bluuebunny/crossref_metadata_2025 huggingface dataset:
Construction and Evaluation of a Sepsis Risk Prediction Model for Urinary Tract Infection
Authors: Zhang Luming , Zhang Feng , Xu Fengshuo , Wang Zichen , Ren Yinlong , Han Didi , Lyu Jun , Yin Haiyan
Published: May 2021

Background: Urinary tract infection (UTI) is one of the common causes of sepsis. However, nomograms predicting the sepsis risk in UTI patients have not been comprehensively researched. The goal of this study was to establish and validate a nomogram to predict the probability of sepsis in UTI patients.

Methods: Patients diagnosed with UTI were extracted from the Medical Information Mart for Intensive Care III database. These patients were randomly divided into training and validation cohorts. Independent prognostic factors for UTI patients were determined using forward stepwise logistic regression. A nomogram containing these factors was established to predict the sepsis incidence in UTI patients. The validity of our nomogram model was determined using multiple indicators, including the area under the receiver operating characteristic curve (AUC), correction curve, Hosmer-Lemeshow test, integrated discrimination improvement (IDI), net reclassification improvement (NRI), and decision-curve analysis (DCA).

Results: This study included 6,551 UTI patients. Stepwise regression analysis revealed that the independent risk factors for sepsis in UTI patients were congestive heart failure, diabetes, liver disease, fluid electrolyte disorders, APSIII, neutrophils, lymphocytes, red blood cell distribution width, urinary protein, urinary blood, and microorganisms. The nomogram was then constructed and validated. The AUC, NRI, IDI and DCA of the nomogram all showed better performance than traditional APSIII score. The calibration curve and Hosmer-Lemeshow test results indicate that the nomogram was well-calibrated. Improved NRI and IDI values indicate that our nomogram scoring system is superior to other commonly used ICU scoring systems. The DCA curve indicates that the DCA map of the nomogram has good clinical application ability.

Conclusion: This study identified the independent risk factors of sepsis in UTI patients and used them to construct a prediction model. The present findings may provide clinical reference information for preventing sepsis in UTI patients.
Regulatory Mechanisms of L-Lactic Acid and Taste Substances in Chinese Acid Rice Soup (Rice-Acid) Fermented With a Lacticaseibacillus paracasei and Kluyveromyces marxianus
Authors: Liu Na , Qin Likang , Miao Song
Published: May 2021

Rice-acid has abundant taste substances and health protection function due to the various bioactive compounds it contains, including organic acids. L-lactic acid is the most abundant organic acid in rice-acid, but the regulatory mechanisms of L-lactic acid accumulation in rice-acid are obscure. In this study, we analyzed the dynamic changes in organic acids and taste substances in rice-acid in various fermentation phases and different inoculation methods. We identified the key genes involved in taste substance biosynthesis by RNA-Seq analysis and compared the data of four experimental groups. We found that the interaction of the differences in key functional genes (L-lactate dehydrogenase and D-lactate dehydrogenase) and key metabolism pathways (glycolysis, pyruvate metabolism, TCA cycle, amino acid biosynthesis, and metabolism) might interpret the accumulation of L-lactic acid, other organic acids, and taste substances in rice-acid fermented with Lacticaseibacillus paracasei. The experimental data provided the basis for exploring regulatory mechanisms of taste substance accumulation in rice-acid.
Prediction of Novel Bacterial Small RNAs From RIL-Seq RNA–RNA Interaction Data
Authors: Bar Amir , Argaman Liron , Altuvia Yael , Margalit Hanah
Published: May 2021

The genomic revolution and subsequent advances in large-scale genomic and transcriptomic technologies highlighted hidden genomic treasures. Among them stand out non-coding small RNAs (sRNAs), shown to play important roles in post-transcriptional regulation of gene expression in both pro- and eukaryotes. Bacterial sRNA-encoding genes were initially identified in intergenic regions, but recent evidence suggest that they can be encoded within other, well-defined, genomic elements. This notion was strongly supported by data generated by RIL-seq, a RNA-seq-based methodology we recently developed for deciphering chaperon-dependent sRNA-target networks in bacteria. Applying RIL-seq to Hfq-bound RNAs in Escherichia coli, we found that ∼64% of the detected RNA pairs involved known sRNAs, suggesting that yet unknown sRNAs may be included in the ∼36% remaining pairs. To determine the latter, we first tested and refined a set of quantitative features derived from RIL-seq data, which distinguish between Hfq-dependent sRNAs and “other RNAs”. We then incorporated these features in a machine learning-based algorithm that predicts novel sRNAs from RIL-seq data, and identified high-scoring candidates encoded in various genomic regions, mostly intergenic regions and 3′ untranslated regions, but also 5′ untranslated regions and coding sequences. Several candidates were further tested and verified by northern blot analysis as Hfq-dependent sRNAs. Our study reinforces the emerging concept that sRNAs are encoded within various genomic elements, and provides a computational framework for the detection of additional sRNAs in Hfq RIL-seq data of E. coli grown under different conditions and of other bacteria manifesting Hfq-mediated sRNA-target interactions.
Azohydromonas caseinilytica sp. nov., a Nitrogen-Fixing Bacterium Isolated From Forest Soil by Using Optimized Culture Method
Authors: Dahal Ram Hari , Chaudhary Dhiraj Kumar , Kim Dong-Uk , Kim Jaisoo
Published: May 2021

A bacterial strain, designated strain G-1-1-14T, was isolated from Kyonggi University forest soil during a study of previously uncultured bacterium. The cells of strain G-1-1-14T were motile by means of peritrichous flagella, Gram-stain-negative, rod-shaped, and able to grow autotrophically with hydrogen and fix nitrogen. Phylogenetic analysis based on 16S rRNA gene sequence indicated that strain G-1-1-14T belonged to the genus Azohydromonas. The closest species of strain G-1-1-14T were Azohydromonas ureilytica UCM-80T (98.4% sequence similarity), Azohydromonas lata IAM 12599T (97.5%), Azohydromonas riparia UCM-11T (97.1%), and Azohydromonas australica IAM 12664T (97.0%). The genome of strain G-1-1-14T was 6,654,139 bp long with 5,865 protein-coding genes. The genome consisted of N2-fixing genes (nifH) and various regulatory genes for CO2 fixation and H2 utilization. The principal respiratory quinone was ubiquinone-8, and the major polar lipids were phosphatidylethanolamine, diphosphatidylglycerol, and phosphatidylglycerol. The major fatty acids were summed feature 3 (iso-C15:0 2-OH and/or C16:1ω7c), C16:0, summed feature 8 (C18:1ω7c and/or C18:1ω6c), and cyclo-C17:0. The DNA G + C content was 69.9%. The average nucleotide identity (OrthoANI), in silico DNA–DNA hybridization (dDDH), and conventional DDH relatedness values were below the species demarcation values for novel species. Based on genomic, genetic, phylogenetic, phenotypic, and chemotaxonomic characterizations, strain G-1-1-14T represents a novel species within the genus Azohydromonas, for which the name Azohydromonas caseinilytica sp. nov. is proposed. The type strain is G-1-1-14T (= KACC 21615T = NBRC 114390T).
The Spatiotemporal Dynamics and Microevolution Events That Favored the Success of the Highly Clonal Multidrug-Resistant Monophasic Salmonella Typhimurium Circulating in Europe
Authors: Cadel-Six Sabrina , Cherchame Emeline , Douarre Pierre-Emmanuel , Tang Yue , Felten Arnaud , Barbet Pauline , Litrup Eva , Banerji Sangeeta , Simon Sandra , Pasquali Federique , Gourmelon Michèle , Mensah Nana , Borowiak Maria , Mistou Michel-Yves , Petrovska Liljana
Published: May 2021

The European epidemic monophasic variant of Salmonella enterica serovar Typhimurium (S. 1,4,[5],12:i:-) characterized by the multi locus sequence type ST34 and the antimicrobial resistance ASSuT profile has become one of the most common serovars in Europe (EU) and the United States (US). In this study, we reconstructed the time-scaled phylogeny and evolution of this Salmonella in Europe. The epidemic S. 1,4,[5],12:i:- ST34 emerged in the 1980s by an acquisition of the Salmonella Genomic Island (SGI)-4 at the 3′ end of the phenylalanine phe tRNA locus conferring resistance to copper and arsenic toxicity. Subsequent integration of the Tn21 transposon into the fljAB locus gave resistance to mercury toxicity and several classes of antibiotics used in food-producing animals (ASSuT profile). The second step of the evolution occurred in the 1990s, with the integration of mTmV and mTmV-like prophages carrying the perC and/or sopE genes involved in the ability to reduce nitrates in intestinal contents and facilitate the disruption of the junctions of the host intestinal epithelial cells. Heavy metals are largely used as food supplements or pesticide for cultivation of seeds intended for animal feed so the expansion of the epidemic S. 1,4,[5],12:i:- ST34 was strongly related to the multiple-heavy metal resistance acquired by transposons, integrative and conjugative elements and facilitated by the escape until 2011 from the regulatory actions applied in the control of S. Typhimurium in Europe. The genomic plasticity of the epidemic S. 1,4,[5],12:i:- was demonstrated in our study by the analysis of the plasmidome. We were able to identify plasmids harboring genes mediating resistance to phenicols, colistin, and fluoroquinolone and also describe for the first time in six of the analyzed genomes the presence of two plasmids (pERR1744967-1 and pERR2174855-2) previously described only in strains of enterotoxigenic Escherichia coli and E. fergusonii.
Preliminary Characterization of Two Small Insulinase-Like Proteases in Cryptosporidium parvum
Authors: Xu Rui , Lai Cong , Yang Fuxian , Zhang Qiang , Li Na , Guo Yaqiong , Xiao Lihua , Feng Yaoyu
Published: May 2021

Cryptosporidium parvum is a major cause of moderate-to-severe diarrhea in humans and animals. Its compact genome contains 22 genes encoding divergent insulinase-like proteases (INS), which are poorly characterized. In this study, two small members of this family, INS-21 encoded by cgd7_2080 and INS-23 encoded by cgd5_3400, were cloned, expressed, and characterized to understand their functions. Recombinant INS-21 and INS-23 were expressed in Escherichia coli and polyclonal antibodies against these two proteins were prepared. The cgd7_2080 gene had a high transcription level during 0–2 h of in vitro C. parvum culture, while cgd5_3400 was highly transcribed at 0–6 h. INS-21 was mostly located in the apical region of sporozoites and merozoites whereas INS-23 was found as spots in sporozoites and merozoites. The immunoelectron microscopy confirmed the expression of INS-21 in the apical region of sporozoites while INS-23 appeared to be expressed in the dense granules of sporozoites. The neutralization efficiency was approximately 35%, when the cultures were treated with anti-INS23 antibodies. These results suggest that INS-21 and INS-23 are expressed in different organelles and might have different functions in the development of C. parvum.
Straw Mulching and Nitrogen Fertilization Affect Diazotroph Communities in Wheat Rhizosphere
Authors: Chen Songhe , Xiang Xiaoling , Ma Hongliang , Penttinen Petri , Zhao Jiarong , Li Han , Gao Rencai , Zheng Ting , Fan Gaoqiong
Published: May 2021

Diazotrophs that carry out the biological fixation of atmospheric dinitrogen (N2) replenish biologically available nitrogen (N) in soil and are influenced by the input of inorganic and organic substrates. To date, little is known about the effects of combined organic substrate addition and N fertilization on the diazotroph community composition and structure in purple soils. We investigated the effects of N fertilization and straw mulching on diazotroph communities by quantifying and sequencing thenifHgene in wheat rhizosphere. The abundance and richness of diazotrophs were greater the higher the fertilization level in the mulched treatments, whereas in the nonmulched treatments (NSMs), richness was lowest with the highest N fertilization level. The abundance and α-diversity of diazotrophs correlated with most of the soil properties but not with pH. At the genus level, the relative abundances ofAzospirillum,Bacillus, andGeobacterwere higher in the NSMs and those ofPseudacidovorax,Skermanella,Azospira,Paraburkholderia,Azotobacter,Desulfovibrio,Klebsiella, andPelomonasin the mulched treatments. The differences in community composition between the mulched and the NSMs were associated with differences in soil temperature and soil organic carbon and available potassium contents and C:N ratio. Overall, straw mulching and N fertilization were associated with changes in diazotroph community composition and higher abundance ofnifHgene in alkaline purple soils.
Reads Binning Improves the Assembly of Viral Genome Sequences From Metagenomic Samples
Authors: Song Kai
Published: May 2021

Metagenomes can be considered as mixtures of viral, bacterial, and other eukaryotic DNA sequences. Mining viral sequences from metagenomes could shed insight into virus–host relationships and expand viral databases. Current alignment-based methods are unsuitable for identifying viral sequences from metagenome sequences because most assembled metagenomic contigs are short and possess few or no predicted genes, and most metagenomic viral genes are dissimilar to known viral genes. In this study, I developed a Markov model-based method, VirMC, to identify viral sequences from metagenomic data. VirMC uses Markov chains to model sequence signatures and construct a scoring model using a likelihood test to distinguish viral and bacterial sequences. Compared with the other two state-of-the-art viral sequence-prediction methods, VirFinder and PPR-Meta, my proposed method outperformed VirFinder and had similar performance with PPR-Meta for short contigs with length less than 400 bp. VirMC outperformed VirFinder and PPR-Meta for identifying viral sequences in contaminated metagenomic samples with eukaryotic sequences. VirMC showed better performance in assembling viral-genome sequences from metagenomic data (based on filtering potential bacterial reads). Applying VirMC to human gut metagenomes from healthy subjects and patients with type-2 diabetes (T2D) revealed that viral contigs could help classify healthy and diseased statuses. This alignment-free method complements gene-based alignment approaches and will significantly improve the precision of viral sequence identification.
Isolation and Molecular Identification of the Native Microflora on Flammulina velutipes Fruiting Bodies and Modeling the Growth of Dominant Microbiota (Lactococcus lactis)
Authors: Wei Qi , Pan Xinyuan , Li Jie , Jia Zhen , Fang Ting , Jiang Yuji
Published: May 2021

The objectives of this study were to isolate and identify the dominant microorganism in Flammulina velutipes fruiting bodies (FVFB) and to develop kinetic models for describing its growth. The native microflora community on FVFB was isolated and identified using morphological examination and high-throughput sequencing analysis. FVFB presented complex microbial communities with dominant microorganisms being Lactococcus lactis. Irradiated FVFB were inoculated with the isolated strain of L. lactis and cultivated at various temperatures (4, 10, 16, 20, 25, 32, and 37°C). Three primary models, namely the Huang, Baranyi and Roberts, and reparameterized Gompertz models, and three secondary models, namely the Huang square-root, Ratkowsky square-root, and Arrhenius-type models, were developed and evaluated. With the lowest values of mean square error (MSE, 0.023–0.161) and root mean square error (RMSE, 0.152–0.401) values, the reparameterized Gompertz model was more suitable to describe the growth of L. lactis on FVFB than both Huang and Baranyi and Roberts models. The Ratkowsky square-root model provided more accurate estimation for the effect of temperature on the specific growth rate of L. lactis. The minimum growth temperature predicted by the Ratkowsky square-root model was −7.1°C. The kinetic models developed in this study could be used to evaluate the growth behavior of L. lactis on FVFB and estimate the shelf-life of FVFB.
Global Advances in Tomato Virome Research: Current Status and the Impact of High-Throughput Sequencing
Authors: Rivarez Mark Paul Selda , Vučurović Ana , Mehle Nataša , Ravnikar Maja , Kutnjak Denis
Published: May 2021

Viruses cause a big fraction of economically important diseases in major crops, including tomato. In the past decade (2011–2020), many emerging or re-emerging tomato-infecting viruses were reported worldwide. In this period, 45 novel viral species were identified in tomato, 14 of which were discovered using high-throughput sequencing (HTS). In this review, we first discuss the role of HTS in these discoveries and its general impact on tomato virome research. We observed that the rate of tomato virus discovery is accelerating in the past few years due to the use of HTS. However, the extent of the post-discovery characterization of viruses is lagging behind and is greater for economically devastating viruses, such as the recently emerged tomato brown rugose fruit virus. Moreover, many known viruses still cause significant economic damages to tomato production. The review of databases and literature revealed at least 312 virus, satellite virus, or viroid species (in 22 families and 39 genera) associated with tomato, which is likely the highest number recorded for any plant. Among those, here, we summarize the current knowledge on the biology, global distribution, and epidemiology of the most important species. Increasing knowledge on tomato virome and employment of HTS to also study viromes of surrounding wild plants and environmental samples are bringing new insights into the understanding of epidemiology and ecology of tomato-infecting viruses and can, in the future, facilitate virus disease forecasting and prevention of virus disease outbreaks in tomato.
Microbial Community Interactions Are Sensitive to Small Changes in Temperature
Authors: Burman Emil , Bengtsson-Palme Johan
Published: May 2021

Microbial communities are essential for human and environmental health, often forming complex interaction networks responsible for driving ecosystem processes affecting their local environment and their hosts. Disturbances of these communities can lead to loss of interactions and thereby important ecosystem functionality. The research on what drives interactions in microbial communities is still in its infancy, and much information has been gained from the study of model communities. One purpose of using these model microbial communities is that they can be cultured under controlled conditions. Yet, it is not well known how fluctuations of abiotic factors such as temperature affect their interaction networks. In this work, we have studied the effect of temperature on interactions between the members of the model community THOR, which consists of three bacterial species: Pseudomonas koreensis, Flavobacterium johnsoniae, and Bacillus cereus. Our results show that the community-intrinsic properties resulting from their interspecies interactions are highly dependent on incubation temperature. We also found that THOR biofilms had remarkably different abundances of their members when grown at 11, 18, and 25°C. The results suggest that the sensitivity of community interactions to changes in temperature is influenced, but not completely dictated, by different growth rates of the individual members at different temperatures. Our findings likely extend to other microbial communities and environmental parameters. Thus, temperature could affect community stability and may influence diverse processes including soil productivity, bioprocessing, and disease suppression. Moreover, to establish reproducibility between laboratories working with microbial model communities, it is crucial to ensure experimental stability, including carefully managed temperature conditions.
Antimicrobial and Genetic Profiles of Vibrio vulnificus and Vibrio parahaemolyticus Isolated From the Maryland Coastal Bays, United States
Authors: da Silva Ligia V. , Ossai Sylvia , Chigbu Paulinus , Parveen Salina
Published: May 2021

Vibrio vulnificus and V. parahaemolyticus, found naturally in marine and estuarine environments, are the leading cause of seafood associated gastrointestinal illness and death. Consumption of improperly cooked crabs and handling of live crabs are potential routes of exposure to pathogenic bacteria such as V. vulnificus and V. parahaemolyticus. Little information is available on serotype genetic and antimicrobial profiles of V. vulnificus and V. parahaemolyticus recovered from Maryland estuaries. The aim of the present study was to determine the serotype of V. parahaemolyticus, evaluate antimicrobial susceptibility and genetic profiles of V. vulnificus and V. parahaemolyticus isolated from water and blue crab (Callinectes sapidus) samples collected from the Maryland Coastal Bays. One hundred and fifty (150) PCR confirmed V. parahaemolyticus including 52 tdh+ (pathogenic) and 129 V. vulnificus strains were tested for susceptibility to twenty (20) different antibiotics chosen by clinical usage for Vibrio species. The O serogroups were determined using an agglutination test with V. parahaemolyticus antisera. Pulsed-field gel electrophoresis (PFGE) was used for molecular subtyping to investigate the genetic diversity among tested strains. The most prevalent serotypes were O5 (33.3%), O3 (18.7%) and O1 (14.7%). More than 41% of all tested Vibrio isolates were resistant to three or more antibiotics. Cephalothin showed the highest resistance (42% and 61%), followed by cefoxitin (42% and 31%) and ceftazidime (36% and 29%) for V. vulnificus and V. parahaemolyticus, respectively. Most strains (99–100%) were susceptible to ampicillin/sulbactam, levofloxacin, piperacillin, piperacillin/tazobactam, and tetracycline. Fifty percent (50%) of the cephalothin resistant strains were crab isolates. Vibrio vulnificus and V. parahaemolyticus isolates demonstrated a high genetic diversity and 31% of V. vulnificus and 16% of V. parahaemolyticus strains were PFGE untypeable. No correlations were found between the V. parahaemolyticus serotype, pathogenicity, genetic and antimicrobial resistance profiles of both species of Vibrio. The observed high multiple drug resistance of V. vulnificus and V. parahaemolyticus from blue crab and its environment is of public health concern. Therefore, there is a need for frequent antibiotic sensitivity surveillance for Vibrio spp.
A Nitric Oxide-Responsive Transcriptional Regulator NsrR Cooperates With Lrp and CRP to Tightly Control the hmpA Gene in Vibrio vulnificus
Authors: Choi Garam , Kim Dukyun , Im Hanhyeok , Choi Sang Ho
Published: May 2021

Nitric oxide (NO) is an important antimicrobial effector produced by the host innate immune system to counteract invading pathogens. To survive and establish a successful infection, a fulminating human pathogen Vibrio vulnificus expresses the hmpA gene encoding an NO dioxygenase in an NO-responsive manner. In this study, we identified an Rrf2-family transcriptional regulator NsrR that is predicted to contain the Fe-S cluster coordinated by three cysteine residues. Transcriptome analysis showed that NsrR controls the expression of multiple genes potentially involved in nitrosative stress responses. Particularly, NsrR acts as a strong repressor of hmpA transcription and relieves the repression of hmpA upon exposure to NO. Notably, nsrR and hmpA are transcribed divergently, and their promoter regions overlap with each other. Molecular biological analyses revealed that NsrR directly binds to this overlapping promoter region, which is alleviated by loss of the Fe-S cluster, leading to the subsequent derepression of hmpA under nitrosative stress. We further found that a leucine-responsive regulatory protein (Lrp) negatively regulates hmpA in an NsrR-dependent manner by directly binding to the promoter region, presumably resulting in a DNA conformation change to support the repression by NsrR. Meanwhile, a cyclic AMP receptor protein (CRP) positively regulates hmpA probably through repression of nsrR and lrp by directly binding to each promoter region in a sequential cascade. Altogether, this collaborative regulation of NsrR along with Lrp and CRP enables an elaborate control of hmpA transcription, contributing to survival under host-derived nitrosative stress and thereby the pathogenesis of V. vulnificus.
Biogenesis of Outer Membrane Vesicles Concentrates the Unsaturated Fatty Acid of Phosphatidylinositol in Capnocytophaga ochracea
Authors: Naradasu Divya , Miran Waheed , Sharma Shruti , Takenawa Satoshi , Soma Takamitsu , Nomura Nobuhiko , Toyofuku Masanori , Okamoto Akihiro
Published: May 2021

Bacterial outer membrane vesicles (OMVs) are spherical lipid bilayer nanostructures released by bacteria that facilitate oral biofilm formation via cellular aggregation and intercellular communication. Recent studies have revealed that Capnocytophaga ochracea is one of the dominant members of oral biofilms; however, their potential for OMV production has yet to be investigated. This study demonstrated the biogenesis of OMVs in C. ochracea associated with the concentration of unsaturated fatty acids of phosphatidylinositol (PI) and characterized the size and protein profile of OMVs produced at growth phases. Transmission electron microscopy showed isolated spherical structures from cells stained with heavy metals, indicating the production of OMVs with a size ranging from 25 to 100 nm. Lipidome analysis revealed the presence of phosphatidic acid, phosphatidylethanolamine, phosphatidylcholine, and PI as the main lipids. Some unsaturated fatty acids of PI were present specifically in OMV and little in the outer membrane, suggesting that OMVs are generated from a specific region of the membrane through blebbing rather than a random process such as cell lysis. Furthermore, the lack of similar PI accumulation in the OMV of Porphyromonas gingivalis suggests that C. ochracea has a different biogenesis mechanism. The blebbing mechanism was further supported by higher OMV production occurring at the exponential phase in comparison to the stationary phase, where cell lysis is more likely to occur. Further, comparative protein profile of OMVs isolated under different growth phases may indicate that the OMV cargo does not largely vary with growth phases. The present study provides a basis for further understanding the roles of C. ochracea OMVs in oral biofilms as well as systemic diseases that C. ochracea involves.
Complete Genome Sequence of Xylella taiwanensis and Comparative Analysis of Virulence Gene Content With Xylella fastidiosa
Authors: Weng Ling-Wei , Lin Yu-Chen , Su Chiou-Chu , Huang Ching-Ting , Cho Shu-Ting , Chen Ai-Ping , Chou Shu-Jen , Tsai Chi-Wei , Kuo Chih-Horng
Published: May 2021

The bacterial genus Xylella contains plant pathogens that are major threats to agriculture in America and Europe. Although extensive research was conducted to characterize different subspecies of Xylella fastidiosa (Xf), comparative analysis at above-species levels was lacking due to the unavailability of appropriate data sets. Recently, a bacterium that causes pear leaf scorch (PLS) in Taiwan was described as the second Xylella species (i.e., Xylella taiwanensis; Xt). In this work, we report the complete genome sequence of Xt type strain PLS229T. The genome-scale phylogeny provided strong support that Xf subspecies pauca (Xfp) is the basal lineage of this species and Xylella was derived from the paraphyletic genus Xanthomonas. Quantification of genomic divergence indicated that different Xf subspecies share ∼87–95% of their chromosomal segments, while the two Xylella species share only ∼66–70%. Analysis of overall gene content suggested that Xt is most similar to Xf subspecies sandyi (Xfs). Based on the existing knowledge of Xf virulence genes, the homolog distribution among 28 Xylella representatives was examined. Among the 11 functional categories, those involved in secretion and metabolism are the most conserved ones with no copy number variation. In contrast, several genes related to adhesins, hydrolytic enzymes, and toxin-antitoxin systems are highly variable in their copy numbers. Those virulence genes with high levels of conservation or variation may be promising candidates for future studies. In summary, the new genome sequence and analysis reported in this work contributed to the study of several important pathogens in the family Xanthomonadaceae.
Development and Validation of a 7-Gene Prognostic Signature to Improve Survival Prediction in Pancreatic Ductal Adenocarcinoma
Authors: Feng Zengyu , Qian Hao , Li Kexian , Lou Jianyao , Wu Yulian , Peng Chenghong
Published: May 2021

Background: Previous prognostic signatures of pancreatic ductal adenocarcinoma (PDAC) are mainly constructed to predict the overall survival (OS), and their predictive accuracy needs to be improved. Gene signatures that efficaciously predict both OS and disease-free survival (DFS) are of great clinical significance but are rarely reported.

Methods: Univariate Cox regression analysis was adopted to screen common genes that were significantly associated with both OS and DFS in three independent cohorts. Multivariate Cox regression analysis was subsequently performed on the identified genes to determine an optimal gene signature in the MTAB-6134 training cohort. The Kaplan–Meier (K-M), calibration, and receiver operating characteristic (ROC) curves were employed to assess the predictive accuracy. Biological process and pathway enrichment analyses were conducted to elucidate the biological role of this signature.

Results: Multivariate Cox regression analysis determined a 7-gene signature that contained ASPH, DDX10, NR0B2, BLOC1S3, FAM83A, SLAMF6, and PPM1H. The signature had the ability to stratify PDAC patients with different OS and DFS, both in the training and validation cohorts. ROC curves confirmed the moderate predictive accuracy of this signature. Mechanically, the signature was related to multiple cancer-related pathways.

Conclusion: A novel OS and DFS prediction model was constructed in PDAC with multi-cohort and cross-platform compatibility. This signature might foster individualized therapy and appropriate management of PDAC patients.
Development of an Active Cable-Driven, Force-Controlled Robotic System for Walking Rehabilitation
Authors: Fang Juan , Haldimann Michael , Marchal-Crespo Laura , Hunt Kenneth J.
Published: May 2021

In a parallel development to traditional rigid rehabilitation robotic systems, cable-driven systems are becoming popular. The robowalk expander product uses passive elastic bands in the training of the lower limbs. However, a well-controlled assistance or resistance is desirable for effective walking relearning and muscle training. To achieve well-controlled force during locomotion training with the robowalk expander, we replaced the elastic bands with actuator-driven cables and implemented force control algorithms for regulation of cable tensions. The aim of this work was to develop an active cable-driven robotic system, and to evaluate force control strategies for walking rehabilitation using frequency-domain analysis. The system parameters were determined through experiment-assisted simulation. Then force-feedback lead controllers were developed for static force tracking, and velocity-feedforward lead compensators were implemented to reduce velocity-related disturbances during walking. The technical evaluation of the active cable-driven robotic system showed that force-feedback lead controllers produced satisfactory force tracking in the static tests with a mean error of 5.5%, but in the dynamic tests, a mean error of 13.2% was observed. Further implementation of the velocity-feedforward lead compensators reduced the force tracking error to 9% in dynamic tests. With the combined control algorithms, the active cable-driven robotic system produced constant force within the four cables during walking on the treadmill, with a mean force-tracking error of 10.3%. This study demonstrates that the force control algorithms are technically feasible. The active cable-driven, force-controlled robotic system has the potential to produce user-defined assistance or resistance in rehabilitation and fitness training.
A New Hydrogen Sensor Fault Diagnosis Method Based on Transfer Learning With LeNet-5
Authors: Sun Yongyi , Liu Shuxia , Zhao Tingting , Zou Zhihui , Shen Bin , Yu Ying , Zhang Shuang , Zhang Hongquan
Published: May 2021

The fault safety monitoring of hydrogen sensors is very important for their practical application. The precondition of traditional machine learning methods for sensor fault diagnosis is that enough fault data with the same distribution and feature space under the same working environment must exist. Widely used fault diagnosis methods are not suitable for real working environments because they are easily complicated by environmental conditions such as temperature, humidity, shock, and vibration. Under the influence of such complex conditions, the acquisition of sensor fault data is limited. In order to improve fault diagnosis accuracy under complex environmental conditions, a novel method of transfer learning (TL) with LeNet-5 is proposed in this paper. Firstly, LeNet-5 is applied to learn the features of the data-rich datasets of gas sensor faults in a normal environment and to adjust the parameters accordingly. The parameters of the LeNet-5 are transferred from the task in the normal environment to a task in a complex environment by using the TL method. Then, the migrated LeNet-5 is used for the fault diagnosis of gas sensors with a small amount of fault data in a complex environment. Finally, a prototype hydrogen sensor array is designed and implemented for experimental verification. The gas sensor fault diagnosis accuracy of the traditional LeNet-5 was 88.48 ± 1.04%, while the fault diagnosis accuracy of TL with LeNet-5 was 92.49 ± 1.28%. The experimental results show that the method adopted presents an excellent solution for the fault diagnosis of a hydrogen sensor using a small quantity of fault data obtained under complex environmental conditions.
Healthcare Expenditures Associated With Comorbid Anxiety and Depression Among Adults With Migraine
Authors: Alwhaibi Monira , Meraya Abdulkarim M. , AlRuthia Yazed
Published: May 2021

Introduction: Depression and anxiety are common among patients with migraine and usually associated with a humanistic and financial burden. This study aims to examine the direct healthcare expenditures among adults with migraine alone or with comorbid anxiety and/or depression.

Methods: This was a retrospective cross-sectional study using 2012, 2014, and 2016 Medical Expenditure Panel Survey data. Adult patients aged ≥22 years with migraine headache were included in the study. The direct healthcare expenditures of four migraine groups (migraine alone, migraine and anxiety, migraine and depression, and migraine and both conditions) were compared.

Results: There were 1,556 patients who met the inclusion criteria and eventually enrolled in the study. Approximately 42% of the study sample had migraine with comorbid depression and/or anxiety (16.1% have depression, 12.3% have anxiety disorder, and 13.9% have both). The mean total healthcare expenditures of adults with migraine alone ($6,461) were significantly lower than those with comorbid depression and anxiety ($11,102), comorbid anxiety ($10,817), and comorbid depression ($14,577). Migraine with comorbid anxiety and depression was significantly associated with incremental costs of $1,027 in outpatient and $662 emergency room healthcare expenditures and prescription drug compared to the migraine alone group.

Conclusions: The healthcare expenditures associated with migraine with comorbid depression and/or anxiety are significantly higher than those without mental health comorbidities. Therefore, regular depression and anxiety screening for patients with migraine may help reduce the healthcare expenditures associated with depression and/or anxiety comorbidities and improve the quality of care.
Retinal Ganglion Cells—Diversity of Cell Types and Clinical Relevance
Authors: Kim Ungsoo Samuel , Mahroo Omar A. , Mollon John D. , Yu-Wai-Man Patrick
Published: May 2021

Retinal ganglion cells (RGCs) are the bridging neurons that connect the retinal input to the visual processing centres within the central nervous system. There is a remarkable diversity of RGCs and the various subtypes have unique morphological features, distinct functions, and characteristic pathways linking the inner retina to the relevant brain areas. A number of psychophysical and electrophysiological tests have been refined to investigate this large and varied population of RGCs. Technological advances, such as high-resolution optical coherence tomography imaging, have provided additional tools to define the pattern of RGC involvement and the chronological sequence of events in both inherited and acquired optic neuropathies. The mechanistic insights gained from these studies, in particular the selective vulnerability and relative resilience of particular RGC subtypes, are of fundamental importance as they are directly relevant to the development of targeted therapies for these invariably progressive blinding diseases. This review provides a comprehensive description of the various types of RGCs, the developments in proposed methods of classification, and the current gaps in our knowledge of how these RGCs are differentially affected depending on the underlying aetiology. The synthesis of the current body of knowledge on the diversity of RGCs and the pathways that are potentially amenable to therapeutic modulation will hopefully lead to much needed effective treatments for patients with optic neuropathies.
Serum Folate, Vitamin B12 Levels, and Systemic Immune-Inflammation Index Correlate With Motor Performance in Parkinson's Disease: A Cross-Sectional Study
Authors: Li Siying , Zhang Qingxi , Gao Yuyuan , Nie Kun , Liang Yanling , Zhang Yuhu , Wang Lijuan
Published: May 2021

This study aimed to investigate the influence of serum folate, vitamin B12 (VitB12) levels, and inflammation-based scores on the motor performance status in Parkinson's disease (PD). We retrospectively collected data from 148 consecutive patients with idiopathic PD first admitted to our hospital. We measured whole blood count, albumin, lactate dehydrogenase, C-reactive protein, folate, and VitB12 levels and calculated the inflammation-based scores. The following scales were applied to assess the motor performance status: activity of daily living scale (ADL, the Barthel Index), the Unified Parkinson's Disease Rating Scale Part III (UPDRS-III), and Hoehn–Yahr (H–Y) classification. The geometric mean of folate and VitB12 levels were 11.87 (ng/ml) and 330.52 (pmol/L), respectively. Folate deficiency (serum level < 4.0 ng/ml) and VitB12 deficiency (serum level < 133 pg/ml) were present in 0.7 and 5.4% of the patients, respectively. The mean prognostic nutritional index (PNI) and systemic immune-inflammation index (SII) were 47.78 ± 4.42 and 470.81 ± 254.05, respectively. The multivariate analyses showed that serum VitB12 level (P = 0.002) and SII (P = 0.005) were significant factors for ADL score; serum folate (P = 0.027) and VitB12 (P = 0.037) levels for UPDRS-III score; and serum folate (P = 0.066) and VitB12 (P = 0.017) levels for H–Y classification. The elevated folate level did correlate with greater decline in UPDRS-III score (P = 0.023) and H–Y classification (P = 0.003), whereas there was an obvious increase in ADL score (P = 0.048). SII was negatively associated (P < 0.001) with the ADL score. The three-dimensional drawing, combined with the effect of folate and VitB12 levels, showed that the lowest level of folate was associated with the lowest ADL score and the highest UPDRS-III score and H–Y classification. This study indicates that serum folate, VitB12 levels, and SII are significant factors influencing the motor performance status in patients with PD. SII is negatively associated with ADL. Elevated serum folate level correlates with mild motor impairment in patients with PD.
Case Report: Rituximab Improved Epileptic Spasms and EEG Abnormalities in an Infant With West Syndrome and Anti-NMDAR Encephalitis Associated With APECED
Authors: Kawano Go , Yokochi Takaoki , Nishikomori Ryuta , Watanabe Yoriko , Ohbu Keizo , Takahashi Yukitoshi , Shintaku Haruo , Matsuishi Toyojiro
Published: May 2021

Background: Autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy is a rare autosomal recessive disorder caused by a mutation in the autoimmune regulator gene. Patients with autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy typically exhibit hypoparathyroidism, adrenocortical failure, and chronic mucocutaneous candidiasis. There are only a few case reports of autoimmune encephalitis during autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy, but not as an initial manifestation. Furthermore, there are no reports of patients with infantile spasms/West syndrome with autoimmune encephalitis, partly because the median age for paediatric patients with anti-N-methyl-D-aspartate receptor encephalitis, which is the most frequent and best characterised in paediatric autoimmune encephalitides, is 13–14 years. Herein, we present a case of a 3-month-old infant with autoimmune encephalitis as an initial manifestation of autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy who later developed infantile spasms/West syndrome.

Case Presentation: A 3-month-old girl was admitted to our hospital with a fever, involuntary movements in all four limbs, and right-side facial palsy. Acute central nervous system demyelination diseases were suspected from neuroimaging findings and the presence of the cerebrospinal fluid oligoclonal band. She did not respond to multiple methylprednisolone pulse therapies and later developed infantile spasms/West syndrome and diabetes mellitus. Rituximab, a chimeric mouse/human monoclonal antibody directed against human CD20 which depletes B cells, was initially administered as a treatment for autoimmune encephalitis. Unexpectedly, this treatment resulted in complete spasm cessation and resolution of hypsarrhythmia. The patient eventually showed severely delayed developmental milestones, and her electroencephalography findings showed periodic generalised slow spike-and-wave pattern.

Conclusions: Despite the limited ability to extrapolate findings from a single case, rituximab's effects may suggest that B cells play a crucial role in infantile spasms/West syndrome mechanisms; use of rituximab as an aetiology-specific treatment for infantile spasms/West syndrome patients with autoimmune encephalitis or its effectiveness for infantile spasms/West syndrome patients with other underlying mechanisms warrants further investigation.
Sweat the Fall Stuff: Physical Activity Moderates the Association of White Matter Hyperintensities With Falls Risk in Older Adults
Authors: Crockett Rachel A. , Falck Ryan. S. , Dao Elizabeth , Hsu Chun Liang , Tam Roger , Alkeridy Walid , Liu-Ambrose Teresa
Published: May 2021

Background: Falls in older adults are a major public health problem. White matter hyperintensities (WMHs) are highly prevalent in older adults and are a risk factor for falls. In the absence of a cure for WMHs, identifying potential strategies to counteract the risk of WMHs on falls are of great importance. Physical activity (PA) is a promising countermeasure to reduce both WMHs and falls risk. However, no study has yet investigated whether PA attenuates the association of WMHs with falls risk. We hypothesized that PA moderates the association between WMHs and falls risk.

Methods: Seventy-six community-dwelling older adults aged 70–80 years old were included in this cross-sectional study. We indexed PA using the Physical Activity Score for the Elderly (PASE) Questionnaire. Falls risk was assessed using the Physiological Profile Assessment (PPA), and WMH volume (mm3) was determined by an experienced radiologist on T2-weighted and PD-weighted MRI scans. We first examined the independent associations of WMH volume and PASE score with PPA. Subsequently, we examined whether PASE moderated the relationship between WMH volume and PPA. We plotted simple slopes to interpret the interaction effects. Age, sex, and Montreal Cognitive Assessment (MoCA) score were included as covariates in all models.

Results: Participants had a mean age of 74 years (SD = 3 years) and 54 (74%) were female. Forty-nine participants (66%) had a Fazekas score of 1, 19 (26%) had a score of 2, and 6 (8%) a score of 3. Both PASE (β = −0.26 ± 0.11; p = 0.022) and WMH volume (β = 0.23 ± 0.11; p = 0.043) were each independently associated with PPA score. The interaction model indicated that PASE score moderated the association between WMH volume and PPA (β = −0.27 ± 0.12; p = 0.030), whereby higher PASE score attenuated the association between WMHs and falls risk.

Conclusion: PA is an important moderator of falls risk. Importantly, older adults with WMH can reduce their risk of falls by increasing their PA.
The Defensive Activation Theory: REM Sleep as a Mechanism to Prevent Takeover of the Visual Cortex
Authors: Eagleman David M. , Vaughn Don A.
Published: May 2021

Regions of the brain maintain their territory with continuous activity: if activity slows or stops (e.g., because of blindness), the territory tends to be taken over by its neighbors. A surprise in recent years has been the speed of takeover, which is measurable within an hour. These findings lead us to a new hypothesis on the origin of REM sleep. We hypothesize that the circuitry underlying REM sleep serves to amplify the visual system’s activity periodically throughout the night, allowing it to defend its territory against takeover from other senses. We find that measures of plasticity across 25 species of primates correlate positively with the proportion of rapid eye movement (REM) sleep. We further find that plasticity and REM sleep increase in lockstep with evolutionary recency to humans. Finally, our hypothesis is consistent with the decrease in REM sleep and parallel decrease in neuroplasticity with aging.