bluuebunny/crossref_metadata_2025 huggingface dataset:
Clinical Characteristics of Patients and Whole Genome Sequencing-Based Surveillance of Escherichia coli Community-Onset Bloodstream Infections at a Non-tertiary Hospital in CHINA
Authors: Chen Fenghong , Lv Tao , Xiao Yupeng , Chen Aizhi , Xiao Yonghong , Chen Yunbo
Published: October 2021

Background:Escherichia coli is the most common pathogens in patients with community-onset blood stream infections (COBSI). Knowledge of the epidemiology of this disease is crucial to improve allocation of health resources, formulate isolation strategies that prevent transmission, and guide empirical antibiotic therapy.

Methods: This retrospective observational study examined patients with E. coli COBSI (EC-COBSI) at a non-tertiary hospital in China. Whole-genome sequencing and analysis of the isolates was performed. The relationships of clinical variables with antimicrobial resistance and the genetic background of the isolates were examined.

Results: There were 148 isolates in patients with EC-COBSI. All isolates were susceptible to ceftazidime/avibactam, carbapenems, and tigecycline; 35.1% were positive for extended spectrum β-lactamase (ESBL+); and blaCTX–M–14 was the most common ESBL gene. Patients with ESBL- isolates were more likely to receive appropriate empiric treatment than those with ESBL+ isolates (61.5% vs. 91.4%, p < 0.001), but these two groups had similar mortality rates. The overall 30-day mortality rate was 9.5%. Phylogenetic analysis showed that the isolates were diverse, and that the main sequence types (STs) were ST95, ST131, and ST69. Intra-abdominal infection was the primary source of disease, and isolates from these patients had lower frequencies of virulence genes.

Conclusion: The mortality rate of patients with EC-COBSI was unrelated to ESBL status of the isolates. Most isolates had low resistance to most of the tested antimicrobial agents. The isolates were diverse, and multiple strains were related. Prevention and control of EC-COBSI should target prevention of patient colonization and the living environment.
Biological Significance of the Genomic Variation and Structural Dynamics of SARS-CoV-2 B.1.617
Authors: Fan Lin-qian , Hu Xiao-yun , Chen Yi-yue , Peng Xiang-lei , Fu Yuan-hui , Zheng Yan-peng , Yu Jie-mei , He Jin-sheng
Published: October 2021

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants have been emerging and circulating globally since the start of the COVID-19 pandemic, of which B.1.617 lineage that was first reported in India at the end of 2020, soon became predominant. Tracing genomic variations and understanding their impact on the viral properties are the foundations for the vaccine and drug development and for the mitigation measures to be taken or lifted. In this study, 1,051 near-complete genomes and 1,559 spike (S) sequences belonging to the B.1.617 were analyzed. A genome-wide spread of single nucleotide polymorphisms (SNPs) was identified. Of the high frequency mutations identified, 61% (11/18) involved structural proteins, despite two third of the viral genome encoding nonstructural proteins. There were 22 positive selection sites, mostly distributed across the S protein, of which 16 were led by non-C to U transition and should be of a special attention. Haplotype network revealed that a large number of daughter haplotypes were continually derived throughout the pandemic, of which H177, H181 H219 and H286 from the ancestor haplotype H176 of B.1.617.2 were widely prevalent. Besides the well known substitutions of L452R, P681R and deletions of E156 and F157, as well as the potential biological significance, structural analysis in this study still indicated that new amino acid changes in B.1.617, such as E484Q and N501Y, had reshaped the viral bonding network, and increasingly sequenced N501Y mutant with a potential enhanced binding ability was detected in many other countries in the follow-up monitoring. Although we can’t conclude the properties of all the mutants including N501Y thoroughly, it merits focusing on their spread epidemically and biologically.
Discovery and Evolution of a Divergent Coronavirus in the Plateau Pika From China That Extends the Host Range of Alphacoronaviruses
Authors: Zhu Wentao , Yang Jing , Lu Shan , Jin Dong , Wu Shusheng , Pu Ji , Luo Xue-lian , Liu Liyun , Li Zhenjun , Xu Jianguo
Published: October 2021

Although plateau pikas are the keystone species in the plateau ecosystem of the Qinghai Province of China, little is known about their role in the evolution and transmission of viral pathogens, especially coronaviruses. Here, we describe the characterization and evolution of a novel alphacoronavirus, termed plateau pika coronavirus (PPCoV) P83, which has a prevalence of 4.5% in plateau pika fecal samples. In addition to classical gene order, the complete viral genome contains a unique nonstructural protein (NS2), several variable transcription regulatory sequences and a highly divergent spike protein. Phylogenetic analysis indicates that the newly discovered PPCoV falls into the genus Alphacoronavirus and is most closely related to rodent alphacoronaviruses. The co-speciation analysis shows that the phylogenetic trees of the alphacoronaviruses and their hosts are not always matched, suggesting inter-species transmission is common in alphacoronaviruses. And, PPCoV origin was estimated by molecular clock based on membrane and RNA-dependent RNA polymerase encoding genes, respectively, which revealed an apparent discrepancy with that of co-speciation analysis. PPCoV was detected mainly in intestinal samples, indicating a potential enteric tropism for the virus. Overall, this study extends the host range of alphacoronaviruses to a new order (Lagomorpha), indicating that plateau pikas may be the natural reservoir of PPCoV and play an important and long-term role in alphacoronavirus evolution.
Intein Inhibitors as Novel Antimicrobials: Protein Splicing in Human Pathogens, Screening Methods, and Off-Target Considerations
Authors: Wall Diana A. , Tarrant Seanan P. , Wang Chunyu , Mills Kenneth V. , Lennon Christopher W.
Published: October 2021

Protein splicing is a post-translational process by which an intervening polypeptide, or intein, catalyzes its own removal from the flanking polypeptides, or exteins, concomitant with extein ligation. Although inteins are highly abundant in the microbial world, including within several human pathogens, they are absent in the genomes of metazoans. As protein splicing is required to permit function of essential proteins within pathogens, inteins represent attractive antimicrobial targets. Here we review key proteins interrupted by inteins in pathogenic mycobacteria and fungi, exciting discoveries that provide proof of concept that intein activity can be inhibited and that this inhibition has an effect on the host organism’s fitness, and bioanalytical methods that have been used to screen for intein activity. We also consider potential off-target inhibition of hedgehog signaling, given the similarity in structure and function of inteins and hedgehog autoprocessing domains.
EEG Alpha and Beta Band Functional Connectivity and Network Structure Mark Hub Overload in Mild Cognitive Impairment During Memory Maintenance
Authors: Fodor Zsuzsanna , Horváth András , Hidasi Zoltán , Gouw Alida A. , Stam Cornelis J. , Csukly Gábor
Published: October 2021

Background: While decreased alpha and beta-band functional connectivity (FC) and changes in network topology have been reported in Alzheimer’s disease, it is not yet entirely known whether these differences can mark cognitive decline in the early stages of the disease. Our study aimed to analyze electroencephalography (EEG) FC and network differences in the alpha and beta frequency band during visuospatial memory maintenance between Mild Cognitive Impairment (MCI) patients and healthy elderly with subjective memory complaints.

Methods: Functional connectivity and network structure of 17 MCI patients and 20 control participants were studied with 128-channel EEG during a visuospatial memory task with varying memory load. FC between EEG channels was measured by amplitude envelope correlation with leakage correction (AEC-c), while network analysis was performed by applying the Minimum Spanning Tree (MST) approach, which reconstructs the critical backbone of the original network.

Results: Memory load (increasing number of to-be-learned items) enhanced the mean AEC-c in the control group in both frequency bands. In contrast to that, after an initial increase, the MCI group showed significantly (p < 0.05) diminished FC in the alpha band in the highest memory load condition, while in the beta band this modulation was absent. Moreover, mean alpha and beta AEC-c correlated significantly with the size of medial temporal lobe structures in the entire sample. The network analysis revealed increased maximum degree, betweenness centrality, and degree divergence, and decreased diameter and eccentricity in the MCI group compared to the control group in both frequency bands independently of the memory load. This suggests a rerouted network in the MCI group with a more centralized topology and a more unequal traffic load distribution.

Conclusion: Alpha- and beta-band FC measured by AEC-c correlates with cognitive load-related modulation, with subtle medial temporal lobe atrophy, and with the disruption of hippocampal fiber integrity in the earliest stages of cognitive decline. The more integrated network topology of the MCI group is in line with the “hub overload and failure” framework and might be part of a compensatory mechanism or a consequence of neural disinhibition.
White-Matter Hyperintensity Load and Differences in Resting-State Network Connectivity Based on Mild Cognitive Impairment Subtype
Authors: Vettore Martina , De Marco Matteo , Pallucca Claudia , Bendini Matteo , Gallucci Maurizio , Venneri Annalena
Published: October 2021

“Mild cognitive impairment” (MCI) is a diagnosis characterised by deficits in episodic memory (aMCI) or in other non-memory domains (naMCI). Although the definition of subtypes is helpful in clinical classification, it provides little insight on the variability of neurofunctional mechanisms (i.e., resting-state brain networks) at the basis of symptoms. In particular, it is unknown whether the presence of a high load of white-matter hyperintensities (WMHs) has a comparable effect on these functional networks in aMCI and naMCI patients. This question was addressed in a cohort of 123 MCI patients who had completed an MRI protocol inclusive of T1-weighted, fluid-attenuated inversion recovery (FLAIR) and resting-state fMRI sequences. T1-weighted and FLAIR images were processed with the Lesion Segmentation Toolbox to quantify whole-brain WMH volumes. The CONN toolbox was used to preprocess all fMRI images and to run an independent component analysis for the identification of four large-scale haemodynamic networks of cognitive relevance (i.e., default-mode, salience, left frontoparietal, and right frontoparietal networks) and one control network (i.e., visual network). Patients were classified based on MCI subtype (i.e., aMCI vs. naMCI) and WMH burden (i.e., low vs. high). Maps of large-scale networks were then modelled as a function of the MCI subtype-by-WMH burden interaction. Beyond the main effects of MCI subtype and WMH burden, a significant interaction was found in the salience and left frontoparietal networks. Having a low WMH burden was significantly more associated with stronger salience-network connectivity in aMCI (than in naMCI) in the right insula, and with stronger left frontoparietal-network connectivity in the right frontoinsular cortex. Vice versa, having a low WMH burden was significantly more associated with left-frontoparietal network connectivity in naMCI (than in aMCI) in the left mediotemporal lobe. The association between WMH burden and strength of connectivity of resting-state functional networks differs between aMCI and naMCI patients. Although exploratory in nature, these findings indicate that clinical profiles reflect mechanistic interactions that may play a central role in the definition of diagnostic and prognostic statuses.
Effect of Pre-exposure Use of Amantadine on COVID-19 Infection: A Hospital-Based Cohort Study in Patients With Parkinson's Disease or Multiple Sclerosis
Authors: Kamel Walaa A. , Kamel Mohmed I. , Alhasawi Almunther , Elmasry Sameh , AlHamdan Fajer , Al-Hashel Jasem Y.
Published: October 2021

Background: Amantadine has been proposed to inhibit E-channel conductance in reconstituted lipid bilayers of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We aimed to study whether patients on amantadine have altered risks of contracting COVID-19 infection.

Methods: We conducted a hospital-based, observational, retrospective cohort study using data for patients on amantadine supported by data given by the patients through an online questionnaire. We included registered amantadine users in our hospital for 6 months or more on March 1, 2020, and non-amantadine users to act as the control group. We used forced entry, multiple logistic regression models to estimate adjusted ORs for amantadine adjusting for the confounders.

Findings: Between September 1, 2019, and March 1, 2020, 212 patients with Parkinson's disease (PD) or multiple sclerosis (MS) received greater than one equal to two prescriptions of amantadine. We selected a random sample of diagnoses which matched 424 patients of non-amantadine users (1:2) as a control group (424 patients). Between March 1, 2020, and March 1, 2021, 256 patients responded to our online questionnaire, 87 patients were on amantadine (group I), and 169 patients were not (control group, group II). COVID-19 disease infection proved to be 5.7 and 11.8% in group I and II patients, respectively. Increased odds of COVID-19 in multivariable-adjusted models were associated with old age and history of contact with COVID cases. Amantadine was associated with a significantly reduced risk of COVID-19 disease infection (adjusted OR 0.256, 95% CI 0.074–0.888).

Interpretation: Amantadine is associated with a reduced risk of COVID-19 infection after adjusting for a broad range of variables. History of contact with COVID cases and old age are risk factors for COVID-19 infection. Therefore, we recommended randomized clinical trials investigating amantadine use for the prevention of COVID-19.
Expression of p16 Within Myenteric Neurons of the Aged Colon: A Potential Marker of Declining Function
Authors: Palmer Alexandra , Epton Sarah , Crawley Ellie , Straface Marilisa , Gammon Luke , Edgar Meghan M. , Xu Yichen , Elahi Shezan , Chin-Aleong Joanne , Martin Joanne E. , Bishop Cleo L. , Knowles Charles H. , Sanger Gareth J.
Published: October 2021

Human colonic neuromuscular functions decline among the elderly. The aim was to explore the involvement of senescence. A preliminary PCR study looked for age-dependent differences in expression of CDKN1A (encoding the senescence-related p21 protein) and CDKN2A (encoding p16 and p14) in human ascending and descending colon (without mucosa) from 39 (approximately 50: 50 male: female) adult (aged 27–60 years) and elderly donors (70–89 years). Other genes from different aging pathways (e.g., inflammation, oxidative stress, autophagy) and cell-types (e.g., neurons, neuron axonal transport) were also examined. Unlike CDKN1A, CDKN2A (using primers for p16 and p14 but not when using p14-specific primers) was upregulated in both regions of colon. Compared with the number of genes appearing to upregulate in association with temporal age, more genes positively associated with increased CDKN2A expression (respectively, 16 and five of 44 genes studied for ascending and descending colon). Confirmation of increased expression of CDKN2A was sought by immunostaining for p16 in the myenteric plexus of colon from 52 patients, using a semi-automated software protocol. The results showed increased staining not within the glial cells (S100 stained), but in the cytoplasm of myenteric nerve cell bodies (MAP2 stained, with identified nucleus) of ascending, but not descending colon of the elderly, and not in the cell nucleus of either region or age group (5,710 neurons analyzed: n = 12–14 for each group). It was concluded that increased p16 staining within the cytoplasm of myenteric nerve cell bodies of elderly ascending (but not descending) colon, suggests a region-dependent, post-mitotic cellular senescence-like activity, perhaps involved with aging of enteric neurons within the colon.
HPV16 E6 Promotes the Progression of HPV Infection-Associated Cervical Cancer by Upregulating Glucose-6-Phosphate Dehydrogenase Expression
Authors: Chang Ye-Fei , Yan Guo-Ji , Liu Guang-Cai , Hong Ying , Chen Hong-Lan , Jiang Shui , Zhong Yong , Xiyang Yan-Bin , Hu Tao
Published: October 2021

Cervical cancer, which is significantly associated with high-risk human papillomavirus (HPV) infection, currently ranks the fourth most common cancer among women worldwide. Previous literature reported that the elevated expression of G6PD was significantly correlated with the occurrence and deterioration of human cervical cancer, especially with the cervical cancer with HPV16 and HPV18 infection. In this study, we verified that G6PD expression has a strong positive correlation with HPV16 E6 levels in cervical cancer tissues and cells. In addition, regulating the expression of HPV16 E6 significantly affected the proliferation, apoptosis, migration, and invasion in the cervical cancer HeLa cells, as well as the transcript and protein levels of G6PD. The luciferase reporter assay and ChIP assay proved that HPV16 E6 stimulated the transcription of G6PD mRNA and subsequently enhanced the expression of G6PD through directly binding to the specific sites in the promoter of G6PD. Our findings reveal that HPV16 E6 is a novel regulatory factor of G6PD. Furthermore, by regulating the expression of G6PD, HPV16 E6 might promote the proliferation and migration potential, and inhibit apoptosis of cervical cancer cells, which ultimately contributed to the progression and metastasis of cervical cancer.
Robust Glycogene-Based Prognostic Signature for Proficient Mismatch Repair Colorectal Adenocarcinoma
Authors: Li Yixi , Li Dehua , Chen Yang , Lu Yongping , Zhou Fangbin , Li Chunhong , Zeng Zhipeng , Cai Wanxia , Lin Liewen , Li Qiang , Ye Mingjun , Dong Jingjing , Yin Lianghong , Tang Donge , Zhang Gong , Dai Yong
Published: October 2021

Background

Proficient mismatch repair (pMMR) colorectal adenocarcinoma (CRAC) metastasizes to a greater extent than MMR-deficient CRAC. Prognostic biomarkers are preferred in clinical practice. However, traditional biomarkers screened directly from sequencing are often not robust and thus cannot be confidently utilized.

Methods

To circumvent the drawbacks of blind screening, we established a new strategy to identify prognostic biomarkers in the conserved and specific oncogenic pathway and its regulatory RNA network. We performed RNA sequencing (RNA-seq) for messenger RNA (mRNA) and noncoding RNA in six pMMR CRAC patients and constructed a glycosylation-related RNA regulatory network. Biomarkers were selected based on the network and their correlation with the clinicopathologic information and were validated in multiple centers (n = 775).

Results

We constructed a competing endogenous RNA (ceRNA) regulatory network using RNA-seq. Genes associated with glycosylation pathways were embedded within this scale-free network. Moreover, we further developed and validated a seven-glycogene prognosis signature, GlycoSig (B3GNT6, GALNT3, GALNT8, ALG8, STT3B, SRD5A3, and ALG6) that prognosticate poor-prognostic subtype for pMMR CRAC patients. This biomarker set was validated in multicenter datasets, demonstrating its robustness and wide applicability. We constructed a simple-to-use nomogram that integrated the risk score of GlycoSig and clinicopathological features of pMMR CRAC patients.

Conclusions

The seven-glycogene signature served as a novel and robust prognostic biomarker set for pMMR CRAC, highlighting the role of a dysregulated glycosylation network in poor prognosis.
Comparison of: (2S,4R)-4-[18F]Fluoroglutamine, [11C]Methionine, and 2-Deoxy-2-[18F]Fluoro-D-Glucose and Two Small-Animal PET/CT Systems Imaging Rat Gliomas
Authors: Miner Maxwell W. G. , Liljenbäck Heidi , Virta Jenni , Helin Semi , Eskola Olli , Elo Petri , Teuho Jarmo , Seppälä Kerttu , Oikonen Vesa , Yang Guangli , Kindler-Röhrborn Andrea , Minn Heikki , Li Xiang-Guo , Roivainen Anne
Published: October 2021

Purpose

The three positron emission tomography (PET) imaging compounds: (2S,4R)-4-[18F]Fluoroglutamine ([18F]FGln), L-[methyl-11C]Methionine ([11C]Met), and 2-deoxy-2-[18F]fluoro-D-glucose ([18F]FDG) were investigated to contrast their ability to image orthotopic BT4C gliomas in BDIX rats. Two separate small animal imaging systems were compared for their tumor detection potential. Dynamic acquisition of [18F]FGln was evaluated with multiple pharmacokinetic models for future quantitative comparison.

Procedures

Up to four imaging studies were performed on each orthotopically grafted BT4C glioma-bearing BDIX rat subject (n = 16) on four consecutive days. First, a DOTAREM® contrast enhanced MRI followed by attenuation correction CT and dynamic PET imaging with each radiopharmaceutical (20 min [11C]Met, 60 min [18F]FDG, and 60 min [18F]FGln with either the Molecubes PET/CT (n = 5) or Inveon PET/CT cameras (n = 11). Ex vivo brain autoradiography was completed for each radiopharmaceutical and [18F]FGln pharmacokinetics were studied by injecting 40 MBq into healthy BDIX rats (n = 10) and collecting blood samples between 5 and 60 min. Erythrocyte uptake, plasma protein binding and plasma parent-fraction were combined to estimate the total blood bioavailability of [18F]FGln over time. The corrected PET-image blood data was then applied to multiple pharmacokinetic models.

Results

Average BT4C tumor-to-healthy brain tissue uptake ratios (TBR) for PET images reached maxima of: [18F]FGln TBR: 1.99 ± 0.19 (n = 13), [18F]FDG TBR: 1.41 ± 0.11 (n = 6), and [11C]Met TBR: 1.08 ± 0.08, (n = 12) for the dynamic PET images. Pharmacokinetic modeling in dynamic [18F]FGln studies suggested both reversible and irreversible uptake play a similar role. Imaging with Inveon and Molecubes yielded similar end-result ratios with insignificant differences (p > 0.25).

Conclusions

In orthotopic BT4C gliomas, [18F]FGln may offer improved imaging versus [11C]Met and [18F]FDG. No significant difference in normalized end-result data was found between the Inveon and Molecubes camera systems. Kinetic modelling of [18F]FGln uptake suggests that both reversible and irreversible uptake play an important role in BDIX rat pharmacokinetics.
A Novel Radiogenomics Biomarker Based on Hypoxic-Gene Subset: Accurate Survival and Prognostic Prediction of Renal Clear Cell Carcinoma
Authors: Gao Jiahao , Ye Fangdie , Han Fang , Wang Xiaoshuang , Jiang Haowen , Zhang Jiawen
Published: October 2021

Purpose

To construct a novel radiogenomics biomarker based on hypoxic-gene subset for the accurate prognostic prediction of clear cell renal cell carcinoma (ccRCC).

Materials and Methods

Initially, we screened for the desired hypoxic-gene subset by analysis using the GSEA database. Through univariate and multivariate cox regression hazard ratio analysis, survival-related hypoxia genes were identified, and a genomics signature was constructed in the TCGA database. Building on this, a hypoxia-gene related radiogenomics biomarker (prediction of hypoxia-genes signature by contrast-enhanced CT radiomics) was constructed in the TCIA-KIRC database by extracting features in the venous phase of contrast-enhanced CT images, selecting features using the mRMR and LASSO algorithms, and building logistic regression models. Finally, we validated the prognostic capability of the new biomarker for patients with ccRCC in an independent validation cohort at Huashan Hospital of Fudan University, Shanghai, China.

Results

The hypoxia-related genomics signature consisting of five genes (IFT57, PABPN1, RNF10, RNF19B and UBE2T) was shown to be significantly associated with survival for patients with ccRCC in the TCGA database, delineated by grouping of the signature expression as either low- or high-risk. In the TCIA database, we constructed a radiogenomics biomarker consisting of 13 radiomics features that were optimal predictors of hypoxia-gene signature expression levels (low- or high-risk) in patients at each institution, that demonstrated AUC values of 0.91 and 0.91 in the training and validation groups, respectively. In the independent validation cohort at Huashan Hospital, our radiogenomics biomarker was significantly associated with prognosis in patients with ccRCC (p=0.0059).

Conclusions

The novel prognostic radiogenomics biomarker that was constructed achieved excellent correlation with prognosis in both the cohort of TCGA/TCIA-KIRC database and the independent validation cohort of Huashan hospital patients with ccRCC. It is anticipated that this work may assist in clinical preferential treatment decisions and promote the process of precision theranostics in the future.
Accelerated Stack-of-Spirals Free-Breathing Three-Dimensional Ultrashort Echo Time Lung Magnetic Resonance Imaging: A Feasibility Study in Patients With Breast Cancer
Authors: Cha Min Jae , Ahn Hye Shin , Choi Hyewon , Park Hyun Jeong , Benkert Thomas , Pfeuffer Josef , Paek Mun Young
Published: October 2021

Purpose

To investigate the clinical feasibility of accelerated free-breathing stack-of-spirals (spiral) three-dimensional (3D) ultrashort echo time (UTE) lung magnetic resonance imaging (MRI) using iterative self‐consistent parallel imaging reconstruction from arbitrary k‐space (SPIRiT) algorithm in patients with breast cancer.

Methods

The institutional review board approved this prospective study and patients’ informed consents were obtained. Between June and August 2018, 29 female patients with breast cancer underwent 3-T MRI including accelerated free-breathing spiral 3D UTE (0.98-mm isotropic spatial resolution; echo time, 0.05 msec) of the lungs and thin-section chest computed tomography (CT). Two radiologists evaluated the image quality and pulmonary nodules on MRI were assessed and compared, CT as a reference.

Results

The pulmonary vessels and bronchi were visible consistently up to the sub-sub-segmental and sub-segmental branch levels, respectively, on accelerated spiral 3D UTE. The overall image quality was evaluated as good and excellent for 70.7% of accelerated spiral 3D UTE images (reviewer [R]1, 72.4% [21/29]; R2, 69.0% [20/29]) and acceptable for 20.7% (both R1 and R2, 20.7% [6/29]). Five patients on CT revealed 141 pulmonary metastatic nodules (5.3 ± 2.6 mm); the overall nodule detection rate of accelerated spiral 3D UTE was sensitivity of 90.8% (128/141), accuracy of 87.7%, and positive predictive value of 96.2%. In the Bland-Altman plot analysis comparing nodule size between CT and MRI, 132/141 nodules (93.6%) were inside the limits of agreement.

Conclusion

Accelerated free-breathing spiral 3D UTE using the SPIRiT algorithm could be a potential alternative to CT for oncology patients.
Integrative Analysis of Metabolomics and Transcriptomics Data Identifies Prognostic Biomarkers Associated With Oral Squamous Cell Carcinoma
Authors: Zuo Lihua , Chen Zhuo , Chen Lihuang , Kang Jian , Shi Yingying , Liu Liwei , Zhang Shuhua , Jia Qingquan , Huang Yi , Sun Zhi
Published: October 2021

Background

Oral squamous cell carcinoma (OSCC) is the most malignant neoplasm in oral cancer. There is growing evidence that its progression involves altered metabolism. The current method of evaluating prognosis is very limited, and metabolomics may provide a new approach for quantitative evaluation. The aim of the study is to evaluate the use of metabolomics as prognostic markers for patients with OSCC.

Methods

An analytical platform, Ultra-Performance Liquid Chromatography-Quadrupole/Orbitrap High Resolution Mass Spectrometry (UHPLC-Q-Orbitrap HRMS), was used to acquire the serum fingerprinting profiles from a total of 103 patients of OSCC before and after the operation. In total, 103 OSCC patients were assigned to either a training set (n = 73) or a test set (n = 30). The potential biomarkers and the changes of serum metabolites were profiled and correlated with the clinicopathological parameters and survival of the patients by statistical analysis. To further verify our results, we linked them to gene expression using data from the Kyoto Encyclopedia of Genes and Genomes (KEGG).

Results

In total, 14 differential metabolites and five disturbed pathways were identified between the preoperative group and postoperative group. Succinic acid change-low, hypoxanthine change-high tumor grade, and tumor stage indicated a trend towards improved recurrence-free survival (RFS), whether in a training set or a test set. In addition, succinic acid change-low, hypoxanthine change-high, and tumor grade provided the highest predictive accuracy of the patients with OSCC. KEGG enrichment analysis showed that the imbalance in the amino acid and purine metabolic pathway may affect the prognosis of OSCC.

Conclusions

The changes of metabolites before and after operation may be related to the prognosis of OSCC patients. UHPLC-Q-Orbitrap HRMS serum metabolomics analysis could be used to further stratify the prognosis of patients with OSCC. These results can better understand the mechanisms related to early recurrence and help develop more effective therapeutic targets.
Radiomic Features of Multi-ROI and Multi-Phase MRI for the Prediction of Microvascular Invasion in Solitary Hepatocellular Carcinoma
Authors: Yang Yan , Fan WeiJie , Gu Tao , Yu Li , Chen HaiLing , Lv YangFan , Liu Huan , Wang GuangXian , Zhang Dong
Published: October 2021

Objectives

To develop and validate an MR radiomics-based nomogram to predict the presence of MVI in patients with solitary HCC and further evaluate the performance of predictors for MVI in subgroups (HCC ≤ 3 cm and > 3 cm).

Materials and Methods

Between May 2015 and October 2020, 201 patients with solitary HCC were analysed. Radiomic features were extracted from precontrast T1WI, arterial phase, portal venous phase, delayed phase and hepatobiliary phase images in regions of the intratumoral, peritumoral and their combining areas. The mRMR and LASSO algorithms were used to select radiomic features related to MVI. Clinicoradiological factors were selected by using backward stepwise regression with AIC. A nomogram was developed by incorporating the clinicoradiological factors and radiomics signature. In addition, the radiomic features and clinicoradiological factors related to MVI were separately evaluated in the subgroups (HCC ≤ 3 cm and > 3 cm).

Results

Histopathological examinations confirmed MVI in 111 of the 201 patients (55.22%). The radiomics signature showed a favourable discriminatory ability for MVI in the training set (AUC, 0.896) and validation set (AUC, 0.788). The nomogram incorporating peritumoral enhancement, tumour growth type and radiomics signature showed good discrimination in the training (AUC, 0.932) and validation sets (AUC, 0.917) and achieved well-fitted calibration curves. Subgroup analysis showed that tumour growth type was a predictor for MVI in the HCC ≤ 3 cm cohort and peritumoral enhancement in the HCC > 3 cm cohort; radiomic features related to MVI varied between the HCC ≤ 3 cm and HCC > 3 cm cohort. The performance of the radiomics signature improved noticeably in both the HCC ≤ 3 cm (AUC, 0.953) and HCC > 3 cm cohorts (AUC, 0.993) compared to the original training set.

Conclusions

The preoperative nomogram integrating clinicoradiological risk factors and the MR radiomics signature showed favourable predictive efficiency for predicting MVI in patients with solitary HCC. The clinicoradiological factors and radiomic features related to MVI varied between subgroups (HCC ≤ 3 cm and > 3 cm). The performance of radiomics signature for MVI prediction was improved in both the subgroups.
Correlation of Early Nutritional Supply and Development of Bronchopulmonary Dysplasia in Preterm Infants <1,000 g
Authors: Thiess Theresa , Lauer Tina , Woesler Annika , Neusius Janine , Stehle Sandro , Zimmer Klaus-Peter , Eckert Gunter Peter , Ehrhardt Harald
Published: October 2021

Background: Bronchopulmonary dysplasia (BPD) has multifactorial origins and is characterized by distorted physiological lung development. The impact of nutrition on the incidence of BPD is less studied so far.

Methods: A retrospective single center analysis was performed on n = 207 preterm infants <1,000 g and <32 weeks of gestation without severe gastrointestinal complications to assess the impact of variations in nutritional supply during the first 2 weeks of life on the pulmonary outcome. Infants were grouped into no/mild and moderate/severe BPD to separate minor and major limitations in lung function.

Results: After risk adjustment for gestational age, birth weight, sex, multiples, and antenatal steroids, a reduced total caloric intake and carbohydrate supply as the dominant energy source during the first 2 weeks of life prevailed statistically significant in infants developing moderate/severe BPD (p < 0.05). Enteral nutritional supply was increased at a slower rate with prolonged need for parenteral nutrition in the moderate/severe BPD group while breast milk provision and objective criteria of feeding intolerance were equally distributed in both groups.

Conclusion: Early high caloric intake is correlated with a better pulmonary outcome in preterm infants <1,000 g. Our results are in line with the known strong impact of nutrient supply on somatic growth and psychomotor development. Our data encourage paying special attention to further decipher the ideal nutritional requirements for unrestricted lung development and promoting progressive enteral nutrition in the absence of objective criteria of feeding intolerance.
Downregulation of ATP1A1 Expression by Panax notoginseng (Burk.) F.H. Chen Saponins: A Potential Mechanism of Antitumor Effects in HepG2 Cells and In Vivo
Authors: Feng Xiao-Yi , Zhao Wei , Yao Zheng , Wei Ning-Yi , Shi An-Hua , Chen Wen-Hui
Published: October 2021

The Na+/K+-ATPase α1 subunit (ATP1A1) is a potential target for hepatic carcinoma (HCC) treatment, which plays a key role in Na+/K+ exchange, metabolism, signal transduction, etc. In vivo, we found that Panax notoginseng saponins (PNS) could inhibit tumor growth and significantly downregulate the expression and phosphorylation of ATP1A1/AKT/ERK in tumor-bearing mice. Our study aims to explore the potential effects of PNS on the regulation of ATP1A1 and the possible mechanisms of antitumor activity. The effects of PNS on HepG2 cell viability, migration, and apoptosis were examined in vitro. Fluorescence, Western blot, and RT-PCR analyses were used to examine the protein and gene expression. Further analysis was assessed with a Na+/K+-ATPase inhibitor (digitonin) and sorafenib in vitro. We found that the ATP1A1 expression was markedly higher in HepG2 cells than in L02 cells and PNS exhibited a dose-dependent effect on the expression of ATP1A and the regulation of AKT/ERK signaling pathways. Digitonin did not affect the expression of ATP1A1 but attenuated the effects of PNS on the regulation of ATP1A1/AKT/ERK signaling pathways and enhanced the antitumor effect of PNS by promoting nuclear fragmentation. Taken together, PNS inhibited the proliferation of HepG2 cells via downregulation of ATP1A1 and signal transduction. Our findings will aid a data basis for the clinical use of PNS.
Metabolite Profiling and Transcriptome Analysis Explains Difference in Accumulation of Bioactive Constituents in Licorice (Glycyrrhiza uralensis) Under Salt Stress
Authors: Wang Chengcheng , Chen Lihong , Cai Zhichen , Chen Cuihua , Liu Zixiu , Liu Shengjin , Zou Lisi , Tan Mengxia , Chen Jiali , Liu Xunhong , Mei Yuqi , Wei Lifang , Liang Juan , Chen Jine
Published: October 2021

Salinity stress significantly affects the contents of bioactive constituents in licorice Glycyrrhiza uralensis. To elucidate the molecular mechanism underlying the difference in the accumulation of these constituents under sodium chloride (NaCl, salt) stress, licorice seedlings were treated with NaCl and then subjected to an integrated transcriptomic and metabolite profiling analysis. The transcriptomic analysis results identified 3,664 differentially expressed genes (DEGs) including transcription factor family MYB and basic helix-loop-helix (bHLH). Most DEGs were involved in flavonoid and terpenoid biosynthesis pathways. In addition, 121 compounds including a triterpenoid and five classes of flavonoids (isoflavone, flavone, flavanone, isoflavan, and chalcone) were identified, and their relative levels were compared between the stressed and control groups using data from the ultrafast liquid chromatography (UFLC)–triple quadrupole–time of flight–tandem mass spectrometry (TOF–MS/MS) analysis. Putative biosynthesis networks of the flavonoids and triterpenoids were created and combined with structural DEGs such as phenylalanine ammonia-lyase (PAL), 4-coumarate-CoA ligase [4CL], cinnamate 4-hydroxylase [C4H], chalcone synthase [CHS], chalcone-flavanone isomerase [CHI], and flavonoid-3′,5′ hydroxylase (F3′,5′H) for flavonoids, and CYP88D6 and CYP72A154 for glycyrrhizin biosynthesis. Notably, significant upregulation of UDP-glycosyltransferase genes (UGT) in salt-stressed licorice indicated that postmodification of glycosyltransferase may participate in downstream biosynthesis of flavonoid glycosides and triterpenoid saponins. Accordingly, the expression trend of the DEGs is positively correlated with the accumulation of glycosides. Our study findings indicate that key DEGs and crucial UGT genes co-regulate flavonoid and saponin biosynthesis in licorice under salt stress.
PacBio and Illumina RNA Sequencing Identify Alternative Splicing Events in Response to Cold Stress in Two Poplar Species
Authors: Yang Jingli , Lv Wanqiu , Shao Liying , Fu Yanrui , Liu Haimei , Yang Chengjun , Chen Aihua , Xie Xieyu , Wang Zhiwei , Li Chenghao
Published: October 2021

In eukaryotes, alternative splicing (AS) is a crucial regulatory mechanism that modulates mRNA diversity and stability. The contribution of AS to stress is known in many species related to stress, but the posttranscriptional mechanism in poplar under cold stress is still unclear. Recent studies have utilized the advantages of single molecular real-time (SMRT) sequencing technology from Pacific Bioscience (PacBio) to identify full-length transcripts. We, therefore, used a combination of single-molecule long-read sequencing and Illumina RNA sequencing (RNA-Seq) for a global analysis of AS in two poplar species (Populus trichocarpa and P. ussuriensis) under cold stress. We further identified 1,261 AS events in P. trichocarpa and 2,101 in P. ussuriensis among which intron retention, with a frequency of more than 30%, was the most prominent type under cold stress. RNA-Seq data analysis and annotation revealed the importance of calcium, abscisic acid, and reactive oxygen species signaling in cold stress response. Besides, the low temperature rapidly induced multiple splicing factors, transcription factors, and differentially expressed genes through AS. In P. ussuriensis, there was a rapid occurrence of AS events, which provided a new insight into the complexity and regulation of AS during cold stress response in different poplar species for the first time.
An Empirical Study on Talent Management Strategies of Knowledge-Based Organizations Using Entrepreneurial Psychology and Key Competence
Authors: Liu Mengqiong
Published: October 2021

The empirical study reported here aims to improve the effectiveness of knowledge-based talent management in science and technology enterprises and promote the stable development of enterprises. First, the impact of entrepreneurs’ psychological cognition and personal characteristics on entrepreneurial activities is analyzed based on entrepreneurial psychology. Then, the theory of key competence is introduced to study the management mode of knowledge-based talents. The advantages of talents in enterprises are sorted out through constructing the key competency model to manage talents efficiently. The technology-based enterprise M is taken as an example for analysis by the key competence model to obtain 18 key capability indexes. Through the principal component analysis of 255 employees’ survey results, finally, four factors are extracted (business execution ability, team cooperation ability, strategic thinking ability, and management decision-making ability), which can reflect 68.92% of the total key competence. The average values of “business execution ability” and “team cooperation ability” in the first-level dimension of key competence index are 4.14 and 4.24, respectively, which can be regarded as the essential key competence. The investigation results of the academic qualifications of staff of M indicate that 6% of employees have a doctorate, 38% have a master’s degree, 37% have a Bachelor’s degree, and 19% have a junior college degree or below. Moreover, knowledge-based employees are basically satisfied with the organization and management of the company, but they are dissatisfied with the training mechanism and promotion mechanism. Therefore, enterprises should pay attention to the psychological needs of knowledge workers and the innovation of talent management. The research results are of significant value for science and technology enterprises to absorb and retain knowledge-based talents and promote the common development of enterprises and employees.
A Pilot Study Exploring Age Differences in Presence, Workload, and Cybersickness in the Experience of Immersive Virtual Reality Environments
Authors: Dilanchian Andrew T. , Andringa Ronald , Boot Walter R.
Published: October 2021

Research is often focused on understanding barriers to the use and adoption of technology to support older adults’ (65+) instrumental activities of daily living (IADLs), such as communication, banking, and transportation. Less attention is paid to technology to support enhanced activities of daily living (EADLs), activities that enrich our daily lives, even though they have the potential to improve wellbeing, promote physical and emotional health, and reduce stress. Here, we explored how older adults interacted with commercial virtual reality (VR) to investigate the feasibility of using VR as an EADL support system. Older adults navigated different VR environments, including environments that were meditation, exploration, and game-oriented. Of particular interest was whether older adults (N = 20) psychologically experienced differing degrees of presence within virtual environments compared to younger adults (N = 20), and potential barriers to use as assessed by measures of workload and system usability. Given previously observed age-related differences in cybersickness, this was also assessed as a potential barrier. Compared to younger adults, older adults expressed a greater sense of presence in virtual environments, with nonsignificant differences in perceived workload and usability according to most measures. Contrary to expectations, older adults reported significantly less cybersickness compared to younger adults. Results suggest that VR is a promising means to support older adults’ EADLs.
Planetary Mass Spectrometry for Agnostic Life Detection in the Solar System
Authors: Chou Luoth , Mahaffy Paul , Trainer Melissa , Eigenbrode Jennifer , Arevalo Ricardo , Brinckerhoff William , Getty Stephanie , Grefenstette Natalie , Da Poian Victoria , Fricke G. Matthew , Kempes Christopher P. , Marlow Jeffrey , Sherwood Lollar Barbara , Graham Heather , Johnson Sarah Stewart
Published: October 2021

For the past fifty years of space exploration, mass spectrometry has provided unique chemical and physical insights on the characteristics of other planetary bodies in the Solar System. A variety of mass spectrometer types, including magnetic sector, quadrupole, time-of-flight, and ion trap, have and will continue to deepen our understanding of the formation and evolution of exploration targets like the surfaces and atmospheres of planets and their moons. An important impetus for the continuing exploration of Mars, Europa, Enceladus, Titan, and Venus involves assessing the habitability of solar system bodies and, ultimately, the search for life—a monumental effort that can be advanced by mass spectrometry. Modern flight-capable mass spectrometers, in combination with various sample processing, separation, and ionization techniques enable sensitive detection of chemical biosignatures. While our canonical knowledge of biosignatures is rooted in Terran-based examples, agnostic approaches in astrobiology can cast a wider net, to search for signs of life that may not be based on Terran-like biochemistry. Here, we delve into the search for extraterrestrial chemical and morphological biosignatures and examine several possible approaches to agnostic life detection using mass spectrometry. We discuss how future missions can help ensure that our search strategies are inclusive of unfamiliar life forms.
Freehand Stereotactic Image-Guidance Tailored to Neurotologic Surgery
Authors: Schneider Daniel , Anschuetz Lukas , Mueller Fabian , Hermann Jan , O'Toole Bom Braga Gabriela , Wagner Franca , Weder Stefan , Mantokoudis Georgios , Weber Stefan , Caversaccio Marco
Published: October 2021

Hypothesis: The use of freehand stereotactic image-guidance with a target registration error (TRE) of μTRE + 3σTRE < 0.5 mm for navigating surgical instruments during neurotologic surgery is safe and useful.

Background: Neurotologic microsurgery requires work at the limits of human visual and tactile capabilities. Anatomy localization comes at the expense of invasiveness caused by exposing structures and using them as orientation landmarks. In the absence of more-precise and less-invasive anatomy localization alternatives, surgery poses considerable risks of iatrogenic injury and sub-optimal treatment. There exists an unmet clinical need for an accurate, precise, and minimally-invasive means for anatomy localization and instrument navigation during neurotologic surgery. Freehand stereotactic image-guidance constitutes a solution to this. While the technology is routinely used in medical fields such as neurosurgery and rhinology, to date, it is not used for neurotologic surgery due to insufficient accuracy of clinically available systems.

Materials and Methods: A freehand stereotactic image-guidance system tailored to the needs of neurotologic surgery–most importantly sub-half-millimeter accuracy–was developed. Its TRE was assessed preclinically using a task-specific phantom. A pilot clinical trial targeting N = 20 study participants was conducted (ClinicalTrials.gov ID: NCT03852329) to validate the accuracy and usefulness of the developed system. Clinically, objective assessment of the TRE is impossible because establishing a sufficiently accurate ground-truth is impossible. A method was used to validate accuracy and usefulness based on intersubjectivity assessment of surgeon ratings of corresponding image-pairs from the microscope/endoscope and the image-guidance system.

Results: During the preclinical accuracy assessment the TRE was measured as 0.120 ± 0.05 mm (max: 0.27 mm, μTRE + 3σTRE = 0.27 mm, N = 310). Due to the COVID-19 pandemic, the study was terminated early after N = 3 participants. During an endoscopic cholesteatoma removal, a microscopic facial nerve schwannoma removal, and a microscopic revision cochlear implantation, N = 75 accuracy and usefulness ratings were collected from five surgeons each grading 15 image-pairs. On a scale from 1 (worst rating) to 5 (best rating), the median (interquartile range) accuracy and usefulness ratings were assessed as 5 (4–5) and 4 (4–5) respectively.

Conclusion: Navigating surgery in the tympanomastoid compartment and potentially in the lateral skull base with sufficiently accurate freehand stereotactic image-guidance (μTRE + 3σTRE < 0.5 mm) is feasible, safe, and useful.

Clinical Trial Registration:www.ClinicalTrials.gov, identifier: NCT03852329.