bluuebunny/crossref_metadata_2025 huggingface dataset:
Modeling and Predicting Heavy-Duty Vehicle Engine-Out and Tailpipe Nitrogen Oxide (NOx) Emissions Using Deep Learning
Authors: Pillai Rinav , Triantopoulos Vassilis , Berahas Albert S. , Brusstar Matthew , Sun Ruonan , Nevius Tim , Boehman André L.
Published: March 2022

As emissions regulations for transportation become stricter, it is increasingly important to develop accurate nitrogen oxide (NOx) emissions models for heavy-duty vehicles. However, estimation of transient NOx emissions using physics-based models is challenging due to its highly dynamic nature, which arises from the complex interactions between power demand, engine operation, and exhaust aftertreatment efficiency. As an alternative to physics-based models, a multi-dimensional data-driven approach is proposed as a framework to estimate NOx emissions across an extensive set of representative engine and exhaust aftertreatment system operating conditions. This paper employs Deep Neural Networks (DNN) to develop two models, an engine-out NOx and a tailpipe NOx model, to predict heavy-duty vehicle NOx emissions. The DNN models were developed using variables that are available from On-board Diagnostics from two datasets, an engine dynamometer and a chassis dynamometer dataset. Results from trained DNN models using the engine dynamometer dataset showed that the proposed approach can predict NOx emissions with high accuracy, where R2 scores are higher than 0.99 for both engine-out and tailpipe NOx models on cold/hot Federal Test Procedure (FTP) and Ramped Mode Cycle (RMC) data. Similarly, the engine-out and tailpipe NOx models using the chassis dynamometer dataset achieved R2 scores of 0.97 and 0.93, respectively. All models developed in this study have a mean absolute error percentage of approximately 1% relative to maximum NOx in the datasets, which is comparable to that of physical NOx emissions measurement analyzers. The input feature importance studies conducted in this work indicate that high accuracy DNN models (R2 = 0.92–0.95) could be developed by utilizing minimal significant engine and aftertreatment inputs. This study also demonstrates that DNN NOx emissions models can be very effective tools for fault detection in Selective Catalytic Reduction (SCR) systems.
Incidence and Characteristics of Retinopathy of Prematurity Patients With Late Gestational Age and Large Birth Weight in South China
Authors: Gao Xiang , Liao Yunru , Lin Duoru , Wang Lisha , Yu Deying , Li Zijing , Zhang Yichi , Lan Yuqing
Published: March 2022

Purpose

To investigate the incidence and characteristics of retinopathy of prematurity (ROP) premature infants with late gestational age (GA) and large birth weight (BW) and show a 7-year trend of ROP incidence in South China.

Methods

This retrospective, cross-sectional study included premature infants who received ROP screening in a 7-year period (from 2010 to 2016) at the Sun Yat-sen Memorial Hospital (SYSMH), Guangzhou, South China. Infants were screened if they had GA <37 weeks or BW <2,500 g. All screened infants were divided into two groups: Group 1 (with both GA ≥ 35 weeks and BW ≥ 1,750 g) and Group 2 (others). The characteristics of ROP infants in Group 1 were analyzed and compared with those in Group 2.

Results

A total of 911 premature infants were screened, with 282 infants in Group 1 and 629 in Group 2. Both the incidences of any ROP (6.7 vs. 8.3%, p = 0.50) and Type 1 ROP (1.4 vs. 1.7%, p = 0.72) in Group 1 were comparable with those in Group 2. Lower proportions of respiratory distress (15.8 vs. 71.2%, p < 0.001), blood transfusion (5.3 vs. 32.7%, p = 0.028), and oxygen administration (31.6 vs. 86.5%, p < 0.001) among ROP patients in Group 1 than those in Group 2 were revealed. Vaginal delivery [OR: 4.73 (1.83–12.26)] was identified as a factor associated with ROP among the infants in Group 1. Forty percent (6/15) of Type 1 ROP in this study would have been missed under the current screening criteria in China (GA ≤ 34 weeks and/or BW ≤ 2,000 g). Trends of increased incidence of Type 1 ROP and decreased BW were exhibited in the 7-year study period.

Conclusions

These findings indicate that even the premature infants with late GA and large BW also have a high risk of developing ROP, especially for those delivered by vagina. The findings may provide a significant reference for ROP screening and neonatal care in South China and other regions with similar conditions.
Ocular Adverse Effects in Atopic Dermatitis Patients Treated With Dupilumab: A Bibliometric Analysis
Authors: Jia Qian-Nan , Qiao Ju , Fang Kai , Zeng Yue-Ping
Published: March 2022

Background

Atopic dermatitis (AD) is one of the most common chronic inflammatory skin disorders. Dupilumab, the first targeted biological drug approved for the treatment of AD, has been widely used, along with increasing ocular adverse effects (AEs).

Objective

To perform a bibliometric analysis of all the qualified literature involving ocular AEs during the treatment of AD with dupilumab.

Methods

Relevant studies were extracted from the Web of Science database and screened by researchers. The bibliographic analysis was performed using the VOSviewer.

Results

A total of 138 articles were enrolled in this study. The first study was published in 2016 by Oregon Health and Science University from the United States. The majority of publications were published in the past 3 years. British Journal of Dermatology published the highest number of articles. The United States was the country with the most publications. Sanofi (France) and Regeneron Pharmaceuticals (USA) were the leading organizations with the most contributions. Conjunctivitis was the most common ocular AE. The management of AD will continue to be the research hotspot and development trend in this area. The milestone research is the first article “Two Phase 3 Trials of Dupilumab vs. Placebo in Atopic Dermatitis” published in the New England Journal of Medicine. Most of the top 10 papers were mainly randomized, placebo-controlled phase 2 and phase 3 clinical trials and real-life large cohort studies.

Conclusions

This study may help better understand ocular AEs in the dupilumab treatment of AD, and grasp the research trends and most influential topics in this field.
A Few-Shot Learning-Based Retinal Vessel Segmentation Method for Assisting in the Central Serous Chorioretinopathy Laser Surgery
Authors: Xu Jianguo , Shen Jianxin , Wan Cheng , Jiang Qin , Yan Zhipeng , Yang Weihua
Published: March 2022

Background

The location of retinal vessels is an important prerequisite for Central Serous Chorioretinopathy (CSC) Laser Surgery, which does not only assist the ophthalmologist in marking the location of the leakage point (LP) on the fundus color image but also avoids the damage of the laser spot to the vessel tissue, as well as the low efficiency of the surgery caused by the absorption of laser energy by retinal vessels. In acquiring an excellent intra- and cross-domain adaptability, the existing deep learning (DL)-based vessel segmentation scheme must be driven by big data, which makes the densely annotated work tedious and costly.

Methods

This paper aims to explore a new vessel segmentation method with a few samples and annotations to alleviate the above problems. Firstly, a key solution is presented to transform the vessel segmentation scene into the few-shot learning task, which lays a foundation for the vessel segmentation task with a few samples and annotations. Then, we improve the existing few-shot learning framework as our baseline model to adapt to the vessel segmentation scenario. Next, the baseline model is upgraded from the following three aspects: (1) A multi-scale class prototype extraction technique is designed to obtain more sufficient vessel features for better utilizing the information from the support images; (2) The multi-scale vessel features of the query images, inferred by the support image class prototype information, are gradually fused to provide more effective guidance for the vessel extraction tasks; and (3) A multi-scale attention module is proposed to promote the consideration of the global information in the upgraded model to assist vessel localization. Concurrently, the integrated framework is further conceived to appropriately alleviate the low performance of a single model in the cross-domain vessel segmentation scene, enabling to boost the domain adaptabilities of both the baseline and the upgraded models.

Results

Extensive experiments showed that the upgraded operation could further improve the performance of vessel segmentation significantly. Compared with the listed methods, both the baseline and the upgraded models achieved competitive results on the three public retinal image datasets (i.e., CHASE_DB, DRIVE, and STARE). In the practical application of private CSC datasets, the integrated scheme partially enhanced the domain adaptabilities of the two proposed models.
Gut Dysbiosis and Kidney Diseases
Authors: Cao Chujin , Zhu Han , Yao Ying , Zeng Rui
Published: March 2022

Gut dysbiosis is defined as disorders of gut microbiota and loss of barrier integrity, which are ubiquitous on pathological conditions and associated with the development of various diseases. Kidney diseases are accompanied with gut dysbiosis and metabolic disorders, which in turn contribute to the pathogenesis and progression of kidney diseases. Microbial alterations trigger production of harmful metabolites such as uremic toxins and a decrease in the number of beneficial ones such as SCFAs, which is the major mechanism of gut dysbiosis on kidney diseases according to current studies. In addition, the activation of immune responses and mitochondrial dysfunction by gut dysbiosis, also lead to the development of kidney diseases. Based on the molecular mechanisms, modification of gut dysbiosis via probiotics, prebiotics and synbiotics is a potential approach to slow kidney disease progression. Fecal microbiota transplantation (FMT) and genetic manipulation of the gut microbiota are also promising choices. However, the clinical use of probiotics in kidney disease is not supported by the current clinical evidence. Further studies are necessary to explore the causal relationships of gut dysbiosis and kidney diseases, the efficiency and safety of therapeutic strategies targeting gut-kidney axis.
Population-Based Study Detailing Cutaneous Melanoma Incidence and Mortality Trends in Canada
Authors: Conte Santina , Ghazawi Feras M. , Le Michelle , Nedjar Hacene , Alakel Akram , Lagacé François , Mukovozov Ilya M. , Cyr Janelle , Mourad Ahmed , Miller Wilson H. , Claveau Joël , Salopek Thomas G. , Netchiporouk Elena , Gniadecki Robert , Sasseville Denis , Rahme Elham , Litvinov Ivan V.
Published: March 2022

Background

Cutaneous melanoma (CM) is one of the most fatal types of skin cancer. Alarmingly, increases in incidence and mortality were noted globally for this malignancy, despite increase in understanding of melanoma pathogenesis and enhanced prevention efforts.

Methods

Data was extracted for CM patients for provinces and territories (except Quebec) using two independent, population-based registries. Analysis was performed using both clinical and pathological characteristics: tumor morphologic classification, age, sex, anatomic site affected and place of residence. Mortality trends were assessed over a 7-year period. Results were compared to prior findings for 1992–2010.

Results

During 2011–2017 39,610 patients were diagnosed with CM, with 5,890 reported deaths. National crude CM incidence was 20.75 (age-standardized incidence: 14.12) cases per 100,000 individuals per year. Females accounted for 45.8% of cases and 37.1% of deaths. While CM incidence rates continue to increase in both sexes, since 2013 the CM mortality is declining. We observed important differences across the provinces/territories, where Nova Scotia, Prince Edward Island, southern Ontario/British Columbia and certain coastal communities of New Brunswick demonstrated higher CM incidence and mortality rates. The observed incidence and mortality trends for 2011–2017 validate and extend earlier observations from 1992 to 2010 for CM.

Conclusion

This population-based study highlights that while melanoma's incidence is increasing in Canada, mortality rates are for the first time decreasing since 2013. We detail regional distribution of this cancer highlighting communities in southern/coastal areas, as being most at risk as well as the latest trends of melanoma incidence by age, sex and anatomic site. In males, melanoma is more common on the head/trunk, while in females on the extremities. Notably, Acral Lentiginous Melanoma was the only CM subtype that was more common in females, which primarily affects hands and feet.
The Impact of the Antibiotic Fosfomycin on Wastewater Communities Measured by Flow Cytometry
Authors: Li Shuang , Liu Zishu , Süring Christine , Chen Luyao , Müller Susann , Zeng Ping
Published: March 2022

Fosfomycin is a re-emergent antibiotic known to be effective against severe bacterial infections even when other antibiotics fail. To avoid overuse and thus the risk of new antibiotic resistance, the European Commission has recommended the intravenous use of fosfomycin only when other antibiotic treatments fail. A release of fosfomycin into the environment via wastewater from not only municipalities but also already from the producing pharmaceutical industry can seriously undermine a sustaining therapeutic value. We showed in long-term continuous-mode bioreactor cultivation and by using microbial community flow cytometry, microbial community ecology tools, and cell sorting that the micro-pollutant altered the bacterial wastewater community (WWC) composition within only a few generations. Under these conditions, fosfomycin was not readily degraded both at lower and higher concentrations. At the same time, operational reactor parameters and typical diversity parameters such as α- and intracommunity β-diversity did not point to system changes. Nevertheless, an intrinsic compositional change occurred, caused by a turnover process in which higher concentrations of fosfomycin selected for organisms known to frequently harbor antibiotic resistance genes. A gfp-labeled Pseudomonas putida strain, used as the model organism and a possible future chassis for fosfomycin degradation pathways, was augmented and outcompeted in all tested situations. The results suggest that WWCs, as complex communities, may tolerate fosfomycin for a time, but selection for cell types that may develop resistance is very likely. The approach presented allows very rapid assessment and visualization of the impact of antibiotics on natural or managed microbial communities in general and on individual members of these communities in particular.
Neutralizing Antibodies and Cellular Immune Responses Against SARS-CoV-2 Sustained One and a Half Years After Natural Infection
Authors: Yan Li-na , Liu Pan-pan , Li Xu-gui , Zhou Shi-jing , Li Hao , Wang Zhi-yin , Shen Feng , Lu Bi-chao , Long Yu , Xiao Xiao , Wang Zhen-dong , Li Dan , Han Hui-ju , Yu Hao , Zhou Shu-han , Lv Wen-liang , Yu Xue-jie
Published: March 2022

Background

COVID-19 has caused more than 2.6 billion infections and several million deaths since its outbreak 2 years ago. We know very little about the long-term cellular immune responses and the kinetics of neutralizing antibodies (NAbs) to SARS-CoV-2 because it has emerged only recently in the human population.

Methods

We collected blood samples from individuals who were from the first wave of the COVID-19 epidemic in Wuhan between December 30, 2019, and February 24, 2020. We analyzed NAbs to SARS-CoV-2 using pseudoviruses and IgG antibodies to SARS-CoV-2 spike (S) and nucleocapsid (N) protein using enzyme-linked immunosorbent assay in patients’ sera and determined SARS-CoV-2-specific T-cell responses of patients with ELISpot assays.

Results

We found that 91.9% (57/62) and 88.9% (40/45) of COVID-19 patients had NAbs against SARS-CoV-2 in a year (10–11 months) and one and a half years (17–18 months), respectively, after the onset of illness, indicating that NAbs against SARS-CoV-2 waned slowly and possibly persisted over a long period time. Over 80% of patients had IgG antibodies to SARS-CoV-2 S and N protein one and a half years after illness onset. Most patients also had robust memory T-cell responses against SARS-CoV-2 one and a half years after the illness. Among the patients, 95.6% (43/45) had an IFN-γ-secreting T-cell response and 93.8% (15/16) had an IL-2-secreting T-cell response. The T-cell responses to SARS-CoV-2 were positively correlated with antibodies (including neutralizing antibodies and IgG antibodies to S and N protein) in COVID-19 patients. Eighty percent (4/5) of neutralizing antibody-negative patients also had SARS-CoV-2-specific T-cell response. After long-term infection, protective immunity was independent of disease severity, sex, and age.

Conclusions

We concluded that SARS-CoV-2 infection elicited a robust and persistent neutralizing antibody and memory T-cell response in COVID-19 patients, indicating that these sustained immune responses, among most SARS-CoV-2-infected people, may play a crucial role in protection against reinfection.
Epidemiological Characteristics and Clinical Manifestations of Hepatitis E in a Tertiary Hospital in China: A Retrospective Study
Authors: Fang Li , Zhang Junli , Chen Huiying , Lv Fangfang , Yu Yunsong , Du Xiaoxing
Published: March 2022

Background

Hepatitis E virus (HEV) infection is the most common cause of acute viral hepatitis worldwide and one of the main causes of death in the last decade, causing chronic hepatitis and liver failure in some populations. The aging population and obesity are two major factors threatening human health. Therefore, we want to understand the relationship between these two groups and HEV infection.

Objectives

The study aimed to analyze the epidemiological, clinical, and laboratory features of HEV infection and evaluate probable high-risk factors for disease progression and the current diagnostic strategies of hepatitis E infection.

Study Design

Patients diagnosed with acute hepatitis E with symptoms and liver dysfunction were enrolled. For statistical analysis, clinical features and laboratory findings were collected between the elderly and non-elderly and HEV+ fatty liver disease (FLD) groups. Statistical analysis was performed using Excel and the platform VassarStats, and statistical significance was taken as P < 0.05.

Results

Jaundice and the bilirubin peak were significantly deeper, the duration of hospitalization was significantly longer, and the proportion of ascites and liver failure was significantly higher in the elderly group. The aging population is one of the risk factors of severe hepatitis E. Hepatitis E becomes more serious in the HEV + FLD group, although the results did not reach statistical significance.

Conclusion

The aging and FLD were suggested to aggravate HEV infection. However, the diagnosis of HEV infection remains a challenge. A prospective study with sufficient sample size is needed to confirm this conclusion.
Comparing Long-Read Assemblers to Explore the Potential of a Sustainable Low-Cost, Low-Infrastructure Approach to Sequence Antimicrobial Resistant Bacteria With Oxford Nanopore Sequencing
Authors: Boostrom Ian , Portal Edward A. R. , Spiller Owen B. , Walsh Timothy R. , Sands Kirsty
Published: March 2022

Long-read sequencing (LRS) can resolve repetitive regions, a limitation of short read (SR) data. Reduced cost and instrument size has led to a steady increase in LRS across diagnostics and research. Here, we re-basecalled FAST5 data sequenced between 2018 and 2021 and analyzed the data in relation to gDNA across a large dataset (n = 200) spanning a wide GC content (25–67%). We examined whether re-basecalled data would improve the hybrid assembly, and, for a smaller cohort, compared long read (LR) assemblies in the context of antimicrobial resistance (AMR) genes and mobile genetic elements. We included a cost analysis when comparing SR and LR instruments. We compared the R9 and R10 chemistries and reported not only a larger yield but increased read quality with R9 flow cells. There were often discrepancies with ARG presence/absence and/or variant detection in LR assemblies. Flye-based assemblies were generally efficient at detecting the presence of ARG on both the chromosome and plasmids. Raven performed more quickly but inconsistently recovered small plasmids, notably a ∼15-kb Col-like plasmid harboring blaKPC. Canu assemblies were the most fragmented, with genome sizes larger than expected. LR assemblies failed to consistently determine multiple copies of the same ARG as identified by the Unicycler reference. Even with improvements to ONT chemistry and basecalling, long-read assemblies can lead to misinterpretation of data. If LR data are currently being relied upon, it is necessary to perform multiple assemblies, although this is resource (computing) intensive and not yet readily available/useable.
Plasma Concentrations of sTREM-1 as Markers for Systemic Adverse Reactions in Subjects Treated With Weekly Rifapentine and Isoniazid for Latent Tuberculosis Infection
Authors: Wang Tsai-Yu , Feng Jia-Yih , Shu Chin-Chung , Lee Susan Shin-jung , Chen Chung-Yu , Wei Yu-Feng , Lin Chih-Bin , Huang Wei-Chang , Su Wei-Juin , Lin Shu-Min
Published: March 2022

Background

A regimen of once-weekly rifapentine plus isoniazid for 3 months (3HP) is an effective treatment for subjects with latent tuberculosis infection; however, no reliable biomarker exists for predicting systemic adverse reactions (SARs) to 3HP treatment.

Methods

This prospective, multi-center study evaluated the plasma concentrations of soluble triggering receptors expressed on myeloid cells (sTREM)-1 and sTREM-2 in subjects undergoing 3HP treatment and examined the associations between these biomarkers and SARs.

Results

This study enrolled 80 consecutive subjects receiving 3HP treatment, 25 of whom had SARs and 55 of whom did not. Subjects with SARs presented higher concentrations of sTREM-1 at baseline than those without SARs (240.1 ± 19.1 vs. 176.7 ± 9.4 pg/mL, P = 0.001). The area under the receiver operating characteristic curves revealed that day 1 plasma levels of sTREM-1 (0.708, 95% CI, 0.584–0.833, P = 0.003) and sTREM-2 (0.343, 95% CI, 0.227–0.459, P = 0.025) as well as the sTREM-1/sTREM-2 ratio (0.748, 95% CI, 0.638–0.858, P = 0.001) had modest discriminative power pertaining to the development of SARs. An sTREM-1 level exceeding the cut-off value (>187.4 pg/mL) (hazard ratio [HR], 6.15; 95% CI 1.67–22.70, P = 0.006) and a sTREM-2 below the cut-off value (<237.2 pg/mL) (HR, 4.46; 95% CI 1.41–14.1, P = 0.011) were independent predictors of SARs after controlling for other variables.

Conclusions

Plasma sTREM-1 and sTREM-2 levels are useful biomarkers for predicting SARs during 3HP treatment.

Clinical trial government

NCT04655794
Exploration of the Potential Relationship Between Gut Microbiota Remodeling Under the Influence of High-Protein Diet and Crohn’s Disease
Authors: Zhao Yiming , Chen Lulu , Chen Liyu , Huang Jing , Chen Shuijiao , Yu Zheng
Published: March 2022

Diet and gut microbiota are both important factors in the pathogenesis of Crohn’s disease, and changes in diet can lead to alteration in gut microbiome. However, there is still insufficient exploration on interaction within the gut microbiota under high-protein diet (HPD) intervention. We analyzed the gut microbial network and marker taxa from patients with Crohn’s disease in public database (GMrepo, https://gmrepo.humangut.info) combined with investigation of the changes of composition and function of intestinal microbiome in mice fed on HPD by metagenomic sequencing. The results showed that there was an indirect negative correlation between Escherichia coli and Lachnospiraceae in patients with Crohn’s disease, and Escherichia coli was a marker for both Crohn’s disease and HPD intervention. Besides, enriched HH_1414 (one of the orthologs in eggNOG) related to tryptophan metabolism was from Helicobacter, whereas reduced orthologs (OGs) mainly contributed by Lachnospiraceae after HPD intervention. Our research indicates that some compositional changes in gut microbiota after HPD intervention are consistent with those in patients with Crohn’s disease, providing insights into potential impact of altered gut microbes under HPD on Crohn’s disease.
DnaK Functions as a Moonlighting Protein on the Surface of Mycoplasma hyorhinis Cells
Authors: Li Yao , Wang Jia , Liu Beibei , Yu Yanfei , Yuan Ting , Wei Yanna , Gan Yuan , Shao Jia , Shao Guoqing , Feng Zhixin , Tu Zhigang , Xiong Qiyan
Published: March 2022

Mycoplasma hyorhinis is a common pathogen of swine and is also associated with various human tumors. It causes systemic inflammation, typically polyserositis and polyarthritis, in some infected pigs. However, the pathogenic mechanism of M. hyorhinis remains unclear. DnaK is a highly conserved protein belonging to the heat-shock protein 70 family of molecular chaperones, which plays important roles as a moonlighting protein in various bacteria. In the present study, we identified the surface exposure of M. hyorhinis DnaK. Two virulent strains expressed more DnaK on their surface than the avirulent strain. Thereafter, the potential moonlighting functions of DnaK were investigated. Recombinant M. hyorhinis DnaK (rMhr-DnaK) was found to be able to adhere to swine PK-15 cells and human NCI-H292 cells. It also bound to four extracellular matrix components—fibronectin, laminin, type IV collagen, and vitronectin—in a dose-dependent manner. ELISA demonstrated an interaction between rMhr-DnaK and plasminogen, which was significantly inhibited by a lysine analog, ε-aminocaproic acid. rMhr-DnaK-bound plasminogen was activated by tissue-type plasminogen activator (tPA), and the addition of rMhr-DnaK significantly enhanced the activation. Finally, a DnaK-specific antibody was detected in the serum of pigs immunized with inactivated vaccines, which indicated good immunogenicity of it. In summary, our findings imply that DnaK is an important multifunctional moonlighting protein in M. hyorhinis and likely participates extensively in the infection and pathogenesis processes of M. hyorhinis.
Production of Putrescine and Cadaverine by Paucilactobacillus wasatchensis
Authors: Berthoud Hélène , Wechsler Daniel , Irmler Stefan
Published: March 2022

Lactic acid bacteria (LAB) play a key role in many food fermentations. However, some LAB species can also cause food spoilage, e.g., through the formation of biogenic amines. Paucilactobacillus wasatchensis is a LAB that causes late gas production in Cheddar cheese, the molecular causes of which are not fully understood. This study reports on the ability of P. wasatchensis WDC04 to produce cadaverine and putrescine in broth supplemented with lysine and ornithine, as well as in a model cheese. The raclette-type semi-hard cheese produced with P. wasatchensis as an adjunct culture contained 1,085 mg kg−1 of cadaverine and 304 mg kg−1 of putrescine after 120 days of ripening. We identified two ornithine decarboxylase genes (odc) and a putrescine-ornithine antiporter gene (potE) in the genome sequence of P. wasatchensis. We could show that the two odc genes, which are located on two contigs, are contiguous and form the genetic cluster odc2-odc1-potE. Alignment searches showed that similar gene clusters exist in the genomes of Levilactobacillus paucivorans DSMZ22467, Lentilactobacillus kribbianus YH-lac9, Levilactobacillus hunanensis 151-2B, and Levilactobacillus lindianensis 220-4. More amino acid sequence comparisons showed that Odc1 and Odc2 shared 72 and 69% identity with a lysine and ornithine decarboxylase from Ligilactobacillus saerimneri 30a, respectively. To clarify the catalytic activities of both enzymes, the odc-coding genes were cloned and heterologously expressed as His-tagged fusion protein. The purified Odc1 protein decarboxylated lysine into cadaverine, while the recombinant Odc2 protein preferentially produced putrescine from ornithine but also exhibited low lysine decarboxylating activity. Both enzymes were active at pH of 5.5, a value often found in cheese. To our knowledge, this is only the second lysine decarboxylase in LAB whose function has been verified. The tandem arrangement of the genes in a single cluster suggests a gene duplication, evolving the ability to metabolize more amino. Divergent substrate preferences highlight the necessity of verifying the functions of genes, in addition to automatic annotation based on sequence similarity. Acquiring new biochemical data allows better predictive models and, in this case, more accurate biogenic amine production potential for LAB strains and microbiomes.
MRI Radiomics Features From Infarction and Cerebrospinal Fluid for Prediction of Cerebral Edema After Acute Ischemic Stroke
Authors: Jiang Liang , Zhang Chuanyang , Wang Siyu , Ai Zhongping , Shen Tingwen , Zhang Hong , Duan Shaofeng , Yin Xindao , Chen Yu-Chen
Published: March 2022

Neuroimaging biomarkers that predict the edema after acute stroke may help clinicians provide targeted therapies and minimize the risk of secondary injury. In this study, we applied pretherapy MRI radiomics features from infarction and cerebrospinal fluid (CSF) to predict edema after acute ischemic stroke. MRI data were obtained from a prospective, endovascular thrombectomy (EVT) cohort that included 389 patients with acute stroke from two centers (dataset 1, n = 292; dataset 2, n = 97), respectively. Patients were divided into edema group (brain swelling and midline shift) and non-edema group according to CT within 36 h after therapy. We extracted the imaging features of infarct area on diffusion weighted imaging (DWI) (abbreviated as DWI), CSF on fluid-attenuated inversion recovery (FLAIR) (CSFFLAIR) and CSF on DWI (CSFDWI), and selected the optimum features associated with edema for developing models in two forms of feature sets (DWI + CSFFLAIR and DWI + CSFDWI) respectively. We developed seven ML models based on dataset 1 and identified the most stable model. External validations (dataset 2) of the developed stable model were performed. Prediction model performance was assessed using the area under the receiver operating characteristic curve (AUC). The Bayes model based on DWI + CSFFLAIR and the RF model based on DWI + CSFDWI had the best performances (DWI + CSFFLAIR: AUC, 0.86; accuracy, 0.85; recall, 0.88; DWI + CSFDWI: AUC, 0.86; accuracy, 0.84; recall, 0.84) and the most stability (RSD% in DWI + CSFFLAIR AUC: 0.07, RSD% in DWI + CSFDWI AUC: 0.09), respectively. External validation showed that the AUC of the Bayes model based on DWI + CSFFLAIR was 0.84 with accuracy of 0.77 and area under precision-recall curve (auPRC) of 0.75, and the AUC of the RF model based on DWI + CSFDWI was 0.83 with accuracy of 0.81 and the auPRC of 0.76. The MRI radiomics features from infarction and CSF may offer an effective imaging biomarker for predicting edema.
Evaluation of a Simple Clinical Language Paradigm With Respect to Sensory Independency, Functional Asymmetry, and Effective Connectivity
Authors: Rødland Erik , Melleby Kathrine Midgaard , Specht Karsten
Published: March 2022

The present study replicates a known visual language paradigm, and extends it to a paradigm that is independent from the sensory modality of the stimuli and, hence, could be administered either visually or aurally, such that both patients with limited sight or hearing could be examined. The stimuli were simple sentences, but required the subject not only to understand the content of the sentence but also to formulate a response that had a semantic relation to the content of the presented sentence. Thereby, this paradigm does not only test perception of the stimuli, but also to some extend sentence and semantic processing, and covert speech production within one task. When the sensory base-line condition was subtracted, both the auditory and visual version of the paradigm demonstrated a broadly overlapping and asymmetric network, comprising distinct areas of the left posterior temporal lobe, left inferior frontal areas, left precentral gyrus, and supplementary motor area. The consistency of activations and their asymmetry was evaluated with a conjunction analysis, probability maps, and intraclass correlation coefficients (ICC). This underlying network was further analyzed with dynamic causal modeling (DCM) to explore whether not only the same brain areas were involved, but also the network structure and information flow were the same between the sensory modalities. In conclusion, the paradigm reliably activated the most central parts of the speech and language network with a great consistency across subjects, and independently of whether the stimuli were administered aurally or visually. However, there was individual variability in the degree of functional asymmetry between the two sensory conditions.
Healthy Serum-Derived Exosomes Improve Neurological Outcomes and Protect Blood–Brain Barrier by Inhibiting Endothelial Cell Apoptosis and Reversing Autophagy-Mediated Tight Junction Protein Reduction in Rat Stroke Model
Authors: Huang Lin-Yan , Song Jin-Xiu , Cai Heng , Wang Pei-Pei , Yin Qi-Long , Zhang Yi-De , Chen Jie , Li Ming , Song Jia-Jia , Wang Yan-Ling , Luo Lan , Wang Wan , Qi Su-Hua
Published: March 2022

Blood–brain barrier (BBB) dysfunction causing edema and hemorrhagic transformation is one of the pathophysiological characteristics of stroke. Protection of BBB integrity has shown great potential in improving stroke outcome. Here, we assessed the efficacy of exosomes extracted from healthy rat serum in protection against ischemic stroke in vivo and in vitro. Exosomes were isolated by gradient centrifugation and ultracentrifugation and exosomes were characterized by transmission electron microscopy (TEM) and nanoparticle tracking video microscope. Exosomes were applied to middle cerebral artery occlusion (MCAO) rats or brain microvascular endothelial cell line (bEnd.3) subjected to oxygen-glucose deprivation (OGD) injury. Serum-derived exosomes were injected intravenously into adult male rats 2 h after transient MCAO. Infarct volume and gross cognitive function were assessed 24 h after reperfusion. Poststroke rats treated with serum-derived exosomes exhibited significantly reduced infarct volumes and enhanced neurological function. Apoptosis was assessed via terminal deoxynucleotidyl transferase (TdT)-mediated dUTP nick-end labeling (TUNEL) staining and the expression of B-cell lymphoma-2 (Bcl-2), Bax, and cleaved caspase-3 24 h after injury. Our data showed that serum exosomes treatment strikingly decreased TUNEL+ cells in the striatum, enhanced the ratio of Bcl-2 to Bax, and inhibited cleaved caspase-3 production in MCAO rats and OGD/reoxygenation insulted bEnd.3 cells. Under the consistent treatment, the expression of microtubule-associated protein 1 light chain 3B-II (LC3B-II), LC3B-I, and Sequestosome-1 (SQSTM1)/p62 was detected by Western blotting. Autolysosomes were observed via TEM. We found that serum exosomes reversed the ratio of LC3B-II to LC3B-I, prevented SQSTM1/p62 degradation, autolysosome formation, and autophagic flux. Together, these results indicated that exosomes isolated from healthy serum provided neuroprotection against experimental stroke partially via inhibition of endothelial cell apoptosis and autophagy-mediated BBB breakdown. Intravenous serum-derived exosome treatment may, therefore, provide a novel clinical therapeutic strategy for ischemic stroke.
Risk of Incident Epilepsy After a Middle Cerebral Artery Territory Infarction
Authors: Hsieh Cheng-Yang , Su Chien-Chou , Lai Edward Chia-Cheng , Chen Yu-Shiue , Huang Tzu-Hsin , Kao Yang Yea-Huei , Chen Chih-Hung , Sung Sheng-Feng , Huang Chin-Wei
Published: March 2022

Background

Among poststroke morbidities, poststroke epilepsy (PSE) has been identified as a significant clinical issue. Although middle cerebral artery (MCA) infarct is the most common type of stroke among all vascular territories, very few studies specifically focused on the risk factors leading to PSE in patients with MCA infarct.

Methods

A population study in Taiwan has been conducted, linking the National Health Insurance Research Database and Hospital Stroke Registry, from 2001 to 2015 and 2006 to 2010, respectively. Patients were divided into MCA and non-MCA groups, and the diagnosis of incident epilepsy between the groups has been compared. The multivariable Cox proportional hazard model was used to identify the risk factors for developing PSE. The distribution of time to PSE was estimated using the Kaplan–Meier method.

Results

In total, 1,838 patients were recruited, with 774 and 1,064 in the MCA and non-MCA groups, respectively. PSE incidence in the MCA group was 15.5% vs. 6.2% in the non-MCA group, with a hazard ratio of (95% CI) 2.06 (1.33–3.19). Factors significantly associated with PSE included atrial fibrillation, depression, National Institutes of Health Stroke Scale (NIHSS) scores of ≥ 16, and alert on arrival. For patients with MCA infarct, higher NIHSS and Glasgow coma scale scores, the presence of visual field defects and weakness, urination control impairment, and complications during hospitalization were associated with a higher risk for PSE development.

Conclusions

This study established the conditions leading to a higher risk of PSE and identified the important clinical risk factors in patients experiencing MCA infarct. Efforts to manage these risk factors may be important in preventing PSE in patients with MCA infarct.
Non-Coding RNA Regulatory Network in Ischemic Stroke
Authors: Cai Zongyan , Li Shuo , Yu Tianci , Deng Jiahui , Li Xinran , Jin Jiaxin
Published: March 2022

Stroke is a worldwide public health problem that has caused a substantial economic burden to families and society. Despite recent major advances, there is still a need for more timely, effective diagnosis and treatment methods for acute ischemic stroke. Non-coding RNAs (ncRNAs), which widely exist in the human body, do not encode proteins. Instead, these mediate various cellular processes as functional regulatory molecules from the RNA level. Each ncRNA node in organisms is not isolated but constitutes a complex regulatory network, regulating multiple molecular targets and triggering specific physiological or pathological reactions, leading to different outcomes. Abundant studies have proclaimed the impact of ncRNAs in ischemic stroke, which may enlighten new inspirations for diagnosing and treating ischemic stroke. This paper outlines the current understanding of the ncRNA regulatory network and reviews the recent evidence for the contribution of ncRNAs in the experimental ischemic stroke model.
Psychometric Properties of the Trail Walking Test for People With Stroke
Authors: Ng Shamay S. M. , Liu Tai-Wa , Tsoh Joshua , Chen Peiming , Cheng Tony S. , Cheung Marco C. H. , Leung Anthony H. H. , Ng Liam L. Y. , So Ken Y. K. , Tse Mimi M. Y.
Published: March 2022

Objective

To investigate (i) the inter-rater and test–retest reliability of the trail walking test (TWT) and the minimum detectable change in the TWT completion time; (ii) the correlations between the TWT completion time and stroke-specific impairments; and (iii) the cutoff TWT completion time to distinguish between people with stroke and healthy older adults according to dual-tasking ambulation ability.

Design

Cross-sectional study.

Setting

University-based rehabilitation center.

Participants

In total, 104 people with stroke and 53 healthy older adults.

Main Outcome Measures

The TWT, the Fugl–Meyer Assessment of Lower Extremity (FMA-LE), the ankle muscle strength test, the limit of stability (LOS) test, the Berg Balance Scale (BBS), the Timed Up and Go test (TUG), and the Community Integration Measure (CIM).

Results

The mean TWT completion time in subjects with stroke was 124.906 s. The TWT demonstrated excellent inter-rater reliability [intraclass correlation (ICC) = 0.999] and good test–retest reliability (ICC = 0.876) in people with stroke. The TWT performance demonstrated significant negative correlations with the FMA-LE scores (r= −0.409), LOS movement velocity (affected and unaffected sides;r= −0.320 and −0.388, respectively), and LOS endpoint excursion (affected and unaffected sides;r= −0.357 and −0.394, respectively); a significant positive correlation with the LOS reaction time (affected side;r= 0.256); a moderate negative correlation with the BBS scores (r= −0.72); and an excellent positive correlation with the TUG completion time (r= 0.944). The receiver operating characteristic curve analysis revealed that an optimal cutoff of 69.61 s for the TWT completion time had an outstanding diagnostic power to distinguish between people with stroke and healthy older adults (area under the curve = 0.919) with high sensitivity (88.5%) and specificity (83.0%).

Conclusion

Results of our preliminary study demonstrated that the TWT is a reliable, valid, sensitive, and specific clinical test for evaluating dual-tasking ambulation ability in people with stroke aged 45 years or above and without cognitive impairments. It can differentiate the dual-tasking ambulation ability between people with stroke and healthy older adults.
Shared CSF Biomarker Profile in Idiopathic Normal Pressure Hydrocephalus and Subcortical Small Vessel Disease
Authors: Jeppsson Anna , Bjerke Maria , Hellström Per , Blennow Kaj , Zetterberg Henrik , Kettunen Petronella , Wikkelsø Carsten , Wallin Anders , Tullberg Mats
Published: March 2022

Introduction

In this study, we examine similarities and differences between 52 patients with idiopathic normal pressure hydrocephalus (iNPH) and 17 patients with subcortical small vessel disease (SSVD), in comparison to 28 healthy controls (HCs) by a panel of cerebrospinal fluid (CSF) biomarkers.

Methods

We analyzed soluble amyloid precursor protein alpha (sAPPα) and beta (sAPPβ), Aβ isoforms −38, −40, and −42, neurofilament light protein (NFL), glial fibrillary acidic protein (GFAP), myelin basic protein (MBP), matrix metalloproteinases (MMP −1, −2, −3, −9, and −10), and tissue inhibitors of metalloproteinase 1 (TIMP1). Radiological signs of white matter damage were scored using the age-related white matter changes (ARWMC) scale.

Results

All amyloid fragments were reduced in iNPH and SSVD (p < 0.05), although more in iNPH than in SSVD in comparison to HC. iNPH and SSVD showed comparable elevations of NFL, MBP, and GFAP (p < 0.05). MMPs were similar in all three groups except for MMP-10, which was increased in iNPH and SSVD. Patients with iNPH had larger ventricles and fewer WMCs than patients with SSVD.

Conclusion

The results indicate that patients with iNPH and SSVD share common features of subcortical neuronal degeneration, demyelination, and astroglial response. The reduction in all APP-derived proteins characterizing iNPH patients is also present, indicating that SSVD encompasses similar pathophysiological phenomena as iNPH.
Case Report: “Clipping” an Internal Carotid Artery Aneurysm With a Duplicated Middle Cerebral Artery and the Anterior Choroidal Artery Arising From the Dome
Authors: Otsuka Nozomi , Yajima Hirohisa , Miyawaki Satoru , Koizumi Satoshi , Kiyofuji Satoshi , Hongo Hiroki , Teranishi Yu , Kin Taichi , Saito Nobuhito
Published: March 2022

Background

A duplicated middle cerebral artery (DMCA) is an anatomical variant that includes duplication of the middle cerebral artery (MCA) and an anomalous vessel originating between the anterior choroidal artery (AChA) and the distal end of the internal carotid artery (ICA). Here, we present a case report of an ICA aneurysm with a DMCA and the AChA originating from the dome, which was successfully treated with clipping.

Case Description

In a 64-year-old man, preoperative angiography revealed an unruptured right ICA aneurysm with a maximum diameter of 4.3 mm, and fusion three-dimensional computer graphics revealed that a DMCA and the AChA originated from the dome. The aneurysm enlarged; therefore, clipping was performed. The closure of the aneurysm while preserving the patency of the DMCA and AChA was identified using intraoperative microvascular Doppler ultrasonography and indocyanine green video angiography. The postoperative course was uneventful, and no ischemic lesions were confirmed on MR imaging.

Conclusion

To the best of our knowledge, this is the first report of an ICA aneurysm with a DMCA and the AChA arising from the dome. In such cases, the anatomy of the DMCA and AChA should be well-characterized before treatment.
Enhanced Resting-State Functional Connectivity With Decreased Amplitude of Low-Frequency Fluctuations of the Salience Network in Mindfulness Novices
Authors: Gan Quan , Ding Ning , Bi Guoli , Liu Ruixiang , Zhao Xingrong , Zhong Jingmei , Wu Shaoyuan , Zeng Yong , Cui Liqian , Wu Kunhua , Fu Yunfa , Chen Zhuangfei
Published: March 2022

Mindfulness and accordant interventions are often used as complementary treatments to psychological or psychosomatic problems. This has also been gradually integrated into daily lives for the promotion of psychological well-being in non-clinical populations. The experience of mindful acceptance in a non-judgmental way brought about the state, which was less interfered by a negative effect. Mindfulness practice often begins with focused attention (FA) meditation restricted to an inner experience. We postulate that the brain areas related to an interoceptive function would demonstrate an intrinsic functional change after mindfulness training for the mindful novices along with paying more attention to internal processes. To further explore the influence of mindfulness on the organization of the brain regions, both functional connectivity (FC) in the voxel and the region of interest (ROI) level were calculated. In the current study, 32 healthy volunteers, without any meditation experiences, were enrolled and randomly assigned to a mindfulness-based stress reduction group (MBSR) or control group (CON). Participants in the MBSR group completed 8 weeks of mindfulness-based stress reduction (MBSR) and rated their mindfulness skills before and after MBSR. All subjects were evaluated via resting-state functional MRI (rs-fMRI) in both baselines and after 8 weeks. They also completed a self-report measure of their state and trait anxiety as well as a positive and negative affect. Pre- and post-MBSR assessments revealed a decreased amplitude of low-frequency fluctuations (ALFF) in the right anterior cingulate gyrus (ACC.R), left anterior and posterior insula (aIC.L, pIC.L), as well as left superior medial frontal gyrus (SFGmed.L) in MBSR practitioners. Strengthened FC between right anterior cingulate cortex (ACC.R) and aIC.R was observed. The mean ALFF values of those regions were inversely and positively linked to newly acquired mindful abilities. Along with a decreased negative affect score, our results suggest that the brain regions related to attention and interoceptive function were involved at the beginning of mindfulness. This study provides new clues in elucidating the time of evaluating the brain mechanisms of mindfulness novices.
Modafinil Reduces Neuronal Pyroptosis and Cognitive Decline After Sleep Deprivation
Authors: Xiong Xiangyang , Zuo Yan , Cheng Lu , Yin Zhenyu , Hu Tianpeng , Guo Mengtian , Han Zhaoli , Ge Xintong , Li Wenzhu , Wang Yan , Wang Dong , Wang Conglin , Zhang Lan , Zhang Yaodan , Liu Qiang , Chen Fanglian , Lei Ping
Published: March 2022

Sleep deprivation (SD) induces systemic inflammation that promotes neuronal pyroptosis. The purpose of this study was to investigate the effect of an antioxidant modafinil on neuronal pyroptosis and cognitive decline following SD. Using a mouse model of SD, we found that modafinil improved learning and memory, reduced proinflammatory factor (IL-1β, TNF-α, and IL-6) production, and increased the expression of anti-inflammatory factors (IL-10). Modafinil treatment attenuated inflammasome activity and reduced neuronal pyroptosis involving the NLRP3/NLRP1/NLRC4-caspase-1-IL-1β pathway. In addition, modafinil induced an upregulation of brain-derived neurotrophic factor (BDNF) and synaptic activity. These results suggest that modafinil reduces neuronal pyroptosis and cognitive decline following SD. These effects should be further investigated in future studies to benefit patients with sleep disorders.