interpretation These findings support elevated D-dimer as an independent predictor for both mortality and complications. The identified D-dimer-associated clinical variables draw a landscape integrating the aggregate effects of systemically suppressive and pulmonary hyperactive derangements of fibrinolysis, and the D-dimer-associated clinical biomarkers, and conceptually parameters could be combined for risk stratification, potentially for tracking thrombolytic therapy or alternative interventions.
Thanachaporn Kittipibul,
Published: 7 May 2021
Frontiers in Medicine, Volume 8; doi:10.3389/fmed.2021.645053

Abstract:
The ocular surface microbiome is an essential factor that maintains ocular surface homeostasis. Since the ocular surface is continuously exposed to the external environment, its microbiome, tears, and local immunity are vital for maintaining normal conditions. Additionally, this microbiome helps prevent pathogen colonization, which commonly leads to opportunistic infection. The abnormal ocular surface microbiome has previously been reported in several conditions, including dry eyes, allergy, blepharitis, graft-versus-host disease (GVHD), and Stevens-Johnson syndrome (SJS). Several approaches were applied to identify the ocular microbiome, including conventional culture techniques and molecular sequencing techniques. By using 16s rRNA sequencing, alterations in the type, proportion, and composition of bacterial communities, described by alpha (α)-and beta (β)-diversity, were observed in SJS patients compared to the healthy group. Conventional culture techniques indicated a higher number of positive bacterial cultures in the SJS group, with a predominance of gram-positive cocci and gram-positive bacilli. Besides, there are increased variations and multiple detections of bacterial genera. Taken together, SJS causes structural changes in the ocular surface and significantly affects its microbiome. Further studies into the area of temporal relationship, metagenomics, proteomics, and metabolomics analysis of the microbiome will lead to a better understanding of this disease. Finally, the treatment using prebiotics and probiotics to re-establish the normal ocular ecosystem and bring back a healthy ocular surface await confirmation.
Minxiao Jiang, Liangliang Ren, Yuanlei Chen, Huan Wang, Haiyang Wu, Sheng Cheng, Gonghui Li, Shicheng Yu
Frontiers in Molecular Biosciences, Volume 8; doi:10.3389/fmolb.2021.613359

Abstract:
Accumulating evidence indicates that hypoxia is highly associated with bladder cancer genesis, progression, and immune microenvironment. Nevertheless, few studies have identified the role of hypoxia-related genes as a prognostic signature in bladder cancer. This study aimed to establish a hypoxia-related signature with high accuracy for prognosis and immune microenvironment prediction in bladder cancer. We obtained expression profiles and clinical information from Gene Expression Omnibus and The Cancer Genome Atlas. Then the univariate Cox regression, random survival forest algorithm, and multivariate Cox regression analysis were conducted to identify the core genes and four hypoxia-related genes (ANXA2, GALK1, COL5A1, and HS3ST1) were selected to construct the signature. Kaplan-Meier survival analysis demonstrated that patients with a low-risk score had a higher disease-specific survival rate (p < 0.0001). The areas under the curve of the signature were 0.829 at 1 year, 0.869 at 3 years, and 0.848 at 5 years, respectively. Additionally, we found this hypoxia-related signature was highly correlated with tumor immune microenvironment and had the potential to predict the efficacy of immunotherapy. In summary, our study developed a hypoxia-related signature, which had high accuracy for prognosis prediction and the potential to guide the immunotherapy for bladder cancer patients.
, Giuseppe De Maria, Ciro Natale
Frontiers in Robotics and AI, Volume 8; doi:10.3389/frobt.2021.672995

Abstract:
Modern scenarios in robotics involve human-robot collaboration or robot-robot cooperation in unstructured environments. In human-robot collaboration, the objective is to relieve humans from repetitive and wearing tasks. This is the case of a retail store, where the robot could help a clerk to refill a shelf or an elderly customer to pick an item from an uncomfortable location. In robot-robot cooperation, automated logistics scenarios, such as warehouses, distribution centers and supermarkets, often require repetitive and sequential pick and place tasks that can be executed more efficiently by exchanging objects between robots, provided that they are endowed with object handover ability. Use of a robot for passing objects is justified only if the handover operation is sufficiently intuitive for the involved humans, fluid and natural, with a speed comparable to that typical of a human-human object exchange. The approach proposed in this paper strongly relies on visual and haptic perception combined with suitable algorithms for controlling both robot motion, to allow the robot to adapt to human behavior, and grip force, to ensure a safe handover. The control strategy combines model-based reactive control methods with an event-driven state machine encoding a human-inspired behavior during a handover task, which involves both linear and torsional loads, without requiring explicit learning from human demonstration. Experiments in a supermarket-like environment with humans and robots communicating only through haptic cues demonstrate the relevance of force/tactile feedback in accomplishing handover operations in a collaborative task.
, Anna Byström, Jenny Yngvesson, Paolo Baragli, Antonio Lanata, Agneta Egenvall
Frontiers in Veterinary Science, Volume 8; doi:10.3389/fvets.2021.652015

Abstract:
When a rider maintains contact on the reins, rein tension will vary continuously in synchronicity with the horse's gait and stride. This continuous variation makes it difficult to isolate the rein tension variations that represent a rein tension signal, complicating interpretation of rein tension data from the perspective of horse-rider interaction. This study investigated (1) the characteristics of a rein tension signal and (2) horse response to a rein tension signal for backing, comparing pressure applied by a bit (bridle), or by a noseband (halter). Twenty Warmblood horses (10 young, 10 adult) wearing a rein tension meter were trained to step back in the aisle of a stable. The handler stood next to the horse's withers, applying tension on the reins until the horse stepped back. This was repeated eight times with the bridle and eight times with the halter. Data analysis was performed using mixed linear and logistic regression models. Horses displaying behaviors other than backing showed significantly increased response latency and rein tension. Inattentive behavior was significantly more common in the halter treatment and in young horses, compared with the bridle treatment and adult horses. Evasive behaviors with the head, neck, and mouth were significantly more common in the bridle treatment than in the halter treatment and the occurrence of head/neck/mouth behaviors increased with increasing rein tension and duration of the rein tension signal. When controlling for behavior, the horses responded significantly faster and to a lighter rein tension signal in the bridle treatment than in the halter treatment. By scrutinizing data on rein tension signals in relation to horse behavior and training exercise, more can be learnt about the horse's experience of the pressures applied and the timing of the release. This can assist in developing ways to evaluate rein tension in relation to correct use of negative reinforcement.
Felipe T. Lee-Montiel, Alexander Laemmle, Verena Charwat, Laure Dumont, Caleb S. Lee, Nathaniel Huebsch, Hideaki Okochi, Matthew J. Hancock, Brian Siemons, Steven C. Boggess, et al.
Frontiers in Pharmacology, Volume 12; doi:10.3389/fphar.2021.667010

Abstract:
Three-dimensional (3D) microphysiological systems (MPSs) mimicking human organ function in vitro are an emerging alternative to conventional monolayer cell culture and animal models for drug development. Human induced pluripotent stem cells (hiPSCs) have the potential to capture the diversity of human genetics and provide an unlimited supply of cells. Combining hiPSCs with microfluidics technology in MPSs offers new perspectives for drug development. Here, the integration of a newly developed liver MPS with a cardiac MPS—both created with the same hiPSC line—to study drug–drug interaction (DDI) is reported. As a prominent example of clinically relevant DDI, the interaction of the arrhythmogenic gastroprokinetic cisapride with the fungicide ketoconazole was investigated. As seen in patients, metabolic conversion of cisapride to non-arrhythmogenic norcisapride in the liver MPS by the cytochrome P450 enzyme CYP3A4 was inhibited by ketoconazole, leading to arrhythmia in the cardiac MPS. These results establish integration of hiPSC-based liver and cardiac MPSs to facilitate screening for DDI, and thus drug efficacy and toxicity, isogenic in the same genetic background.
, Jessica Wilson, Joelle LeMoult
Frontiers in Psychology, Volume 12; doi:10.3389/fpsyg.2021.660062

Abstract:
Rumination has been linked to the onset and course of depression. Theoretical models and empirical evidence suggest that deficits controlling negative material in working memory underlie rumination. However, we do not know which component of cognitive control (inhibition, shifting, or updating) contributes most to rumination, and whether different components predict the more maladaptive (brooding) versus the more adaptive (reflection) forms of rumination. We aimed to advance theory and research by examining the contribution of different facets of cognitive control to the level and trajectory of brooding and reflection. At baseline, participants completed three cognitive tasks that assessed their inhibition, shifting, and updating biases, respectively. Next, using experience sampling methodology, participants rated their level of rumination and negative affect nine times during the 48 h after their most stressful exam. At each time point, higher levels of brooding, but not reflection, predicted higher levels of negative affect at the next time point. Furthermore, several facets of shifting and inhibition, but not updating, predicted brooding immediately after the exam and its trajectory of change over 48 h. Additionally, difficulty inhibiting neutral words predicted both brooding and reflection. These findings inform theoretical models describing the role of cognitive control in brooding and reflection.
Giulia Besutti, Fulvio Massaro, Efrem Bonelli, Luca Braglia, Massimiliano Casali, Annibale Versari, Guido Ligabue, Pierpaolo Pattacini, Silvio Cavuto, Domenico F. Merlo, et al.
Published: 7 May 2021
Frontiers in Nutrition, Volume 8; doi:10.3389/fnut.2021.620696

Abstract:
Baseline CT scans of 116 patients (48% female, median 64 years) with diffuse large B-cell lymphoma (DLBCL) were retrospectively reviewed to investigate the prognostic role of sarcopenia and fat compartment distributions on overall survival (OS), progression-free survival (PFS), and early therapy termination. Skeletal muscle index (SMI), skeletal muscle density (SMD), and intermuscular adipose tissue (IMAT) were quantified at the level of the third lumbar vertebra (L3) and proximal thigh (PT). Low L3-SMD, but not low L3-SMI, was associated with early therapy termination (p = 0.028), shorter OS (HR = 6.29; 95% CI = 2.17–18.26; p < 0.001), and shorter PFS (HR = 2.42; 95% CI = 1.26–4.65; p = 0.008). After correction for sex, International Prognostic Index (IPI), BMI, and R-CHOP therapy (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone), low L3-SMD remained associated with poor OS (HR = 3.54; 95% CI = 1.10–11.40; p = 0.034) but not with PFS. Increased PT-IMAT was prognostic for poor OS and PFS after correction for sex, IPI, BMI, and R-CHOP therapy (HR = 1.35; CI = 1.03–1.7; p = 0.03, and HR = 1.30; CI = 1.04–1.64; p = 0.024, respectively). Reduced muscle quality (SMD) and increased intermuscular fat (IMAT), rather than low muscle quantity (SMI), are associated with poor prognosis in DLBCL, when measured at the L3 level, and particularly at the level of the proximal thigh. The proximal thigh represents a novel radiological landmark to study body composition.
, Nutsa Nanuashvili, Flavie Waters
Frontiers in Psychiatry, Volume 12; doi:10.3389/fpsyt.2021.668633

Abstract:
Of the perceptual distortions characteristic of Alice in Wonderland syndrome, substantial alterations in the immediate experience of time are probably the least known and the most fascinating. We reviewed original case reports to examine the phenomenology and associated pathology of these time distortions in this syndrome. A systematic search in PubMed, Ovid Medline, and the historical literature yielded 59 publications that described 168 people experiencing time distortions, including 84 detailed individual case reports. We distinguished five different types of time distortion. The most common category comprises slow-motion and quick-motion phenomena. In 39% of all cases, time distortions were unimodal in nature, while in 61% there was additional involvement of the visual (49%), kinaesthetic (18%), and auditory modalities (14%). In all, 40% of all time distortions described were bimodal in nature and 19% trimodal, with 1% involving four modalities. Underlying neurological mechanisms are varied and may be triggered by intoxications, infectious diseases, metabolic disorders, CNS lesions, paroxysmal neurological disorders, and psychiatric disorders. Bizarre sensations of time alteration—such as time going backwards or moving in circles—were mostly associated with psychosis. Pathophysiologically, mainly occipital areas appear to be involved, although the temporal network is widely disseminated, with separate component timing mechanisms not always functioning synchronously, thus occasionally creating temporal mismatches within and across sensory modalities (desynchronization). Based on our findings, we propose a classification of time distortions and formulate implications for research and clinical practice.
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