bluuebunny/crossref_metadata_2025 huggingface dataset:
Comparative Study of the Effects of Machine Parameters on DFIG and PMSG Variable Speed Wind Turbines During Grid Fault
Authors: Okedu Kenneth E. , Al Tobi Maamar , Al Araimi Saleh
Published: May 2021

This study investigates the transient performance of two variable speed wind turbines (VSWTs), namely doubly fed induction generator (DFIG) and the permanent magnet synchronous generator (PMSG), that are widely employed in wind energy conversion, considering their machine parameters. The machine parameters of both wind turbines were changed considering different scenarios, while keeping other parameters constant, to study the behavior of the wind generators. This study was carried out using the same operating conditions of rated wind speed, based on the characteristics of both wind turbine technologies. The wind turbines were subjected to a severe three phase to ground bolted fault to test the robustness of their controllers during grid fault conditions. Efforts were made to carry out an extensive comparative study to investigate the machine parameters that have more influence on the stability of the different wind turbines considered in this study. Simulations were carried out using power system computer-aided design and electromagnetic transient including DC (PSCAD/EMTDC). Effective machine parameter selection could help solve fault ride-through (FRT) problems cost-effectively for both VSWTs, without considering the external circuitry of and changing the original architecture of the wind turbines.
How Many Cars in the City Are Too Many? Towards Finding the Optimal Modal Split for a Multi-Modal Urban Road Network
Authors: Loder Allister , Bressan Lea , Wierbos Maria J. , Becker Henrik , Emmonds Andy , Obee Martin , Knoop Victor L. , Menendez Monica , Axhausen Kay W.
Published: May 2021

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.
Monitoring Spatial-Temporal Transition Dynamics of Transport Infrastructure Space in Urban Growth Phenomena: A Case Study of Lagos—Nigeria
Authors: Otuoze Suleiman Hassan , Hunt Dexter V.L. , Jefferson Ian
Published: May 2021

Lagos is one of the fastest growing world mega-cities with a huge urban mobility crisis, the traditional aggregate city’s development model could not provide reliable scientific solutions to monitor the competing demands of various land-use components and the urbanization’s effects on transport infrastructure space. This study uses a disaggregated predictive spatial modeling approach to investigate the evolutionary dynamics of transportation infrastructure space to address the fragmented urban chain process. The methodology involves analysis and modeling of the land-use spatial transition changes that have occurred over the past three decades using three Landsat imagery epochs (1984, 2013, and 2019) in remote sensing ARC-GIS 10.7. Furthermore, the prediction of the two-temporal milestones (2030 and 2050) using hybrid cellular automata-Markov (CA-Markov) implemented in IDIRISI SELVA 17.0 software when the tides of social-demographic factors were expected to bring about significant urban spatial transformation. The forecast results are expected to increase the area for transport infrastructure spaces by 93 km2 (7.3%) in 2030 and 157 km2 (12.4%) in 2050. The model’s kappa reliability coefficient estimates for the three temporal scales (k1984 = 85%; k2013 = 88% and k2019 = 89%) are higher than the 80% minimum adjudged strong agreement between the ground truth and prediction classified images in literature. The model provides efficient tool in urban development planning and sustainable transport decisions.
Case Report: Complete Maternal Uniparental Isodisomy of Chromosome 5 (iUPD(5)mat) With PCSK1 Nonsense Variant in an Infant With Recurrent Diarrhea
Authors: Qian Yanyan , Wu Bingbing , Liu Renchao , Lu Yulan , Zhang Ping , Shao Caihong , Huang Ying , Wang Huijun
Published: May 2021

Congenital diarrhea diseases are a heterogeneous group of conditions and are the major cause of neonatal mortality worldwide. Proprotein convertase 1/3 (PC1/3) deficiency has been associated with severe malabsorptive diarrhea, obesity, and certain endocrine abnormalities. We report an infant born to non-consanguineous parents who is diagnosed with PC1/3 deficiency due to nonsense homozygous variant (c.238 C>T, p.Arg80Ter) in the PCSK1 gene, identified by Trio-exome sequencing (Trio-ES). The baby girl presented with recurrent diarrhea, transient liver dysfunction and hypoglycemia. Trio-ES showed complete maternal uniparental isodisomy (iUPD) of chromosome 5. Our finding provides accurate genetic counseling to this family and expands the clinical spectrum of iUPD with pathogenic variants causing recessive disease.
Early-Warning Immune Predictors for Invasive Pulmonary Aspergillosis in Severe Patients With Severe Fever With Thrombocytopenia Syndrome
Authors: Hu Lifen , Kong Qinxiang , Yue Chengcheng , Xu Xihai , Xia Lingling , Bian Tingting , Liu Yanyan , Zhang Hui , Ma Xuejiao , Yin Huafa , Sun Qiulin , Gao Yufeng , Ye Ying , Li Jiabin
Published: May 2021

Aspergillus-related disease was confirmed to be associated with immune disorders in patients, severe patients with severe fever with thrombocytopenia syndrome (SFTS) infected by novel phlebovirus were confirmed to have severe immune damage including cellular immunosuppression and cytokine storms. Secondary invasive pulmonary aspergillosis (IPA) in severe SFTS patients can increase fatality rate. This study investigated early-warning predictive factors of secondary IPA in severe SFTS patients. Receiver operating characteristic analysis was used to assess the value of immune parameters to predict IPA in SFTS patients. The cut-off values of CD4+ and CD8+ T-cell counts to predict IPA were 68 and 111 cells/mm3, with sensitivities of 82.6% and 72%, and specificities of 56.7% and 83.3%, respectively. Cut-off values of IL-6, TNF-α, IL-8, and IL-10 to predict IPA incidence in critically ill SFTS patients were 99 pg/mL, 63 pg/mL, 120 pg/mL, and 111 pg/mL, with sensitivities of 90.0%, 86.7%, 83.3% and 90.0% and specificities of 80.4%, 71.7%, 82.6% and 65.2%, respectively. Lower CD4+ and CD8+ T-cells counts, higher levels of IL-6, TNF-α, IL-8 and IL-10, higher incidence of pancreatic and renal damage, early antibacterial therapy of carbapenems, and intensive care unit admission were risk factors of IPA in SFTS patients. Multivariate logistic regression analysis indicated counts of CD4+ T-cells <68 cells/mm3 combined with CD8+ T-cells <111 cells/mm3 (odds ratio [OR] 0.218, 95% confidence interval [CI] 0.059–0.803, p=0.022), IL-6 >99 pg/ml combined with IL-10 >111 pg/ml (OR 17.614, 95% CI 2.319–133.769, p=0.006), and brain natriuretic peptide level >500 pg/ml (OR 13.681, 95% CI 1.994–93.871, p=0.008) were independent risk factors for IPA in SFTS patients. The mortality in the IPA group was significantly higher than in the non-IPA group (p=0.001). Early antifungal treatment of IPA patients was significantly associated with improved survival (log-rank, p=0.022). Early diagnosis of IPA and antifungal treatment can improve the prognosis of SFTS patients. Besides, we speculate SFTS may be as a host factor for IPA.
Combination of Immunotherapy and Radiotherapy for Recurrent Malignant Gliomas: Results From a Prospective Study
Authors: Jiang Haihui , Yu Kefu , Cui Yong , Ren Xiaohui , Li Mingxiao , Yang Chuanwei , Zhao Xuzhe , Zhu Qinghui , Lin Song
Published: May 2021

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.
Detection of MOG-IgG in Clinical Samples by Live Cell-Based Assays: Performance of Immunofluorescence Microscopy and Flow Cytometry
Authors: Marchionatti Amanda , Hansel Gisele , Avila Gabriela Urbanski , Sato Douglas Kazutoshi
Published: May 2021

Human antibodies against Myelin Oligodendrocyte Glycoprotein (MOG) from immunoglobulin-G subclasses (MOG-IgG) have been recently associated with a new subgroup of neurological autoimmune diseases with distinct clinical characteristics from multiple sclerosis and neuromyelitis optica spectrum disorders. The use of MOG-IgG as a biomarker is an essential tool to assist in the diagnosis and clinical prognosis. The cell-based assay (CBA) is a methodology that expresses high levels of natively folded human MOG protein in the cell membrane being the methodology most used for clinical MOG-IgG diagnosis. However, there is still no consensus about the best approach to perform CBA to improve the results. The CBA using flow cytometry (CBA-FC) is an automated technique with objective quantification, reducing the subject of human bias that occurred at CBA using immunofluorescence (CBA-IF). In this study, we compared the performance of CBA-IF and CBA-FC as an acquisition tool analysis. The sera of 104 patients diagnosed with inflammatory Central Nervous System diseases were tested in both CBA-IF and CBA-FC. We used the dilution of 1:128 for CBA-IF and three different dilutions (1:20, 1:100, and 1:640) for CBA-FC. The CBA-FC and CBA-IF results had 88.5% agreement between assays and the CBA-IF titers by endpoint-dilution correlated with the CBA-FC titers. The highest serum dilution resulted in an increased CBA-FC specificity, but there was a reduction in the CBA-FC sensitivity. Our study showed that CBA-FC can be used in clinical practice as a diagnostic technique for MOG-IgG. In addition, in some specific cases, the combination of both techniques could be used as a tool to discriminate unspecific binding and overcome single assay limitations.
Altered Functional Connectivity of the Primary Visual Cortex in Patients With Iridocyclitis and Assessment of Its Predictive Value Using Machine Learning
Authors: Tong Yan , Huang Xin , Qi Chen-Xing , Shen Yin
Published: May 2021

Purpose

To explore the intrinsic functional connectivity (FC) alteration of the primary visual cortex (V1) between individuals with iridocyclitis and healthy controls (HCs) by the resting-state functional magnetic resonance imaging (fMRI) technique, and to investigate whether FC findings be used to differentiate patients with iridocyclitis from HCs.

Methods

Twenty-six patients with iridocyclitis and twenty-eight well-matched HCs were recruited in our study and underwent resting-state fMRI examinations. The fMRI data were analyzed by Statistical Parametric Mapping (SPM12), Data Processing and Analysis for Brain Imaging (DPABI), and Resting State fMRI Data Analysis Toolkit (REST) software. Differences in FC signal values of the V1 between the individuals with iridocyclitis and HCs were compared using independent two-sample t-tests. Significant differences in FC between two groups were chosen as classification features for distinguishing individuals with iridocyclitis from HCs using a support vector machine (SVM) classifier that involved machine learning. Classifier performance was evaluated using permutation test analysis.

Results

Compared with HCs, patients with iridocyclitis displayed significantly increased FC between the left V1 and left cerebellum crus1, left cerebellum 10, bilateral inferior temporal gyrus, right hippocampus, and left superior occipital gyrus. Moreover, patients with iridocyclitis displayed significantly lower FC between the left V1 and both the bilateral calcarine and bilateral postcentral gyrus. Patients with iridocyclitis also exhibited significantly higher FC values between the right V1 and left cerebellum crus1, bilateral thalamus, and left middle temporal gyrus; while they displayed significantly lower FC between the right V1 and both the bilateral calcarine and bilateral postcentral gyrus (voxel-level P<0.01, Gaussian random field correction, cluster-level P<0.05). Our results showed that 63.46% of the participants were correctly classified using the leave-one-out cross-validation technique with an SVM classifier based on the FC of the left V1; and 67.31% of the participants were correctly classified based on the FC of the right V1 (P<0.001, non-parametric permutation test).

Conclusion

Patients with iridocyclitis displayed significantly disturbed FC between the V1 and various brain regions, including vision-related, somatosensory, and cognition-related regions. The FC variability could distinguish patients with iridocyclitis from HCs with substantial accuracy. These findings may aid in identifying the potential neurological mechanisms of impaired visual function in individuals with iridocyclitis.
Serum Short-Chain Fatty Acids and Associations With Inflammation in Newly Diagnosed Patients With Multiple Sclerosis and Healthy Controls
Authors: Olsson Anna , Gustavsen Stefan , Nguyen Thao Duy , Nyman Margareta , Langkilde Annika R. , Hansen Tue H. , Sellebjerg Finn , Oturai Annette B. , Bach Søndergaard Helle
Published: May 2021

Multiple sclerosis (MS) is a chronic immune-mediated disease characterized by demyelination and neuroaxonal damage in the central nervous system. The etiology is complex and is still not fully understood. Accumulating evidence suggests that our gut microbiota and its metabolites influence the MS pathogenesis. Short-chain fatty acids (SCFAs), such as acetate, propionate and butyrate, are metabolites produced by gut microbiota through fermentation of indigestible carbohydrates. SCFAs and kynurenine metabolites have been shown to have important immunomodulatory properties, and propionate supplementation in MS patients has been associated with long-term clinical improvement. However, the underlying mechanisms of action and its importance in MS remain incompletely understood. We analyzed serum levels of SCFAs and performed targeted metabolomics in relation to biomarkers of inflammation, and clinical and MRI measures in newly diagnosed patients with relapsing-remitting MS before their first disease modifying therapy and healthy controls (HCs). We demonstrated that serum acetate levels were nominally reduced in MS patients compared with HCs. The ratios of acetate/butyrate and acetate/(propionate + butyrate) were significantly lower in MS patients in a multivariate analysis (orthogonal partial least squares discriminant analysis; OPLS-DA). The mentioned ratios and acetate levels correlated negatively with the pro-inflammatory biomarker IFNG, indicating an inverse relation between acetate and inflammation. In contrast, the proportion of butyrate was found higher in MS patients in the multivariate analysis, and both butyrate and valerate correlated positively with proinflammatory cytokines (IFNG and TNF), suggesting complex bidirectional regulatory properties of SCFAs. Branched SCFAs were inversely correlated with clinical disability, at a nominal significance level. Otherwise SCFAs did not correlate with clinical variables or MRI measures. There were signs of an alteration of the kynurenine pathway in MS, and butyrate was positively correlated with the immunomodulatory metabolite 3-hydroxyanthranilic acid. Other variables that influenced the separation between MS and HCs were NfL, ARG1 and IL1R1, D-ribose 5-phosphate, pantothenic acid and D-glucuronic acid. In conclusion, we provide novel results in this rapidly evolving field, emphasizing the complexity of the interactions between SCFAs and inflammation; therefore, further studies are required to clarify these issues before supplementation of SCFAs can be widely recommended.
Implications the Role of miR-155 in the Pathogenesis of Autoimmune Diseases
Authors: Pashangzadeh Salar , Motallebnezhad Morteza , Vafashoar Fatemeh , Khalvandi Azadeh , Mojtabavi Nazanin
Published: May 2021

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.
Nutrigenetic Interactions Might Modulate the Antioxidant and Anti-Inflammatory Status in Mastiha-Supplemented Patients With NAFLD
Authors: Kanoni Stavroula , Kumar Satish , Amerikanou Charalampia , Kurth Mary Jo , Stathopoulou Maria G. , Bourgeois Stephane , Masson Christine , Kannt Aimo , Cesarini Lucia , Kontoe Maria-Spyridoula , Milanović Maja , Roig Francisco J. , Beribaka Mirjana , Campolo Jonica , Jiménez-Hernández Nuria , Milošević Nataša , Llorens Carlos , Smyrnioudis Ilias , Francino M. Pilar , Milić Nataša , Kaliora Andriana C. , Trivella Maria Giovanna , Ruddock Mark W. , Medić-Stojanoska Milica , Gastaldelli Amalia , Lamont John , Deloukas Panos , Dedoussis George V. , Visvikis-Siest Sophie
Published: May 2021

Non-alcoholic fatty liver disease (NAFLD) is the most common liver disease with no therapeutic consensus. Oxidation and inflammation are hallmarks in the progression of this complex disease, which also involves interactions between the genetic background and the environment. Mastiha is a natural nutritional supplement known to possess antioxidant and anti-inflammatory properties. This study investigated how a 6-month Mastiha supplementation (2.1 g/day) could impact the antioxidant and inflammatory status of patients with NAFLD, and whether genetic variants significantly mediate these effects. We recruited 98 patients with obesity (BMI ≥ 30 kg/m2) and NAFLD and randomly allocated them to either the Mastiha or the placebo group for 6 months. The anti-oxidative and inflammatory status was assessed at baseline and post-treatment. Genome-wide genetic data was also obtained from all participants, to investigate gene-by-Mastiha interactions. NAFLD patients with severe obesity (BMI > 35kg/m2) taking the Mastiha had significantly higher total antioxidant status (TAS) compared to the corresponding placebo group (P value=0.008). We did not observe any other significant change in the investigated biomarkers as a result of Mastiha supplementation alone. We identified several novel gene-by-Mastiha interaction associations with levels of cytokines and antioxidant biomarkers. Some of the identified genetic loci are implicated in the pathological pathways of NAFLD, including the lanosterol synthase gene (LSS) associated with glutathione peroxidase activity (Gpx) levels, the mitochondrial pyruvate carrier-1 gene (MPC1) and the sphingolipid transporter-1 gene (SPNS1) associated with hemoglobin levels, the transforming growth factor‐beta‐induced gene (TGFBI) and the micro-RNA 129-1 (MIR129-1) associated with IL-6 and the granzyme B gene (GZMB) associated with IL-10 levels. Within the MAST4HEALTH randomized clinical trial (NCT03135873, www.clinicaltrials.gov) Mastiha supplementation improved the TAS levels among NAFLD patients with severe obesity. We identified several novel genome-wide significant nutrigenetic interactions, influencing the antioxidant and inflammatory status in NAFLD.

Clinical Trial Registration

ClinicalTrials.gov, identifier NCT03135873.
Modeling Influencing Factors in B-Cell Reconstitution After Hematopoietic Stem Cell Transplantation in Children
Authors: van der Maas Nicolaas G. , von Asmuth Erik G. J. , Berghuis Dagmar , van Schouwenburg Pauline A. , Putter Hein , van der Burg Mirjam , Lankester Arjan C.
Published: May 2021

Reduced total and memory B-cell numbers in peripheral blood long term after hematopoietic stem cell transplantation (HSCT) are associated with an increased incidence of infections and immune complications. Using novel modelling strategies, baseline factors influencing B-cell reconstitution can be comprehensively studied. This study aims to investigate the numerical total and memory B-cell reconstitution in children and the association with baseline determinants 0.5-2 years after allogeneic HSCT. Eligible for inclusion were children transplanted in our center between 2004-2017 who received a first HSCT for malignant or non-malignant disorders. The continuous absolute counts of total and memory B-cells were evaluated as outcome measure. Exploratory analysis at one year was done to identify possible determinants. Linear mixed effect modelling was used to analyze the association of these determinants with total and memory B-cell reconstitution 0.5-2 years after HSCT. In a cohort of 223 evaluable patients analyzed at 1-year after HSCT donor age, stem cell source, donor type, recipient age and conditioning were identified as significant determinants for total and memory B-cell numbers. Multivariable analysis revealed that both donor and recipient age were inversely correlated with the size of total and memory B-cell reconstitution. In contrast, no correlation was found with stem cell source, donor type and conditioning. Making use of linear mixed modelling both stem cell donor and recipient age were identified as independent determinants of total and memory B-cell reconstitution 0.5-2 years after HSCT.
When Beneficial Biofilm on Materials Is Needed: Electrostatic Attachment of Living Bacterial Cells Induces Biofilm Formation
Authors: Deev Dmitrii , Rybkin Iaroslav , Rijavec Tomaž , Lapanje Aleš
Published: May 2021

Bacterial attachment is crucial in many biotechnological applications, but many important bacterial strains cannot form biofilms. Biofilms can damage materials, and current strategies to manage biofilms are focused on inhibition and removal of biofilm. Biofilm formation is inevitable when materials are exposed to microbes and instead of biofilm prevention, we propose management of microbial composition by formation of biofilms with beneficial microbes. Since bacteria need to overcome a high repulsive force to attach to the surface and later to grow and multiply on it, electrostatic modification of the surfaces of cells or the material by polyelectrolytes (PE) was used in our approach, enabling efficient attachment of viable bacterial cells. Since highly positively charged PEs are known to be bactericidal, they were acetylated to reduce their toxicity, while preserving their net positive charge and ensuring cell viability. In our study bacterial strains were selected according to their intrinsic capability of biofilm formation, their shape variety and cell wall structure. These strains were tested to compare how the artificially prepared vs. natural biofilms can be used to populate the surface with beneficial bacteria. Using an artificial biofilm constructed of the potentially probiotic isolate Bacillus sp. strain 25.2. M, reduced the attachment and induced complete inhibition of E. coli growth over the biofilm. This study also revealed that the modification of the surfaces of cells or material by polyelectrolytes allows the deposition of bacterial cells, biofilm formation and attachment of biofilm non-forming cells onto surfaces. In this way, artificial biofilms with extended stability can be constructed, leading to selective pressure on further colonization of environmental bacteria.
Itch in Atopic Dermatitis – What Is New?
Authors: Legat Franz J.
Published: May 2021

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.
The Role of Ferroptosis in Acute Respiratory Distress Syndrome
Authors: Qu Mengdi , Zhang Hao , Chen Zhaoyuan , Sun Xingfeng , Zhu Shuainan , Nan Ke , Chen Wankun , Miao Changhong
Published: May 2021

Ferroptosis is a newly discovered type of regulated cell death that is different from apoptosis, necrosis and autophagy. Ferroptosis is characterized by iron-dependent lipid peroxidation, which induces cell death. Iron, lipid and amino acid metabolism is associated with ferroptosis. Ferroptosis is involved in the pathological development of various diseases, such as neurological diseases and cancer. Recent studies have shown that ferroptosis is also closely related to acute lung injury (ALI)/ acute respiratory distress syndrome (ARDS), suggesting that it can be a novel therapeutic target. This article mainly introduces the metabolic mechanism related to ferroptosis and discusses its role in ALI/ARDS to provide new ideas for the treatment of these diseases.
Bacillus pumilus Group Comparative Genomics: Toward Pangenome Features, Diversity, and Marine Environmental Adaptation
Authors: Fu Xiaoteng , Gong Linfeng , Liu Yang , Lai Qiliang , Li Guangyu , Shao Zongze
Published: May 2021

Background

Members of the Bacillus pumilus group (abbreviated as the Bp group) are quite diverse and ubiquitous in marine environments, but little is known about correlation with their terrestrial counterparts. In this study, 16 marine strains that we had isolated before were sequenced and comparative genome analyses were performed with a total of 52 Bp group strains. The analyses included 20 marine isolates (which included the 16 new strains) and 32 terrestrial isolates, and their evolutionary relationships, differentiation, and environmental adaptation.

Results

Phylogenomic analysis revealed that the marine Bp group strains were grouped into three species: B. pumilus, B. altitudinis and B. safensis. All the three share a common ancestor. However, members of B. altitudinis were observed to cluster independently, separating from the other two, thus diverging from the others. Consistent with the universal nature of genes involved in the functioning of the translational machinery, the genes related to translation were enriched in the core genome. Functional genomic analyses revealed that the marine-derived and the terrestrial strains showed differences in certain hypothetical proteins, transcriptional regulators, K+ transporter (TrK) and ABC transporters. However, species differences showed the precedence of environmental adaptation discrepancies. In each species, land specific genes were found with possible functions that likely facilitate survival in diverse terrestrial niches, while marine bacteria were enriched with genes of unknown functions and those related to transcription, phage defense, DNA recombination and repair.

Conclusion

Our results indicated that the Bp isolates show distinct genomic features even as they share a common core. The marine and land isolates did not evolve independently; the transition between marine and non-marine habitats might have occurred multiple times. The lineage exhibited a priority effect over the niche in driving their dispersal. Certain intra-species niche specific genes could be related to a strain’s adaptation to its respective marine or terrestrial environment(s). In summary, this report describes the systematic evolution of 52 Bp group strains and will facilitate future studies toward understanding their ecological role and adaptation to marine and/or terrestrial environments.
Prevalence and Distribution of Rotavirus Genotypes Among Children With Acute Gastroenteritis in Areas Other Than Java Island, Indonesia, 2016–2018
Authors: Wahyuni Rury Mega , Utsumi Takako , Dinana Zayyin , Yamani Laura Navika , Juniastuti  , Wuwuti Ishak Samuel , Fitriana Elsa , Gunawan Emily , Liang Yujiao , Ramadhan Fitratul , Soetjipto  , Lusida Maria Inge , Shoji Ikuo
Published: May 2021

Group A rotaviruses (RVAs) are the leading cause of acute gastroenteritis, which is often associated with severe symptoms in children under 5 years old. Genetic reassortments and interspecies transmission commonly occur, resulting in a great diversity of RVA circulating in the world. The aim of this study is to determine the prevalence and distribution of RVA genotypes among children in Indonesia over the years 2016–2018 across representative areas of the country. Stool samples were collected from 202 pediatric patients with acute gastroenteritis in three regions of Indonesia (West Nusa Tenggara, South Sumatra, and West Papua) in 2016–2018. Rotavirus G and P genotypes were determined by reverse transcription PCR (RT-PCR) and direct sequencing analysis. The prevalences of RVA in South Sumatra (55.4%) and West Papua (54.0%) were significantly higher than that in East Java (31.7%) as determined in our previous study. The prevalence in West Nusa Tenggara (42.6%) was the lowest among three regions, but higher than that in East Java. Interestingly, equine-like G3 rotavirus strains were found as predominant strains in South Sumatra in 2016 and in West Papua in 2017–2018. Moreover, the equine-like G3 strains in South Sumatra detected in 2016 were completely replaced by human G1 and G2 in 2018. In conclusion, RVA infection in South Sumatra and West Papua was highly endemic. Equine-like G3 strains were also spread to South Sumatra (West Indonesia) and West Papua (East Indonesia), as well as Java Island. Dynamic change in rotavirus genotypes from equine-like G3 to human genotypes was also observed. Continuous monitoring may be warranted in isolated areas in Indonesia.
Dietary Habits and Nutrient Intakes Are Associated to Age-Related Central Auditory Processing Disorder in a Cohort From Southern Italy
Authors: Lampignano Luisa , Quaranta Nicola , Bortone Ilaria , Tirelli Sarah , Zupo Roberta , Castellana Fabio , Donghia Rossella , Guerra Vito , Griseta Chiara , Pesole Pasqua Letizia , Chieppa Marcello , Logroscino Giancarlo , Lozupone Madia , Cisternino Anna Maria , De Pergola Giovanni , Panza Francesco , Giannelli Gianluigi , Boeing Heiner , Sardone Rodolfo
Published: May 2021

Objectives

Central auditory processing disorder (CAPD) commonly occurs in older age. However, few studies of a possible link between age-related CAPD and diet in an older population have been conducted. The objective of the present study was to investigate the relationship between eating habits and age-related CAPD in a population >65 years, using cross-sectional and retrospective data obtained in the same population-based study about 12 years ago.

Methods

We selected 734 participants (403 men) from a large population-based study. For age-related CAPD assessment, we used the Synthetic Sentence Identification with Ipsilateral Competitive Message test. Dietary habits were assessed by a Food Frequency Questionnaire. Associations between age-related CAPD and food groups/macro-and micronutrients were explored using adjusted logistic regression models.

Results

Age-related CAPD subjects consumed more dairy (111 vs. 98 g/d), olives and vegetable oil (63 vs. 52 g/d) and spirits (2 vs.1 g/d), and less fruits (536 vs. 651 g/d) in the cross-sectional analysis. Age-related CAPD subjects had a lower intake of potassium, vitamin C, and a higher fat intake. Further analyses identified dietary fiber as being inversely related to age-related CAPD.

Discussion

The present study provided evidence that the dietary hypotheses proposed for explaining the development of cognitive disorders in older age might also hold for age-related CAPD. Further data from other large and prospective population-based studies are needed for confirming these findings.
Risks and Prognoses of Alzheimer's Disease and Vascular Dementia in Patients With Insomnia: A Nationwide Population-Based Study
Authors: Baek Min Seok , Han Kyungdo , Kwon Hyuk-Sung , Lee Yong-ho , Cho Hanna , Lyoo Chul Hyoung
Published: May 2021

This study aimed to investigate the risk and prognosis of Alzheimer's disease (AD) and vascular dementia (VaD) in patients with insomnia using the National Health Insurance Service database covering the entire population of the Republic of Korea from 2007 to 2014. In total, 2,796,871 patients aged 40 years or older with insomnia were enrolled, and 5,593,742 controls were matched using a Greedy digit match algorithm. Mortality and the rate of admission to a long-term care facility were estimated using multivariable Cox analysis. Of all patients with insomnia, 138,270 (4.94%) and 26,706 (0.96%) were newly diagnosed with AD and VaD, respectively. The incidence rate ratios for AD and VaD were 1.73 and 2.10, respectively, in patients with insomnia compared with those without. Higher mortality rates and long-term care facility admission rates were also observed in patients with dementia in the insomnia group. Known cardiovascular risk factors showed interactions with the effects of insomnia on the risk of AD and VaD. However, the effects of insomnia on the incidence of AD and VaD were consistent between the groups with and without cardiovascular risk factors. Insomnia is a medically modifiable and policy-accessible risk factor and prognostic marker of AD and VaD.
Effect of Dance on Balance, Mobility, and Activities of Daily Living in Adults With Cerebral Palsy: A Pilot Study
Authors: Joung Hee Joung , Yang Hye Kyung , Lee Yongho
Published: May 2021

The age-related decline in motor function with respect to balance and mobility may hamper the activities of daily living, quality of life, and social participation. Despite the importance of managing secondary conditions leading to premature aging, the literature regarding appropriate physical activity for adults with cerebral palsy (CP) is still scarce. Dance forms have emerged as an effective physical activity that improves balance and mobility in individuals with neurological conditions and boosts social engagement. However, its effect on adults with CP has yet to be examined. This pilot study aimed to examine the long-term effect of dance on improving balance and mobility in adults with CP. This single-cohort study included 10 adults with CP. They attended two 90-min-long creative dance sessions per week for 12 weeks. The outcomes measured effects on balance, mobility, balance confidence, and level of functional independence. These measurements were obtained at pre-intervention, post-intervention, and the 3-month follow-up. Outcome data of pre- to post-intervention and pre-intervention to 3-month follow-up were analyzed and compared. Statistically significant differences were found in the pre- and post-intervention displacement of the center of pressure (CoP) in the eyes-opened (EO) condition, timed up and go test (TUG), and Berg Balance Scale (BBS), Dynamic Gait Index (DGI), and Korean-Activity of Balance Confidence (K-ABC) scores. Significant improvements were also observed for the CoP-EO, BBS, TUG, DGI, and K-ABC between the pre-intervention and 3-month follow-up assessments. However, there were no significant differences in the CoP in the eyes-closed condition and Korean modified Barthel Index score. Participants expressed enjoyment without any pain or fatigue. Our findings suggest that dance may have a positive impact in improving balance and mobility and may consequently contribute to healthy aging in adults with CP.
A New Statistical Approach for fNIRS Hyperscanning to Predict Brain Activity of Preschoolers’ Using Teacher’s
Authors: Barreto Candida , Bruneri Guilherme de Albuquerque , Brockington Guilherme , Ayaz Hasan , Sato Joao Ricardo
Published: May 2021

Hyperscanning studies using functional Near-Infrared Spectroscopy (fNIRS) have been performed to understand the neural mechanisms underlying human-human interactions. In this study, we propose a novel methodological approach that is developed for fNIRS multi-brain analysis. Our method uses support vector regression (SVR) to predict one brain activity time series using another as the predictor. We applied the proposed methodology to explore the teacher-student interaction, which plays a critical role in the formal learning process. In an illustrative application, we collected fNIRS data of the teacher and preschoolers’ dyads performing an interaction task. The teacher explained to the child how to add two numbers in the context of a game. The Prefrontal cortex and temporal-parietal junction of both teacher and student were recorded. A multivariate regression model was built for each channel in each dyad, with the student’s signal as the response variable and the teacher’s ones as the predictors. We compared the predictions of SVR with the conventional ordinary least square (OLS) predictor. The results predicted by the SVR model were statistically significantly correlated with the actual test data at least one channel-pair for all dyads. Overall, 29/90 channel-pairs across the five dyads (18 channels 5 dyads = 90 channel-pairs) presented significant signal predictions withthe SVR approach. The conventional OLS resulted in only 4 out of 90 valid predictions. These results demonstrated that the SVR could be used to perform channel-wise predictions across individuals, and the teachers’ cortical activity can be used to predict the student brain hemodynamic response.
Neural Biomarkers Distinguish Severe From Mild Autism Spectrum Disorder Among High-Functioning Individuals
Authors: Chen Di , Jia Tianye , Zhang Yuning , Cao Miao , Loth Eva , Lo Chun-Yi Zac , Cheng Wei , Liu Zhaowen , Gong Weikang , Sahakian Barbara Jacquelyn , Feng Jianfeng
Published: May 2021

Several previous studies have reported atypicality in resting-state functional connectivity (FC) in autism spectrum disorder (ASD), yet the relatively small effect sizes prevent us from using these characteristics for diagnostic purposes. Here, canonical correlation analysis (CCA) and hierarchical clustering were used to partition the high-functioning ASD group (i.e., the ASD discovery group) into subgroups. A support vector machine (SVM) model was trained through the 10-fold strategy to predict Autism Diagnostic Observation Schedule (ADOS) scores within the ASD discovery group (r = 0.30, P < 0.001, n = 260), which was further validated in an independent sample (i.e., the ASD validation group) (r = 0.35, P = 0.031, n = 29). The neuroimage-based partition derived two subgroups representing severe versus mild autistic patients. We identified FCs that show graded changes in strength from ASD-severe, through ASD-mild, to controls, while the same pattern cannot be observed in partitions based on ADOS score. We also identified FCs that are specific for ASD-mild, similar to a partition based on ADOS score. The current study provided multiple pieces of evidence with replication to show that resting-state functional magnetic resonance imaging (rsfMRI) FCs could serve as neural biomarkers in partitioning high-functioning autistic individuals based on their symptom severity and showing advantages over traditional partition based on ADOS score. Our results also indicate a compensatory role for a frontocortical network in patients with mild ASD, indicating potential targets for future clinical treatments.
Advanced Analysis of Diffusion Tensor Imaging Along With Machine Learning Provides New Sensitive Measures of Tissue Pathology and Intra-Lesion Activity in Multiple Sclerosis
Authors: Oladosu Olayinka , Liu Wei-Qiao , Pike Bruce G. , Koch Marcus , Metz Luanne M. , Zhang Yunyan
Published: May 2021

Tissue pathology in multiple sclerosis (MS) is highly complex, requiring multi-dimensional analysis. In this study, our goal was to test the feasibility of obtaining high angular resolution diffusion imaging (HARDI) metrics through single-shell modeling of diffusion tensor imaging (DTI) data, and investigate how advanced measures from single-shell HARDI and DTI tractography perform relative to classical DTI metrics in assessing MS pathology. We examined 52 relapsing-remitting MS patients who had 3T anatomical brain MRI and DTI. Single-shell HARDI modeling yielded 5 sub-voxel-based metrics, totalling 11 diffusion measures including 4 DTI and 2 tractography metrics. Based on machine learning of 3-dimensional regions of interest, we evaluated the importance of the measures through several tissue classification tasks. These included two within-subject comparisons: lesion versus normal appearing white matter (NAWM); and lesion core versus shell. Further, by stratifying patients as having high (above 75%ile) and low (below 25%ile) number of MS lesions, we also performed 2 classifications between subjects for lesions and NAWM respectively. Results showed that in lesion-NAWM analysis, HARDI orientation distribution function (ODF) energy, DTI fractional anisotropy (FA), and HARDI orientation dispersion index were the top three metrics, which together achieved 65.2% accuracy and 0.71 area under the receiver operating characteristic curve (AUROC). In core-shell analysis, DTI mean diffusivity (MD), radial diffusivity, and FA were the top three metrics, and MD dominated the classification, which achieved 59.3% accuracy and 0.59 AUROC alone. Between patients, FA was the leading feature in lesion comparisons, while ODF energy was the best in NAWM separation. Collectively, single-shell modeling of common diffusion data can provide robust orientation measures of lesion and NAWM pathology, and DTI metrics are most sensitive to intra-lesion abnormality. Combined analysis of both advanced and classical diffusion measures may be critical for improved understanding of MS pathology.
Tetramethylpyrazine Alleviates Behavioral and Psychological Symptoms of Dementia Through Facilitating Hippocampal Synaptic Plasticity in Rats With Chronic Cerebral Hypoperfusion
Authors: Tan Zihu , Qiu Jing , Zhang Yuting , Yang Qiong , Yin Xixi , Li Jia , Liu Guangya , Li Hengfei , Yang Guang
Published: May 2021

Behavioral and psychological symptoms of dementia (BPSD) ubiquitously disturb all patients with dementia at some point in the disease course. Although a plethora of non-pharmacological and pharmacological methods targeting the relief BPSD have been developed, the therapeutic effect is still far from ideal. Here, a rat BPSD model combining the physiological changes with mental insults was successfully established. Meanwhile, our results indicated that TMP attenuated anxious behavior using an elevated plus maze (EPM) test, ameliorated recognitive ability and sociability through a novel object recognition test (NORT) and social interaction test (SIT), and improved learning and memory impairments via a Barnes maze in rats with bilateral common carotid arteries occlusion (BCCAO) plus chronic restraint stress (CRS). Given that hippocampus chronic cerebral hypoperfusion (CCH) always causes damage to the hippocampus, and the majority of cognitive impairments, behaviors, and stress responses are associated with pathology in the hippocampus including anxiety and depression, we paid attention to investigate the role of the hippocampus in BPSD. Our results indicated that Tetramethylpyrazine (TMP) attenuated anxiety and ameliorated recognitive ability, sociability, learning, and memory impairments due to alleviating dendritic and spine deficits, and upregulating the expression of synapse-related proteins (including PSD95, SYN, GAP43, SYP) in the hippocampus. We also found that the underlying mechanism was that TMP could activate the TrkB/ERK/CREB signaling pathway to promote synaptic remodeling in vivo and in vitro. Mechanically, the present study enlarges the therapeutic scope of TMP in neurodegenerative disorders and provides basic knowledge and feasible candidates for treating BPSD, particularly for vascular dementia.