bluuebunny/crossref_metadata_2025 huggingface dataset:
Interleukin 23 Produced by Hepatic Monocyte-Derived Macrophages Is Essential for the Development of Murine Primary Biliary Cholangitis
Authors: Reuveni Debby , Brezis Miriam R. , Brazowski Eli , Vinestock Philip , Leung Patrick S. C. , Thakker Paresh , Gershwin M. Eric , Zigmond Ehud
Published: August 2021

Background and Aims

Primary Biliary Cholangitis (PBC) is an organ-specific autoimmune liver disease. Mononuclear phagocytes (MNPs), comprise of monocyte, dendritic cells and monocyte-derived macrophages, constitute major arm of the innate immune system known to be involved in the pathogenesis of autoimmune disorders. MNPs were shown to accumulate around intra-hepatic bile ducts in livers of PBC patients. Interleukin 23 (IL-23) is a pro-inflammatory cytokine. IL-23-positive cells were detected in livers of patients with advanced stage PBC and IL-23 serum levels found to be in correlation with PBC disease severity. Our overall goal was to assess the importance of IL-23 derived from MNPs in PBC pathogenesis.

Methods

We utilized an inducible murine model of PBC and took advantage of transgenic mice targeting expression of IL-23 by specific MNP populations. Analysis included liver histology assessment, flow cytometry of hepatic immune cells and hepatic cytokine profile evaluation. Specific MNPs sub-populations were sorted and assessed for IL-23 expression levels.

Results

Flow cytometry analysis of non-parenchymal liver cells in autoimmune cholangitis revealed massive infiltration of the liver by MNPs and neutrophils and a decrease in Kupffer cells numbers. In addition, a 4-fold increase in the incidence of hepatic IL-17A producing CD4+ T cells was found to be associated with an increase in hepatic IL23-p19 and IL17A expression levels. Disease severity was significantly ameliorated in both CD11ccreP19flox/flox and CX3CR1creP19 flox/flox mice as assessed by reduced portal inflammation and decreased hepatic expression of various inflammatory cytokines. Amelioration of disease severity was associated with reduction in IL-17A producing CD4+ T cells percentages and decreased hepatic IL23-p19 and IL17A expression levels. qRT-PCR analysis of sorted hepatic MNPs demonstrated high expression levels of IL-23 mRNA specifically by CX3CR1hiCD11c+ monocyte-derived macrophages.

Conclusion

Our results indicate a major role for IL-23 produced by hepatic monocyte-derived macrophages in the pathogenesis of PBC. These results may pave the road for the development of new immune-based and cell specific therapeutic modalities for PBC patients not responding to current therapies.
The Role of Retinal Pigment Epithelial Cells in Regulation of Macrophages/Microglial Cells in Retinal Immunobiology
Authors: Taylor Andrew W. , Hsu Samuel , Ng Tat Fong
Published: August 2021

The ocular tissue microenvironment is immune privileged and uses several mechanisms of immunosuppression to prevent the induction of inflammation. Besides being a blood-barrier and source of photoreceptor nutrients, the retinal pigment epithelial cells (RPE) regulate the activity of immune cells within the retina. These mechanisms involve the expression of immunomodulating molecules that make macrophages and microglial cells suppress inflammation and promote immune tolerance. The RPE have an important role in ocular immune privilege to regulate the behavior of immune cells within the retina. Reviewed is the current understanding of how RPE mediate this regulation and the changes seen under pathological conditions.
Using Forecasting Methods to Incorporate Social, Economic, and Political Considerations Into Marine Protected Area Planning
Authors: Sykora-Bodie Seth T. , Álvarez-Romero Jorge G. , Arata Javier A. , Dunn Alistair , Hinke Jefferson T. , Humphries Grant , Jones Christopher , Skogrand Pål , Teschke Katharina , Trathan Philip N. , Welsford Dirk , Ban Natalie C. , Murray Grant , Gill David A.
Published: August 2021

As the global environmental crisis grows in scale and complexity, conservation professionals and policymakers are increasingly called upon to make decisions despite high levels of uncertainty, limited resources, and insufficient data. Global efforts to protect biodiversity in areas beyond national jurisdiction require substantial international cooperation and negotiation, both of which are characterized by unpredictability and high levels of uncertainty. Here we build on recent studies to adapt forecasting techniques from the fields of hazard prediction, risk assessment, and intelligence analysis to forecast the likelihood of marine protected area (MPA) designation in the Southern Ocean. We used two questionnaires, feedback, and a discussion round in a Delphi-style format expert elicitation to obtain forecasts, and collected data on specific biophysical, socioeconomic, geopolitical, and scientific factors to assess how they shape and influence these forecasts. We found that areas further north along the Western Antarctic Peninsula were considered to be less likely to be designated than areas further south, and that geopolitical factors, such as global politics or events, and socioeconomic factors, such as the presence of fisheries, were the key determinants of whether an area was predicted to be more or less likely to be designated as an MPA. Forecasting techniques can be used to inform protected area design, negotiation, and implementation in highly politicized situations where data is lacking by aiding with spatial prioritization, targeting scarce resources, and predicting the success of various spatial arrangements, interventions, or courses of action.
A Modified Preparation Method of Ideal Platelet-Rich Fibrin Matrix From Whole Blood
Authors: Reksodiputro Mirta Hediyati , Harahap Alida Roswita , Setiawan Lyana , Yosia Mikhael
Published: August 2021

One bioproduct that is widely used in the wound healing process is platelet-rich plasma (PRP). PRP is a liquid solution with high autologous platelet concentration, making it a good source of growth factors to accelerate wound healing. Recent development in PRP had created a new product called platelet-rich fibrin matrix (PRFM), which has a denser and more flexible structure. PRFM is the newest generation of platelet concentrate with a fibrin matrix that holds platelet in it. The key concept in creating PRFM from PRP is the addition of CaCl2 followed by centrifugation, which converts fibrinogen to fibrin, and the fibrin cross-links to form a matrix that contains viable platelets. There are many commercially available kits to create PRFM, but they are often expensive and uneconomical. This research will test a modified method of making ideal PRFM from PRP without any commercial kits. The modified method will include determining the minimum level of CaCl2 used, the type of centrifuge, and the speed and duration of centrifugation. By performing a modified preparation method on five samples of whole blood, it was found that the ideal PRFM could be made by mixing PRP with 25 mM CaCl2 and centrifuging it at a speed of 2,264 × g for 25 min at room temperature. The PRP and PRFM platelet counts of this method tend to be lower than the platelet counts found in other studies. Although visually comparable, further study is needed to compare the performance of PRFMs made with this method and PRFMs made with commercial kits.
Comparative Genomic Analysis Reveals Genetic Variation and Adaptive Evolution in the Pathogenicity-Related Genes of Phytophthora capsici
Authors: Lee Joung-Ho , Siddique Muhammad Irfan , Kwon Jin-Kyung , Kang Byoung-Cheorl
Published: August 2021

Phytophthora capsici is an oomycete pathogen responsible for damping off, root rot, fruit rot, and foliar blight in popular vegetable and legume crops. The existence of distinct aggressiveness levels and physiological races among the P. capsici population is a major constraint to developing resistant varieties of host crops. In the present study, we compared the genomes of three P. capsici isolates with different aggressiveness levels to reveal their genomic differences. We obtained genome sequences using short-read and long-read technologies, which yielded an average genome size of 76 Mbp comprising 514 contigs and 15,076 predicted genes. A comparative genomic analysis uncovered the signatures of accelerated evolution, gene family expansions in the pathogenicity-related genes among the three isolates. Resequencing two additional P. capsici isolates enabled the identification of average 1,023,437 SNPs, revealing the frequent accumulation of non-synonymous substitutions in pathogenicity-related gene families. Furthermore, pathogenicity-related gene families, cytoplasmic effectors and ATP binding cassette (ABC) transporters, showed expansion signals in the more aggressive isolates, with a greater number of non-synonymous SNPs. This genomic information explains the plasticity, difference in aggressiveness levels, and genome structural variation among the P. capsici isolates, providing insight into the genomic features related to the evolution and pathogenicity of this oomycete pathogen.
Whole Genome Sequencing of Pediatric Klebsiella pneumoniae Strains Reveals Important Insights Into Their Virulence-Associated Traits
Authors: Flores-Valdez Mauricio , Ares Miguel A. , Rosales-Reyes Roberto , Torres Javier , Girón Jorge A. , Weimer Bart C. , Mendez-Tenorio Alfonso , De la Cruz Miguel A.
Published: August 2021

Klebsiella pneumoniae is recognized as a common cause of nosocomial infections and outbreaks causing pneumonia, septicemia, and urinary tract infections. This opportunistic bacterium shows an increasing acquisition of antibiotic-resistance genes, which complicates treatment of infections. Hence, fast reliable strain typing methods are paramount for the study of this opportunistic pathogen’s multi-drug resistance genetic profiles. In this study, thirty-eight strains of K. pneumoniae isolated from the blood of pediatric patients were characterized by whole-genome sequencing and genomic clustering methods. Genes encoding β-lactamase were found in all the bacterial isolates, among which the blaSHV variant was the most prevalent (53%). Moreover, genes encoding virulence factors such as fimbriae, capsule, outer membrane proteins, T4SS and siderophores were investigated. Additionally, a multi-locus sequence typing (MLST) analysis revealed 24 distinct sequence types identified within the isolates, among which the most frequently represented were ST76 (16%) and ST70 (11%). Based on LPS structure, serotypes O1 and O3 were the most prevalent, accounting for approximately 63% of all infections. The virulence capsular types K10, K136, and K2 were present in 16, 13, and 8% of the isolates, respectively. Phylogenomic analysis based on virtual genome fingerprints correlated with the MLST data. The phylogenomic reconstruction also denoted association between strains with a higher abundance of virulence genes and virulent serotypes compared to strains that do not possess these traits. This study highlights the value of whole-genomic sequencing in the surveillance of virulence attributes among clinical K. pneumoniae strains.
Using Fractional Amplitude of Low-Frequency Fluctuations and Functional Connectivity in Patients With Post-stroke Cognitive Impairment for a Simulated Stimulation Program
Authors: Wang Sirui , Rao Bo , Chen Linglong , Chen Zhuo , Fang Pinyan , Miao Guofu , Xu Haibo , Liao Weijing
Published: August 2021

Stroke causes alterations in local spontaneous neuronal activity and related networks functional connectivity. We hypothesized that these changes occur in patients with post-stroke cognitive impairment (PSCI). Fractional amplitude of low-frequency fluctuations (fALFF) was calculated in 36 patients with cognitive impairment, including 16 patients with hemorrhagic stroke (hPSCI group), 20 patients with ischemic stroke (iPSCI group). Twenty healthy volunteers closely matched to the patient groups with respect to age and gender were selected as the healthy control group (HC group). Regions with significant alteration were regarded as regions of interest (ROIs) using the one-way analysis of variance, and then the seed-based functional connectivity (FC) with other regions in the brain was analyzed. Pearson correlation analyses were performed to investigate the correlation between functional indexes and cognitive performance in patients with PSCI. Our results showed that fALFF values of bilateral posterior cingulate cortex (PCC)/precuneus and bilateral anterior cingulate cortex in the hPSCI group were lower than those in the HC group. Compared with the HC group, fALFF values were lower in the superior frontal gyrus and basal ganglia in the iPSCI group. Correlation analysis showed that the fALFF value of left PCC was positively correlated with MMSE scores and MoCA scores in hPSCI. Besides, the reduction of seed-based FC values was reported, especially in regions of the default-mode network (DMN) and the salience network (SN). Abnormalities of spontaneous brain activity and functional connectivity are observed in PSCI patients. The decreased fALFF and FC values in DMN of patients with hemorrhagic and SN of patients with ischemic stroke may be the pathological mechanism of cognitive impairment. Besides, we showed how to use fALFF values and functional connectivity maps to specify a target map on the cortical surface for repetitive transcranial magnetic stimulation (rTMS).
Postmortem Neocortical 3H-PiB Binding and Levels of Unmodified and Pyroglutamate Aβ in Down Syndrome and Sporadic Alzheimer’s Disease
Authors: Pivtoraiko Violetta N. , Racic Tamara , Abrahamson Eric E. , Villemagne Victor L. , Handen Benjamin L. , Lott Ira T. , Head Elizabeth , Ikonomovic Milos D.
Published: August 2021

Individuals with Down syndrome (DS) have a genetic predisposition for amyloid-β (Aβ) overproduction and earlier onset of Aβ deposits compared to patients with sporadic late-onset Alzheimer’s disease (AD). Positron emission tomography (PET) with Pittsburgh Compound-B (PiB) detects fibrillar Aβ pathology in living people with DS and AD, but its relationship with heterogeneous Aβ forms aggregated within amyloid deposits is not well understood. We performed quantitative in vitro3H-PiB binding assays and enzyme-linked immunosorbent assays of fibrillar (insoluble) unmodified Aβ40 and Aβ42 forms and N-terminus truncated and pyroglutamate-modified AβNpE3-40 and AβNpE3-42 forms in postmortem frontal cortex and precuneus samples from 18 DS cases aged 43–63 years and 17 late-onset AD cases aged 62–99 years. Both diagnostic groups had frequent neocortical neuritic plaques, while the DS group had more severe vascular amyloid pathology (cerebral amyloid angiopathy, CAA). Compared to the AD group, the DS group had higher levels of Aβ40 and AβNpE3-40, while the two groups did not differ by Aβ42 and AβNpE3-42 levels. This resulted in lower ratios of Aβ42/Aβ40 and AβNpE3-42/AβNpE3-40 in the DS group compared to the AD group. Correlations of Aβ42/Aβ40 and AβNpE3-42/AβNpE3-40 ratios with CAA severity were strong in DS cases and weak in AD cases. Pyroglutamate-modified Aβ levels were lower than unmodified Aβ levels in both diagnostic groups, but within group proportions of both pyroglutamate-modified Aβ forms relative to both unmodified Aβ forms were lower in the DS group but not in the AD group. The two diagnostic groups did not differ by 3H-PiB binding levels. These results demonstrate that compared to late-onset AD cases, adult DS individuals with similar severity of neocortical neuritic plaques and greater CAA pathology have a preponderance of both pyroglutamate-modified AβNpE3-40 and unmodified Aβ40 forms. Despite the distinct molecular profile of Aβ forms and greater vascular amyloidosis in DS cases, cortical 3H-PiB binding does not distinguish between diagnostic groups that are at an advanced level of amyloid plaque pathology. This underscores the need for the development of CAA-selective PET radiopharmaceuticals to detect and track the progression of cerebral vascular amyloid deposits in relation to Aβ plaques in individuals with DS.
A Topographic Atlas of the Human Brainstem in the Ponto-Mesencephalic Junction Plane
Authors: Coulombe Vincent , Saikali Stephan , Goetz Laurent , Takech Mohamad A. , Philippe Éric , Parent André , Parent Martin
Published: August 2021

The human brainstem harbors neuronal aggregates that ensure the maintenance of several vital functions. It also acts as a major relay structure for the neuronal information that travels between the cerebral cortex, the cerebellum and the spinal cord. As such, this relatively small portion of the human brain houses a multitude of ascending and descending fibers that course among numerous nuclei whose exact boundaries are still uncertain. Such a large number of nuclei and fiber tracts confined to a relatively small and compact brain region imposes upon the brainstem a highly complex cytoarchitectonic organization that still needs to be deciphered. The present work provides a topographic atlas of the human brainstem composed of 45 anatomical plates, each containing a pair of adjacent sections stained with Cresyl Violet and Luxol Fast Blue to help delineating brainstem nuclei and fiber tracts, respectively. The plates, which cover the entire midbrain, pons and medulla oblongata, are composed of equally-spaced sections referenced and aligned parallel to the ponto-mesencephalic junction rather than the fastigium or the obex. This topographic landmark is particularly suitable for neurosurgical interventions aiming at specific nuclei of the mesencephalic tegmentum. In complement, we provide 8 anatomical plates containing adjacent sections stained for choline acetyltransferase and Luxol Fast Blue, taken through the midbrain and the pons. This open access atlas of the human brainstem is intended to assist neuroanatomists, neurosurgeons and neuropathologists in their work.
Neuroinflammation in Autoimmune Disease and Primary Brain Tumors: The Quest for Striking the Right Balance
Authors: Mitchell Dana , Shireman Jack , Sierra Potchanant Elizabeth A. , Lara-Velazquez Montserrat , Dey Mahua
Published: August 2021

According to classical dogma, the central nervous system (CNS) is defined as an immune privileged space. The basis of this theory was rooted in an incomplete understanding of the CNS microenvironment, however, recent advances such as the identification of resident dendritic cells (DC) in the brain and the presence of CNS lymphatics have deepened our understanding of the neuro-immune axis and revolutionized the field of neuroimmunology. It is now understood that many pathological conditions induce an immune response in the CNS, and that in many ways, the CNS is an immunologically distinct organ. Hyperactivity of neuro-immune axis can lead to primary neuroinflammatory diseases such as multiple sclerosis and antibody-mediated encephalitis, whereas immunosuppressive mechanisms promote the development and survival of primary brain tumors. On the therapeutic front, attempts are being made to target CNS pathologies using various forms of immunotherapy. One of the most actively investigated areas of CNS immunotherapy is for the treatment of glioblastoma (GBM), the most common primary brain tumor in adults. In this review, we provide an up to date overview of the neuro-immune axis in steady state and discuss the mechanisms underlying neuroinflammation in autoimmune neuroinflammatory disease as well as in the development and progression of brain tumors. In addition, we detail the current understanding of the interactions that characterize the primary brain tumor microenvironment and the implications of the neuro-immune axis on the development of successful therapeutic strategies for the treatment of CNS malignancies.
Voxel-Wise Analysis of Structural and Functional MRI for Lateralization of Handedness in College Students
Authors: Wang Haha , Zhou Hong , Guo Yihao , Gao Lei , Xu Haibo
Published: August 2021

The brain structural and functional basis of lateralization in handedness is largely unclear. This study aimed to explore this issue by using voxel-mirrored homotopic connectivity (VMHC) measured by resting-state functional MRI (R-fMRI) and gray matter asymmetry index (AI) by high-resolution anatomical images. A total of 50 healthy subjects were included, among them were 13 left-handers, 24 right-handers, and 13 mixed-handers. Structural and R-fMRI data of all subjects were collected. There were significant differences in VMHC among the three groups in lateral temporal-occipital, orbitofrontal, and primary hand motor regions. Meanwhile, there were significant differences in AI that existed in medial prefrontal, superior frontal, and superior temporal regions. Besides, the correlation analysis showed that the closer the handedness score to the extreme of the left-handedness (LH), the stronger the interhemispheric functional connectivity, as well as more leftward gray matter. In general, left/mixed-handedness (MH) showed stronger functional homotopy in the transmodal association regions that depend on the integrity of the corpus callosum, but more variable in primary sensorimotor cortices. Furthermore, the group differences in VMHC largely align with that in AI. We located the specific regions for LH/MH from the perspective of structural specification and functional integration, suggesting the plasticity of hand movement and different patterns of emotional processing.
Toward EEG-Based BCI Applications for Industry 4.0: Challenges and Possible Applications
Authors: Douibi Khalida , Le Bars Solène , Lemontey Alice , Nag Lipsa , Balp Rodrigo , Breda Gabrièle
Published: August 2021

In the last few decades, Brain-Computer Interface (BCI) research has focused predominantly on clinical applications, notably to enable severely disabled people to interact with the environment. However, recent studies rely mostly on the use of non-invasive electroencephalographic (EEG) devices, suggesting that BCI might be ready to be used outside laboratories. In particular, Industry 4.0 is a rapidly evolving sector that aims to restructure traditional methods by deploying digital tools and cyber-physical systems. BCI-based solutions are attracting increasing attention in this field to support industrial performance by optimizing the cognitive load of industrial operators, facilitating human-robot interactions, and make operations in critical conditions more secure. Although these advancements seem promising, numerous aspects must be considered before developing any operational solutions. Indeed, the development of novel applications outside optimal laboratory conditions raises many challenges. In the current study, we carried out a detailed literature review to investigate the main challenges and present criteria relevant to the future deployment of BCI applications for Industry 4.0.
Simulating Macular Degeneration to Investigate Activities of Daily Living: A Systematic Review
Authors: Macnamara Anne , Chen Celia , Schinazi Victor R. , Saredakis Dimitrios , Loetscher Tobias
Published: August 2021

Purpose: Investigating difficulties during activities of daily living is a fundamental first step for the development of vision-related intervention and rehabilitation strategies. One way to do this is through visual impairment simulations. The aim of this review is to synthesize and assess the types of simulation methods that have been used to simulate age-related macular degeneration (AMD) in normally sighted participants, during activities of daily living (e.g., reading, cleaning, and cooking).

Methods: We conducted a systematic literature search in five databases and a critical analysis of the advantages and disadvantages of various AMD simulation methods (following PRISMA guidelines). The review focuses on the suitability of each method for investigating activities of daily living, an assessment of clinical validation procedures, and an evaluation of the adaptation periods for participants.

Results: Nineteen studies met the criteria for inclusion. Contact lenses, computer manipulations, gaze contingent displays, and simulation glasses were the main forms of AMD simulation identified. The use of validation and adaptation procedures were reported in approximately two-thirds and half of studies, respectively.

Conclusions: Synthesis of the methodology demonstrated that the choice of simulation has been, and should continue to be, guided by the nature of the study. While simulations may never completely replicate vision loss experienced during AMD, consistency in simulation methodology is critical for generating realistic behavioral responses under vision impairment simulation and limiting the influence of confounding factors. Researchers could also come to a consensus regarding the length and form of adaptation by exploring what is an adequate amount of time and type of training required to acclimatize participants to vision impairment simulations.
Effects of Frontal Theta Rhythms in a Prior Resting State on the Subsequent Motor Imagery Brain-Computer Interface Performance
Authors: Kang Jae-Hwan , Youn Joosang , Kim Sung-Hee , Kim Junsuk
Published: August 2021

Dealing with subjects who are unable to attain a proper level of performance, that is, those with brain–computer interface (BCI) illiteracy or BCI inefficients, is still a major issue in human electroencephalography (EEG) BCI systems. The most suitable approach to address this issue is to analyze the EEG signals of individual subjects independently recorded before the main BCI tasks, to evaluate their performance on these tasks. This study mainly focused on non-linear analyses and deep learning techniques to investigate the significant relationship between the intrinsic characteristics of a prior idle resting state and the subsequent BCI performance. To achieve this main objective, a public EEG motor/movement imagery dataset that constituted two individual EEG signals recorded from an idle resting state and a motor imagery BCI task was used in this study. For the EEG processing in the prior resting state, spectral analysis but also non-linear analyses, such as sample entropy, permutation entropy, and recurrent quantification analyses (RQA), were performed to obtain individual groups of EEG features to represent intrinsic EEG characteristics in the subject. For the EEG signals in the BCI tasks, four individual decoding methods, as a filter-bank common spatial pattern-based classifier and three types of convolution neural network-based classifiers, quantified the subsequent BCI performance in the subject. Statistical linear regression and ANOVA with post hoc analyses verified the significant relationship between non-linear EEG features in the prior resting state and three types of BCI performance as low-, intermediate-, and high-performance groups that were statistically discriminated by the subsequent BCI performance. As a result, we found that the frontal theta rhythm ranging from 4 to 8 Hz during the eyes open condition was highly associated with the subsequent BCI performance. The RQA findings that higher determinism and lower mean recurrent time were mainly observed in higher-performance groups indicate that more regular and stable properties in the EEG signals over the frontal regions during the prior resting state would provide a critical clue to assess an individual BCI ability in the following motor imagery task.
Reelin Is Required for Maintenance of Granule Cell Lamination in the Healthy and Epileptic Hippocampus
Authors: Orcinha Catarina , Kilias Antje , Paschen Enya , Follo Marie , Haas Carola A.
Published: August 2021

One characteristic feature of mesial temporal lobe epilepsy is granule cell dispersion (GCD), a pathological widening of the granule cell layer in the dentate gyrus. The loss of the extracellular matrix protein Reelin, an important positional cue for neurons, correlates with GCD formation in MTLE patients and in rodent epilepsy models. Here, we used organotypic hippocampal slice cultures (OHSC) from transgenic mice expressing enhanced green fluorescent protein (eGFP) in differentiated granule cells (GCs) to monitor GCD formation dynamically by live cell video microscopy and to investigate the role of Reelin in this process. We present evidence that following treatment with the glutamate receptor agonist kainate (KA), eGFP-positive GCs migrated mainly toward the hilar region. In the hilus, Reelin-producing neurons were rapidly lost following KA treatment as shown in a detailed time series. Addition of recombinant Reelin fragments to the medium effectively prevented the KA-triggered movement of eGFP-positive GCs. Placement of Reelin-coated beads into the hilus of KA-treated cultures stopped the migration of GCs in a distance-dependent manner. In addition, quantitative Western blot analysis revealed that KA treatment affects the Reelin signal transduction pathway by increasing intracellular adaptor protein Disabled-1 synthesis and reducing the phosphorylation of cofilin, a downstream target of the Reelin pathway. Both events were normalized by addition of recombinant Reelin fragments. Finally, following neutralization of Reelin in healthy OHSC by incubation with the function-blocking CR-50 Reelin antibody, GCs started to migrate without any direction preference. Together, our findings demonstrate that normotopic position of Reelin is essential for the maintenance of GC lamination in the dentate gyrus and that GCD is the result of a local Reelin deficiency.
Neuroplastic Reorganization Induced by Sensory Augmentation for Self-Localization During Locomotion
Authors: Sakai Hiroyuki , Ueda Sayako , Ueno Kenichi , Kumada Takatsune
Published: August 2021

Sensory skills can be augmented through training and technological support. This process is underpinned by neural plasticity in the brain. We previously demonstrated that auditory-based sensory augmentation can be used to assist self-localization during locomotion. However, the neural mechanisms underlying this phenomenon remain unclear. Here, by using functional magnetic resonance imaging, we aimed to identify the neuroplastic reorganization induced by sensory augmentation training for self-localization during locomotion. We compared activation in response to auditory cues for self-localization before, the day after, and 1 month after 8 days of sensory augmentation training in a simulated driving environment. Self-localization accuracy improved after sensory augmentation training, compared with the control (normal driving) condition; importantly, sensory augmentation training resulted in auditory responses not only in temporal auditory areas but also in higher-order somatosensory areas extending to the supramarginal gyrus and the parietal operculum. This sensory reorganization had disappeared by 1 month after the end of the training. These results suggest that the use of auditory cues for self-localization during locomotion relies on multimodality in higher-order somatosensory areas, despite substantial evidence that information for self-localization during driving is estimated from visual cues on the proximal part of the road. Our findings imply that the involvement of higher-order somatosensory, rather than visual, areas is crucial for acquiring augmented sensory skills for self-localization during locomotion.
Integrative Strategies for Preventing Nutritional Problems in the Development of Children in Brazil
Authors: Fisberg Mauro , Duarte Batista Lais , Nogueira-de-Almeida Carlos Alberto , Sarti Flávia Mori , Albuquerque Maria Paula de , Fisberg Regina Mara
Published: August 2021

Child healthcare has been a priority subject in several programs and public policies developed over the decades. However, initiatives implemented seem insufficient to overcome the challenges regarding the integral development and improvement of the nutritional status of children in Brazil. The initial developmental stages of a child include pregnancy, breastfeeding, and complementary feeding, which are determinants in future aspects of health and nutritional status. Therefore, the strategies addressing problems during these three periods of life have the potential to positively impact the promotion of healthy eating habits and food security throughout life. Developing countries with huge dimensions and vast inequalities, like Brazil, are marked by differences in regional, cultural, and social contexts that may hinder the implementation of programs and policies with a broad scope. Extensive operational and professional costs, in addition to time-consuming activities that are necessary to apply, monitor, and evaluate interventions may jeopardize the proper assessment of programs and policy goals, generating the inefficiency and waste of resources in the health system. Thus, programs and policies aimed at creating and modifying habits should consider an intersectoral action within local contexts, involving health professionals, universities, policy managers, and the community. Therefore, this article aimed to discuss the preliminary conception of an integrated approach of decentralized strategies to promote healthy eating habits and food security of children in Brazil.
Spleen Radiomics Signature: A Potential Biomarker for Prediction of Early and Late Recurrences of Hepatocellular Carcinoma After Resection
Authors: Li Pinxiong , Wu Lei , Li Zhenhui , Li Jiao , Ye Weitao , Shi Zhenwei , Xu Zeyan , Zhu Chao , Ye Huifen , Liu Zaiyi , Liang Changhong
Published: August 2021

Objectives

To explore the usefulness of spleen radiomics features based on contrast-enhanced computed tomography (CECT) in predicting early and late recurrences of hepatocellular carcinoma (HCC) patients after curative resection.

Methods

This retrospective study included 237 HCC patients who underwent CECT and curative resection between January 2006 to January 2016. Radiomic features were extracted from CECT images, and then the spleen radiomics signatures and the tumor radiomics signatures were built. Cox regression analysis was performed to identify the independent risk factors of early and late recurrences. Then, multiple models were built to predict the recurrence-free survival of HCC after resection, and the incremental value of the radiomics signature to the clinicopathologic model was assessed and validated. Kaplan–Meier survival analysis was used to assess the association of the models with RFS.

Results

The spleen radiomics signature was independent risk factor of early recurrence of HCC. The mixed model that integrated microvascular invasion, tumor radiomics signature and spleen radiomics signature for the prediction of early recurrence achieved the highest C-index of 0.780 (95% CI: 0.728,0.831) in the primary cohort and 0.776 (95% CI: 0.716,0.836) in the validation cohort, and presented better predictive performance than clinicopathological model and combined model. In the analysis of late recurrence, the spleen radiomics signature was the only prognostic factor associated with late recurrence of HCC.

Conclusions

The identified spleen radiomics signatures are prognostic factors of both early and late recurrences of HCC patients after surgery and improve the predictive performance of model for early recurrence.
Maternal-Neonatal Serum Albumin Level and Neonatal Respiratory Distress Syndrome in Late-Preterm Infants
Authors: Ying Qian , You Xue-qin , Luo Fei , Wang Ji-mei
Published: August 2021

Background: To determine the correlation between maternal-neonatal serum albumin level and respiratory distress syndrome (RDS) in late-preterm infants.

Methods: This case-control study included 112 late-preterm newborns admitted to the neonatal intensive care unit of our hospital between January 2018 and July 2019. Those infants were divided into the RDS group (n = 56) and the non-RDS group (n = 56). Levels of maternal-neonatal serum albumin, pregnancy complications, and baseline information of the infants were compared between the two groups.

Results: 1. There was no correlation between maternal and neonatal serum albumin measures. The maternal albumin level in the RDS group was lower than that in the control group (33.38 ± 3.31 vs. 33.60 ± 3.31, P > 0.05), but the difference was not statistically significant. The neonatal albumin level in the RDS group was significantly lower than that in the control group (32.70 ± 2.48 vs. 35.66 ± 3.27, P < 0.05). To predict RDS in late-preterm infants, using the albumin cutoff level of 34 g/L provides a sensitivity of 83.9% with a specificity of 62.5%. 2. Gestational age, primipara, placenta previa, antenatal corticosteroid therapy, delivery mode, and neonatal serum albumin level were associated with RDS in the late-preterm infant. 3. After adjustment for gestational age, logistic regression analysis showed that neonatal serum albumin level, placenta previa, and delivery mode were independent risk factors for RDS in late-preterm infants. However, albumin level did not related to the severity of RDS.

Conclusion: The decrease in serum albumin within the first day after birth was closely related to the occurrence of RDS in late-preterm infants.
Fetal Hemoglobin and Tissue Oxygenation Measured With Near-Infrared Spectroscopy—A Systematic Qualitative Review
Authors: Pritišanac Ena , Urlesberger Berndt , Schwaberger Bernhard , Pichler Gerhard
Published: August 2021

Fetal hemoglobin (HbF) is a principal oxygen carrier in the blood of preterm and term neonates. Compared to adult hemoglobin, it has a significantly higher affinity for oxygen and its oxyhemoglobin dissociation curve (ODC) is left-shifted accordingly. Tissue oxygenation measured with near-infrared spectroscopy (NIRS) during neonatal intensive care is directly affected by hemoglobin concentration. We performed a systematic qualitative review regarding the impact of HbF on tissue oxygenation monitoring by NIRS. The PubMed/Medline, EMBASE, Cochrane library and CINAHL databases were searched from inception to May 2021 for studies relating to HbF and NIRS in preterm and term neonates in the first days and weeks after birth. Out of 1,429 eligible records, four observational studies were included. Three studies found no effect of HbF on cerebral tissue oxygenation. One peripheral NIRS study found a positive correlation between HbF and peripheral fractional oxygen extraction (FOE). Currently available limited data suggest that FHbF could affect peripheral muscle FOE, but seems not to affect cerebral oxygenation in preterm neonates. More studies are needed to draw a final conclusion on this matter, especially concerning the oxygenation changes driven by adult RBC transfusions.
The Role of miR-181c in Mechanisms of Diabetes-Impaired Angiogenesis: An Emerging Therapeutic Target for Diabetic Vascular Complications
Authors: Solly Emma L. , Psaltis Peter J. , Bursill Christina A. , Tan Joanne T. M.
Published: August 2021

Diabetes mellitus is estimated to affect up to 700 million people by the year 2045, contributing to an immense health and economic burden. People living with diabetes have a higher risk of developing numerous debilitating vascular complications, leading to an increased need for medical care, a reduced quality of life and increased risk of early death. Current treatments are not satisfactory for many patients who suffer from impaired angiogenesis in response to ischaemia, increasing their risk of ischaemic cardiovascular conditions. These vascular pathologies are characterised by endothelial dysfunction and abnormal angiogenesis, amongst a host of impaired signaling pathways. Therapeutic stimulation of angiogenesis holds promise for the treatment of diabetic vascular complications that stem from impaired ischaemic responses. However, despite significant effort and research, there are no established therapies that directly stimulate angiogenesis to improve ischaemic complications such as ischaemic heart disease and peripheral artery disease, highlighting the immense unmet need. However, despite significant effort and research, there are no established therapies that directly stimulate angiogenesis in a clinical setting, highlighting the immense unmet need. MicroRNAs (miRNAs) are emerging as powerful targets for multifaceted diseases including diabetes and cardiovascular disease. This review highlights the potential role of microRNAs as therapeutic targets for rescuing diabetes-impaired angiogenesis, with a specific focus on miR-181c, which we have previously identified as an important angiogenic regulator. Here we summarise the pathways currently known to be regulated by miR-181c, which include the classical angiogenesis pathways that are dysregulated in diabetes, mitochondrial function and axonal guidance, and describe how these relate both directly and indirectly to angiogenesis. The pleiotropic actions of miR-181c across multiple key angiogenic signaling pathways and critical cellular processes highlight its therapeutic potential as a novel target for treating diabetic vascular complications.
Huangqi Shengmai Yin Ameliorates Myocardial Fibrosis by Activating Sirtuin3 and Inhibiting TGF-β/Smad Pathway
Authors: Pan Jianheng , Cao Zhanhong , Fang Chunqiu , Lei Yuting , Sun Jiaming , Huang Xiaowei , Han Dong
Published: August 2021

Myocardial fibrosis (MF) is an important pathological process in which a variety of cardiovascular diseases transform into heart failure. The main manifestation of MF is the excessive deposition of collagen in the myocardium. Here, we explored whether Huangqi Shengmai Yin (HSY) can inhibit isoprenaline (ISO)-induced myocardial collagen deposition in rats, thereby reducing the cardiac dysfunction caused by MF. The results of echocardiography showed that HSY upregulated fractional shortening and ejection fraction, and reduced the left ventricular systolic dysfunction in the rats with MF. Pathological results showed that HSY protected myocardium, inhibited apoptosis, and effectively reduced collagen deposition. HSY also inhibited the expression of collagen I and III and α-smooth muscle actin (α-SMA) in the heart tissue. HSY increased the expression of Sirtuin 3 (Sirt3) and inhibited the protein levels of the components in the transforming growth factor-β (TGF-β)/Smad pathway. At the same time, it also regulated the expression of related proteins in the matrix metalloproteinases family. In summary, HSY played a therapeutic role in rats with ISO-induced MF by protecting myocardium and inhibiting collagen deposition. Therefore, HSY is a potential therapeutic agent for ameliorating MF.
Samotolisib Attenuates Acute Liver Injury Through Inhibiting Caspase-11-Mediated Pyroptosis Via Regulating E3 Ubiquitin Ligase Nedd4
Authors: Zhao Yang-Yang , Wu Dong-Ming , He Miao , Zhang Feng , Zhang Ting , Liu Teng , Li Jin , Li Li , Xu Ying
Published: August 2021

Acute liver injury (ALI) is associated with poor survival in patients with sepsis. During sepsis, the liver is the main site of bacterial endotoxin-induced inflammation. Lipopolysaccharide (LPS) promotes caspase-4/5/11 activation, leading to pyroptosis, a major sepsis driver. This study aimed to identify novel drugs that can control hepatocyte caspase-4/5/11 activation during sepsis. We performed LPS-induced caspase-11 activation and pyroptosis in RAW 264.7 cells and established an LPS-induced ALI mouse model. We identified samotolisib (ST), a novel dual phosphoinositide 3-kinase (PI3K) and mammalian target of rapamycin (mTOR) inhibitor, by screening a library of 441 pyroptosis compounds with known targets, which dose-dependently inhibited caspase-11 activation and N-terminal fragment of gasdermin D (GSDMD-NT) generation, reducing RAW 264.7 cell pyroptosis. In mice, ST preconditioning improved survival, attenuated LPS-induced serum alanine aminotransferase and aspartate aminotransferase activity, and inhibited severe liver inflammation and damage. Importantly, ST treatment activated Nedd4, which directly interacts with and mediates caspase-11 ubiquitination and degradation. This was largely abrogated by insulin-like growth factor 1. ST ameliorated LPS-induced hepatotoxicity by inhibiting caspase-11/GSDMD-NT pyroptosis signaling via regulating PI3K/AKT/mTOR/Nedd4 signaling. Hence, ST may play a key role in the prevention of liver injury in patients with sepsis.
Dietary Intervention, When Not Associated With Exercise, Upregulates Irisin/FNDC5 While Reducing Visceral Adiposity Markers in Obese Rats
Authors: Furino Vanessa de Oliveira , Alves João Manoel , Marine Diego Adorna , Sene-Fiorese Marcela , Rodrigues Carla Nascimento dos Santos , Arrais-Lima Cristina , Mattiello Stela Márcia , Castro Cynthia Aparecida de , Borra Ricardo Carneiro , Rocha Marina Campos , Malavazi Iran , Duarte Ana Cláudia Garcia de Oliveira
Published: August 2021

Obesity is an epidemic disease and the expansion of adipose tissue, especially visceral fat, promotes the secretion of factors that lead to comorbidities such as diabetes and cardiovascular diseases. Thus, diet and exercise have been proposed as an intervention to reverse these complications. An adipocytokine, known as irisin, mediates the beneficial effects of exercise. It has been proposed as a therapeutic potential in controlling obesity. In view of the above, this paper attempts to determine the modulation of irisin, visceral adiposity and biochemical markers in response to dietary intervention and aerobic exercise. To do this, 52 diet-induced obese male Wistar rats were divided into the following four groups: high-fat diet and exercise (HFD-Ex); HFD-Sedentary (HFD-Sed); chow-diet and exercise (CD-Exercise); and CD-Sed. The exercise-trained group performed a treadmill protocol for 60 min/day, 3 days/week for 8 weeks. Body mass (BM), body fat (BF), fat mass (FM), and fat-free mass (FFM) were analyzed. Mesenteric (MES), epididymal (EPI), and retroperitoneal (RET) adipose tissue was collected and histological analysis was performed. Biochemical irisin, triglycerides, glucose, insulin and inflammatory markers were determined and, FNDC5 protein expression was analyzed. In this study, the diet was the most important factor in reducing visceral adiposity in the short and long term. Exercise was an important factor in preserving muscle mass and reducing visceral depots after a long term. Moreover, the combination of diet and exercise can enhance these effects. Diet and exercise exclusively were the factors capable of increasing the values of irisin/FNDC5, however it did not bring cumulative effects of both interventions. Prescriptions to enhance the obesity treatments should involve reducing visceral adiposity by reducing the fat content in the diet associated with aerobic exercise.
Activation of the Thiazide-Sensitive Sodium-Chloride Cotransporter by Beta3-Adrenoreceptor in the Distal Convoluted Tubule
Authors: Milano Serena , Carmosino Monica , Gerbino Andrea , Saponara Ilenia , Lapi Dominga , Dal Monte Massimo , Bagnoli Paola , Svelto Maria , Procino Giuseppe
Published: August 2021

We previously showed that the beta-3 adrenergic receptor (BAR3) is expressed in most segments of the nephron where its agonism promotes a potent antidiuretic effect. We localized BAR3 in distal convoluted tubule (DCT) cells expressing the thiazide-sensitive sodium-chloride cotransporter (NCC). Aim of this study is to investigate the possible functional role of BAR3 on NCC modulation in DCT cells. Here, we found that, in mice, the knockout of BAR3 was paralleled by a significant attenuation of NCC phosphorylation, paralleled by reduced expression and activation of STE-20/SPS1-related proline-alanine-rich kinase (SPAK) and WNKs the main kinases involved in NCC activation. Conversely, in BAR1/2 knockout mice, we found reduced NCC abundance with no changes in the phosphorylation state of NCC. Moreover, selective BAR3 agonism promotes both SPAK and NCC activation in wild-type mouse kidney slices. In conclusion, our findings suggest a novel role for BAR3 in the regulation of NCC in DCT.