bluuebunny/crossref_metadata_2025 huggingface dataset:
High Levels of Multiple Phage WO Infections and Its Evolutionary Dynamics Associated With Wolbachia-Infected Butterflies
Authors: Gao Shuo , Ren Ye-Song , Su Cheng-Yuan , Zhu Dao-Hong
Published: April 2022

Wolbachia is a maternally inherited bacterium that is widely distributed among arthropods, in which it manipulates the reproduction of its hosts. Phage WO is the only bacteriophage known to infect Wolbachia, and may provide benefit to its host or arthropods. We screened for the presence of phage WO in Wolbachia-infected butterfly species for the first time, to investigate their diversity and evolutionary dynamics. All Wolbachia-infected butterfly species, including members of the families Hesperiidae, Lycaenidae, Nymphalidae, Papilionidae, and Pieridae, were found to harbor phage WO. Interestingly, 84% of 19 butterfly species, which were infected with a single Wolbachia strain harbored high levels of multiple phage types (ranging from 3 to 17 types), another three species harbored one or two phage types. For Wolbachia strains (ST-41, ST-19, ST-125 and ST-374) shared among various butterfly species, their host insects all harbored multiple phage types, while two Wolbachia strains (ST-297 and ST-wPcau) were found to infect one butterfly species, whose insect hosts harbored a single phage type, suggesting that horizontal transfer of Wolbachia between insects increased the likelihood of exposure to phages, resulting in increased phage genetic diversity. Twelve horizontal transmission events of phage WO were found, which shared common phage WO types among different Wolbachia strains associated with butterflies. Most horizontal transfer events involved different Wolbachia supergroups (A and B). Horizontal acquisition of phage WO might also occur between eukaryotes without Wolbachia transfer. Furthermore, 22 putative recombination events were identified in 13 of 16 butterfly species which harbored multiple phage types. These results showed that horizontal transfer of Wolbachia caused it to be exposed to the phage gene pool, and that horizontal transmission of phage WO, as well as intragenic recombination were important dynamics for phage WO genome evolution, which effectively promoted the high level of phage WO diversity associated with butterflies.
Nanopore Sequencing for Detection and Characterization of Phosphorothioate Modifications in Native DNA Sequences
Authors: Wadley Taylor , Moon Sun Hee , DeMott Michael S. , Wanchai Visanu , Huang En , Dedon Peter C. , Boysen Gunnar , Nookaew Intawat
Published: April 2022

Bacterial DNA is subject to various modifications involved in gene regulation and defense against bacteriophage attacks. Phosphorothioate (PT) modifications are protective modifications in which the non-bridging oxygen in the DNA phosphate backbone is replaced with a sulfur atom. Here, we expand third-generation sequencing techniques to allow for the sequence-specific mapping of DNA modifications by demonstrating the application of Oxford Nanopore Technologies (ONT) and the ELIGOS software package for site-specific detection and characterization of PT modifications. The ONT/ELIGOS platform accurately detected PT modifications in a plasmid carrying synthetic PT modifications. Subsequently, studies were extended to the genome-wide mapping of PT modifications in the Salmonella enterica genomes within the wild-type strain and strains lacking the PT regulatory gene dndB (ΔdndB) or the PT synthetic gene dndC (ΔdndC). PT site-specific signatures were observed in the established motifs of GAAC/GTTC. The PT site locations were in close agreement with PT sites previously identified using the Nick-seq technique. Compared to the wild-type strain, the number of PT modifications are 1.8-fold higher in ΔdndB and 25-fold lower in ΔdndC, again consistent with known regulation of the dnd operon. These results demonstrate the suitability of the ONT platform for accurate detection and identification of the unusual PT backbone modifications in native genome sequences.
An Efficient Tetraplex Surveillance Tool for Salmonid Pathogens
Authors: von Ammon Ulla , Averink Tessa , Kumanan Karthiga , Brosnahan Cara L. , Pochon Xavier , Hutson Kate S. , Symonds Jane E.
Published: April 2022

Fish disease surveillance methods can be complicated and time consuming, which limits their value for timely intervention strategies on aquaculture farms. Novel molecular-based assays using droplet digital Polymerase Chain Reaction (ddPCR) can produce immediate results and enable high sample throughput with the ability to multiplex several targets using different fluorescent dyes. A ddPCR tetraplex assay was developed for priority salmon diseases for farmers in New Zealand including New Zealand Rickettsia-like organism 1 (NZ-RLO1), NZ-RLO2, Tenacibaculum maritimum, and Yersinia ruckeri. The limit of detection in singleplex and tetraplex assays was reached for most targets at 10−9 ng/μl with, respectively, NZ-RLO1 = 0.931 and 0.14 copies/μl, NZ-RLO2 = 0.162 and 0.21 copies/μl, T. maritimum = 0.345 and 0.93 copies/μl, while the limit of detection for Y. ruckeri was 10−8 with 1.0 copies/μl and 0.7 copies/μl. While specificity of primers was demonstrated in previous studies, we detected cross-reactivity of T. maritimum with some strains of Tenacibaculum dicentrarchi and Y. ruckeri with Serratia liquefaciens, respectively. The tetraplex assay was applied as part of a commercial fish disease surveillance program in New Zealand for 1 year to demonstrate the applicability of tetraplex tools for the salmonid aquaculture industry.
Brain Computer Interfaces and Communication Disabilities: Ethical, Legal, and Social Aspects of Decoding Speech From the Brain
Authors: Chandler Jennifer A. , Van der Loos Kiah I. , Boehnke Susan , Beaudry Jonas S. , Buchman Daniel Z. , Illes Judy
Published: April 2022

A brain-computer interface technology that can decode the neural signals associated with attempted but unarticulated speech could offer a future efficient means of communication for people with severe motor impairments. Recent demonstrations have validated this approach. Here we assume that it will be possible in future to decode imagined (i.e., attempted but unarticulated) speech in people with severe motor impairments, and we consider the characteristics that could maximize the social utility of a BCI for communication. As a social interaction, communication involves the needs and goals of both speaker and listener, particularly in contexts that have significant potential consequences. We explore three high-consequence legal situations in which neurally-decoded speech could have implications:Testimony, where decoded speech is used as evidence;Consent and Capacity, where it may be used as a means of agency and participation such as consent to medical treatment; andHarm, where such communications may be networked or may cause harm to others. We then illustrate how design choices might impact the social and legal acceptability of these technologies.
Separating Glioma Hyperintensities From White Matter by Diffusion-Weighted Imaging With Spherical Tensor Encoding
Authors: Brabec Jan , Durmo Faris , Szczepankiewicz Filip , Brynolfsson Patrik , Lampinen Björn , Rydelius Anna , Knutsson Linda , Westin Carl-Fredrik , Sundgren Pia C. , Nilsson Markus
Published: April 2022

Background

Tumor-related hyperintensities in high b-value diffusion-weighted imaging (DWI) are radiologically important in the workup of gliomas. However, the white matter may also appear as hyperintense, which may conflate interpretation.

Purpose

To investigate whether DWI with spherical b-tensor encoding (STE) can be used to suppress white matter and enhance the conspicuity of glioma hyperintensities unrelated to white matter.

Materials and Methods

Twenty-five patients with a glioma tumor and at least one pathology-related hyperintensity on DWI underwent conventional MRI at 3 T. The DWI was performed both with linear and spherical tensor encoding (LTE-DWI and STE-DWI). The LTE-DWI here refers to the DWI obtained with conventional diffusion encoding and averaged across diffusion-encoding directions. Retrospectively, the differences in contrast between LTE-DWI and STE-DWI, obtained at a b-value of 2,000 s/mm2, were evaluated by comparing hyperintensities and contralateral normal-appearing white matter (NAWM) both visually and quantitatively in terms of the signal intensity ratio (SIR) and contrast-to-noise ratio efficiency (CNReff).

Results

The spherical tensor encoding DWI was more effective than LTE-DWI at suppressing signals from white matter and improved conspicuity of pathology-related hyperintensities. The median SIR improved in all cases and on average by 28%. The median (interquartile range) SIR was 1.9 (1.6 – 2.1) for STE and 1.4 (1.3 – 1.7) for LTE, with a significant difference of 0.4 (0.3 –0.5) (p < 10–4, paired U-test). In 40% of the patients, the SIR was above 2 for STE-DWI, but with LTE-DWI, the SIR was below 2 for all patients. The CNReff of STE-DWI was significantly higher than of LTE-DWI: 2.5 (2 – 3.5) vs. 2.3 (1.7 – 3.1), with a significant difference of 0.4 (−0.1 –0.6) (p < 10–3, paired U-test). The STE improved CNReff in 70% of the cases. We illustrate the benefits of STE-DWI in three patients, where STE-DWI may facilitate an improved radiological description of tumor-related hyperintensity, including one case that could have been missed out if only LTE-DWI was inspected.

Conclusion

The contrast mechanism of high b-value STE-DWI results in a stronger suppression of white matter than conventional LTE-DWI, and may, therefore, be more sensitive and specific for assessment of glioma tumors and DWI-hyperintensities.
Acute (R,S)-Ketamine Administration Induces Sex-Specific Behavioral Effects in Adolescent but Not Aged Mice
Authors: Mastrodonato Alessia , Pavlova Ina , Kee Noelle , McGowan Josephine C. , Mann J. John , Denny Christine A.
Published: April 2022

(R,S)-ketamine is an N-methyl-D-aspartate (NMDA) receptor antagonist that was originally developed as an anesthetic. Most recently, (R,S)-ketamine has been used as a rapid-acting antidepressant, and we have reported that (R,S)-ketamine can also be a prophylactic against stress in adult mice. However, most pre-clinical studies have been performed in adult mice. It is still unknown how an acute (R,S)-ketamine injection influences behavior across the lifespan (e.g., to adolescent or aged populations). Here, we administered saline or (R,S)-ketamine at varying doses to adolescent (5-week-old) and aged (24-month-old) 129S6/SvEv mice of both sexes. One hour later, behavioral despair, avoidance, locomotion, perseverative behavior, or contextual fear discrimination (CFD) was assessed. A separate cohort of mice was sacrificed 1 h following saline or (R,S)-ketamine administration. Brains were processed to quantify the marker of inflammation Cyclooxygenase 2 (Cox-2) expression to determine whether the acute effects of (R,S)-ketamine were partially mediated by changes in brain inflammation. Our findings show that (R,S)-ketamine reduced behavioral despair and perseverative behavior in adolescent female, but not male, mice and facilitated CFD in both sexes at specific doses. (R,S)-ketamine reduced Cox-2 expression specifically in ventral CA3 (vCA3) of male mice. Notably, (R,S)-ketamine was not effective in aged mice. These results underscore the need for sex- and age-specific approaches to test (R,S)-ketamine efficacy across the lifespan.
In vivo Estimation of Axonal Morphology From Magnetic Resonance Imaging and Electroencephalography Data
Authors: Oliveira Rita , Pelentritou Andria , Di Domenicantonio Giulia , De Lucia Marzia , Lutti Antoine
Published: April 2022

Purpose

We present a novel approach that allows the estimation of morphological features of axonal fibers from data acquired in vivo in humans. This approach allows the assessment of white matter microscopic properties non-invasively with improved specificity.

Theory

The proposed approach is based on a biophysical model of Magnetic Resonance Imaging (MRI) data and of axonal conduction velocity estimates obtained with Electroencephalography (EEG). In a white matter tract of interest, these data depend on (1) the distribution of axonal radius [P(r)] and (2) the g-ratio of the individual axons that compose this tract [g(r)]. P(r) is assumed to follow a Gamma distribution with mode and scale parameters, M and θ, and g(r) is described by a power law with parameters α and β.

Methods

MRI and EEG data were recorded from 14 healthy volunteers. MRI data were collected with a 3T scanner. MRI-measured g-ratio maps were computed and sampled along the visual transcallosal tract. EEG data were recorded using a 128-lead system with a visual Poffenberg paradigm. The interhemispheric transfer time and axonal conduction velocity were computed from the EEG current density at the group level. Using the MRI and EEG measures and the proposed model, we estimated morphological properties of axons in the visual transcallosal tract.

Results

The estimated interhemispheric transfer time was 11.72 ± 2.87 ms, leading to an average conduction velocity across subjects of 13.22 ± 1.18 m/s. Out of the 4 free parameters of the proposed model, we estimated θ – the width of the right tail of the axonal radius distribution – and β – the scaling factor of the axonal g-ratio, a measure of fiber myelination. Across subjects, the parameter θ was 0.40 ± 0.07 μm and the parameter β was 0.67 ± 0.02 μm−α.

Conclusion

The estimates of axonal radius and myelination are consistent with histological findings, illustrating the feasibility of this approach. The proposed method allows the measurement of the distribution of axonal radius and myelination within a white matter tract, opening new avenues for the combined study of brain structure and function, and for in vivo histological studies of the human brain.
Computational Analysis of the Immune Infiltration Pattern and Candidate Diagnostic Biomarkers in Lumbar Disc Herniation
Authors: Li Kai , Li Shijue , Zhang Haojie , Lei Di , Lo Wai Leung Ambrose , Ding Minghui
Published: April 2022

Objectives

Lumbar disc herniation (LDH) is a musculoskeletal disease that contributes to low back pain, sciatica, and movement disorder. Existing studies have suggested that the immune environment factors are the primary contributions to LDH. However, its etiology remains unknown. We sought to identify the potential diagnostic biomarkers and analyze the immune infiltration pattern in LDH.

Methods

The whole-blood gene expression level profiles of GSE124272 and GSE150408 were downloaded from the Gene Expression Omnibus (GEO) database, including that of 25 patients with LDH and 25 healthy volunteers. After merging the two microarray datasets, Differentially Expressed Genes (DEGs) were screened, and a functional correlation analysis was performed. The Least Absolute Shrinkage and Selection Operator (LASSO) logistic regression algorithm and support vector machine recursive feature elimination (SVM-RFE) were applied to identify diagnostic biomarkers by a cross-validation method. Then, the GSE42611 dataset was used as a validation dataset to detect the expression level of these diagnostic biomarkers in the nucleus pulposus and evaluate their accuracy. The hub genes in the network were identified by the CIBERSORT tool and the Weighted Gene Coexpression Network Analysis (WGCNA). A Spearman correlation analysis between diagnostic markers and infiltrating immune cells was conducted to further illustrate the molecular immune mechanism of LDH.

Results

The azurophil granule and the systemic lupus erythematosus pathway were significantly different between the healthy group and the LDH group after gene enrichment analysis. The XLOC_l2_012836, lnc-FGD3-1, and scavenger receptor class A member 5 were correlated with the immune cell infiltration in various degrees. In addition, five hub genes that correlated with LDH were identified, including AQP9, SIRPB2, SLC16A3, LILRB3, and HSPA6.

Conclusion

The XLOC_l2_012836, lnc-FGD3-1, and SCARA5 might be adopted for the early diagnosis of LDH. The five identified hub genes might have similar pathological mechanisms that contribute to the degeneration of the lumbar disc. The identified hub genes and immune infiltrating pattern extend the knowledge on the potential functioning mechanisms, which offer guidance for the development of therapeutic targets of LDH.
Endoscopic Submucosal Dissection vs. Surgery for Superficial Esophageal Squamous Cancer: A Systematic Review and Meta-Analysis
Authors: Liu Zhifeng , Zhao Renping
Published: April 2022

Background

Esophageal cancer is one of the leading causes of morbidity and mortality across the world. Only one systematic review and meta-analysis has attempted to compare the morbidity and mortality outcomes in superficial esophageal squamous cancer patients undergoing endoscopic submucosal dissection (ESD) and esophagectomy (ESO), but with several limitations. This study aimed at comparing the outcomes of hospital stay duration, procedure duration, recurrence, complications, all-cause mortality, short-term survival, and long-term survival in patients with superficial esophageal squamous cancer undergoing ESD and ESO.

Methods

Six databases (Web of Science, PubMed, EMBASE, CENTRAL, Scopus, and MEDLINE) were systematically searched according to PRISMA guidelines for eligible studies. With the available literature, we conducted a random-effect meta-analysis to evaluate weighted effect size and odds ratios to determine the comparative morbidity and mortality outcomes between patients with superficial esophageal squamous cancer undergoing ESD and ESO.

Results

We found 16 eligible studies detailing 5,213 and 8,049 age- and sex-matched patients undergoing ESD and ESO, respectively. Meta-analysis revealed reduced hospital stay (Hedge’s g: -1.22) and procedure duration (g: -4.54) for patients undergoing ESD. We also observed significantly reduced risks for complications (odds ratio: 0.35) and all-cause mortality (OR: 0.56) in patients undergoing ESD. Differences in recurrence (OR: 0.95), short-term outcomes (OR: 1.10), and long-term survival (OR: 0.81) outcomes were not significantly different between ESD and ESO.

Conclusions

This meta-analysis provides evidence concerning the improved morbidity and mortality outcomes in superficial esophageal squamous cancer patients undergoing ESD as compared to ESO. The findings herein may aid in developing clinical awareness and assisting best practice guideline development for managing superficial esophageal squamous cancer.

Registration

PROSPERO, https://www.crd.york.ac.uk/prospero/#searchadvanced, CRD42021286212.
Distinct Functional Metagenomic Markers Predict the Responsiveness to Anti-PD-1 Therapy in Chinese Non-Small Cell Lung Cancer Patients
Authors: Fang Chao , Fang Wenfeng , Xu Liqin , Gao Fangfang , Hou Yong , Zou Hua , Ma Yuxiang , Moll Janne Marie , Yang Yunpeng , Wang Dan , Huang Yan , Ren Huahui , Zhao Hongyun , Qin Shishang , Zhong Huanzi , Li Junhua , Liu Sheng , Yang Huanming , Wang Jian , Brix Susanne , Kristiansen Karsten , Zhang Li
Published: April 2022

Background

Programmed death 1 (PD-1) and the ligand of PD-1 (PD-L1) are central targets for immune-checkpoint therapy (ICT) blocking immune evasion-related pathways elicited by tumor cells. A number of PD-1 inhibitors have been developed, but the efficacy of these inhibitors varies considerably and is typically below 50%. The efficacy of ICT has been shown to be dependent on the gut microbiota, and experiments using mouse models have even demonstrated that modulation of the gut microbiota may improve efficacy of ICT.

Methods

We followed a Han Chinese cohort of 85 advanced non-small cell lung cancer (NSCLC) patients, who received anti-PD-1 antibodies. Tumor biopsies were collected before treatment initiation for whole exon sequencing and variant detection. Fecal samples collected biweekly during the period of anti-PD-1 antibody administration were used for metagenomic sequencing. We established gut microbiome abundance profiles for identification of significant associations between specific microbial taxa, potential functionality, and treatment responses. A prediction model based on random forest was trained using selected markers discriminating between the different response groups.

Results

NSCLC patients treated with antibiotics exhibited the shortest survival time. Low level of tumor-mutation burden and high expression level of HLA-E significantly reduced progression-free survival. We identified metagenomic species and functional pathways that differed in abundance in relation to responses to ICT. Data on differential enrichment of taxa and predicted microbial functions in NSCLC patients responding or non-responding to ICT allowed the establishment of random forest algorithm-adopted models robustly predicting the probability of whether or not a given patient would benefit from ICT.

Conclusions

Overall, our results identified links between gut microbial composition and immunotherapy efficacy in Chinese NSCLC patients indicating the potential for such analyses to predict outcome prior to ICT.
Comparison of Deep Inspiration Breath Hold Versus Free Breathing in Radiotherapy for Left Sided Breast Cancer
Authors: Lu Yongkai , Yang Di , Zhang Xiaowei , Teng Yonggang , Yuan Wei , Zhang Yuemei , He Ruixin , Tang Fengwen , Pang Jie , Han Bo , Chen Ruijuan , Li Yi
Published: April 2022

Objectives

Modern breast cancer techniques, such as the deep inspiration breath-hold (DIBH) technique has been applied for left-sided breast cancer. Whether the DIBH regimen is the optimal solution for left-sided breast cancer remains unclear. This meta-analysis aims to elucidate the differences of DIBH and free-breathing (FB) for patients receiving radiotherapy for left-sided breast cancer and provide a practical reference for clinical practice.

Methods

Relevant research available on PubMed, Embase, Cochrane Library, and the Web of Science published before November 30, 2021 was independently and systematically examined by two investigators. Data were extracted from eligible studies for assessing their qualities and calculating the standardized mean difference (SMD) and 95% confidence intervals (CIs) using Review Manager software 5.4 (RevMan 5.4).

Results

Forty-one studies with a total of 3599 left-sided breast cancer patients were included in the meta-analysis. Compared with FB, DIBH reduced heart dose (Dmean, Dmax, V30, V10, V5), left anterior descending branch (LAD) dose (Dmean, Dmax), ipsilateral lung dose (Dmean, V20, V10, V5), and heart volume significantly. Lung volume increased greatly, and a statistically significant difference. For contralateral breast mean dose, DIBH has no obvious advantage over FB. The funnel plot suggested this study has no significant publication bias.

Conclusions

Although DIBH has no obvious advantage over FB in contralateral breast mean dose, it can significantly reduce heart dose, LAD dose, ipsilateral lung dose, and heart volume. Conversely, it can remarkably increase the ipsilateral lung volume. This study suggests that soon DIBH could be more widely utilized in clinical practice because of its excellent dosimetric performance.
Xeroderma Pigmentosum Complementation Group C (XPC): Emerging Roles in Non-Dermatologic Malignancies
Authors: Nasrallah Nawar Al , Wiese Benjamin M. , Sears Catherine R.
Published: April 2022

Xeroderma pigmentosum complementation group C (XPC) is a DNA damage recognition protein essential for initiation of global-genomic nucleotide excision repair (GG-NER). Humans carrying germline mutations in the XPC gene exhibit strong susceptibility to skin cancer due to defective removal via GG-NER of genotoxic, solar UV-induced dipyrimidine photoproducts. However, XPC is increasingly recognized as important for protection against non-dermatologic cancers, not only through its role in GG-NER, but also by participating in other DNA repair pathways, in the DNA damage response and in transcriptional regulation. Additionally, XPC expression levels and polymorphisms likely impact development and may serve as predictive and therapeutic biomarkers in a number of these non-dermatologic cancers. Here we review the existing literature, focusing on the role of XPC in non-dermatologic cancer development, progression, and treatment response, and highlight possible future applications of XPC as a prognostic and therapeutic biomarker.
Single-Cell Sequencing and Its Applications in Liver Cancer
Authors: Tian Binle , Li Qi
Published: April 2022

As one of the most lethal cancers, primary liver cancer (PLC) has high tumor heterogeneity, including the heterogeneity between cancer cells. Traditional methods which have been used to identify tumor heterogeneity for a long time are based on large mixed cell samples, and the research results usually show average level of the cell population, ignoring the heterogeneity between cancer cells. In recent years, single-cell sequencing has been increasingly applied to the studies of PLCs. It can detect the heterogeneity between cancer cells, distinguish each cell subgroup in the tumor microenvironment (TME), and also reveal the clonal characteristics of cancer cells, contributing to understand the evolution of tumor. Here, we introduce the process of single-cell sequencing, review the applications of single-cell sequencing in the heterogeneity of cancer cells, TMEs, oncogenesis, and metastatic mechanisms of liver cancer, and discuss some of the current challenges in the field.
Iron Transporters and Ferroptosis in Malignant Brain Tumors
Authors: Zhao Jingyu , Wang Yaqi , Tao Lei , Chen Ligong
Published: April 2022

Malignant brain tumors represent approximately 1.5% of all malignant tumors. The survival rate among patients is relatively low and the mortality rate of pediatric brain tumors ranks first among all childhood malignant tumors. At present malignant brain tumors remain incurable. Although some tumors can be treated with surgery and chemotherapy, new treatment strategies are urgent owing to the poor clinical prognosis. Iron is an essential trace element in many biological processes of the human body. Iron transporters play a crucial role in iron absorption and transport. Ferroptosis, an iron-dependent form of nonapoptotic cell death, is characterized by the accumulation of lipid peroxidation products and lethal reactive oxygen species (ROS) derived from iron metabolism. Recently, compelling evidence has shown that inducing ferroptosis of tumor cells is a potential therapeutic strategy. In this review, we will briefly describe the significant regulatory factors of ferroptosis, iron, its absorption and transport under physiological conditions, especially the function of iron transporters. Then we will summarize the relevant mechanisms of ferroptosis and its role in malignant brain tumors, wherein the role of transporters is not to be ignored. Finally, we will introduce the current research progress in the treatment of malignant brain tumors by inducing ferroptosis in order to explain the current biological principles of potential treatment targets and treatment strategies for malignant brain tumors.
Risk Assessment in Diffuse Large B-Cell Lymphoma by Combining Baseline Metabolic Tumor Volume and Peking Criteria When Evaluating Series 18F-Fluorodeoxyglucose Positron Emission Tomography Scans
Authors: Yuan Tingting , Zhang Yuewei , Chen Xuetao , Wei Maomao , Zhu Hua , Song Yuqin , Yang Zhi , Zhu Jun , Wang Xuejuan
Published: April 2022

This study aimed to determine the predictive and prognostic value of baseline metabolic tumor volume (MTV) and the Peking criteria from serial positron emission tomography (PET) scans in diffuse large B-cell lymphoma, including 300 newly diagnosed patients who were prospectively treated with 2–4 cycles of standard first-line treatment (clinicaltrials.gov identifier: NCT02928861). PET/computed tomography (CT) examinations were performed at baseline, after two (PET-2) or four cycles (PET-4). PET during the interim was evaluated using Deauville 5-point scales (5-PS), ΔSUVmax criteria, and the Peking criteria which interpreted based on the maximum standard uptake of the liver (SUVmax-liver). Peking criteria had better accuracy, positive predictive value (PPV), and specificity than other two methods. The MTV and Peking criteria both significantly predicted progression-free survival (PFS) and overall survival (OS). An MTV > 191 cm2 and Peking criteria of PET-2 and PET-4 > 1.6-fold SUVmax-liver was used as the cutoff for a positive result. PET-4 achieved higher accuracy, PPV, and specificity for 2-year PFS (83.3%, 86.7%, and 98.4%, respectively) and OS (92.6%, 73.3%, and 97.2%, respectively) than PET-2. Various prognostic models containing different risk factors were established via Cox regression analysis. The MTV and PET-2/PET-4 results were used to categorized patients into low-risk, intermediate-risk, and high-risk prognostic groups (with 0, 1, and 2 risk factors, respectively) (P < 0.0001). High burden MTV and positive PET-2 and PET-4 (>1.6-fold SUVmax-liver) could identify high-risk patients with 2-year PFS and OS of 0.0% and 26.3% (95% confidence interval [CI]: N/A to 54.3%). When PET-2 and PET-4 were evaluated by 5-PS, the 2-year PFS and OS from high risk patients of three-parameters model achieved 31.4% (95%CI: 6.9%–55.9%) and 42.7% (95%CI: 14.6%–70.7%). In conclusion, combining baseline MTV and any regular response on PET/CT evaluated using the Peking criteria can improve prognostic value. Serial PET/CT from baseline MTV to PET-4 may have relatively greater predictive power for poor prognosis in diffuse large B-cell lymphoma.

Clinical Trial Registration

ClinicalTrials.gov, identifier (NCT02928861).
LAMP2 as a Biomarker Related to Prognosis and Immune Infiltration in Esophageal Cancer and Other Cancers: A Comprehensive Pan-Cancer Analysis
Authors: Liu Shan-peng , Li Xiao-min , Liu Dan-man , Xie Shu-huan , Zhang Shao-bo , Li Yu , Xie Ze-feng
Published: April 2022

Esophageal cancer (ESCA) is a common malignant tumor with poor prognosis. Accumulating evidence indicates an important role of lysosomal-associated membrane protein 2 (LAMP2) in the progression and development of various cancers. In this study, we obtained RNA-sequencing raw count data and the corresponding clinical information for ESCA samples from The Cancer Genome Atlas and Gene Expression Omnibus databases. We comprehensively investigated the expression and prognostic significance of LAMP2 and relationships between LAMP2 expression and prognosis, different clinicopathological parameters, and immune cell infiltration in ESCA. We also obtained the differentially expressed genes between the high LAMP2 expression and low LAMP2 expression groups in ESCA and performed a functional enrichment analysis of the 250 linked genes most positively related to LAMP2 expression. Moreover, we performed the pan-cancer analysis of LAMP2 to further analyze the role of LAMP2 in 25 commonly occurring types of human cancer. We also verified and compared the expression of LAMP2 in 40 samples of human ESCA tissue and adjacent tissues. The results indicated that LAMP2 expression was significantly upregulated in ESCA and various human cancers. In addition, LAMP2 expression was associated with certain clinicopathological parameters, prognosis, and immune infiltration in ESCA and the other types of cancer. Our study represents a comprehensive pan-cancer analysis of LAMP2 and supports the potential use of the modulation of LAMP2 in the management of ESCA and various cancers.
Fever-Associated Seizures or Epilepsy: An Overview of Old and Recent Literature Acquisitions
Authors: Pavone Piero , Pappalardo Xena Giada , Parano Enrico , Falsaperla Raffaele , Marino Simona Domenica , Fink John Kane , Ruggieri Martino
Published: April 2022

In addition to central nervous system infections, seizures and fever may occur together in several neurological disorders. Formerly, based on the clinical features and prognostic evolution, the co-association of seizure and fever included classical febrile seizures (FS) divided into simple, complex, and prolonged FS (also called febrile status epilepticus). Later, this group of disorders has been progressively indicated, with a more inclusive term, as “fever-associated seizures or epilepsy” (FASE) that encompasses: (a) FS divided into simple, complex, and prolonged FS; (b) FS plus; (c) severe myoclonic epilepsy in infancy (Dravet syndrome); (d) genetic epilepsy with FS plus; and (e) febrile infection-related epilepsy syndrome (FIRES). Among the FASE disorders, simple FS, the most common and benign condition, is rarely associated with subsequent epileptic seizures. The correlation of FS with epilepsy and other neurological disorders is highly variable. The pathogenesis of FASE is unclear but immunological and genetic factors play a relevant role and the disorders belonging to the FASE group show to have an underlying common clinical, immunological, and genetic pathway. In this study, we have reviewed and analyzed the clinical data of each of the heterogeneous group of disorders belonging to FASE.
Modulation of Morphine Analgesia, Antinociceptive Tolerance, and Mu-Opioid Receptor Binding by the Cannabinoid CB2 Receptor Agonist O-1966
Authors: Reichenbach Zachary W. , DiMattio Kelly , Rajakaruna Suren , Ambrose David , Cornwell William D. , Tallarida Ronald J. , Rogers Thomas , Liu-Chen Lee-Yuan , Tuma Ronald F. , Ward Sara Jane
Published: April 2022

Acutely, non-selective cannabinoid (CB) agonists have been shown to increase morphine antinociceptive effects, and we and others have also demonstrated that non-selective CB agonists attenuate morphine antinociceptive tolerance. Activation of cannabinoid CB2 receptors reverses allodynia and hyperalgesia in models of chronic pain, and co-administration of morphine with CB2 receptor selective agonists has been shown to be synergistic. CB2 receptor activation has also been shown to reduce morphine-induced hyperalgesia in rodents, an effect attributed to CB2 receptor modulation of inflammation. In the present set of experiments, we tested both the acute and chronic interactions between morphine and the CB2 receptor selective agonist O-1966 treatments on antinociception and antinociceptive tolerance in C57Bl6 mice. Co-administration of morphine and O-1966 was tested under three dosing regimens: simultaneous administration, morphine pre-treated with O-1966, and O-1966 pre-treated with morphine. The effects of O-1966 on mu-opioid receptor binding were determined using [3H]DAMGO and [35S]GTPγS binding assays, and these interactions were further examined by FRET analysis linked to flow cytometry. Results yielded surprising evidence of interactions between the CB2 receptor selective agonist O-1966 and morphine that were dependent upon the order of administration. When O-1966 was administered prior to or simultaneous with morphine, morphine antinociception was attenuated and antinociceptive tolerance was exacerbated. When O-1966 was administered following morphine, morphine antinociception was not affected and antinociceptive tolerance was attenuated. The [35S]GTPγS results suggest that O-1966 interrupts functional activity of morphine at the mu-opioid receptor, leading to decreased potency of morphine to produce acute thermal antinociceptive effects and potentiation of morphine antinociceptive tolerance. However, O-1966 administered after morphine blocked morphine hyperalgesia and led to an attenuation of morphine tolerance, perhaps due to well-documented anti-inflammatory effects of CB2 receptor agonism.
Edaravone Dexborneol Treatment Attenuates Neuronal Apoptosis and Improves Neurological Function by Suppressing 4-HNE-Associated Oxidative Stress After Subarachnoid Hemorrhage
Authors: Chen Qian , Cai Yichen , Zhu Xiaoyu , Wang Jing , Gao Feng , Yang Mingfeng , Mao Leilei , Zhang Zongyong , Sun Baoliang
Published: April 2022

Edaravone dexborneol is a novel neuroprotective drug that comprises edaravone and (+)-borneol in a 4:1 ratio. Phase II and III studies have demonstrated that Chinese patients treated with edaravone dexborneol within 48 h of AIS onset have better functional outcomes than those treated with edaravone alone. However, the effect of edaravone dexborneol on subarachnoid hemorrhage (SAH) has not yet been elucidated. This study aimed to investigate the therapeutic effects of edaravone dexborneol on SAH-induced brain injury and long-term behavioral deficits and to explore the possible mechanisms. The experimental rat SAH model was induced by an intraluminal puncture of the left middle cerebral artery (MCA). Edaravone dexborneol or edaravone at a clinical dose was infused into the tail vein for 3 days post-SAH surgery. Behavioral outcomes were assessed by a modified Garcia scoring system and rotarod, foot-fault, and corner tests. Immunofluorescence, Western blot, and ELISA methods were used to evaluate neuronal damage and oxidative stress. Our results showed that a post-SAH therapeutic regimen with edaravone dexborneol helped improve neurological function up to 21 days after SAH surgery and demonstrated a greater beneficial effect than edaravone alone, accompanied by an obvious inhibition of neuronal apoptosis in the CA1 hippocampus and basal cortex regions. Mechanistically, edaravone dexborneol not only suppressed the lipid peroxidation product malondialdehyde (MDA) but also improved the total antioxidant capability (TAC) 3 days after SAH. Notably, edaravone dexborneol treatment significantly inhibited the expression of another lipid peroxidation product, 4-hydroxynonenal (4-HNE), in the CA1 hippocampus and basal cortex, which are vital participants in the process of neuronal oxidative damage and death after SAH because of their acute cytotoxicity. Together, our results demonstrate that edaravone dexborneol confers neuroprotection and stabilizes long-term behavioral ability after SAH injury, possibly by suppressing 4-HNE-associated oxidative stress. These results may help develop new clinical strategies for SAH treatment.
Naringin Relieves Diabetic Cardiac Autonomic Neuropathy Mediated by P2Y14 Receptor in Superior Cervical Ganglion
Authors: Tang Gan , Pi Lingzhi , Guo Hongmin , Hu Zihui , Zhou Congfa , Hu Qixing , Peng Hao , Xiao Zehao , Zhang Zhihua , Wang Miaomiao , Peng Taotao , Huang Jiaqi , Liang Shangdong , Li Guilin
Published: April 2022

Diabetes mellitus (DM), an emerging chronic epidemic, contributes to mortality and morbidity around the world. Diabetic cardiac autonomic neuropathy (DCAN) is one of the most common complications associated with DM. Previous studies have shown that satellite glial cells (SGCs) in the superior cervical ganglia (SCG) play an indispensable role in DCAN progression. In addition, it has been shown that purinergic neurotransmitters, as well as metabotropic GPCRs, are involved in the pathophysiological process of DCAN. Furthermore, one traditional Chinese medicine, naringin may potently alleviate the effects of DCAN. Ferroptosis may be involved in DCAN progression. However, the role of naringin in DCAN as well as its detailed mechanism requires further investigation. In this research, we attempted to identify the effect and relevant mechanism of naringin in DCAN mitigation. We observed that compared with those of normal subjects, there were significantly elevated expression levels of P2Y14 and IL-1β in diabetic rats, both of which were remarkably diminished by treatment with either P2Y14 shRNA or naringin. In addition, abnormalities in blood pressure (BP), heart rate (HR), heart rate variability (HRV), sympathetic nerve discharge (SND), and cardiac structure in the diabetic model can also be partially returned to normal through the use of those treatments. Furthermore, a reduced expression of NRF2 and GPX4, as well as an elevated level of ROS, were detected in diabetic cases, which can also be improved with those treatments. Our results showed that naringin can effectively relieve DCAN mediated by the P2Y14 receptor of SGCs in the SCG. Moreover, the NRF2/GPX4 pathway involved in ferroptosis may become one of the principal mechanisms participating in DCAN progression, which can be modulated by P2Y14-targeted naringin and thus relieve DCAN. Hopefully, our research can supply one novel therapeutic target and provide a brilliant perspective for the treatment of DCAN.
Medicinal Cannabis and Central Nervous System Disorders
Authors: Ortiz Yuma T. , McMahon Lance R. , Wilkerson Jenny L.
Published: April 2022

Cannabinoids, including those found in cannabis, have shown promise as potential therapeutics for numerous health issues, including pathological pain and diseases that produce an impact on neurological processing and function. Thus, cannabis use for medicinal purposes has become accepted by a growing majority. However, clinical trials yielding satisfactory endpoints and unequivocal proof that medicinal cannabis should be considered a frontline therapeutic for most examined central nervous system indications remains largely elusive. Although cannabis contains over 100 + compounds, most preclinical and clinical research with well-controlled dosing and delivery methods utilize the various formulations of Δ9-tetrahydrocannabinol (THC) and cannabidiol (CBD), the two most abundant compounds in cannabis. These controlled dosing and delivery methods are in stark contrast to most clinical studies using whole plant cannabis products, as few clinical studies using whole plant cannabis profile the exact composition, including percentages of all compounds present within the studied product. This review will examine both preclinical and clinical evidence that supports or refutes the therapeutic utility of medicinal cannabis for the treatment of pathological pain, neurodegeneration, substance use disorders, as well as anxiety-related disorders. We will predominately focus on purified THC and CBD, as well as other compounds isolated from cannabis for the aforementioned reasons but will also include discussion over those studies where whole plant cannabis has been used. In this review we also consider the current challenges associated with the advancement of medicinal cannabis and its derived potential therapeutics into clinical applications.
Big Five Personality, Academic Entrepreneurial Motivation, and Academic Entrepreneurial Intention: A Research Method Based on Fuzzy Set Qualitative Comparative Analysis
Authors: Zhang Yuying , Wang Peng , Zhao Yanzhi
Published: April 2022

Scholars are the main force behind academic entrepreneurship. The method of how to stimulate scholars’ academic entrepreneurial intention and how to further promote social and economic development are important questions for the academic community. Research on the “net effect” of the factors affecting academic entrepreneurial intention has achieved some theoretical results. However, the results that affect academic entrepreneurial intention are complex and not influenced by a single factor, but rather by the interaction between various factors. Therefore, this study used a fuzzy set qualitative comparative analysis research method to explore how various factors can affect scholars’ academic entrepreneurial intention from two dimensions: the Big Five personality traits and academic entrepreneurial motivation. Our findings showed two configurations that affect high academic entrepreneurial intention of university scholars: the openness to experience—ribbon—dominant path, and the ribbon—dominant path. Additionally, two configurations were revealed for the formation of not-high academic entrepreneurial intention: extraversion—conscientiousness—inhibition and extraversion—agreeableness—gold—hindrance paths. Moreover, this study revealed that a causal asymmetry exists between the high and the not-high academic entrepreneurial intention configurations. This study broadens the application of the fuzzy set qualitative comparative analysis method in the research of academic entrepreneurial intention and provides theoretical and practical insights for researchers and practitioners on how to effectively stimulate scholars’ academic entrepreneurial intention.
The Effect and Mechanism of Cultural Capital on Chinese Residents’ Participation in Physical Activities
Authors: Ren Huitao , Liu Wei
Published: April 2022

Background

Using Bourdieu’s cultural capital theory, this paper discusses the inequality of Chinese urban residents’ participation in physical activities caused by cultural capital and explores the relationship and role of residents’ income and self-rated health in cultural capital and physical activity participation.

Methods

Using Chinese social survey data (2017), the proposed assumptions were tested and analyzed by using a linear regression model.

Results

Cultural capital can promote the participation of Chinese urban residents in physical activities, and personal income and health self-assessment play an intermediary role in promoting residents’ participation in physical activities.

Conclusion

Promoting Chinese residents’ participation in physical activities can be realized not only through traditional publicity and sports venue construction but also by increasing residents’ educational level, art appreciation level and health awareness.
Consumer Consciousness in Multisensory Extended Reality
Authors: Petit Olivia , Velasco Carlos , Wang Qian Janice , Spence Charles
Published: April 2022

The reality-virtuality continuum encompasses a multitude of objects, events and environments ranging from real-world multisensory inputs to interactive multisensory virtual simulators, in which sensory integration can involve very different combinations of both physical and digital inputs. These different ways of stimulating the senses can affect the consumer’s consciousness, potentially altering their judgements and behaviours. In this perspective paper, we explore how technologies such as Augmented Reality (AR) and Virtual Reality (VR) can, by generating and modifying the human sensorium, act on consumer consciousness. We discuss the potential impact of this altered consciousness for consumer behaviour while, at the same time, considering how it may pave the way for further research.
Validation of the Student Athletes’ Motivation Toward Sports and Academics Questionnaire (SAMSAQ) for Korean College Student-Athletes: An Application of Exploratory Structural Equation Modeling
Authors: Lee Youngjik , Immekus Jason , Lim Dayoun , Hums Mary , Greenwell Chris , Cocco Adam , Kang Minuk
Published: April 2022

The purpose of this study was to validate the Korean version of the Student-Athletes’ Motivation toward Sports and Academics Questionnaire (SAMSAQ) using exploratory structural equation modeling (ESEM). A total of 412 (men 77%; women 23%) South Korean collegiate student-athletes competing in 27 types of sports from 13 different public and private universities across South Korea were analyzed for this study. ESEM statistical approach was employed to examine the psychometric properties of SAMSAQ-KR. To assess content validity, the SAMSAQ-KR was inspected by a panel of content subject experts. The Athletic Identity Measurement Scale was used to obtain convergent validity. The results of this study illustrated that the SAMSAQ-KR appears to be a robust and reliable instrument.
The Effect of the Image of Destinations on Household Income and Distribution: Evidence From China’s Tourist Cities
Authors: Xu Sheng , Zhang Yunzhi , Yin Jinghua , Huang Guan
Published: April 2022

This paper examines the effect of the image of destinations on the wage income of resident households, and the corresponding income inequality, from a novel perspective. This work uses China’s excellent tourism city image program, which is an urban planning policy implemented by the central government across cities to enhance the image of the city destination in the minds of tourists, and then promote tourist motivation and local tourism development to assess the effect on household wage income and its distribution. Results show that the program significantly increases household wage income by increasing employment opportunities, promoting business and population agglomeration, and improving urban infrastructure. Additionally, the image of the city destination promotion causes an increase in income inequality among households.