bluuebunny/crossref_metadata_2025 huggingface dataset:
Genomic Comparison and Genetic Marker Identification of the White-Spotted Bamboo Shark Chiloscyllium plagiosum
Authors: Zhao Ruirui , Cai Shanshan , Lu Dingfang , Li Pengfei , Xu Shengyong , Li Yuan
Published: July 2022

The white-spotted bamboo shark (Chiloscyllium plagiosum) is an ecologically and commercially important marine cartilaginous fish in the Indo-Western Pacific. However, the resources of this species are declining in recent years due to habitat degradation and overfishing. Studies on genomics and genetic markers can provide valuable information for sound management and conservation of C. plagiosum. In this study, genome resequencing data of a domesticated C. plagiosum individual were generated for genomic comparison between wild and domesticated samples. Based on 281.17 Gb of clean sequencing data, the genome size of the domesticated sample was estimated as 4.99 Gb, with heterozygosity of 0.51% and repeat ratio of 74.67%, which is about 1 Gb larger than that of the wild sample (3.85 Gb with a repeat ratio of 63.53%). By using a reference-based approach, we assembled a nearly 3.45 Gb genome sequence of the domesticated sample, with the scaffold N50 of 69.45 Mb. Subsequent identification of genome-wide microsatellite markers confirmed the different abundance of repeat elements in wild and domesticated C. plagiosum. Additionally, a total of 8,703,211 single-nucleotide polymorphisms (SNPs) were detected and annotated. The demographic analysis based on identified SNPs revealed a large and constant effective population size of C. plagiosum after the last population expansion (~0.3 million years ago). The genomic data and identified genetic markers in this study can provide fundamental and useful information for further comparative genomics, evolutionary biology, and conservation genetics of C. plagiosum.
Research and Design of a Wing-Wall-Free Guardrail in Transition Between the Subgrade and the Bridge
Authors: Shen Linlin , Hu Ran , Wang Tingyu
Published: July 2022

Considering the difficulty and high cost of guardrail installation in the transition between the highway subgrade and the bridge, this paper proposes a wing-wall-free guardrail based on comprehensive research. It has carried out a performance analysis of material Q690 before proposing the scheme. It is found that this type of material has high yield strength and tensile strength as well as high plasticity. Accordingly, the guardrail structure of the transition section of the wing-wall-free guardrail is designed, and the DYNA numerical simulation is carried out to optimize the structure. Moreover, vehicle crash tests are used to verify the performance of the newly designed guardrail. The results of the above-mentioned research methods are as follows: the vehicle crash tests show that the wing-wall-free guardrail can reach a protection level of Grade SB, with a collision energy of 280 KJ. All performance indicators meet the industry standards. The guardrail can be used in the transition between W-beam subgrade guardrails and concrete or combined bridge barriers. This proposed guardrail is beautifully designed with low cost and great conveniency for installation and maintenance.
Demographic Characteristics, Comorbidities, and Length of Stay of COVID-19 Patients Admitted Into Intensive Care Units in Saudi Arabia: A Nationwide Retrospective Study
Authors: Al-Otaiby Maram , Almutairi Khalid M. , Vinluan Jason M. , Al Seraihi Ahad , Alonazi Wadi B. , Qahtani Mohammad Hassan , Aljeri Thamer , Alhumud Manal A. , Alobaidi Nadhar , Alhurishi Sultana A.
Published: July 2022

Background

This study aimed to describe the demographic characteristics and determine the risk factors associated with disease severity and length of hospital and intensive care unit (ICU) stay in a cohort of COVID-19 patients admitted into ICU in Saudi Arabia.

Methods

This was a national, multi-center, retrospective cross-sectional study of all COVID-19 cases admitted into different ICUs in Saudi Arabia between March 2020 and September 202l. Demographic, clinical features, comorbidities, and length of stay (LOS) data were retrieved from the national Health Electronic Surveillance Network (HESN) and Taqassi databases at the Saudi Ministry of Health (MOH) for subsequent analyses. We used multiple linear regression models to determine risk factors associated with critical outcomes (including LOS in ICU) among COVID-19 cases.

Results

A total of 12,436 COVID-19 patients were included in this study, with a mean age of 59.57 ± 18.30 years and 7,679 (62%) were <65 years old. COVID-19 was more common in males (N = 7,686, 61.9%) and Saudi nationals (N = 8,516, 68.5%). The clinical characteristic findings showed that 36.3% of patients required invasive ventilation whilst 65.4% received tracheostomies for ventilation, and 4% were on dialysis. Our analysis revealed that 2,978 (23.9%) patients had one comorbidity, 4,977 (47.4%) had two or more comorbidities, and diabetes (48.2%) was the most prevalent comorbidity, followed by hypertension (44.2%), and chronic cardiovascular disease (10.5%). Thirteen variables emerged as significant predictors of LOS in ICU using multiple linear regression analyses, with invasive ventilation as the strongest predictor of LOS in the ICU (beta = −0.68, p = 0.001) and hospital admission (beta = −0.65, p = 0.001).

Conclusions

COVID-19 continues to affect millions of people around the world, with a mortality rate of about 2–3% of all infected patients. Our analysis revealed that comorbidities such as chronic kidney disease, cardiovascular disease, diabetes, and older age were significant risk factors associated with a poorer prognosis and longer duration of stay in hospitals and ICU.
Microbial Diversity in Groundwater and Its Response to Seawater Intrusion in Beihai City, Southern China
Authors: Ma Zhonglin , Gao Long , Sun Mingxue , Liao Yongjie , Bai Shijie , Wu Zijun , Li Jiangtao
Published: July 2022

Seawater intrusion is a major concern commonly found in coastal aquifers worldwide. Because of the intense aquifer exploitation and land-based marine aquaculture in the coastal area of Beihai City, Guangxi Zhuang Autonomous Region, China, numerous underground aquifers in this area have been affected by seawater intrusion. However, the microbial communities in freshwater aquifers and their response to seawater intrusion are still unclear. In this study, groundwater from three aquifers was collected from three monitoring sites at different distances from the coastline in the coastal area of Beihai City, and the hydrochemical characteristics of these groundwater samples and the structure of the associated microbial communities were analyzed. The Cl− concentration of the samples indicated that seawater intrusion had occurred in the research area up to 1.5 km away from the coastline, but the monitoring site 2 km away from the coastline had yet to be affected. Statistical analysis showed that the bacterial communities in different groundwater aquifers were significantly correlated with the Cl− concentration, thereby suggesting that the extent of seawater intrusion might be one of the primary factors shaping bacterial composition in groundwater of this area, but the composition and distribution of archaea did not show a significant response to seawater intrusion and presented no apparent correlation with the Cl− concentration. α-, γ-Proteobacteria and Bacteroidota were the dominant bacterial lineages, accounting for about 58–95% of the bacterial communities. Meanwhile, the predominant archaeal taxa were mainly composed of Crenarchaeota, Nanoarchaeota, and Thermoplasmatota, as accounting for 83–100%. Moreover, there was significant spatial heterogeneity of microbial communities in the aquifers affected by varying degrees of seawater intrusion. The microbial communities inhabiting the unconfined aquifer were influenced by the geochemical fluctuation caused by seawater infiltration from land-based marine aquaculture ponds and the diffusion of eutrophic surface water. In contrast, changes in microbial community structure in the confined aquifers were closely related to the environmental gradient caused by different degrees of seawater intrusion. In addition, we also found that the tidal cycle did not significantly affect the structure of microbial communities inhabiting confined aquifers that had been long affected by seawater intrusion.
Genome Functional Analysis of the Psychrotrophic Lignin-Degrading Bacterium Arthrobacter sp. C2 and the Role of DyP in Catalyzing Lignin Degradation
Authors: Jiang Cheng , Yan Haohao , Shen Xiaohui , Zhang Yuting , Wang Yue , Sun Shanshan , Jiang Hanyi , Zang Hailian , Zhao Xinyue , Hou Ning , Li Ziwei , Wang Liwen , Wang Hanjun , Li Chunyan
Published: July 2022

In the cold regions of China, lignin-rich corn straw accumulates at high levels due to low temperatures. The application of psychrotrophic lignin-degrading bacteria should be an effective means of overcoming the low-temperature limit for lignin degradation and promoting the utilization of corn straw. However, this application is limited by the lack of suitable strains for decomposition of lignin; furthermore, the metabolic mechanism of psychrotrophic lignin-degrading bacteria is unclear. Here, the whole genome of the psychrotrophic lignin-degrading bacterium Arthrobacter sp. C2, isolated in our previous work, was sequenced. Comparative genomics revealed that C2 contained unique genes related to lignin degradation and low-temperature adaptability. DyP may participate in lignin degradation and may be a cold-adapted enzyme. Moreover, DyP was proven to catalyze lignin Cα-Cβ bond cleavage. Deletion and complementation of the DyP gene verified its ability to catalyze the first-step reaction of lignin degradation. Comparative transcriptomic analysis revealed that the transcriptional expression of the DyP gene was upregulated, and the genetic compensation mechanism allowed C2ΔDyP to degrade lignin, which provided novel insights into the survival strategy of the psychrotrophic mutant strain C2ΔdyP. This study improved our understanding of the metabolic mechanism of psychrotrophic lignin-degrading bacteria and provided potential application options for energy-saving production using cold-adapted lignin-degrading enzymes.
Isolation and Characterization of Human Intestinal Bacteria Cytobacillus oceanisediminis NB2 for Probiotic Potential
Authors: Yadav Monika , Kumar Tarun , Kanakan Akshay , Maurya Ranjeet , Pandey Rajesh , Chauhan Nar Singh
Published: July 2022

Systemic characterization of the human gut microbiota highlighted its vast therapeutic potential. Despite having enormous potential, the non-availability of their culture representatives created a bottleneck to understand the concept of microbiome-based therapeutics. The present study is aimed to isolate and evaluate the probiotic potential of a human gut isolate. Physiochemical, morphological, and phylogenetic characterization of a human gut isolate identifies it as a rod-shaped gram-negative microbe taxonomically affiliated with the Cytobacillus genus, having an optimal growth at 37°C in a partially alkaline environment (pH 8.0). This human gut isolate showed continuous growth in the presence of salts (up to 7% NaCl and 10% KCl), antibiotics, metals and metalloids [silver nitrate (up to 2 mM); lead acetate (up to 2 mM); sodium arsenate (up to 10 mM); potassium dichromate (up to 2 mM)], gastric and intestinal conditions, diverse temperature (25–50°C), and pH (5–9) conditions making it fit to survive in the highly variable gut environment. Genomic characterization identified the presence of gene clusters for diverse bio-catalytic activity, stress response, and antimicrobial activity, as well as it indicated the absence of pathogenic gene islands. A combination of functional features like anti-amylase, anti-lipase, glutenase, prolyl endopeptidase, lactase, bile salt hydrolase, cholesterol oxidase, and anti-pathogenic activity is indicative of its probiotic potential in various disorders. This was further substantiated by the CaCo-2 cell line assay confirming its cellular adherence and biosafety. Conclusively, human gut isolate possessed significant probiotic potential that can be used to promote animal and human health.
Genome-Wide Insights Into the Organelle Translocation of Photosynthetic NDH-1 Genes During Evolution
Authors: Yu Jie , Ran Zhaoxing , Zhang Jingsong , Wei Lanzhen , Ma Weimin
Published: July 2022

Translocation of chloroplast-located genes to mitochondria or nucleus is considered to be a safety strategy that impedes mutation of photosynthetic genes and maintains their household function during evolution. The organelle translocation strategy is also developed in photosynthetic NDH-1 (pNDH-1) genes but its understanding is still far from complete. Here, we found that the mutation rate of the conserved pNDH-1 genes was gradually reduced but their selection pressure was maintained at a high level during evolution from cyanobacteria to angiosperm. By contrast, oxygenic photosynthesis-specific (OPS) pNDH-1 genes had an opposite trend, explaining the reason why they were transferred from the reactive oxygen species (ROS)-enriched chloroplast to the ROS-barren nucleus. Further, genome-wide sequence analysis supported the possibility that all conserved pNDH-1 genes lost in chloroplast genomes of Chlorophyceae and Pinaceae were transferred to the ROS-less mitochondrial genome as deduced from their truncated pNDH-1 gene fragments. Collectively, we propose that the organelle translocation strategy of pNDH-1 genes during evolution is necessary to maintain the function of the pNDH-1 complex as an important antioxidant mechanism for efficient photosynthesis.
Identifying and Assessing the Required I4.0 Skills for Manufacturing Companies’ Workforce
Authors: Acerbi Federica , Rossi Monica , Terzi Sergio
Published: July 2022

Nowadays, the diffusion of digital and industry 4.0 (I4.0) technologies is affecting the manufacturing sector with a twofold effect. While on one side it represents the boost fastening the competitive advantage of companies, on the other hand it is often accompanied by several challenges that companies need to face. Among all, companies are required to invest in technologies to empower their production activities on the shopfloor without lagging behind their workforce in order to undertake a linear, aware, and structured path toward digitization. The extant literature presents some research conducted to support companies toward digitization, and they usually rely on maturity models in this intention. Nevertheless, few studies included the assessment of workforce skills and competencies in the overall assessment, and in this case, they provide a high level perspective of the investigation, mainly based on check lists which may limit the objectivity of the assessment, and usually they do not customize the assessment based on companies’ requirements. Therefore, considering the importance to balance investments in technologies with those in the workforce to move toward the same direction, this contribution aims to develop a structured, customizable, and objective skill assessment model. With this intention, it has been first clarified the set of job profiles required in I4.0, together with the needed related skills based on the extant literature findings; second, it has been identified the set of key criteria to be considered while performing the assessment of the workforce; third, it has been defined the method to be integrated in the maturity model to enable the initial setting of the weights of the criteria identified according to the company needs; and fourth, based on these findings, it has been developed the assessment model. The developed model facilitates the elaboration of the proper workforce improvement plans to be put in practice to support the improvement of the skills of the whole workforce based on company’s needs.
Brain Region- and Age-Dependent 5-Hydroxymethylcytosine Activity in the Non-Human Primate
Authors: Xu Yanru , Zhong Liying , Wei Huixian , Li Yuwei , Xie Jiaxiang , Xie Leijie , Chen Xiusheng , Guo Xiangyu , Yin Peng , Li Shihua , Zeng Junwei , Li Xiao-Jiang , Lin Li
Published: July 2022

Because of the difficulty in collecting fresh brains of humans at different ages, it remains unknown how epigenetic regulation occurs in the primate brains during aging. In the present study, we examined the genomic distribution of 5hmC, an indicator of DNA methylation, in the brain regions of non-human primates (rhesus monkey) at the ages of 2 (juvenile), 8 (young adult), and 17 (old) years. We found that genomic 5hmC distribution was accumulated in the monkey brain as age increased and displayed unique patterns in the cerebellum and striatum in an age-dependent manner. We also observed a correlation between differentially hydroxymethylated regions (DhMRs) and genes that contribute to brain region-related functions and diseases. Our studies revealed, for the first time, the brain-region and age-dependent 5hmC modifications in the non-human primate and the association of these 5hmC modifications with brain region-specific function and potentially aging-related brain diseases.
Social Learning of a Spatial Task by Observation Alone
Authors: Doublet Thomas , Nosrati Mona , Kentros Clifford G.
Published: July 2022

Interactions between conspecifics are central to the acquisition of useful memories in the real world. Observational learning, i.e., learning a task by observing the success or failure of others, has been reported in many species, including rodents. However, previous work in rats with NMDA-receptor blockade has shown that even extensive observation of an unexplored space through a clear barrier is not sufficient to generate a stable hippocampal representation of that space. This raises the question of whether rats can learn a spatial task in a purely observed space from watching a conspecific, and if so, does this somehow stabilize their hippocampal representation? To address these questions, we designed an observational spatial task in a two-part environment that is nearly identical to that of the aforementioned electrophysiological study, in which an observer rat watches a demonstrator animal to learn the location of a hidden reward. Our results demonstrate that rats do not need to physically explore an environment to learn a reward location, provided a conspecific demonstrates where it is. We also show that the behavioral memory is not affected by NMDA receptor blockade, suggesting that the spatial representation underlying the behavior has been consolidated by observation alone.
Effects of the Prolong Life With Nine Turn Method (Yan Nian Jiu Zhuan) Qigong on Brain Functional Changes in Patients With Chronic Fatigue Syndrome in Terms of Fatigue and Quality of Life
Authors: Xie Fangfang , Guan Chong , Gu Yuanjia , You Yanli , Yao Fei
Published: July 2022

Background

Chronic fatigue syndrome (CFS) is characterized by persistent fatigue, which often leads to physical and psychological damage. The Prolong Life with Nine Turn method (PLWNT) Qigong is considered as one of the complementary treatments for improving symptoms in patients with CFS. In this study, we used functional magnetic resonance imaging (fMRI) to explore the effects of PLWNT intervention on the subjects with CFS.

Methods

Thirty four CFS patients were randomly divided into PLWNT group and cognitive behavioral therapy (CBT) group. Both groups were taught by a highly qualified professor at the Shanghai University of Traditional Chinese Medicine once a week and were supervised online during the remaining 6 days at home, over 12 consecutive weeks. We calculated the regional rs-fMRI index amplitude of low-frequency fluctuations (ALFF) for all subjects. To study the changes of the brain network, we used the brain regions with significant differences in ALFF as the regions of interest for whole-brain functional connectivity (FC) analysis. The Multi-dimensional Fatigue Inventory 20 (MFI-20) and Short Form 36-item Health Survey (SF-36) were used for clinical symptom assessment to explore the possible correlation between the rs-fMRI indicators and clinical variations.

Results

The ALFF values of the right superior frontal gyrus (SFG), and left median cingulate gyrus (DCG) were increased, whereas those of the left middle occipital gyrus (OG), right middle OG and left middle temporal gyrus (MTG) were decreased in PLWNT group. The FC values between the DCG and middle temporal gyrus (MTG), and those between the left OG and the right OG were enhanced. In addition, the SF-36 were positively with the left OG (r = 0.524), SFG (r = 0.517), and DCG (r = 0.533), MFI-20 were negatively with the SFG (r = −0.542) and DCG (r = −0.578). These results were all corrected by FWE (voxel level p < 0.001, cluster level p < 0.05).

Conclusion

CFS patients have abnormal regional spontaneous neuronal activity and abnormal functional connections between regions after PLWNT intervention. PLWNT can relieve the fatigue symptoms of CFS patients and improve their quality of life. The study was registered in the American Clinical Trial Registry (12/04/2018). Registration Number is NCT03496961.
Novel PLA2G6 Pathogenic Variants in Chinese Patients With PLA2G6-Associated Neurodegeneration
Authors: Wan Yalan , Jiang Yanyan , Xie Zhiying , Ling Chen , Du Kang , Li Ran , Yuan Yun , Wang Zhaoxia , Sun Wei , Jin Haiqiang
Published: July 2022

Background

PLA2G6-associated neurodegeneration (PLAN) is a heterogeneous group of neurodegenerative diseases caused by biallelic PLA2G6 mutations, covering diseases such as infantile neuroaxonal dystrophy (INAD), atypical neuroaxonal dystrophy (ANAD), dystonia parkinsonism (DP), and autosomal recessive early-onset parkinsonism (AREP). The study aims to report the clinical and genetic features of a series of PLAN patients.

Methods

The clinical and radiological findings of five Chinese patients from three families were collected. Whole-exome next generation sequencing (NGS) was applied to identify the genetic causes. Co-segregation analysis of the detected candidate variants were performed in their families. The pathogenicity of identified novel variants was predicted by in silico analysis.

Results

NGS revealed compound heterozygous variants of PLA2G6 gene in all five patients. There were six PLA2G6 variants identified, including two known variants (c.116G>A, c.238G>A) and four novel variants (c.2120dupA, c.2071C>G, c.967G>A, c1534T>A). ACMG predicts c.2120dupA to be pathogenic, c.2071C>G and c.1534T>A to be likely pathogenic, and c1534T>A to be of uncertain significance. Clinically, four patients fell into the diagnosis of ANAD, and 1 into the diagnosis of AREP. Brain imaging revealed cerebellar atrophy, iron deposition in bilateral globus pallidus, and substantia nigra in three cases.

Conclusions

Four novel pathogenic variants were discovered and the pathogenic variant spectrum of the PLA2G6 gene was expanded.
Association Between Previous Stroke and Severe COVID-19: A Retrospective Cohort Study and an Overall Review of Meta-Analysis
Authors: Huang Huayao , Chen Junnian , Fang Shuangfang , Chen Xiaoling , Pan Xiaobin , Lei Hanhan , Zhang Yixian , Lin Hailong , Yuan Qilin , Xia Pincang , Liu Nan , Du Houwei
Published: July 2022

Objective

The objective of this study was to investigate the association between previous stroke and the risk of severe coronavirus disease 2019 (COVID-19).

Methods

We included 164 (61.8 ± 13.6 years) patients with COVID-19 in a retrospective study. We evaluated the unadjusted and adjusted associations between previous stroke and severe COVID-19, using a Cox regression model. We conducted an overall review of systematic review and meta-analysis to investigate the relationship of previous stroke with the unfavorable COVID-19 outcomes.

Results

The rate of severe COVID-19 in patients with previous stroke was 28.37 per 1,000 patient days (95% confidence interval [CI]: 10.65–75.59), compared to 3.94 per 1,000 patient days (95% CI: 2.66–5.82) in those without previous stroke (p < 0.001). Previous stroke was significantly associated with severe COVID-19 using a Cox regression model (unadjusted [hazard ratio, HR]: 6.98, 95% CI: 2.42–20.16, p < 0.001; adjusted HR [per additional 10 years]: 4.62, 95% CI: 1.52–14.04, p = 0.007). An overall review of systematic review and meta-analysis showed that previous stroke was significantly associated with severe COVID-19, mortality, need for intensive care unit admission, use of mechanical ventilation, and an unfavorable composite outcome.

Conclusion

Previous stroke seems to influence the course of COVID-19 infection; such patients are at high risk of severe COVID-19 and might benefit from early hospital treatment measures and preventive strategies.
Simulation Study of Canal Switching in BPPV
Authors: Wu Shuzhi , Li Jianxin , Zhou Mi , Yang Xiaokai
Published: July 2022

The objective of this research was to investigate the mechanism of canal switching in benign paroxysmal positional vertigo through a virtual simulation model. Using Unity 3D software and a built-in NVIDIA Physx physics engine, the virtual simulation software is developed using a browser-server architecture, and different models are imported. Based on the benign paroxysmal positional vertigo virtual simulation model, we constructed five different virtual reality scenes of diagnosis and treatment, set otoliths in different positions of the semicircular canals, and analyzed the effects of diagnostic and therapeutic procedures on otolith location. Through the analysis of otolith movement in five virtual scenes, we found that canal switching may be caused by otoliths in the utricle entering the semicircular canal in the supine position. Then, we used different methods to reposition the otolith, improved the repositioning maneuver, and explored in depth the mechanism of the canal switching. The results showed that the main reason for the canal switch is that in the supine position, the otolith in the utricle enters the semicircular canal. The repositioning maneuvers, including the Epley maneuver and Barbecue maneuver, will not directly lead to the canal switch in the ipsilateral inner ear. The supine roll maneuver leads to the otolith in the utricle entering the posterior or lateral semicircular canal, which is the most likely mechanism for canal switching.
Characterization of Early Stage Parkinson's Disease From Resting-State fMRI Data Using a Long Short-Term Memory Network
Authors: Guo Xueqi , Tinaz Sule , Dvornek Nicha C.
Published: July 2022

Parkinson's disease (PD) is a common and complex neurodegenerative disorder with five stages on the Hoehn and Yahr scaling. Characterizing brain function alterations with progression of early stage disease would support accurate disease staging, development of new therapies, and objective monitoring of disease progression or treatment response. Functional magnetic resonance imaging (fMRI) is a promising tool in revealing functional connectivity (FC) differences and developing biomarkers in PD. While fMRI and FC data have been utilized for diagnosis of PD through application of machine learning approaches such as support vector machine and logistic regression, the characterization of FC changes in early-stage PD has not been investigated. Given the complexity and non-linearity of fMRI data, we propose the use of a long short-term memory (LSTM) network to distinguish the early stages of PD and understand related functional brain changes. The study included 84 subjects (56 in stage 2 and 28 in stage 1) from the Parkinson's Progression Markers Initiative (PPMI), the largest-available public PD dataset. Under a repeated 10-fold stratified cross-validation, the LSTM model reached an accuracy of 71.63%, 13.52% higher than the best traditional machine learning method and 11.56% higher than a CNN model, indicating significantly better robustness and accuracy compared with other machine learning classifiers. Finally, we used the learned LSTM model weights to select the top brain regions that contributed to model prediction and performed FC analyses to characterize functional changes with disease stage and motor impairment to gain better insight into the brain mechanisms of PD.
A Spiking Neural Network Builder for Systematic Data-to-Model Workflow
Authors: Gutierrez Carlos Enrique , Skibbe Henrik , Musset Hugo , Doya Kenji
Published: July 2022

In building biological neural network models, it is crucial to efficiently convert diverse anatomical and physiological data into parameters of neurons and synapses and to systematically estimate unknown parameters in reference to experimental observations. Web-based tools for systematic model building can improve the transparency and reproducibility of computational models and can facilitate collaborative model building, validation, and evolution. Here, we present a framework to support collaborative data-driven development of spiking neural network (SNN) models based on the Entity-Relationship (ER) data description commonly used in large-scale business software development. We organize all data attributes, including species, brain regions, neuron types, projections, neuron models, and references as tables and relations within a database management system (DBMS) and provide GUI interfaces for data registration and visualization. This allows a robust “business-oriented” data representation that supports collaborative model building and traceability of source information for every detail of a model. We tested this data-to-model framework in cortical and striatal network models by successfully combining data from papers with existing neuron and synapse models and by generating NEST simulation codes for various network sizes. Our framework also helps to check data integrity and consistency and data comparisons across species. The framework enables the modeling of any region of the brain and is being deployed to support the integration of anatomical and physiological datasets from the brain/MINDS project for systematic SNN modeling of the marmoset brain.
Decoding the Heterogeneity of Malignant Gliomas by PET and MRI for Spatial Habitat Analysis of Hypoxia, Perfusion, and Diffusion Imaging: A Preliminary Study
Authors: Bailo Michele , Pecco Nicolò , Callea Marcella , Scifo Paola , Gagliardi Filippo , Presotto Luca , Bettinardi Valentino , Fallanca Federico , Mapelli Paola , Gianolli Luigi , Doglioni Claudio , Anzalone Nicoletta , Picchio Maria , Mortini Pietro , Falini Andrea , Castellano Antonella
Published: July 2022

Background

Tumor heterogeneity poses major clinical challenges in high-grade gliomas (HGGs). Quantitative radiomic analysis with spatial tumor habitat clustering represents an innovative, non-invasive approach to represent and quantify tumor microenvironment heterogeneity. To date, habitat imaging has been applied mainly on conventional magnetic resonance imaging (MRI), although virtually extendible to any imaging modality, including advanced MRI techniques such as perfusion and diffusion MRI as well as positron emission tomography (PET) imaging.

Objectives

This study aims to evaluate an innovative PET and MRI approach for assessing hypoxia, perfusion, and tissue diffusion in HGGs and derive a combined map for clustering of intra-tumor heterogeneity.

Materials and Methods

Seventeen patients harboring HGGs underwent a pre-operative acquisition of MR perfusion (PWI), Diffusion (dMRI) and 18F-labeled fluoroazomycinarabinoside (18F-FAZA) PET imaging to evaluate tumor vascularization, cellularity, and hypoxia, respectively. Tumor volumes were segmented on fluid-attenuated inversion recovery (FLAIR) and T1 post-contrast images, and voxel-wise clustering of each quantitative imaging map identified eight combined PET and physiologic MRI habitats. Habitats’ spatial distribution, quantitative features and histopathological characteristics were analyzed.

Results

A highly reproducible distribution pattern of the clusters was observed among different cases, particularly with respect to morphological landmarks as the necrotic core, contrast-enhancing vital tumor, and peritumoral infiltration and edema, providing valuable supplementary information to conventional imaging. A preliminary analysis, performed on stereotactic bioptic samples where exact intracranial coordinates were available, identified a reliable correlation between the expected microenvironment of the different spatial habitats and the actual histopathological features. A trend toward a higher representation of the most aggressive clusters in WHO (World Health Organization) grade IV compared to WHO III was observed.

Conclusion

Preliminary findings demonstrated high reproducibility of the PET and MRI hypoxia, perfusion, and tissue diffusion spatial habitat maps and correlation with disease-specific histopathological features.
The Spectrum of Vestibular Disorders Presenting With Acute Continuous Vertigo
Authors: Yao Qingxiu , Li Zhuangzhuang , Xu Maoxiang , Jiang Yumeng , Wang Jingjing , Wang Hui , Yu Dongzhen , Yin Shankai
Published: July 2022

Objective

To explore the composition of vestibular disorders presenting with the acute vestibular syndrome (AVS).

Methods

We performed a case analysis of 209 AVS patients between January 2016 and December 2020. These patients were grouped into different disorder categories according to the relevant diagnostic criteria.

Results

We classified the 209 patients into 14 disorder categories, including 110 cases of vestibular neuritis, 30 of idiopathic sudden sensorineural hearing loss with vertigo, 17 of the first attack of continuous vertigo with migraine, 15 of Ramsay Hunt syndrome, 11 of acute labyrinthitis secondary to chronic otitis media, 8 of vestibular schwannoma, 6 of posterior circulation infarction and/or ischemia, 3 of cerebellar abscess secondary to chronic otitis media, 3 of AVS caused by trauma or surgery, 2 of AVS with down-beating nystagmus, 1 of multiple sclerosis of the medulla oblongata, 1 of epidermoid cyst of the posterior cranial fossa, 1 of a probable acute otolithic lesion, and 1 of AVS without measurable vestibular dysfunction.

Conclusion

When a group of disorders present with AVS, characteristic clinical manifestations and imaging help with an accurate diagnosis.
Effects of Aroclor 1254 on Intestinal Immunity, Metabolism, and Microflora in Zebrafish
Authors: Zhu Di-Hua , Nie Fang-Hong , Zhang Min , Wei Wan , Song Qing-Lang , Hu Yao , Kang Dan-Ju , Chen Zhi-Bao , Lin Hong-Ying , Chen Jin-Jun
Published: July 2022

Polychlorinated biphenyls (PCBs) are widely distributed environmental toxicants, whose biological toxicity is magnified step by step through the transmission of the food chain. However, there is little research about the effect of PCBs on intestinal epithelial barrier function. In this experiment, the effects of PCB exposure on the intestines of zebrafish were evaluated. Animals were exposed to Aroclor 1254 (5 μg/L, 10 μg/L, 15 μg/L). After 21 days, the changes in histology, enzyme biomarkers, intestinal microorganisms, and metabolomics were detected. The inflammation and oxidative stress in the intestines of zebrafish were observed. Additionally, there were significant changes in intestinal microbiota and tissue metabolism, most of which were associated with oxidative stress, inflammation, and lipid metabolism. The results showed that PCBs exposure resulted in intestinal inflammation and oxidative stress in zebrafish.Moreover, intestinal metabolites and intestinal microflora of zebrafish were also disturbed. This study verified that exposure can lead to intestinal damage and changes in intestinal metabolic capacity and microorganisms, enlightening the consequences of PCB exposure.
An Integrated Analysis of Prognostic Signature and Immune Microenvironment in Tongue Squamous Cell Carcinoma
Authors: Jin Yi , Wang Zhanwang , Tang Weizhi , Liao Muxing , Wu Xiangwei , Wang Hui
Published: July 2022

Tongue squamous cell carcinoma (TSCC) is a prevalent cancer of the oral cavity. Survival metrics are usually unsatisfactory, even using combined treatment with surgery, radiation, and chemotherapy. Immune checkpoint inhibitors can prolong survival, especially in patients with recurrent or metastatic disease. However, there are few effective biomarkers to provide prognosis and guide immunotherapy. Here, we utilized weighted gene co-expression network analysis to identify the co-expression module and selected the turquoise module for further scrutiny. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses revealed the innate pathways. The findings indicated that cell junction organization, response to topologically incorrect protein, and regulation of cell adhesion pathways may be essential. Eleven crucial predictive genes (PLXNB1, N4BP3, KDELR2, INTS8, PLAU, PPFIBP2, OAF, LMF1, IL34, ZFP3, and MAP7D3) were used to establish a risk model based on Cox and LASSO analyses of The Cancer Genome Atlas and GSE65858 databases (regarding overall survival). Kaplan–Meier analysis and receiver operating characteristic curve suggested that the risk model had better prognostic effectiveness than other clinical traits. Consensus clustering was used to classify TSCC samples into two groups with significantly different survival rates. ESTIMATE and CIBERSORT were used to display the immune landscape of TSCC and indicate the stromal score; specific types of immune cells, including naïve B cells, plasma cells, CD8 T cells, CD4 memory resting and memory activated T cells, follicular helper T cells, and T regulatory cells, may influence the heterogeneous immune microenvironment in TSCC. To further identify hub genes, we downloaded GEO datasets (GSE41613 and GSE31056) and successfully validated the risk model. Two hub genes (PLAU and PPFIBP2) were strongly associated with CD4+ and CD8+ T cells and programmed cell death protein 1 (PD1) and PD-ligand 1.
Skin Cancer Classification With Deep Learning: A Systematic Review
Authors: Wu Yinhao , Chen Bin , Zeng An , Pan Dan , Wang Ruixuan , Zhao Shen
Published: July 2022

Skin cancer is one of the most dangerous diseases in the world. Correctly classifying skin lesions at an early stage could aid clinical decision-making by providing an accurate disease diagnosis, potentially increasing the chances of cure before cancer spreads. However, achieving automatic skin cancer classification is difficult because the majority of skin disease images used for training are imbalanced and in short supply; meanwhile, the model’s cross-domain adaptability and robustness are also critical challenges. Recently, many deep learning-based methods have been widely used in skin cancer classification to solve the above issues and achieve satisfactory results. Nonetheless, reviews that include the abovementioned frontier problems in skin cancer classification are still scarce. Therefore, in this article, we provide a comprehensive overview of the latest deep learning-based algorithms for skin cancer classification. We begin with an overview of three types of dermatological images, followed by a list of publicly available datasets relating to skin cancers. After that, we review the successful applications of typical convolutional neural networks for skin cancer classification. As a highlight of this paper, we next summarize several frontier problems, including data imbalance, data limitation, domain adaptation, model robustness, and model efficiency, followed by corresponding solutions in the skin cancer classification task. Finally, by summarizing different deep learning-based methods to solve the frontier challenges in skin cancer classification, we can conclude that the general development direction of these approaches is structured, lightweight, and multimodal. Besides, for readers’ convenience, we have summarized our findings in figures and tables. Considering the growing popularity of deep learning, there are still many issues to overcome as well as chances to pursue in the future.
Highly Invasive Fluorescent/Bioluminescent Patient-Derived Orthotopic Model of Glioblastoma in Mice
Authors: Yuzhakova Diana , Kiseleva Elena , Shirmanova Marina , Shcheslavskiy Vladislav , Sachkova Daria , Snopova Ludmila , Bederina Evgeniya , Lukina Maria , Dudenkova Varvara , Yusubalieva Gaukhar , Belovezhets Tatyana , Matvienko Daria , Baklaushev Vladimir
Published: July 2022

Development of the novel diagnostic and therapeutic approaches in neuro-oncology requires tumor models that closely reproduce the biological features of patients’ tumors. Patient-derived xenografts (PDXs) are recognized as a valuable and the most “close-to-patient” tool for preclinical studies. However, their establishment is complicated by the factors related to both the surgical material and technique of the orthotopic implantation. The aim of this work was to develop a patient-derived glioblastoma multiform (GBM) model that stably co-expresses luciferase and a far-red fluorescent protein for monitoring of tumor progression in the brain and, using this model, to validate new diagnostic methods—macroscopic fluorescence lifetime imaging (macro-FLIM) and cross-polarization optical coherence tomography (CP OCT). The established model was similar to the original patient’s GBM in terms of histological and immunohistochemical features and possessed reproducible growth in nude mice, which could be observed by both fluorescence and bioluminescence imaging. Our results demonstrated the high potential of macro-FLIM and CP OCT for intraoperative differentiation of GBM from the white matter. Thus, the dual-labeled PDX model of GBM proved to be an excellent approach for observation of tumor development by optical methods.
Gemcitabine Plus Anlotinib Is Effective and Safe Compared to Gemcitabine Plus Docetaxel in Advanced Soft Tissue Sarcoma
Authors: Liu Zhiyong , Wang Xin , Wang Jiaqiang , Zhang Peng , Li Chao , Wang Bangmin , Liu Guancong , Yao Weitao
Published: July 2022

Objective

The aim of this study is to compare gemcitabine (G) plus docetaxel (D) versus G plus anlotinib (A) for advanced soft tissue sarcoma (STS).

Methods

We retrospectively investigated 122 patients with locally advanced or metastatic STS who were treated with either G+D or G+A between July 2016 and October 2021 and compared the efficacy and toxicity of G+D and G+A. The primary endpoints were median progression-free survival (PFS) and the proportion of patients with grade ≥3 adverse events. We also analyzed differences in the clinical efficacy of G+D and G+A in leiomyosarcoma, and the differences in the clinical efficacy of G+D and G+A as first-line therapy.

Results

Overall, 122 patients were included (81 patients receiving G+D and 41 patients receiving G+A) with a median age of 55 years. The main histological types are leiomyosarcoma, undifferentiated pleomorphic sarcoma, and liposarcoma. After a median follow-up of 25 months, PFS did not differ between patients treated with G+D and those treated with G+A (median PFS: 5.8 months and 6.8 months, p = 0.39), and overall survival (OS) was similar (median OS: 14.7 vs. 13.3 months, p = 0.75) with a similar objective response rate (18.5% vs. 14.6%, p = 0.17), whereas the proportion of patients with grade ≥3 adverse events treated with G+D was significantly higher than those treated with G+A (68% vs. 44%, p < 0.05). Subgroup analysis of leiomyosarcoma patients (47.5% of the patients) and first-line treatment patients (46.7% of the patients) shows that PFS was not significantly different between the two groups (LMS: median PFS: 6.5 months vs. 7.5 months, p = 0.08; first-line treatment: median PFS: 6.2 months vs. 7.1 months, p = 0.51).

Conclusion

Compared with gemcitabine plus docetaxel for advanced STS, gemcitabine plus anlotinib achieved a similar response rate on median PFS and OS, but lower toxicity. These results suggest that gemcitabine plus anlotinib may be an effective and safe strategy for advanced STS.
Recent Advances on the Role of ATGL in Cancer
Authors: Zhang Renshuai , Meng Jingsen , Yang Shanbo , Liu Wenjing , Shi Lingyu , Zeng Jun , Chang Jing , Liang Bing , Liu Ning , Xing Dongming
Published: July 2022

The hypoxic state of the tumor microenvironment leads to reprogramming lipid metabolism in tumor cells. Adipose triglyceride lipase, also known as patatin-like phospholipase= domain-containing protein 2 and Adipose triglyceride lipase (ATGL), as an essential lipid metabolism-regulating enzyme in cells, is regulated accordingly under hypoxia induction. However, studies revealed that ATGL exhibits both tumor-promoting and tumor-suppressing effects, which depend on the cancer cell type and the site of tumorigenesis. For example, elevated ATGL expression in breast cancer is accompanied by enhanced fatty acid oxidation (FAO), enhancing cancer cells’ metastatic ability. In prostate cancer, on the other hand, tumor activity tends to be negatively correlated with ATGL expression. This review outlined the regulation of ATGL-mediated lipid metabolism pathways in tumor cells, emphasizing the Hypoxia-inducible factors 1 (HIF-1)/Hypoxia-inducible lipid droplet-associated (HIG-2)/ATGL axis, peroxisome proliferator-activated receptor (PPAR)/G0/G1 switch gene 2 (G0S2)/ATGL axis, and fat-specific protein 27 (FSP-27)/Early growth response protein 1 (EGR-1)/ATGL axis. In the light of recent research on different cancer types, the role of ATGL on tumorigenesis, tumor proliferation, and tumor metastasis was systemically reviewed.
Genomics Analysis and Nomogram Risk Prediction of Occult Lymph Node Metastasis in Non-Predominant Micropapillary Component of Lung Adenocarcinoma Measuring ≤ 3 cm
Authors: Wang Kun , Xue Mengchao , Qiu Jianhao , Liu Ling , Wang Yueyao , Li Rongyang , Qu Chenghao , Yue Weiming , Tian Hui
Published: July 2022

Background

The efficacy of sublobar resection and selective lymph node dissection is gradually being accepted by thoracic surgeons for patients within early-stage non-small cell lung cancer (NSCLC). Nevertheless, there are still some NSCLC patients develop lymphatic metastasis at clinical T1 stage. Lung adenocarcinoma with a micropapillary (MP) component poses a higher risk of lymph node metastasis and recurrence even when the MP component is not predominant. Our study aimed to explore the genetic features and occult lymph node metastasis (OLNM) risk factors in patients with a non-predominant micropapillary component (NP-MPC) in a large of patient’s cohort with surgically resected lung adenocarcinoma.

Methods

Between January 2019 and December 2021, 6418 patients who underwent complete resection for primary lung adenocarcinoma at the Qilu Hospital of Shandong University. In our study, 442 patients diagnosed with lung adenocarcinoma with NP-MPC with a tumor size ≤3 cm were included. Genetic alterations were analyzed using amplification refractory mutation system-polymerase chain reaction (ARMS-PCR). Abnormal protein expression of gene mutations was validated using immunohistochemistry. A nomogram risk model based on clinicopathological parameters was developed to predict OLNM. This model was invalidated using the calibration plot and concordance index.

Results

In our retrospective cohort, the incidence rate of the micropapillary component was 11.17%, and OLNM was observed in 20.13% of the patients in our study. ARMS-PCR suggested that EGFR exon 19 del was the most frequent alteration in NP-MCP patients compared with other gene mutations (frequency: 21.2%, P<0.001). Patients harboring exon 19 del showed significantly higher risk of OLNM (P< 0.001). A nomogram was developed based on five risk parameters, which showed good calibration and reliable discrimination ability (C-index = 0.84) for evaluating OLNM risk.

Conclusions.

Intense expression of EGFR exon 19 del characterizes lung adenocarcinoma in patients with NP-MCP and it’s a potential risk factor for OLNM. We firstly established a nomogram based on age, CYFRA21-1 level, tumor size, micropapillary and solid composition, that was effective in predicting OLNM among NP-MCP of lung adenocarcinoma measuring ≤ 3 cm.