bluuebunny/crossref_metadata_2025 huggingface dataset:
Identifying Key Somatic Copy Number Alterations Driving Dysregulation of Cancer Hallmarks in Lower-Grade Glioma
Authors: Zhou Yao , Wang Shuai , Yan Haoteng , Pang Bo , Zhang Xinxin , Pang Lin , Wang Yihan , Xu Jinyuan , Hu Jing , Lan Yujia , Ping Yanyan
Published: June 2021

Somatic copy-number alterations (SCNAs) are major contributors to cancer development that are pervasive and highly heterogeneous in human cancers. However, the driver roles of SCNAs in cancer are insufficiently characterized. We combined network propagation and linear regression models to design an integrative strategy to identify driver SCNAs and dissect the functional roles of SCNAs by integrating profiles of copy number and gene expression in lower-grade glioma (LGG). We applied our strategy to 511 LGG patients and identified 98 driver genes that dysregulated 29 cancer hallmark signatures, forming 143 active gene-hallmark pairs. We found that these active gene-hallmark pairs could stratify LGG patients into four subtypes with significantly different survival times. The two new subtypes with similar poorest prognoses were driven by two different gene sets (one including EGFR, CDKN2A, CDKN2B, INFA8, and INFA5, and the other including CDK4, AVIL, and DTX3), respectively. The SCNAs of the two gene sets could disorder the same cancer hallmark signature in a mutually exclusive manner (including E2F_TARGETS and G2M_CHECKPOINT). Compared with previous methods, our strategy could not only capture the known cancer genes and directly dissect the functional roles of their SCNAs in LGG, but also discover the functions of new driver genes in LGG, such as IFNA5, IFNA8, and DTX3. Additionally, our method can be applied to a variety of cancer types to explore the pathogenesis of driver SCNAs and improve the treatment and diagnosis of cancer.
Automated Facial Recognition for Noonan Syndrome Using Novel Deep Convolutional Neural Network With Additive Angular Margin Loss
Authors: Yang Hang , Hu Xin-Rong , Sun Ling , Hong Dian , Zheng Ying-Yi , Xin Ying , Liu Hui , Lin Min-Yin , Wen Long , Liang Dong-Po , Wang Shu-Shui
Published: June 2021

Background

Noonan syndrome (NS), a genetically heterogeneous disorder, presents with hypertelorism, ptosis, dysplastic pulmonary valve stenosis, hypertrophic cardiomyopathy, and small stature. Early detection and assessment of NS are crucial to formulating an individualized treatment protocol. However, the diagnostic rate of pediatricians and pediatric cardiologists is limited. To overcome this challenge, we propose an automated facial recognition model to identify NS using a novel deep convolutional neural network (DCNN) with a loss function called additive angular margin loss (ArcFace).

Methods

The proposed automated facial recognition models were trained on dataset that included 127 NS patients, 163 healthy children, and 130 children with several other dysmorphic syndromes. The photo dataset contained only one frontal face image from each participant. A novel DCNN framework with ArcFace loss function (DCNN-Arcface model) was constructed. Two traditional machine learning models and a DCNN model with cross-entropy loss function (DCNN-CE model) were also constructed. Transfer learning and data augmentation were applied in the training process. The identification performance of facial recognition models was assessed by five-fold cross-validation. Comparison of the DCNN-Arcface model to two traditional machine learning models, the DCNN-CE model, and six physicians were performed.

Results

At distinguishing NS patients from healthy children, the DCNN-Arcface model achieved an accuracy of 0.9201 ± 0.0138 and an area under the receiver operator characteristic curve (AUC) of 0.9797 ± 0.0055. At distinguishing NS patients from children with several other genetic syndromes, it achieved an accuracy of 0.8171 ± 0.0074 and an AUC of 0.9274 ± 0.0062. In both cases, the DCNN-Arcface model outperformed the two traditional machine learning models, the DCNN-CE model, and six physicians.

Conclusion

This study shows that the proposed DCNN-Arcface model is a promising way to screen NS patients and can improve the NS diagnosis rate.
A 8-mer Peptide of PGLYRP1/Tag7 Innate Immunity Protein Binds to TNFR1 Receptor and Inhibits TNFα-Induced Cytotoxic Effect and Inflammation
Authors: Telegin Georgii B. , Chernov Aleksandr S. , Kazakov Vitaly A. , Romanova Elena A. , Sharapova Tatiana N. , Yashin Denis V. , Gabibov Alexander G. , Sashchenko Lidia P.
Published: June 2021

Search for novel regulatory protein fragments with potential functional roles is required both for understanding the immune response mechanisms and the development of targeted immunotherapy. Earlier we demonstrated that the PGLYRP1/Tag7 innate immunity protein can be regarded as an inhibitor of TNFα cytotoxic activityviathe interaction with its TNF receptor 1 (TNFR1). A C-terminal peptide fragment 17.1 of the molecule is responsible for this function. In this study we have identified a minimal 8-mer region of this peptide (hereinafter – 17.1A) capable to bind to TNFR1. As a result of such interaction, the cytotoxic signals induced by this receptor are blocked. Also, this peptide demonstrates an anti-inflammatory activityin vivoin the complete Freund’s adjuvant (CFA)-induced arthritis model in laboratory mice. Peptide 17.1A is capable to reduce periarticular inflammation, inhibit the development of synovitis and exhibit a protective effect on cartilage and bone tissues. This peptide can turn out to be a promising medicinal agent for autoimmune arthritis and other diseases.
Fractalkine (CX3CL1) and Its Receptor CX3CR1: A Promising Therapeutic Target in Chronic Kidney Disease?
Authors: Cormican Sarah , Griffin Matthew D.
Published: June 2021

Innate immune cells are key contributors to kidney inflammation and fibrosis. Infiltration of the renal parenchyma by innate immune cells is governed by multiple signalling pathways. Since the discovery of the chemokine fractalkine (CX3CL1) and its receptor, CX3CR1 over twenty years ago, a wealth of evidence has emerged linking CX3CL1-CX3CR1 signalling to renal pathologies in both acute and chronic kidney diseases (CKD). However, despite the extent of data indicating a pathogenic role for this pathway in kidney disease and its complications, no human trials of targeted therapeutic agents have been reported. Although acute autoimmune kidney disease is often successfully treated with immunomodulatory medications, there is a notable lack of treatment options for patients with progressive fibrotic CKD. In this article we revisit the CX3CL1-CX3CR1 axis and its functional roles. Furthermore we review the accumulating evidence that CX3CL1-CX3CR1 interactions mediate important events in the intra-renal pathophysiology of CKD progression, particularly via recruitment of innate immune cells into the kidney. We also consider the role that systemic activation of the CX3CL1-CX3CR1 axis in renal disease contributes to CKD-associated cardiovascular disease. Based on this evidence, we highlight the potential for therapies targeting CX3CL1 or CX3CR1 to benefit people living with CKD.
Next-Generation Sequencing Identifies Extended HLA Class I and II Haplotypes Associated With Early-Onset and Late-Onset Myasthenia Gravis in Italian, Norwegian, and Swedish Populations
Authors: Creary Lisa E. , Gangavarapu Sridevi , Caillier Stacy J. , Cavalcante Paola , Frangiamore Rita , Lie Benedicte A. , Bengtsson Mats , Harbo Hanne Flinstad , Brauner Susanna , Hollenbach Jill A. , Oksenberg Jorge R. , Bernasconi Pia , Maniaol Angelina Hatlø , Hammarström Lennart , Mantegazza Renato , Fernández-Viña Marcelo A.
Published: June 2021

Genetic susceptibility to myasthenia gravis (MG) associates with specific HLA alleles and haplotypes at the class I and II regions in various populations. Previous studies have only examined alleles at a limited number of HLA loci that defined only broad serotypes or alleles defined at the protein sequence level. Consequently, genetic variants in noncoding and untranslated HLA gene segments have not been fully explored but could also be important determinants for MG. To gain further insight into the role of HLA in MG, we applied next-generation sequencing to analyze sequence variation at eleven HLA genes in early-onset (EO) and late-onset (LO) non-thymomatous MG patients positive for the acetylcholine receptor (AChR) antibodies and ethnically matched controls from Italy, Norway, and Sweden. For all three populations, alleles and haplotype blocks present on the ancestral haplotype AH8.1 were associated with risk in AChR-EOMG patients. HLA-B*08:01:01:01 was the dominant risk allele in Italians (OR = 3.28, P = 1.83E−05), Norwegians (OR = 3.52, P = 4.41E−16), and in Swedes HLA-B*08:01 was the primary risk allele (OR = 4.24, P <2.2E-16). Protective alleles and haplotype blocks were identified on the HLA-DRB7, and HLA-DRB13.1 class II haplotypes in Italians and Norwegians, whereas in Swedes HLA-DRB7 exhibited the main protective effect. For AChR-LOMG patients, the HLA-DRB15.1 haplotype and associated alleles were significantly associated with susceptibility in all groups. The HLA-DR13–HLA-DR–HLA-DQ haplotype was associated with protection in all AChR-LOMG groups. This study has confirmed and extended previous findings that the immunogenetic predisposition profiles for EOMG and LOMG are distinct. In addition, the results are consistent with a role for non-coding HLA genetic variants in the pathogenesis of MG.
Sodium Thiosulfate Improves Intestinal and Hepatic Microcirculation Without Affecting Mitochondrial Function in Experimental Sepsis
Authors: Schulz Jan , Kramer Sandra , Kanatli Yasin , Kuebart Anne , Bauer Inge , Picker Olaf , Vollmer Christian , Truse Richard , Herminghaus Anna
Published: June 2021

Introduction

In the immunology of sepsis microcirculatory and mitochondrial dysfunction in the gastrointestinal system are important contributors to mortality. Hydrogen sulfide (H2S) optimizes gastrointestinal oxygen supply and mitochondrial respiration predominantly via K(ATP)-channels. Therefore, we tested the hypothesis that sodium thiosulfate (STS), an inducer of endogenous H2S, improves intestinal and hepatic microcirculation and mitochondrial function via K(ATP)-channels in sepsis.

Methods

In 40 male Wistar rats colon ascendens stent peritonitis (CASP) surgery was performed to establish sepsis. Animals were randomized into 4 groups (1: STS 1 g • kg-1 i.p., 2: glibenclamide (GL) 5 mg • kg-1 i.p., 3: STS + GL, 4: vehicle (VE) i.p.). Treatment was given directly after CASP-surgery and 24 hours later. Microcirculatory oxygenation (µHBO2) and flow (µflow) of the colon and the liver were continuously recorded over 90 min using tissue reflectance spectrophotometry. Mitochondrial oxygen consumption in tissue homogenates was determined with respirometry. Statistic: two-way ANOVA + Dunnett´s and Tukey post - hoc test (microcirculation) and Kruskal-Wallis test + Dunn’s multiple comparison test (mitochondria). p < 0.05 was considered significant.

Results

STS increased µHbO2 (colon: 90 min: + 10.4 ± 18.3%; liver: 90 min: + 5.8 ± 9.1%; p < 0.05 vs. baseline). Furthermore, STS ameliorated µflow (colon: 60 min: + 51.9 ± 71.1 aU; liver: 90 min: + 22.5 ± 20.0 aU; p < 0.05 vs. baseline). In both organs, µHbO2 and µflow were significantly higher after STS compared to VE. The combination of STS and GL increased colonic µHbO2 and µflow (µHbO2 90 min: + 8.7 ± 11.5%; µflow: 90 min: + 41.8 ± 63.3 aU; p < 0.05 vs. baseline), with significantly higher values compared to VE. Liver µHbO2 and µflow did not change after STS and GL. GL alone did not change colonic or hepatic µHbO2 or µflow. Mitochondrial oxygen consumption and macrohemodynamic remained unaltered.

Conclusion

The beneficial effect of STS on intestinal and hepatic microcirculatory oxygenation in sepsis seems to be mediated by an increased microcirculatory perfusion and not by mitochondrial respiratory or macrohemodynamic changes. Furthermore, the effect of STS on hepatic but not on intestinal microcirculation seems to be K(ATP)-channel-dependent.
Hyper-Enriched Anti-RSV Immunoglobulins Nasally Administered: A Promising Approach for Respiratory Syncytial Virus Prophylaxis
Authors: Jacque Emilie , Chottin Claire , Laubreton Daphné , Nogre Michel , Ferret Cécile , de Marcos Sandrine , Baptista Linda , Drajac Carole , Mondon Philippe , De Romeuf Christophe , Rameix-Welti Marie-Anne , Eléouët Jean-François , Chtourou Sami , Riffault Sabine , Perret Gérald , Descamps Delphyne
Published: June 2021

Respiratory syncytial virus (RSV) is a public health concern that causes acute lower respiratory tract infection. So far, no vaccine candidate under development has reached the market and the only licensed product to prevent RSV infection in at-risk infants and young children is a monoclonal antibody (Synagis®). Polyclonal human anti-RSV hyper-immune immunoglobulins (Igs) have also been used but were superseded by Synagis® owing to their low titer and large infused volume. Here we report a new drug class of immunoglobulins, derived from human non hyper-immune plasma that was generated by an innovative bioprocess, called Ig cracking, combining expertises in plasma-derived products and affinity chromatography. By using the RSV fusion protein (F protein) as ligand, the Ig cracking process provided a purified and concentrated product, designated hyper-enriched anti-RSV IgG, composed of at least 15-20% target-specific-antibodies from normal plasma. These anti-RSV Ig displayed a strong in vitro neutralization effect on RSV replication. Moreover, we described a novel prophylactic strategy based on local nasal administration of this unique hyper-enriched anti-RSV IgG solution using a mouse model of infection with bioluminescent RSV. Our results demonstrated that very low doses of hyper-enriched anti-RSV IgG can be administered locally to ensure rapid and efficient inhibition of virus infection. Thus, the general hyper-enriched Ig concept appeared a promising approach and might provide solutions to prevent and treat other infectious diseases.

Importance

Respiratory Syncytial Virus (RSV) is the major cause of acute lower respiratory infections in children, and is also recognized as a cause of morbidity in the elderly. There are still no vaccines and no efficient antiviral therapy against this virus. Here, we described an approach of passive immunization with a new class of hyper-enriched anti-RSV immunoglobulins (Ig) manufactured from human normal plasma. This new class of immunoglobulin plasma derived product is generated by an innovative bioprocess, called Ig cracking, which requires a combination of expertise in both plasma derived products and affinity chromatography. The strong efficacy in a small volume of these hyper-enriched anti-RSV IgG to inhibit the viral infection was demonstrated using a mouse model. This new class of immunoglobulin plasma-derived products could be applied to other pathogens to address specific therapeutic needs in the field of infectious diseases or even pandemics, such as COVID-19.
PD-L1 Dysregulation in COVID-19 Patients
Authors: Sabbatino Francesco , Conti Valeria , Franci Gianluigi , Sellitto Carmine , Manzo Valentina , Pagliano Pasquale , De Bellis Emanuela , Masullo Alfonso , Salzano Francesco Antonio , Caputo Alessandro , Peluso Ilaria , Zeppa Pio , Scognamiglio Giosuè , Greco Giuseppe , Zannella Carla , Ciccarelli Michele , Cicala Claudia , Vecchione Carmine , Filippelli Amelia , Pepe Stefano
Published: June 2021

The COVID-19 pandemic has reached direct and indirect medical and social consequences with a subset of patients who rapidly worsen and die from severe-critical manifestations. As a result, there is still an urgent need to identify prognostic biomarkers and effective therapeutic approaches. Severe-critical manifestations of COVID-19 are caused by a dysregulated immune response. Immune checkpoint molecules such as Programmed death-1 (PD-1) and its ligand programmed death-ligand 1 (PD-L1) play an important role in regulating the host immune response and several lines of evidence underly the role of PD-1 modulation in COVID-19. Here, by analyzing blood sample collection from both hospitalized COVID-19 patients and healthy donors, as well as levels of PD-L1 RNA expression in a variety of model systems of SARS-CoV-2, including in vitro tissue cultures, ex-vivo infections of primary epithelial cells and biological samples obtained from tissue biopsies and blood sample collection of COVID-19 and healthy individuals, we demonstrate that serum levels of PD-L1 have a prognostic role in COVID-19 patients and that PD-L1 dysregulation is associated to COVID-19 pathogenesis. Specifically, PD-L1 upregulation is induced by SARS-CoV-2 in infected epithelial cells and is dysregulated in several types of immune cells of COVID-19 patients including monocytes, neutrophils, gamma delta T cells and CD4+ T cells. These results have clinical significance since highlighted the potential role of PD-1/PD-L1 axis in COVID-19, suggest a prognostic role of PD-L1 and provide a further rationale to implement novel clinical studies in COVID-19 patients with PD-1/PD-L1 inhibitors.
A Novel Hierarchical Deep Learning Framework for Diagnosing Multiple Visual Impairment Diseases in the Clinical Environment
Authors: Hong Jiaxu , Liu Xiaoqing , Guo Youwen , Gu Hao , Gu Lei , Xu Jianjiang , Lu Yi , Sun Xinghuai , Ye Zhengqiang , Liu Jian , Peters Brock A. , Chen Jason
Published: June 2021

Early detection and treatment of visual impairment diseases are critical and integral to combating avoidable blindness. To enable this, artificial intelligence–based disease identification approaches are vital for visual impairment diseases, especially for people living in areas with a few ophthalmologists. In this study, we demonstrated the identification of a large variety of visual impairment diseases using a coarse-to-fine approach. We designed a hierarchical deep learning network, which is composed of a family of multi-task & multi-label learning classifiers representing different levels of eye diseases derived from a predefined hierarchical eye disease taxonomy. A multi-level disease–guided loss function was proposed to learn the fine-grained variability of eye disease features. The proposed framework was trained for both ocular surface and retinal images, independently. The training dataset comprised 7,100 clinical images from 1,600 patients with 100 diseases. To show the feasibility of the proposed framework, we demonstrated eye disease identification on the first two levels of the eye disease taxonomy, namely 7 ocular diseases with 4 ocular surface diseases and 3 retinal fundus diseases in level 1 and 17 subclasses with 9 ocular surface diseases and 8 retinal fundus diseases in level 2. The proposed framework is flexible and extensible, which can be inherently trained on more levels with sufficient training data for each subtype diseases (e.g., the 17 classes of level 2 include 100 subtype diseases defined as level 3 diseases). The performance of the proposed framework was evaluated against 40 board-certified ophthalmologists on clinical cases with various visual impairment diseases and showed that the proposed framework had high sensitivity and specificity with the area under the receiver operating characteristic curve ranging from 0.743 to 0.989 in identifying all identified major causes of blindness. Further assessment of 4,670 cases in a tertiary eye center also demonstrated that the proposed framework achieved a high identification accuracy rate for different visual impairment diseases compared with that of human graders in a clinical setting. The proposed hierarchical deep learning framework would improve clinical practice in ophthalmology and broaden the scope of service available, especially for people living in areas with a few ophthalmologists.
Major Characteristics of Severity and Mortality in Diabetic Patients With COVID-19 and Establishment of Severity Risk Score
Authors: Xiao Yu-Feng , He Jia-Lin , Xu Yu , Liu Xi , Lin Hui , Li Qi , Xu Zhi , Hu Ming-Dong , Ren Xiao-Bao , Zhang Cheng , Zhang Wen-Jing , Duan Wei , Tian Yong-Feng , Li Ping , Wu Hao , Song Cai-Ping , Liu En , Yang Shi-Ming
Published: June 2021

Objectives: Diabetes is a risk factor for poor COVID-19 prognosis. The analysis of related prognostic factors in diabetic patients with COVID-19 would be helpful for further treatment of such patients.

Methods: This retrospective study involved 3623 patients with COVID-19 (325 with diabetes). Clinical characteristics and laboratory tests were collected and compared between the diabetic group and the non-diabetic group. Binary logistic regression analysis was applied to explore risk factors associated in diabetic patients with COVID-19. A prediction model was built based on these risk factors.

Results: The risk factors for higher mortality in diabetic patients with COVID-19 were dyspnea, lung disease, cardiovascular diseases, neutrophil, PLT count, and CKMB. Similarly, dyspnea, cardiovascular diseases, neutrophil, PLT count, and CKMB were risk factors related to the severity of diabetes with COVID-19. Based on these factors, a risk score was built to predict the severity of disease in diabetic patients with COVID-19. Patients with a score of 7 or higher had an odds ratio of 7.616.

Conclusions: Dyspnea is a critical clinical manifestation that is closely related to the severity of disease in diabetic patients with COVID-19. Attention should also be paid to the neutrophil, PLT count and CKMB levels after admission.
A Review: Microbial Diversity and Function of Fermented Meat Products in China
Authors: Wang Zhengli , Wang Zhengxi , Ji Lili , Zhang Jiamin , Zhao Zhiping , Zhang Rui , Bai Ting , Hou Bo , Zhang Yin , Liu Dayu , Wang Wei , Chen Lin
Published: June 2021

Fermented meat products have a long history in China. These products exhibit a characteristic unique flavor, compact meat quality, clear color, long shelf life and wide variety and are easy to transport. During the processing and storage of fermented meat products, microorganisms are present and exhibit diverse characteristics. Microorganisms can accelerate the degradation of proteins and fats to produce flavor compounds, inhibit the growth and reproduction of heterozygous bacteria, and reduce the content of chemical pollutants. This paper reviews the microbial diversity of Chinese ham, sausage, preserved meat, pressed salted duck, preserved fish and air-dried meat and provides analyses of the microbial compositions of various products. Due to the differences in raw materials, technology, auxiliary materials, and fermentation technology, the microbial species found in various fermented meat products in China are different. However, most fermented meat products in China are subjected to pickling and fermentation, so their microbial compositions also have similarities. Microorganisms in fermented meat products mainly include staphylococci, lactobacilli, micrococci, yeasts, and molds. The study of microbial diversity is of great significance for the formation of quality flavor and the safety control of fermented meat products, and it provides some theoretical reference for the study of fermented meat products in China.
Divergent Temporal Response of Abundant and Rare Bacterial Communities to Transient Escherichia coli O157:H7 Invasion
Authors: Zhang Nan , Liang Chunling , Liu Xiangjun , Yao Zhiyuan , Zhu David Z. , Du Shicong , Zhang Huajun
Published: June 2021

The release of Escherichia coli (E. coli) O157:H7 has been widely found in various environments, but little is known about the probable influence of the transient E. coli O157:H7 invasion on the native microbial community. Here, we investigated the temporal response of two bacterial biospheres (abundant and rare) of two marsh sediments against E. coli O157:H7 during a 60-day incubation. The diversity of both biospheres showed no evident response to O157:H7 invasion. Temporal factor exhibited greater effects on bacterial variation than O157:H7 invasion. We found that O157:H7 invasion led to an increase in the niche breadth of the bacterial community while decreasing the efficiency of bacterial interaction of the abundant taxa. Moreover, the rare biosphere exhibited enhanced stability against O157:H7 invasion compared with the abundant biosphere, acting as the backbone in resisting external disturbance. Furthermore, each subcommunity assembly showed different randomness levels. The stochastic events were relatively more important in constraining the abundant taxa assembly after invasion. Collectively, E. coli O157:H7 exhibited diverse tangible impact on both biospheres, which unearthed differential responses of abundant and rare biosphere against transient microbial invasion.
Genome-Wide CRISPR/Cas9 Screen Identifies New Genes Critical for Defense Against Oxidant Stress in Toxoplasma gondii
Authors: Chen Yun , Liu Qi , Xue Jun-Xin , Zhang Man-Yu , Geng Xiao-Ling , Wang Quan , Jiang Wei
Published: June 2021

Toxoplasma gondiiis one of the most widespread apicomplexans and can cause serious infections in humans and animals. Its antioxidant system plays an important role in defending against oxidant stress imposed by the host. Some genes encoding the antioxidant enzymes ofT. gondiihave been identified; however, critical genes that function in response to reactive oxygen species (ROS) stress are still poorly understood. Here, we performed genome-wide CRISPR/Cas9 loss-of-function screening in theT. gondiiRH strain to identify potential genes contributing to the ROS stress response. Under hydrogen peroxide treatment, 30 single guide RNAs targeting high-confidence genes were identified, including some known important antioxidant genes such as catalase and peroxiredoxin PRX3. In addition, several previously uncharacterized genes were identified, among which five hypothetical protein-coding genes, namely,HP1–HP5, were selected for further functional characterization. Targeted deletion ofHP1inT. gondiiRH led to significant sensitivity to H2O2, suggesting thatHP1is critical for oxidative stress management. Furthermore, loss ofHP1led to decreased antioxidant capacity, invasion efficiency, and proliferationin vitro.In vivoresults also revealed that the survival time of mice infected with theHP1-KO strain was significantly prolonged relative to that of mice infected with the wild-type strain. Altogether, these findings demonstrate that the CRISPR/Cas9 system can be used to identify potential genes critical for oxidative stress management. Furthermore,HP1may confer protection against oxidative damage and contributes toT. gondiivirulence in mice.
Evaluation of Laccase Activities by Three Newly Isolated Fungal Species in Submerged Fermentation With Single or Mixed Lignocellulosic Wastes
Authors: Han Mei-Ling , Yang Jing , Liu Ze-Yang , Wang Chun-Rui , Chen Si-Yu , Han Ning , Hao Wen-Yao , An Qi , Dai Yu-Cheng
Published: June 2021

Three newly isolated fungal species, namely, Cerrena unicolor Han 849, Lenzites betulina Han 851, and Schizophyllum commune Han 881, isolated from their native habitats in Wulingshan National Nature Reserve of Hebei Province of northern China, were screened for laccase production with single or mixed lignocellulosic wastes. C. unicolor Han 849 was found to express the highest levels of laccase with single or mixed lignocellulosic wastes compared with L. betulina Han 851 and S. commune Han 881. The highest laccase activity from the mixed fungal culture of C. unicolor Han 849 and S. commune Han 881 or L. betulina Han 851 on Firmiana platanifolia was 1,373.12 ± 55.93 and 1,144.85 ± 34.97 U/L, respectively, higher than that from other tested conditions. L. betulina Han 851 or S. commune Han 881 mixed with other species was also helpful for accelerating laccase secretion due to reach maximum enzyme activity quickly. The treatment of mixing different species, including the mixture of two or three species, was obviously conducive to the improvement of laccase activity on Firmiana platanifolia. These results revealed that the fungal co-culture and the mixed lignocellulosic wastes contribute to the improvement of laccase activities and enhance laccase activities within a short period. These findings would be helpful for providing a new method for rapid production of low-cost laccase and for optimization of integrated industrial laccase production.
Discovery of Viral Myosin Genes With Complex Evolutionary History Within Plankton
Authors: Kijima Soichiro , Delmont Tom O. , Miyazaki Urara , Gaia Morgan , Endo Hisashi , Ogata Hiroyuki
Published: June 2021

Nucleocytoplasmic large DNA viruses (NCLDVs) infect diverse eukaryotes and form a group of viruses with capsids encapsulating large genomes. Recent studies are increasingly revealing a spectacular array of functions encoded in their genomes, including genes for energy metabolisms, nutrient uptake, as well as cytoskeleton. Here, we report the discovery of genes homologous to myosins, the major eukaryotic motor proteins previously unrecognized in the virosphere, in environmental genomes of NCLDVs from the surface of the oceans. Phylogenetic analyses indicate that most viral myosins (named “virmyosins”) belong to the Imitervirales order, except for one belonging to the Phycodnaviridae family. On the one hand, the phylogenetic positions of virmyosin-encoding Imitervirales are scattered within the Imitervirales. On the other hand, Imitervirales virmyosin genes form a monophyletic group in the phylogeny of diverse myosin sequences. Furthermore, phylogenetic trends for the virmyosin genes and viruses containing them were incongruent. Based on these results, we argue that multiple transfers of myosin homologs have occurred not only from eukaryotes to viruses but also between viruses, supposedly during co-infections of the same host. Like other viruses that use host motor proteins for their intracellular transport or motility, these viruses may use the virally encoded myosins for the intracellular trafficking of giant viral particles.
Multi-Dimensional Display of Wang’s Lymph Node Map Using Virtual Bronchoscopic Navigation System
Authors: Lan Fen , Yue Yaling , Shen Hong , Shen Hui , Wang Qiyuan , Yu Xiujing , Chen Laijuan , Li Qin , Wang Kopen , Liu Qinghua , Xia Yang
Published: June 2021

Background:Transbronchial needle aspiration (TBNA) is a classical technique for diagnosing mediastinal-hilar lymph node enlargement. However, the diagnostic value of conventional TBNA (cTBNA) is limited in small lymph nodes.

Methods:Here, we generated an innovative multi-dimensional virtual lymph node map on top of Wang’s lymph node map using a Lungpoint Virtual Bronchoscopic Navigation System.

Results:The virtual bronchoscopic navigation (VBN) system was combined with computed tomography (CT) images to generate extrabronchial, endobronchial, sagittal, coronal as well as horizontal views of the 11 intrathoracic lymph node stations and their adjacent tissues and blood vessels. We displayed the specific puncture site of each lymph node station. The 11 stations were divided into four groups: right mediastinal stations, left mediastinal stations, central mediastinal stations and hilar stations.

Conclusion:The VBN system provides a precise view of the intrabronchial landmarks, which may increase the diagnostic accuracy of intrathoracic lymph node adenopathy and assist bronchoscopists with practicing TBNA.
Spiking Neural Network for Fourier Transform and Object Detection for Automotive Radar
Authors: López-Randulfe Javier , Duswald Tobias , Bing Zhenshan , Knoll Alois
Published: June 2021

The development of advanced autonomous driving applications is hindered by the complex temporal structure of sensory data, as well as by the limited computational and energy resources of their on-board systems. Currently, neuromorphic engineering is a rapidly growing field that aims to design information processing systems similar to the human brain by leveraging novel algorithms based on spiking neural networks (SNNs). These systems are well-suited to recognize temporal patterns in data while maintaining a low energy consumption and offering highly parallel architectures for fast computation. However, the lack of effective algorithms for SNNs impedes their wide usage in mobile robot applications. This paper addresses the problem of radar signal processing by introducing a novel SNN that substitutes the discrete Fourier transform and constant false-alarm rate algorithm for raw radar data, where the weights and architecture of the SNN are derived from the original algorithms. We demonstrate that our proposed SNN can achieve competitive results compared to that of the original algorithms in simulated driving scenarios while retaining its spike-based nature.
Variability and Randomness of the Instantaneous Firing Rate
Authors: Tomar Rimjhim , Kostal Lubomir
Published: June 2021

The apparent stochastic nature of neuronal activity significantly affects the reliability of neuronal coding. To quantify the encountered fluctuations, both in neural data and simulations, the notions of variability and randomness of inter-spike intervals have been proposed and studied. In this article we focus on the concept of the instantaneous firing rate, which is also based on the spike timing. We use several classical statistical models of neuronal activity and we study the corresponding probability distributions of the instantaneous firing rate. To characterize the firing rate variability and randomness under different spiking regimes, we use different indices of statistical dispersion. We find that the relationship between the variability of interspike intervals and the instantaneous firing rate is not straightforward in general. Counter-intuitively, an increase in the randomness (based on entropy) of spike times may either decrease or increase the randomness of instantaneous firing rate, in dependence on the neuronal firing model. Finally, we apply our methods to experimental data, establishing that instantaneous rate analysis can indeed provide additional information about the spiking activity.
Network Mapping of Time to Antithrombotic Therapy Among Patients With Ischemic Stroke and Transient Ischemic Attack (TIA)
Authors: Phan Thanh G. , Clissold Benjamin , Singhal Shaloo , Ly John Van , Lim Andy , Vuong Jason , Ho Stella , Matley Chelsea , Kooblal Talvika , Ma Henry
Published: June 2021

Background: There is emphasis on timely administration of thrombolysis and clot retrieval but not antithrombotic therapy within 48 h for ischemic stroke (frequency of 64% in Australia and 97% in North America). We planned to assess the time metrics and variables associated with delaying antithrombotics (antiplatelet and anticoagulant therapy) administration.

Methods: This was a retrospective study at Monash Health over 12 months in 2015. We plotted the cumulative event and mapped the key drivers (dimensionless variable Shapley value/SV) of antithrombotics.

Results: There were 42 patients with transient ischemic attack/TIA and 483 with ischemic stroke [mean age was 71.8 ± 15.4; 56.0% male; nil by mouth (NBM) 74.5 and 49.3% of patients received “stat” (immediate and one off) dose antithrombotics]. The median time to imaging for the patients who did not have stroke code activated was 2.3 h (IQR 1.4–3.7), from imaging to dysphagia screen was 14.6 h (IQR 6.2–20.3), and from stopping NBM to antithrombotics was 1.7 h (IQR 0–16.5). TIA patients received antithrombotics earlier than those with ischemic stroke (90.5 vs. 86.5%, p = 0.01). Significant variables in regression analysis for time to antithrombotics were time to dysphagia screen (β 0.20 ± 0.03, SV = 3.2), nasogastric tube (β 19.8 ± 5.9, SV = −0.20), Alteplase (β 8.6 ± 3.6, SV = −1.9), stat dose antithrombotic (β −18.9 ± 2.9, SV = −10.8) and stroke code (β −5.9 ± 2.5, SV = 2.8). The partial correlation network showed that the time to antithrombotics increased with delay in dysphagia screen (coefficient = 0.33) and decreased if “stat” dose of antithrombotics was given (coefficient = −0.32).

Conclusion: The proportion of patients receiving antithrombotics within 48 h was higher than previously reported in Australia but remained lower than the standard achieved in North American hospitals. Our process map and network analysis show avenues to shorten the time to antithrombotic.
Endovascular Treatment of Acute Ischemic Stroke in Clinical Practice: Analysis of Workflow and Outcome in a Tertiary Care Center
Authors: Weissenborn Karin , Gruber Sam , Grosse Gerrit M. , Gabriel Maria , Schuppner Ramona , Worthmann Hans , Abu-Fares Omar , Götz Friedrich
Published: June 2021

Background and Purpose: Pre- and intra-hospital workflow in mechanical recanalization of large cervicocephalic arteries in patients with acute ischemic stroke still needs optimization. In this study, we analyze workflow and outcome in our routine care of stroke patients undergoing mechanical thrombectomy as a precondition for such optimization.

Methods: Processes of pre- and intra-hospital management, causes of treatment delay, imaging results (Alberta Stroke Program Early Computed Tomography Score, localization of vessel occlusion), recanalization (modified thrombolysis in cerebral infarction score), and patient outcome (modified Rankin scale at discharge and at the end of inpatient rehabilitation) were analyzed for all patients who underwent mechanical thrombectomy between April 1, 2016, and September 30, 2018, at our site.

Results: Finally, data of 282 patients were considered, of whom 150 (53%) had been referred from external hospitals. Recanalization success and patient outcome were similar to randomized controlled thrombectomy studies and registries. Delay in treatment occurred when medical treatment of a hypertensive crisis, epileptic fits, vomiting, or agitation was mandatory but also due to missing prenotification of the hospital emergency staff by the rescue service, multiple mode or repeated brain imaging, and transfer from another hospital. Even transfer from external hospitals located within a 10-km radius of our endovascular treatment center led to a median increase of the onset-to-groin time of ~60 min.

Conclusion: The analysis revealed several starting points for an improvement in the workflow of thrombectomy in our center. Analyses of workflow and treatment results should be carried out regularly to identify the potential for optimization of operational procedures and selection criteria for patients who could benefit from endovascular treatment.
Computed Tomography Based Score of Early Ischemic Changes Predicts Malignant Infarction
Authors: Bechstein Matthias , Meyer Lukas , Breuel Silke , Faizy Tobias D. , Hanning Uta , van Horn Noel , McDonough Rosalie , Fiehler Jens , Broocks Gabriel
Published: June 2021

Background and Purpose:Identification of ischemic stroke patients at high risk of developing life-threatening malignant infarction at an early stage is critical to consider more rigorous monitoring and further therapeutic measures. We hypothesized that a score consisting of simple measurements of visually evident ischemic changes in non-enhanced CT (NEMMI score) predicts malignant middle cerebral artery (MCA) infarctions (MMI) with similar diagnostic power compared to other baseline clinical and imaging parameters.

Methods:One hundred and nine patients with acute proximal MCA occlusion were included. Fifteen (13.8%) patients developed MMI. NEMMI score was defined using the sum of the maximum diameter (anterior-posterior plus medio-lateral) of the hypoattenuated lesion in baseline-CT multiplied by a hypoattenuation factor (3-point visual grading in non-enhanced CT, no/subtle/clear hypoattenuation = 1/2/3). Receiver operating characteristic (ROC) curve analysis and multivariable logistic regression analysis were used to calculate the predictive values of the NEMMI score, baseline clinical and other imaging parameters.

Results:The median NEMMI score at baseline was 13.6 (IQR: 11.6–31.1) for MMI patients, and 7.7 (IQR: 3.9–11.2) for patients with non-malignant infarctions (p< 0.0001). Based on ROC curve analysis, a NEMMI score >10.5 identified MMI with good discriminative power (AUC: 0.84, sensitivity/specificity: 93.3/70.7%), which was higher compared to age (AUC: 0.76), NIHSS (AUC: 0.61), or ischemic core volume (AUC: 0.80). In multivariable logistic regression analysis, NEMMI score was significantly and independently associated with MMI (OR: 1.33, 95%CI: 1.13–1.56,p< 0.001), adjusted for recanalization status.

Conclusion:The NEMMI score is a quick and simple rating tool of early ischemic changes on CT and could serve as an important surrogate marker for developing malignant edema. Its diagnostic accuracy was similar to CTP and clinical parameters.
Characterization of Brain Iron Deposition Pattern and Its Association With Genetic Risk Factor in Alzheimer’s Disease Using Susceptibility-Weighted Imaging
Authors: You Peiting , Li Xiang , Wang Zhijiang , Wang Huali , Dong Bin , Li Quanzheng
Published: June 2021

The presence of iron is an important factor for normal brain functions, whereas excessive deposition of iron may impair normal cognitive function in the brain and lead to Alzheimer’s disease (AD). MRI has been widely applied to characterize brain structural and functional changes caused by AD. However, the effectiveness of using susceptibility-weighted imaging (SWI) for the analysis of brain iron deposition is still unclear, especially within the context of early AD diagnosis. Thus, in this study, we aim to explore the relationship between brain iron deposition measured by SWI with the progression of AD using various feature selection and classification methods. The proposed model was evaluated on a 69-subject SWI imaging dataset consisting of 24 AD patients, 21 mild cognitive impairment patients, and 24 normal controls. The identified AD progression-related regions were then compared with the regions reported from previous genetic association studies, and we observed considerable overlap between these two. Further, we have identified a new potential AD-related gene (MEF2C) closely related to the interaction between iron deposition and AD progression in the brain.
EPOS: EEG Processing Open-Source Scripts
Authors: Rodrigues Johannes , Weiß Martin , Hewig Johannes , Allen John J. B.
Published: June 2021

Background

Since the replication crisis, standardization has become even more important in psychological science and neuroscience. As a result, many methods are being reconsidered, and researchers’ degrees of freedom in these methods are being discussed as a potential source of inconsistencies across studies.

New Method

With the aim of addressing these subjectivity issues, we have been working on a tutorial-like EEG (pre-)processing pipeline to achieve an automated method based on the semi-automated analysis proposed by Delorme and Makeig.

Results

Two scripts are presented and explained step-by-step to perform basic, informed ERP and frequency-domain analyses, including data export to statistical programs and visual representations of the data. The open-source software EEGlab in MATLAB is used as the data handling platform, but scripts based on code provided by Mike Cohen (2014) are also included.

Comparison with existing methods

This accompanying tutorial-like article explains and shows how the processing of our automated pipeline affects the data and addresses, especially beginners in EEG-analysis, as other (pre)-processing chains are mostly targeting rather informed users in specialized areas or only parts of a complete procedure. In this context, we compared our pipeline with a selection of existing approaches.

Conclusion

The need for standardization and replication is evident, yet it is equally important to control the plausibility of the suggested solution by data exploration. Here, we provide the community with a tool to enhance the understanding and capability of EEG-analysis. We aim to contribute to comprehensive and reliable analyses for neuro-scientific research.
Is Peripheral Motion Detection Affected by Myopia?
Authors: Wei Junhan , Kong Deying , Yu Xi , Wei Lili , Xiong Yue , Yang Adeline , Drobe Björn , Bao Jinhua , Zhou Jiawei , Gao Yi , He Zhifen
Published: June 2021

Purpose

The current study was to investigate whether myopia affected peripheral motion detection and whether the potential effect interacted with spatial frequency, motion speed, or eccentricity.

Methods

Seventeen young adults aged 22–26 years participated in the study. They were six low to medium myopes [spherical equivalent refractions −1.0 to −5.0 D (diopter)], five high myopes (<-5.5 D) and six emmetropes (+0.5 to −0.5 D). All myopes were corrected by self-prepared, habitual soft contact lenses. A four-alternative forced-choice task in which the subject was to determine the location of the phase-shifting Gabor from the four quadrants (superior, inferior, nasal, and temporal) of the visual field, was employed. The experiment was blocked by eccentricity (20° and 27°), spatial frequency (0.6, 1.2, 2.4, and 4.0 cycles per degree (c/d) for 20° eccentricity, and 0.6, 1.2, 2.0, and 3.2 c/d for 27° eccentricity), as well as the motion speed [2 and 6 degree per second (d/s)].

Results

Mixed-model analysis of variances showed no significant difference in the thresholds of peripheral motion detection between three refractive groups at either 20° (F[2,14] = 0.145, p = 0.866) or 27° (F[2,14] = 0.475, p = 0.632). At 20°, lower motion detection thresholds were associated with higher myopia (p < 0.05) mostly for low spatial frequency and high-speed targets in the nasal and superior quadrants, and for high spatial frequency and high-speed targets in the temporal quadrant in myopic viewers. Whereas at 27°, no significant correlation was found between the spherical equivalent and the peripheral motion detection threshold under all conditions (all p > 0.1). Spatial frequency, speed, and quadrant of the visual field all showed significant effect on the peripheral motion detection threshold.

Conclusion

There was no significant difference between the three refractive groups in peripheral motion detection. However, lower motion detection thresholds were associated with higher myopia, mostly for low spatial frequency targets, at 20° in myopic viewers.
Methyl-Donor Micronutrient for Gestating Sows: Effects on Gut Microbiota and Metabolome in Offspring Piglets
Authors: He Qin , Zou Tiande , Chen Jun , He Jia , Jian Li , Xie Fei , You Jinming , Wang Zirui
Published: June 2021

This study aimed to investigate the effects of maternal methyl-donor micronutrient supplementation during gestation on gut microbiota and the fecal metabolic profile in offspring piglets. Forty-three Duroc × Erhualian gilts were assigned to two dietary groups during gestation: control diet (CON) and CON diet supplemented with MET (folic acid, methionine, choline, vitamin B6, and vitamin B12). The body weights of offspring piglets were recorded at birth and weaning. Besides this, fresh fecal samples of offspring piglets were collected at 7, 14, and 21 days. The gut microbiota composition, metabolic profile, and short-chain fatty acid (SCFA) profiles in the fecal samples were determined using 16S rDNA sequencing, liquid chromatography-mass spectrometry metabolomics, and gas chromatography methods, respectively. The results showed that maternal methyl-donor micronutrient supplementation increased the microbiota diversity and uniformity in feces of offspring piglets as indicated by increased Shannon and Simpson indices at 7 days, and greater Simpson, ACE, Chao1 and observed species indices at 21 days. Specifically, at the phylum level, the relative abundance of Firmicutes and the Firmicutes to Bacteroidetes ratio were elevated by maternal treatment. At the genus level, the relative abundance of SCFA-producing Dialister, Megasphaera, and Turicibacter, and lactate-producing Sharpea as well as Akkermansia, Weissella, and Pediococcus were increased in the MET group. The metabolic analyses show that maternal methyl-donor micronutrient addition increased the concentrations of individual and total SCFAs of 21-day piglets and increased metabolism mainly involving amino acids, pyrimidine, and purine biosynthesis. Collectively, maternal methyl-donor micronutrient addition altered gut microbiota and the fecal metabolic profile, resulting in an improved weaning weight of offspring piglets.