bluuebunny/crossref_metadata_2025 huggingface dataset:
The Development and Clinical Application of Innovative Optical Ophthalmic Imaging Techniques
Authors: Alexopoulos Palaiologos , Madu Chisom , Wollstein Gadi , Schuman Joel S.
Published: June 2022

The field of ophthalmic imaging has grown substantially over the last years. Massive improvements in image processing and computer hardware have allowed the emergence of multiple imaging techniques of the eye that can transform patient care. The purpose of this review is to describe the most recent advances in eye imaging and explain how new technologies and imaging methods can be utilized in a clinical setting. The introduction of optical coherence tomography (OCT) was a revolution in eye imaging and has since become the standard of care for a plethora of conditions. Its most recent iterations, OCT angiography, and visible light OCT, as well as imaging modalities, such as fluorescent lifetime imaging ophthalmoscopy, would allow a more thorough evaluation of patients and provide additional information on disease processes. Toward that goal, the application of adaptive optics (AO) and full-field scanning to a variety of eye imaging techniques has further allowed the histologic study of single cells in the retina and anterior segment. Toward the goal of remote eye care and more accessible eye imaging, methods such as handheld OCT devices and imaging through smartphones, have emerged. Finally, incorporating artificial intelligence (AI) in eye images has the potential to become a new milestone for eye imaging while also contributing in social aspects of eye care.
Mortality Prediction in Sepsis With an Immune-Related Transcriptomics Signature: A Multi-Cohort Analysis
Authors: Kreitmann Louis , Bodinier Maxime , Fleurie Aurore , Imhoff Katia , Cazalis Marie-Angelique , Peronnet Estelle , Cerrato Elisabeth , Tardiveau Claire , Conti Filippo , Llitjos Jean-François , Textoris Julien , Monneret Guillaume , Blein Sophie , Brengel-Pesce Karen
Published: June 2022

Background

Novel biomarkers are needed to progress toward individualized patient care in sepsis. The immune profiling panel (IPP) prototype has been designed as a fully-automated multiplex tool measuring expression levels of 26 genes in sepsis patients to explore immune functions, determine sepsis endotypes and guide personalized clinical management. The performance of the IPP gene set to predict 30-day mortality has not been extensively characterized in heterogeneous cohorts of sepsis patients.

Methods

Publicly available microarray data of sepsis patients with widely variable demographics, clinical characteristics and ethnical background were co-normalized, and the performance of the IPP gene set to predict 30-day mortality was assessed using a combination of machine learning algorithms.

Results

We collected data from 1,801 arrays sampled on sepsis patients and 598 sampled on controls in 17 studies. When gene expression was assayed at day 1 following admission (1,437 arrays sampled on sepsis patients, of whom 1,161 were alive and 276 (19.2%) were dead at day 30), the IPP gene set showed good performance to predict 30-day mortality, with an area under the receiving operating characteristics curve (AUROC) of 0.710 (CI 0.652–0.768). Importantly, there was no statistically significant improvement in predictive performance when training the same models with all genes common to the 17 microarray studies (n= 7,122 genes), with an AUROC = 0.755 (CI 0.697–0.813,p= 0.286). In patients with gene expression data sampled at day 3 following admission or later, the IPP gene set had higher performance, with an AUROC = 0.804 (CI 0.643–0.964), while the total gene pool had an AUROC = 0.787 (CI 0.610–0.965,p= 0.811).

Conclusion

Using pooled publicly-available gene expression data from multiple cohorts, we showed that the IPP gene set, an immune-related transcriptomics signature conveys relevant information to predict 30-day mortality when sampled at day 1 following admission. Our data also suggests that higher predictive performance could be obtained when assaying gene expression at later time points during the course of sepsis. Prospective studies are needed to confirm these findings using the IPP gene set on its dedicated measurement platform.
Characterising the Gut Microbiomes in Wild and Captive Short-Beaked Echidnas Reveals Diet-Associated Changes
Authors: Perry Tahlia , West Ella , Eisenhofer Raphael , Stenhouse Alan , Wilson Isabella , Laming Belinda , Rismiller Peggy , Shaw Michelle , Grützner Frank
Published: June 2022

The gut microbiome plays a vital role in health and wellbeing of animals, and an increasing number of studies are investigating microbiome changes in wild and managed populations to improve conservation and welfare. The short-beaked echidna (Tachyglossus aculeatus) is an iconic Australian species, the most widespread native mammal, and commonly held in zoos. Echidnas are cryptic animals, and much is still unknown about many aspects of their biology. Furthermore, some wild echidna populations are under threat, while echidnas held in captivity can have severe gastric health problems. Here, we used citizen science and zoos to collect echidna scats from across Australia to perform the largest gut microbiome study on any native Australian animal. Using 16S rRNA gene metabarcoding of scat samples, we characterised and compared the gut microbiomes of echidnas in wild (n = 159) and managed (n = 44) populations, which were fed four different diets. Wild echidna samples were highly variable, yet commonly dominated by soil and plant-fermenting bacteria, while echidnas in captivity were dominated by gut commensals and plant-fermenting bacteria, suggesting plant matter may play a significant role in echidna diet. This work demonstrates significant differences between zoo held and wild echidnas, as well as managed animals on different diets, revealing that diet is important in shaping the gut microbiomes in echidnas. This first analysis of echidna gut microbiome highlights extensive microbial diversity in wild echidnas and changes in microbiome composition in managed populations. This is a first step towards using microbiome analysis to better understand diet, gastrointestinal biology, and improve management in these iconic animals.
Dynamics of Mismatch and Alternative Excision-Dependent Repair in Replicating Bacillus subtilis DNA Examined Under Conditions of Neutral Selection
Authors: Patlán-Vázquez Adriana G. , Ayala-García Víctor M. , Vallin Carmen , Cortés Jonathan , Vásquez-Morales Suria G. , Robleto Eduardo A. , Nudler Evgeny , Pedraza-Reyes Mario
Published: June 2022

Spontaneous DNA deamination is a potential source of transition mutations. In Bacillus subtilis, EndoV, a component of the alternative excision repair pathway (AER), counteracts the mutagenicity of base deamination-induced mispairs. Here, we report that the mismatch repair (MMR) system, MutSL, prevents the harmful effects of HNO2, a deaminating agent of Cytosine (C), Adenine (A), and Guanine (G). Using Maximum Depth Sequencing (MDS), which measures mutagenesis under conditions of neutral selection, in B. subtilis strains proficient or deficient in MutSL and/or EndoV, revealed asymmetric and heterogeneous patterns of mutations in both DNA template strands. While the lagging template strand showed a higher frequency of C → T substitutions; G → A mutations, occurred more frequently in the leading template strand in different genetic backgrounds. In summary, our results unveiled a role for MutSL in preventing the deleterious effects of base deamination and uncovered differential patterns of base deamination processing by the AER and MMR systems that are influenced by the sequence context and the replicating DNA strand.
Potential of Meta-Omics to Provide Modern Microbial Indicators for Monitoring Soil Quality and Securing Food Production
Authors: Djemiel Christophe , Dequiedt Samuel , Karimi Battle , Cottin Aurélien , Horrigue Walid , Bailly Arthur , Boutaleb Ali , Sadet-Bourgeteau Sophie , Maron Pierre-Alain , Chemidlin Prévost-Bouré Nicolas , Ranjard Lionel , Terrat Sébastien
Published: June 2022

Soils are fundamental resources for agricultural production and play an essential role in food security. They represent the keystone of the food value chain because they harbor a large fraction of biodiversity—the backbone of the regulation of ecosystem services and “soil health” maintenance. In the face of the numerous causes of soil degradation such as unsustainable soil management practices, pollution, waste disposal, or the increasing number of extreme weather events, it has become clear that (i) preserving the soil biodiversity is key to food security, and (ii) biodiversity-based solutions for environmental monitoring have to be developed. Within the soil biodiversity reservoir, microbial diversity including Archaea, Bacteria, Fungi and protists is essential for ecosystem functioning and resilience. Microbial communities are also sensitive to various environmental drivers and to management practices; as a result, they are ideal candidates for monitoring soil quality assessment. The emergence of meta-omics approaches based on recent advances in high-throughput sequencing and bioinformatics has remarkably improved our ability to characterize microbial diversity and its potential functions. This revolution has substantially filled the knowledge gap about soil microbial diversity regulation and ecology, but also provided new and robust indicators of agricultural soil quality. We reviewed how meta-omics approaches replaced traditional methods and allowed developing modern microbial indicators of the soil biological quality. Each meta-omics approach is described in its general principles, methodologies, specificities, strengths and drawbacks, and illustrated with concrete applications for soil monitoring. The development of metabarcoding approaches in the last 20 years has led to a collection of microbial indicators that are now operational and available for the farming sector. Our review shows that despite the recent huge advances, some meta-omics approaches (e.g., metatranscriptomics or meta-proteomics) still need developments to be operational for environmental bio-monitoring. As regards prospects, we outline the importance of building up repositories of soil quality indicators. These are essential for objective and robust diagnosis, to help actors and stakeholders improve soil management, with a view to or to contribute to combining the food and environmental quality of next-generation farming systems in the context of the agroecological transition.
EspF of Enterohemorrhagic Escherichia coli Enhances Apoptosis via Endoplasmic Reticulum Stress in Intestinal Epithelial Cells: An Isobaric Tags for Relative and Absolute Quantitation-Based Comparative Proteomic Analysis
Authors: Wang Xiangyu , Yan Kaina , Fu Muqing , Liang Song , Zhao Haiyi , Fu Changzhu , Yang Lan , Song Zhihong , Sun Dayong , Wan Chengsong
Published: June 2022

There have been large foodborne outbreaks related to Enterohemorrhagic Escherichia coli (EHEC) around the world. Among its virulence proteins, the EspF encoded by locus of enterocyte effacement is one of the most known functional effector proteins. In this research, we infected the HT-29 cells with the EHEC wild type strain and EspF-deficient EHEC strain. Via the emerging technique isobaric tags for relative and absolute quantitation (iTRAQ), we explored the pathogenic characteristics of EspF within host cells. Our data showed that the differences regarding cellular responses mainly contained immune regulation, protein synthesis, signal transduction, cellular assembly and organization, endoplasmic reticulum (ER) stress, and apoptosis. Notably, compared with the EspF-deficient strain, the protein processing in the ER and ribosome were upregulated during wild type (WT) infection. Our findings proved that the EspF of Enterohemorrhagic Escherichia coli induced ER stress in intestinal epithelial cells; the ER stress-dependent apoptosis pathway was also activated within the host cells. This study provides insight into the virulence mechanism of protein EspF, which will deepen our general understanding of A/E pathogens and their interaction with host proteins.
Transcriptome Analysis to Understand Salt Stress Regulation Mechanism of Chromohalobacter salexigens ANJ207
Authors: Srivastava Alok Kumar , Srivastava Ruchi , Sharma Anjney , Bharati Akhilendra Pratap , Yadav Jagriti , Singh Alok Kumar , Tiwari Praveen Kumar , Srivatava Anchal Kumar , Chakdar Hillol , Kashyap Prem Lal , Saxena Anil Kumar
Published: June 2022

Soil salinity is one of the major global issues affecting soil quality and agricultural productivity. The plant growth-promoting halophilic bacteria that can thrive in regions of high salt (NaCl) concentration have the ability to promote the growth of plants in salty environments. In this study, attempts have been made to understand the salinity adaptation of plant growth-promoting moderately halophilic bacteriaChromohalobacter salexigensANJ207 at the genetic level through transcriptome analysis. In order to identify the stress-responsive genes, the transcriptome sequencing ofC. salexigensANJ207 under different salt concentrations was carried out. Among the 8,936 transcripts obtained, 93 were upregulated while 1,149 were downregulated when the NaCl concentration was increased from 5 to 10%. At 10% NaCl concentration, genes coding for lactate dehydrogenase, catalase, and OsmC-like protein were upregulated. On the other hand, when salinity was increased from 10 to 25%, 1,954 genes were upregulated, while 1,287 were downregulated. At 25% NaCl, genes coding for PNPase, potassium transporter, aconitase, excinuclease subunit ABC, and transposase were found to be upregulated. The quantitative real-time PCR analysis showed an increase in the transcript of genes related to the biosynthesis of glycine betaine coline genes (gbcA, gbcB, andL-pro) and in the transcript of genes related to the uptake of glycine betaine (OpuAC, OpuAA, and OpuAB). The transcription of the genes involved in the biosynthesis ofL-hydroxyproline (proD and proS) and one stress response proteolysis gene for periplasmic membrane stress sensing (serP) were also found to be increased. The presence of genes for various compatible solutes and their increase in expression at the high salt concentration indicated that a coordinated contribution by various compatible solutes might be responsible for salinity adaptation in ANJ207. The investigation provides new insights into the functional roles of various genes involved in salt stress tolerance and oxidative stress tolerance produced by high salt concentration in ANJ207 and further support the notion regarding the utilization of bacterium and their gene(s) in ameliorating salinity problem in agriculture.
Risk Factors Associated With Human Papillomavirus Infection, Cervical Cancer, and Precancerous Lesions in Large-Scale Population Screening
Authors: Yang Di , Zhang Jing , Cui Xiaoli , Ma Jian , Wang Chunyan , Piao Haozhe
Published: June 2022

Cervical cancer is the most common gynecological malignancy and screening for risk factors with early detection has been shown to reduce the mortality. In this study, we aimed to analyze the characteristics and risk factors of human papillomavirus (HPV) infection and precancerous lesions in women and provide clinical evidence for developing strategies to prevent cervical precancerous lesions and cancer in women. Furthermore, we evaluated the influencing factors for high-risk HPV infection. From April 2018 to December 2021, 10,628 women were recruited for cervical cancer screening at Liaoning Cancer Hospital, Shenyang Sujiatun District Women’s and Infants Hospital, Benxi Manchu Autonomous County People’s Hospital, and Shandong Affiliated Hospital of Qingdao University. The study participants were tested to determine if they were HPV-positive (HPV +) or underwent thinprep cytology test (TCT) for atypical squamous cells of undetermined significance (ASCUS) and above. Furthermore, colposcopies and biopsies were performed for the histopathological examination. Finally, 9991 cases were included in the statistical analysis, and the factors influencing HPV infection and those related to cervical cancer and precancerous lesions were analyzed. HPV + infection, high-grade squamous intraepithelial lesion-positive (CINII +) in cervical high-grade intraepithelial neoplasia, and early cervical cancer diagnosis rates were 12.45, 1.09, and 95.41%, respectively. The potential risk factors for HPV were education ≤ high school [odds ratio (OR) = 1.279 (1.129–1.449), P < 0.001], age at initial sexual activity ≤ 19 years [OR = 1.517 (1.080–2.129), P = 0.016], sexual partners > 1 [OR = 1.310 (1.044–1.644), P = 0.020], ASCUS and above [OR = 11.891 (10.105–13.993), P < 0.001], non-condom contraception [OR = 1.255 (1.059–1.487), P = 0.009], and HSIL and above [OR = 1.541 (1.430–1.662), P < 0.001]. Compared with women aged 56–65 and 35–45 years [OR = 0.810 (0.690–0.950), P = 0.010] the HPV infection rate was significantly lower in those aged 46–55 years [OR = 0.79 (0.683–0.915), P = 0.002]. Furthermore, ≤ high school age [OR = 1.577 (1.042–2.387), P = 0.031], not breastfeeding [OR = 1.763 (1.109–2.804), P = 0.017], ASCUS and above [OR = 42.396 (28.042–64.098), P < 0.001] were potential risk factors for cervical cancer and precancerous lesions. In women with HPV infection, ≤ high school education level, initial sexual activity at ≤ 19 years of age, number of sexual partners > 1, ASCUS and above, non-condom contraception, HSIL and above were risk factors for HPV infection. Compared with women aged 56–65 years, those aged 35–45 and 46–55 years had significantly lower HPV infection rates, and high school age and below, non-breastfeeding, and ASCUS and above were all potential risk factors for cervical cancer and precancerous lesions.
BcMettl4-Mediated DNA Adenine N6-Methylation Is Critical for Virulence of Botrytis cinerea
Authors: Miao Zhengang , Wang Guangyuan , Shen Heng , Wang Xue , Gabriel Dean W. , Liang Wenxing
Published: June 2022

DNA adenine N6-methylation (6mA) plays a critical role in various biological functions, but its occurrence and functions in filamentous plant pathogens are largely unexplored. Botrytis cinerea is an important pathogenic fungus worldwide. A systematic analysis of 6mA in B. cinerea was performed in this study, revealing that 6mA is widely distributed in the genome of this fungus. The 2 kb regions flanking many genes, particularly the upstream promoter regions, were susceptible to methylation. The role of BcMettl4, a 6mA methyltransferase, in the virulence of B. cinerea was investigated. BcMETTL4 disruption and point mutations of its catalytic motif “DPPW” both resulted in significant 6mA reduction in the genomic DNA and in reduced virulence of B. cinerea. RNA-Seq analysis revealed a total of 13 downregulated genes in the disruption mutant ΔBcMettl4 in which methylation occurred at the promoter sites. These were involved in oxidoreduction, secretory pathways, autophagy and carbohydrate metabolism. Two of these genes, BcFDH and BcMFS2, were independently disrupted. Knockout of BcFDH led to reduced sclerotium formation, while disruption of BcMFS2 resulted in dramatically decreased conidium formation and pathogenicity. These observations indicated that 6mA provides potential epigenetic markers in B. cinerea and that BcMettl4 regulates virulence in this important plant pathogen.
Advances in Nanotechnology as a Potential Alternative for Plant Viral Disease Management
Authors: Dutta Pranab , Kumari Arti , Mahanta Madhusmita , Biswas K. K. , Dudkiewicz Agnieszka , Thakuria D. , Abdelrhim Abdelrazek S. , Singh S. Basanta , Muthukrishnan Gomathy , Sabarinathan K. G. , Mandal Mihir K. , Mazumdar N.
Published: June 2022

Plant viruses cause enormous losses in agricultural production accounting for about 47% of the total overall crop losses caused by plant pathogens. More than 50% of the emerging plant diseases are reported to be caused by viruses, which are inevitable or unmanageable. Therefore, it is essential to devise novel and effective management strategies to combat the losses caused by the plant virus in economically important crops. Nanotechnology presents a new tendency against the increasing challenges in the diagnosis and management of plant viruses as well as plant health. The application of nanotechnology in plant virology, known as nanophytovirology, includes disease diagnostics, drug delivery, genetic transformation, therapeutants, plant defense induction, and bio-stimulation; however, it is still in the nascent stage. The unique physicochemical properties of particles in the nanoscale allow greater interaction and it may knock out the virus particles. Thus, it opens up a novel arena for the management of plant viral diseases. The main objective of this review is to focus on the mounting collection of tools and techniques involved in the viral disease diagnosis and management and to elucidate their mode of action along with toxicological concerns.
Effects of Different Daqu on Microbial Community Domestication and Metabolites in Nongxiang Baijiu Brewing Microecosystem
Authors: Mao Fengjiao , Huang Jun , Zhou Rongqing , Qin Hui , Zhang Suyi , Cai Xiaobo , Qiu Chuanfeng
Published: June 2022

The quality and yield of the fresh Baijiu mainly depend on the activity of pit mud (PM) and the quality of Daqu. However, the cultivation of PM is a long-term process, and high-quality Daqu can change the community structure of fermented grain (FG) and accelerate the evolution of PM communities. The present research aimed to investigate the four different types of Daqu on the FG-fermenting microbial community structure and metabolites and their interphase interactions with PM. These results show that Kroppenstedtia in the bacterial community of Taikong Daqu (TK) was positively correlated with ethyl caproate, which significantly increased the content of FG volatile metabolites, especially lipid components, and facilitated the accelerated evolution of Methanobacteriales and Methanosarcinales in PM. Bacillus has a high relative abundance in Qianghua Daqu (QH), which shows obvious advantages to improving the alcoholic strength of FG and contributing to increasing the abundance of Methanomicrobiales in PM. Qianghua and traditional-mixed Daqu (HH) have a similar bacterial composition to QH and a similar fungal composition to traditional Daqu (DZ), and thus also showed the advantage of increased yield, but the volatile flavor metabolites produced were not as dominant as DZ. β-diversity analysis showed that in TK fermentation systems, FG is more likely to domesticate the structure of PM microorganisms. These results indicated that the interaction between microbial communities in Baijiu fermentation niches was significantly influenced by different Daqu. It can not only enhance the key volatiles in FG but also accelerate the evolving direction of the community in PM. Daqu fortified by functional genera or microbiota can evolve a community structure more suitable for Baijiu fermentation. The microbiota composition and interaction between the communities in both Daqu and PM significantly impacts the yield and quality of the base liquor.
Interpretation of the Genotype by Tissue Interactions of Four Genes (AFP1, CIRP, YB-1, and HMGB1) in Takifugu rubripes Under Different Low-Temperature Conditions
Authors: Wang Xinan , Liu Zhifeng , Ma Aijun
Published: June 2022

Background: The differential expression of the same gene in different tissues could be due to the genotype effect, tissue effect, and/or genotype × tissue interactions. However, the genetic mechanisms responsible for this differential expression have not been reported to date.

Methods: Four resistance genes to low temperature, the genes for antifreeze protein (AFP), cold induced RNA binding protein (CIRP), high mobility group protein box-1 (HMGB1), and Y-box binding protein (YB-1), were measured by PCR in the liver, spleen, kidney, brain, heart, intestine, muscle, gonad, and skin of Takifugu rubripes cultured under different temperature conditions (18, 13, 8, and 5°C). Split-split-plot analysis of variance, additive main effects and multiplicative interaction (AMMI) and genotype main effects and genotype × environment interaction (GGE) biplot analysis were used to evaluate the effects of genotype × tissue interactions on gene expression.

Results: The results of split-split-plot analysis of variance showed that water temperature has a significant effect on the expression of T. rubripes cold resistant genes, while tissue × gene interaction has a highly significant effect on it. AMMI analysis showed that the contributions of genotype, tissue, and genotype × tissue interactions to the total variation in gene expression followed two trends: 1) as temperature decreased, the gene effect increased gradually and the genotype × tissue interaction decreased gradually; 2) the gene effect at 18 and 13°C was significantly lower than that at 8 and 5°C, while the interaction at 18 and 13°C was significantly higher than that at 8 and 5°C. GGE analysis showed that: at all temperatures except 8°C, the expression rankings of all four genes were highly positively correlated in all tissues except muscle; the expression stability of the genes was the same at 18°C/13°C and at 8°C/5°C; and AFP1 showed the best expression and stability among the four genes.

Conclusion: 8°C/5°C as the suitable temperature for such experiments for T. rubripes. Among the four antifreeze genes evaluated in this study, AFP1 had the best expression and stability.
Losac and Lopap Recombinant Proteins from Lonomia obliqua Bristles Positively Modulate the Myoblast Proliferation Process
Authors: Alvarez Angela María , Alvarez-Flores Miryam Paola , DeOcesano-Pereira Carlos , Goldfeder Mauricio Barbugiani , Chudzinski-Tavassi Ana Marisa , Moreira Vanessa , Teixeira Catarina
Published: June 2022

The pursuit of better therapies for disorders creating deficiencies in skeletal muscle regeneration is in progress, and several biotoxins are used in skeletal muscle research. Since recombinant proteins derived from Lonomia obliqua bristles, recombinant Lonomia obliqua Stuart-factor activator (rLosac) and recombinant Lonomia obliqua prothrombin activator protease (rLopap) act as cytoprotective agents and promote cell survival, we hypothesize that both rLosac and rLopap favour the skeletal muscle regeneration process. In the present work, we investigate the ability of these recombinant proteins rLosac and rLopap to modulate the production of key mediators of the myogenic process. The expression of myogenic regulatory factors (MRFs), cell proliferation, the production of prostaglandin E2 (PGE2) and the protein expression of cyclooxygenases COX-1 and COX-2 were evaluated in C2C12 mouse myoblasts pre-treated with rLosac and rLopap. We found an increased proliferation of myoblasts, stimulated by both recombinant proteins. Moreover, these proteins modulated PGE2 release and MRFs activities. We also found an increased expression of the EP4 receptor in the proliferative phase of C2C12 cells, suggesting the involvement of this receptor in the effects of PGE2 in these cells. Moreover, the recombinant proteins inhibited the release of IL-6 and PGE2, which is induced by an inflammatory stimulus by IL-1β. This work reveals rLopap and rLosac as promising proteins to modulate processes involving tissue regeneration as occurs during skeletal muscle injury.
Development and Validation of a Novel Ferroptosis-Related Gene Signature for Prognosis and Immunotherapy in Hepatocellular Carcinoma
Authors: Zhang Bo , Zhao Jilong , Liu Bing , Shang Yanan , Chen Fei , Zhang Sidi , He Jiayao , Fan Yumei , Tan Ke
Published: June 2022

Hepatocellular carcinoma (HCC) is a cancer that is sensitive to ferroptosis, and immunotherapy has emerged as a promising treatment for HCC patients. However, the prognostic potential of ferroptosis-related genes (FRGs) and the effect of ferroptosis on the tumor immune microenvironment in HCC remain largely obscure. Here, we analyzed the expression pattern of FRGs using the TCGA, ICGC and GEO databases. The expression of most FRGs was upregulated in HCC tissues compared with normal liver tissues. Three independent clusters were determined by consensus clustering analysis based on FRG expression in HCC. Cluster 3 exhibited higher expression, unfavorable prognosis, and higher histological tumor stage and grade than clusters 1 and 2. CIBERSORT analysis indicated different infiltrating levels of various immune cells among the three clusters. Moreover, most immune checkpoint genes were highly expressed in cluster 3. Univariate Cox regression and LASSO regression analyses were performed to develop a five FRG-based prognostic risk model using the TCGA and ICGC datasets. Kaplan–Meier analysis and ROC curves were performed to verify the prognostic potential of the risk model. A nomogram containing independent prognostic factors was further developed. Compared with low-risk patients, high-risk HCC patients exhibited worse overall survival (OS). In addition, this risk model was significantly correlated with the infiltrating levels of six major types of immune cells in HCC. Finally, the relationships between the five FRGs and drug sensitivity were investigated. The present study suggests that the five FRGs could elucidate the molecular mechanisms of HCC and lead to a new direction for the improvement of predictive, preventive, and personalized medicine for HCC.
Observation of Thickness-Dependent Exchange Interaction in EuO Ultrathin Films
Authors: Miyazaki Hidetoshi , Hajiri Tetsuya , Matsunami Masaharu , Inukai Manabu , Ito Takahiro , Kimura Shin-ichi
Published: June 2022

The electronic structure of single-crystalline EuO (100) ultrathin films, together with their exchange splitting energy (ΔEEX) and ferromagnetic phase transition temperature (TC), was investigated by temperature- and thickness-dependent angle-resolved photoemission spectroscopy. Both ΔEEX and TC decreased monotonically with decreasing film thickness. The band shift showed an opposite thickness dependence at the Γ and X points, reflecting the balance of the hybridization between the Eu 4f and O 2p states (super-exchange interaction) and between the Eu 4f, O 2p, and Eu 5d states (indirect-exchange interaction). The observed transition from an indirect energy gap in the bulk to a direct gap in the ultrathin films of the ferromagnetic semiconductor EuO could be potential in future spintronic devices.
Weighting of Celestial and Terrestrial Cues in the Monarch Butterfly Central Complex
Authors: Nguyen Tu Anh Thi , Beetz M. Jerome , Merlin Christine , Pfeiffer Keram , el Jundi Basil
Published: June 2022

Monarch butterflies rely on external cues for orientation during their annual long-distance migration from Northern US and Canada to Central Mexico. These external cues can be celestial cues, such as the sun or polarized light, which are processed in a brain region termed the central complex (CX). Previous research typically focused on how individual simulated celestial cues are encoded in the butterfly's CX. However, in nature, the butterflies perceive several celestial cues at the same time and need to integrate them to effectively use the compound of all cues for orientation. In addition, a recent behavioral study revealed that monarch butterflies can rely on terrestrial cues, such as the panoramic skyline, for orientation and use them in combination with the sun to maintain a directed flight course. How the CX encodes a combination of celestial and terrestrial cues and how they are weighted in the butterfly's CX is still unknown. Here, we examined how input neurons of the CX, termed TL neurons, combine celestial and terrestrial information. While recording intracellularly from the neurons, we presented a sun stimulus and polarized light to the butterflies as well as a simulated sun and a panoramic scene simultaneously. Our results show that celestial cues are integrated linearly in these cells, while the combination of the sun and a panoramic skyline did not always follow a linear integration of action potential rates. Interestingly, while the sun and polarized light were invariantly weighted between individual neurons, the sun stimulus and panoramic skyline were dynamically weighted when both stimuli were simultaneously presented. Taken together, this dynamic weighting between celestial and terrestrial cues may allow the butterflies to flexibly set their cue preference during navigation.
Characterization of Meningitis and Meningoencephalitis in the Israeli Defense Forces From 2004 to 2015: A Population-Based Study
Authors: Gofrit Shany Guly , Pikkel Yoav Yechezkel , Levine Hagai , Fraifeld Shifra , Kahana Merhavi Shlomzion , Friedensohn Limor , Eliahou Ruth , Ben-Hur Tamir , Honig Asaf
Published: June 2022

Background

Meningitis and meningoencephalitis (MME) are potential medical emergencies. Mandatory reporting of all MME cases in the Israel Defense Force (IDF) allows accurate characterization of MME incidence and course. In the present study, we described the epidemiology of MME in soldiers.

Methods

Medical charts of 860,000 combat and non-combat soldiers serving during the years 2004–2015, accounting for 2,256,060 patient years, were retrospectively evaluated. The diagnosis of MME was based on signs of meningeal irritation and a count of > 5 white blood cells (WBC) in the cerebrospinal fluid (CSF). Data on the diagnosis of bacterial or aseptic MME, significant sequelae, and associated mortality were collected.

Results

Approximately 273 cases of MME were diagnosed. Overall, MME incidence was 12.1/100,000 patient-years. Bacterial and viral pathogens were identified in 31/273 (11.4%) and 52/273 (19%) cases, respectively. Combat soldiers had higher incidence of bacterial meningitis [14/40 (35%) vs. 31/212 (14.6%); p = 0.002] and meningoencephalitis [13/40 (32.5%) vs. 33/212 (15.6%); p = 0.023] compared to non-combat soldiers. Their clinical presentation was more severe, including confusion [10/40 (25%) vs. 22/212 (10.4%); p = 0.018], focal neurological deficits [12/40 (30%) vs. 11/212 (5.2%); p < 0.0001], and status epilepticus [3/40 (7.5%) vs. 0/212 (0.0%); p < 0.01]. Mortality among combat soldiers was higher [5/40 (15%) vs. 1/212 (0.5%); p < 0.001]. N. meningitidis was the most frequently isolated bacteria, despite universal preventative vaccination.

Conclusion

The incidence of bacterial MME in the IDF is higher than in the civilian population. Combat soldiers present with higher incidence of meningoencephalitis and bacterial meningitis.
Depression and Severity Detection Based on Body Kinematic Features: Using Kinect Recorded Skeleton Data of Simple Action
Authors: Yu Yanhong , Li Wentao , Zhao Yue , Ye Jiayu , Zheng Yunshao , Liu Xinxin , Wang Qingxiang
Published: June 2022

Relative limb movement is an important feature in assessing depression. In this study, we looked into whether a skeleton-mimetic task using natural stimuli may help people recognize depression. We innovatively used Kinect V2 to collect participant data. Sequential skeletal data was directly extracted from the original Kinect-3D and tetrad coordinates of the participant's 25 body joints. Two constructed skeletal datasets of whole-body joints (including binary classification and multi classification) were input into the proposed model for depression recognition after data preparation. We improved the temporal convolution network (TCN), creating novel spatial attention dilated TCN (SATCN) network that included a hierarchy of temporal convolution groups with different dilated convolution scales to capture important skeletal features and a spatial attention block for final result prediction. The depression and non-depression groups can be classified automatically with a maximum accuracy of 75.8% in the binary classification task, and 64.3% accuracy in the multi classification dataset to recognize more fine-grained identification of depression severity, according to experimental results. Our experiments and methods based on Kinect V2 can not only identify and screen depression patients but also effectively observe the recovery level of depression patients during the recovery process. For example, in the change from severe depression to moderate or mild depression multi classification dataset.
Continuous Decoding of Hand Movement From EEG Signals Using Phase-Based Connectivity Features
Authors: Hosseini Seyyed Moosa , Shalchyan Vahid
Published: June 2022

The principal goal of the brain-computer interface (BCI) is to translate brain signals into meaningful commands to control external devices or neuroprostheses to restore lost functions of patients with severe motor disabilities. The invasive recording of brain signals involves numerous health issues. Therefore, BCIs based on non-invasive recording modalities such as electroencephalography (EEG) are safer and more comfortable for the patients. The BCI requires reconstructing continuous movement parameters such as position or velocity for practical application of neuroprostheses. The BCI studies in continuous decoding have extensively relied on extracting features from the amplitude of brain signals, whereas the brain connectivity features have rarely been explored. This study aims to investigate the feasibility of using phase-based connectivity features in decoding continuous hand movements from EEG signals. To this end, the EEG data were collected from seven healthy subjects performing a 2D center-out hand movement task in four orthogonal directions. The phase-locking value (PLV) and magnitude-squared coherence (MSC) are exploited as connectivity features along with multiple linear regression (MLR) for decoding hand positions. A brute-force search approach is employed to find the best channel pairs for extracting features related to hand movements. The results reveal that the regression models based on PLV and MSC features achieve the average Pearson correlations of 0.43 ± 0.03 and 0.42 ± 0.06, respectively, between predicted and actual trajectories over all subjects. The delta and alpha band features have the most contribution in regression analysis. The results also demonstrate that both PLV and MSC decoding models lead to superior results on our data compared to two recently proposed feature extraction methods solely based on the amplitude or phase of recording signals (p < 0.05). This study verifies the ability of PLV and MSC features in the continuous decoding of hand movements with linear regression. Thus, our findings suggest that extracting features based on brain connectivity can improve the accuracy of trajectory decoder BCIs.
Bio-Inspired Autonomous Learning Algorithm With Application to Mobile Robot Obstacle Avoidance
Authors: Liu Junxiu , Hua Yifan , Yang Rixing , Luo Yuling , Lu Hao , Wang Yanhu , Yang Su , Ding Xuemei
Published: June 2022

Spiking Neural Networks (SNNs) are often considered the third generation of Artificial Neural Networks (ANNs), owing to their high information processing capability and the accurate simulation of biological neural network behaviors. Though the research for SNNs has been quite active in recent years, there are still some challenges to applying SNNs to various potential applications, especially for robot control. In this study, a biologically inspired autonomous learning algorithm based on reward modulated spike-timing-dependent plasticity is proposed, where a novel rewarding generation mechanism is used to generate the reward signals for both learning and decision-making processes. The proposed learning algorithm is evaluated by a mobile robot obstacle avoidance task and experimental results show that the mobile robot with the proposed algorithm exhibits a good learning ability. The robot can successfully avoid obstacles in the environment after some learning trials. This provides an alternative method to design and apply the bio-inspired robot with autonomous learning capability in the typical robotic task scenario.
Mechanistic Models of Protein Aggregation Across Length-Scales and Time-Scales: From the Test Tube to Neurodegenerative Disease
Authors: Meisl Georg , Knowles Tuomas P. J. , Klenerman David
Published: June 2022

Through advances in the past decades, the central role of aberrant protein aggregation has been established in many neurodegenerative diseases. Crucially, however, the molecular mechanisms that underlie aggregate proliferation in the brains of affected individuals are still only poorly understood. Under controlled in vitro conditions, significant progress has been made in elucidating the molecular mechanisms that take place during the assembly of purified protein molecules, through advances in both experimental methods and the theories used to analyse the resulting data. The determination of the aggregation mechanism for a variety of proteins revealed the importance of intermediate oligomeric species and of the interactions with promotors and inhibitors. Such mechanistic insights, if they can be achieved in a disease-relevant system, provide invaluable information to guide the design of potential cures to these devastating disorders. However, as experimental systems approach the situation present in real disease, their complexity increases substantially. Timescales increase from hours an aggregation reaction takes in vitro, to decades over which the process takes place in disease, and length-scales increase to the dimension of a human brain. Thus, molecular level mechanistic studies, like those that successfully determined mechanisms in vitro, have only been applied in a handful of living systems to date. If their application can be extended to further systems, including patient data, they promise powerful new insights. Here we present a review of the existing strategies to gain mechanistic insights into the molecular steps driving protein aggregation and discuss the obstacles and potential paths to achieving their application in disease. First, we review the experimental approaches and analysis techniques that are used to establish the aggregation mechanisms in vitro and the insights that have been gained from them. We then discuss how these approaches must be modified and adapted to be applicable in vivo and review the existing works that have successfully applied mechanistic analysis of protein aggregation in living systems. Finally, we present a broad mechanistic classification of in vivo systems and discuss what will be required to further our understanding of aggregate formation in living systems.
Novel HCN1 Mutations Associated With Epilepsy and Impacts on Neuronal Excitability
Authors: Xie Changning , Liu Fangyun , He Hailan , He Fang , Mao Leilei , Wang Xiaole , Yin Fei , Peng Jing
Published: June 2022

Hyperpolarization-activated cyclic nucleotide-gated (HCN) channel plays a critical role in regulating the resting membrane potential and integrating synaptic transmission. Variants of HCN1 have been recognized as causes of epilepsy, and mutant HCN1 channels could act with loss-of-function (LOF), loss- and gain-of-function (LOF and GOF) and gain-of-function (GOF) mechanisms. However, phenotypes and pathogenesis of HCN1-related epilepsy are still poorly understood. This study enrolled five epileptic cases carrying five different HCN1 variants: two pathogenic variants (I380F and S710Rfs*71), two likely pathogenic variants (E240G and A395G), and a paternally inherited variant (V572A). Four variants were novel. Electrophysiological experiments revealed impaired biophysical properties of the identified mutants, including current densities and activation/deactivation kinetics. Moreover, three variants exerted effects on the biophysical properties of wild-type HCN1 channels in heterozygous conditions. Immunofluorescence experiments showed that two variants reduced the protein expression of HCN1channels in neurons. Neurons expressing E240G (GOF) variant showed increased input resistance. However, the variant of I380F (LOF) increased the neuronal firing rate, thus leading to neuronal hyperexcitability. In conclusion, the present study expands the genotypic and phenotypic spectrum of patients with HCN1-related epilepsy and clarifies the underlying mechanisms. We reported five new cases including four unreported likely/pathogenic variants. We provided assessments of biophysical function for each variant, which could help patients to receive individual therapy in the future. We confirmed that HCN1 variants contributed to neuronal hyperexcitability by regulating input resistance and the action potential firing rate, and we have shown that they can affect protein expression in neurons for the first time.
Actions of the TrkB Agonist Antibody ZEB85 in Regulating the Architecture and Synaptic Plasticity in Hippocampal Neurons
Authors: Tacke Charlotte , DiStefano Peter S. , Lindsay Ronald M. , Metzdorf Kristin , Zagrebelsky Marta , Korte Martin
Published: June 2022

Signaling of BDNFviaits TrkB receptor is crucial in regulating several critical aspects of the architecture and function of neurons both during development and in the adult central nervous system. Indeed, several neurological conditions, such as neurodevelopmental and neurodegenerative disorders are associated with alterations both in the expression levels of BDNF and TrkB, and in their intracellular signaling. Thus, the possibility of promoting BDNF/TrkB signaling has become relevant as a potential therapeutic intervention for neurological disorders. However, the clinical potential of BDNF itself has been limited due to its restricted diffusion rate in biological tissue, poor bioavailability and pharmacological properties, as well as the potential for unwanted side effects due to its ability to also signalviathe p75NTRpathway. Several small molecule and biologic drug candidate TrkB agonists have been developed and are reported to have effects in rescuing both the pathological alterations and disease related symptoms in mouse models of several neurological diseases. However, recent side-by-side comparative studies failed to show their specificity for activating TrkB signaling cascades, suggesting the need for the generation and validation of improved candidates. In the present study, we examine the ability of the novel, fully human TrkB agonist antibody ZEB85 to modulate the architecture, activity and synaptic plasticity of hippocampal murine neurons under physiological conditions. Moreover, we show here that ZEB85 prevents β-amyloid toxicity in cultured hippocampal neurons, in a manner which is comparable to BDNF.