bluuebunny/crossref_metadata_2025 huggingface dataset:
Multi-Omics Data Integration Analysis of an Immune-Related Gene Signature in LGG Patients With Epilepsy
Authors: Cheng Quan , Duan Weiwei , He Shiqing , Li Chen , Cao Hui , Liu Kun , Ye Weijie , Yuan Bo , Xia Zhiwei
Published: July 2021

Background

The tumor immune microenvironment significantly affects tumor occurrence, progression, and prognosis, but its impact on the prognosis of low-grade glioma (LGG) patients with epilepsy has not been reported. Hence, the purpose of this study is to explore its effect on LGG patients with epilepsy.

Methods

The data of LGG patients derived from the TCGA database. The level of immune cell infiltration and the proportion of 22 immune cells were evaluated by ESTIMATE and CIBERSORT algorithms, respectively. The Cox and LASSO regression analysis was adopted to determine the DEGs, and further established the clustering and risk score models. The association between genomic alterations and risk score was investigated using CNV and somatic mutation data. GSVA was adopted to identify the immunological pathways, immune infiltration and inflammatory profiles related to the signature genes. The Tumor Immune Dysfunction and Exclusion (TIDE) algorithm and GDSC database were used to predict the patient’s response to immunotherapy and chemotherapy, respectively.

Results

The prognosis of LGG patients with epilepsy was associated with the immune score. Three prognostic DEGs (ABCC3, PDPN, and INA) were screened out. The expression of signature genes was regulated by DNA methylation. The clustering and risk score models could stratify glioma patients into distinct prognosis groups. The risk score was an independent predictor in prognosis, with a high risk-score indicating a poor prognosis, more malignant clinicopathological and genomic aberration features. The nomogram had the better predictive ability. Patients at high risk had a higher level of macrophage infiltration and increased inflammatory activities associated with T cells and macrophages. While the higher percentage of NK CD56bright cell and more active inflammatory activity associated with B cell were present in the low-risk patients. The signature genes participated in the regulation of immune-related pathways, such as IL6-JAK-STAT3 signaling, IFN-α response, IFN-γ response, and TNFA-signaling-via-NFKB pathways. The high-risk patients were more likely to benefit from anti-PD1 and temozolomide (TMZ) treatment.

Conclusion

An immune-related gene signature was established based on ABCC3, PDPN, and INA, which can be used to predict the prognosis, immune infiltration status, immunotherapy and chemotherapy response of LGG patients with epilepsy.
Metabolic Profile and Neurogenic Potential of Human Amniotic Fluid Stem Cells From Normal vs. Fetus-Affected Gestations
Authors: Valiulienė Giedrė , Zentelytė Aistė , Beržanskytė Elizabet , Navakauskienė Rūta
Published: July 2021

Human amniotic fluid stem cells (hAFSCs) possess some characteristics with mesenchymal stem cells (MSCs) and embryonic stem cells and have a broader differentiation potential compared to MSCs derived from other sources. Although hAFSCs are widely researched, their analysis mainly involves stem cells (SCs) obtained from normal, fetus-unaffected gestations. However, in clinical settings, knowledge about hAFSCs from normal gestations could be poorly translational, as hAFSCs from healthy and fetus-diseased gestations may differ in their differentiation and metabolic potential. Therefore, a more thorough investigation of hAFSCs derived from pathological gestations would provide researchers with the knowledge about the general characteristics of these cells that could be valuable for further scientific investigations and possible future clinical applicability. The goal of this study was to look into the neurogenic and metabolic potential of hAFSCs derived from diseased fetuses, when gestations were concomitant with polyhydramnios and compare them to hAFSCs derived from normal fetuses. Results demonstrated that these cells are similar in gene expression levels of stemness markers (SOX2, NANOG, LIN28A, etc.). However, they differ in expression of CD13, CD73, CD90, and CD105, as flow cytometry analysis revealed higher expression in hAFSCs from unaffected gestations. Furthermore, hAFSCs from “Normal” and “Pathology” groups were different in oxidative phosphorylation rate, as well as level of ATP and reactive oxygen species production. Although the secretion of neurotrophic factors BDNF and VEGF was of comparable degree, as evaluated with enzyme-linked immunosorbent assay (ELISA) test, hAFSCs from normal gestations were found to be more prone to neurogenic differentiation, compared to hAFSCs from polyhydramnios. Furthermore, hAFSCs from polyhydramnios were distinguished by higher secretion of pro-inflammatory cytokine TNFα, which was significantly downregulated in differentiated cells. Overall, these observations show that hAFSCs from pathological gestations with polyhydramnios differ in metabolic and inflammatory status and also possess lower neurogenic potential compared to hAFSCs from normal gestations. Therefore, further in vitro and in vivo studies are necessary to dissect the potential of hAFSCs from polyhydramnios in stem cell-based therapies. Future studies should also search for strategies that could improve the characteristics of hAFSCs derived from diseased fetuses in order for those cells to be successfully applied for regenerative medicine purposes.
Evaluation of a Prototype of a Novel Galactomannan Sandwich Assay Using the VIDAS® Technology for the Diagnosis of Invasive Aspergillosis
Authors: Gallet Salomé , Garnaud Cécile , Dragonetti Céline , Rivoiron Sophie , Cognet Odile , Guo Yuping , Lesénéchal Mylène , Maubon Danièle , Cornet Muriel
Published: July 2021

Objectives

To evaluate the analytical and clinical performance of a prototype of a VIDAS® Galactomannan (GM) unitary test (bioMérieux, Marcy l’Etoile, France) and compare to that of the Platelia™ Aspergillus Ag assay (Bio-Rad, CA, USA).

Methods

Repeatability, reproducibility, and freeze-thaw stability of VIDAS®GM were evaluated. Sera from patients at risk of IA were concurrently tested with both the VIDAS®GM and Platelia™ Aspergillus Ag assays. Correlations between the two assays were assessed by Passing Bablok (PB) regression and performance by ROC analysis.

Results

The correlations between the VIDAS®GM indexes after one and two cycles of freezing/thawing were r=1.00 and r=0.989, respectively. The coefficients of variation for negative, low-positive, and positive sera were 13%, 6%, and 5% for repeatability and 14.4%, 7.2%, and 5.5% for reproducibility. Overall, 126 sera were tested with both assays (44 fresh and 82 frozen). The correlation between VIDAS®GM and Platelia™ Aspergillus Ag was r=0.798. The areas under the curve of the ROC analyses were 0.892 and 0.894, for VIDAS®GM and Platelia™ Aspergillus Ag, respectively.

Conclusions

This new VIDAS®GM prototype assay showed adequate analytical and clinical performance and a good correlation with that of Platelia™ Aspergillus Ag with 126 sera, although these results need to be confirmed in a larger prospective and multicentric study. As for the other VIDAS® assays, VIDAS®GM is a single-sample automated test using a solid reagent strip and receptacle. It is easy to use and suitable for rapid on-demand test results.
The Representation of Earthquakes in Hindu Religion: A Literature Review to Improve Educational Communications in Nepal
Authors: Subedi Shiba , Hetényi György
Published: July 2021

In Nepal, after every large earthquake, local people appear to be motivated to get better prepared for future earthquakes. However, their motivation vanishes before effective preparation, mainly due to the lack of earthquake education in their community. Promoting up-to-date scientific knowledge to a society living under high earthquake hazard is important and contributes to reduce the related risk. The dissemination of information in Nepal lags far behind modern seismological knowledge, and part of the local population still believes in religious explanations and stories about earthquakes. We run an educational program in Nepal to make people better aware of earthquakes and to improve their preparedness through obligatory school education, but the dichotomy between scientific and religious visions of earthquakes remains a challenge. For more efficient acceptance of earthquake preparatory advices, it is important to better perceive the religious narration of earthquakes and to include these in the educational communications. Thereby, we reviewed the main sources of Hindu literature and gathered relevant and interesting explanations on earthquake evidences and causes. The primary religious interpretations of earthquakes in different Hindu texts are related to the Gods and their actions, and some sources also include physical descriptions of earthquakes related situations or processes. We found that most of the stories, causes and explanations of earthquake do not match with the concepts of modern science, yet there are exceptions such as a historically old advice to leave buildings during the shaking. The collected findings are important not only from a religious literature review perspective, but also and mainly to develop an inclusive and more efficient strategy to communicate about earthquake related topics in the classroom as well as with the public in Nepal.
Influence of Regional Erosion and Sedimentary Loading on Fault Activities in Active Fold-Thrust Belts: Insights From Discrete Element Simulation and the Southern and Central Longmen Shan Fold-Thrust Belt
Authors: Wu Zhenyun , Yin Hongwei , Li Changsheng , Yang Xiulei , Wang Li , Wang Fuyuan , Dong Shaochun , Jia Dong
Published: July 2021

Four groups of discrete element models (DEMs) were set-up to simulate and analyze the influence of regional erosion and sedimentary loading on the formation and spatial-temporal evolution of faults in the southern and central Longmen Shan (LMS) active fold-thrust belt. The interior characteristics of faults in the southern and central LMS fold-thrust belt were also evaluated during the interaction of tectonic processes and surface processes according to the stress-strain analysis from DEM results. The results showed that synkinematic erosion promoted the reactivation of pre-existing faults in thrust wedges and also retarded the formation and development of new incipient faults in the pre-wedge regions. Meanwhile, synkinematic sedimentation also delayed the development of new incipient faults in the pre-wedge regions by promoting the development of thrust faults in the front of thrust wedges, causing these thrust wedges in supercritical stages with relatively narrow wedge lengths. According to these DEM results, we infer that: 1) The characteristics of erosion and sedimentation in the central and southern LMS have important influences on the activities of large faults which are extended into the deep detachment layer; 2) Besides differential erosion, the differential sedimentary loading may also be one of the important factors for the along-strike differential evolution of the LMS fold-thrust belt. This kind of differential deposition may lead to differential fault activity and uplift in the interior thrust wedge and pre-wedge region in the central and southern LMS; 3) Compared to the northern LMS, the central LMS and southern LMS is more conducive to the occurrence of earthquakes, because of synkinematic sedimentation (such as the growth of Chengdu plain) has a greater blocking effect on the stress propagation and strain convergence on the fault planes of front faults of an active thrust wedge.
Dismantling Persistent Deficit Narratives About the Language and Literacy of Culturally and Linguistically Minoritized Children and Youth: Counter-Possibilities
Authors: Wang Su-hua , Lang Nora , Bunch George C. , Basch Samantha , McHugh Sam R. , Huitzilopochtli Salvador , Callanan Maureen
Published: July 2021

Despite decades of efforts, deficit narratives regarding language development and use by children and students from historically marginalized backgrounds remain persistent in the United States. Examining selective literature, we discuss the ideologies that undergird two deficit narratives: the notion that some children have a “word gap” when compared to their White middle-class peers, and students must develop “academic language” to engage in rigorous content learning. The “word gap” concept came from a study wherein a group of young children in low-income families heard fewer words than those in middle-class families. It assumes that language can only be acquired in one way—vocabulary exchange from one parent to one child—and ignores decades of research on diverse pathways for language development. We highlight an alternative perspective that language development builds on children’s experience with cultural practices and the harm on minoritized children by privileging a specific form of vocabulary acquisition. The second deficit narrative concerns “academic language,” a concept championed by scholars aiming to address educational inequity. The construct runs the risk of undervaluing the potential of students from historically marginalized backgrounds to engage in learning using language that is “informal,” nonconventional, or “non-native like.” It also is sometimes used as a rationale to relegate students to special programs isolated from more rigorous academic discourse, thus ironically removing them from opportunities to develop the academic registers they are deemed to be missing. We explore alternative frameworks that shift the focus from linguistic features of academic talk and texts as prerequisites for academic work to the broad range of linguistic resources that students employ for academic purposes in the classroom. Finally, we turn to a positive approach to youths’ language development and use: translanguaging by multilingual learners and their teachers. Translanguaging demonstrates the power of a resource-oriented perspective that values students’ rich communicative repertoires and actively seeks to disrupt language hierarchies. We argue that this approach, however, must be considered in relation to the broader social context to meet its transformative aims. Together, our analysis suggests counter-possibilities to dismantle deficit-oriented narratives and points to promising directions for research and practices to reduce inequity in education.
Evaluation of Passive Safety Injection System Performance Under Large Break LOCA for Qinshan PWR
Authors: Wang Xuesong , Sun Lin , Liu Meiru , Xia Genglei
Published: July 2021

In this work, a brand new passive safety injection system has been designed for the ocean-based Qinshan Phase I nuclear power plant to update and replace the traditional active ones. The passive safety injection system is made up of high pressure, medium pressure, lower pressure safety injection system, and a two-stage automatic depressurization system. To evaluate the safety injection system performance, double-ended cold leg large break LOCA has been analyzed by best-estimated safety analysis RELAP5 code. The main operation and safety parameters such as primary system pressure, safe injection mass flow rates, core water level, and peak cladding temperature have been presented. The results conclude that the safety injection system can act as similar to that of the AP1000, which can assure sufficient core cooling and keep the reactor covered by the cold water under the most severe LBLOCA condition.
Predicting lncRNA–Protein Interaction With Weighted Graph-Regularized Matrix Factorization
Authors: Sun Xibo , Cheng Leiming , Liu Jinyang , Xie Cuinan , Yang Jiasheng , Li Fu
Published: July 2021

Long non-coding RNAs (lncRNAs) are widely concerned because of their close associations with many key biological activities. Though precise functions of most lncRNAs are unknown, research works show that lncRNAs usually exert biological function by interacting with the corresponding proteins. The experimental validation of interactions between lncRNAs and proteins is costly and time-consuming. In this study, we developed a weighted graph-regularized matrix factorization (LPI-WGRMF) method to find unobserved lncRNA–protein interactions (LPIs) based on lncRNA similarity matrix, protein similarity matrix, and known LPIs. We compared our proposed LPI-WGRMF method with five classical LPI prediction methods, that is, LPBNI, LPI-IBNRA, LPIHN, RWR, and collaborative filtering (CF). The results demonstrate that the LPI-WGRMF method can produce high-accuracy performance, obtaining an AUC score of 0.9012 and AUPR of 0.7324. The case study showed that SFPQ, SNHG3, and PRPF31 may associate with Q9NUL5, Q9NUL5, and Q9UKV8 with the highest linking probabilities and need to further experimental validation.
Crosslink: An R Package for Network Visualization of Grouped Nodes
Authors: Liu Di , Bai Zhijie , Liu Bing , Li Zongcheng
Published: July 2021

The demand for network visualization of relationships between nodes attributed to different categories grows in various biomedical research scenarios, such as gene regulatory networks, drug-target networks, ligand-receptor interactions and association networks of multi-omics elements. Elegantly visualizing the relationships between nodes with complex metadata of nodes and edges appended may inspire new insights. Here, we developed the crosslink R package, tailored for network visualization of grouped nodes, to provide a series of flexible functions for generating network diagrams. We first designed a CrossLink class for storage of metadata about nodes and edges and manipulation of node coordinates. Then affine transformation and function mapping transformation are implemented to perform fundamental node coordinates transformation by groups, based on which various network layouts can be defined easily. For convenience, we predefined several commonly used layouts, including row, column, arc, polygon and hive, which also can be combined in one layout. Finally, we designed a user-friendly wrapper function to draw network connections, aesthetic mappings of metadata and decoration with related annotation graphs in one interface by taking advantage of the powerful ggplot2 system. Overall, the crosslink R package is easy-to-use for achieving complex visualization of a network diagram of grouped nodes surrounded by associated annotation graphs.

Availability and Implementation

Cosslink is an open-source R package, freely available from github:https://github.com/zzwch/crosslink; A detailed user documentation can be found inhttps://zzwch.github.io/crosslink/.
Trade Exports Predict Regional Ballast Water Discharge by Ships in San Francisco Bay
Authors: Verna Danielle E. , Minton Mark S. , Ruiz Gregory M.
Published: July 2021

Biological invasions often result from transfers of organisms during trade activities. In coastal ecosystems, commercial ships are a dominant source of species transfers globally, and ships’ ballast water (BW) is a major focus of biosecurity management and policy to reduce invasions. While trade drives shipping patterns, diverse vessel types and behaviors exist such that the quantitative relationship between trade and BW dynamics is still poorly resolved, limiting both science and management. Here, we evaluated a new method to predict BW discharge using trade data, by explicitly considering known BW practices according to vessel and commodity type. Specifically, we estimated the relationship between tonnage of overseas exports and BW discharge volume for San Francisco Bay (SFB), California, as a model system to demonstrate this approach. Using extensive datasets on shipborne exports and BW discharge, we (a) evaluated spatial and temporal patterns across nearly 20 ports in this estuary from 2006 to 2014 and (b) developed a predictive model to estimate overseas BW discharge volume from foreign export tonnage for the whole estuary. Although vessel arrivals in SFB remained nearly constant from 2006 to 2014, associated tonnage of exported commodities more than doubled and BW discharge more than tripled. Increased BW volume resulted from increased frequency and per capita discharge of bulk carriers from Asia and tankers from western Central America and Hawaii, reflecting shifts in direction of commodity movement. The top 11 export commodities (59% of total export tonnage) were transported on bulk carriers or tankers. In a multivariate linear model, annual tonnage of these top 11 export commodities by vessel type were strong predictors of total bay-wide overseas BW discharge (adjusted R2 = 0.92), creating the potential to estimate past or future BW delivery in SFB. Bulk export tonnage provides valuable insights into BW flux, since most BW discharge to ports is driven by trade of bulk commodities and the behavior of bulk and tank ships. BW discharge data are unavailable for many regions and time periods, whereas trade data are widely available and can provide a reliable proxy estimate of BW volume and geographic source, which are both critical to evaluate invasion risk.
The Characteristic of Critical Genes in Neuroendocrine System and Their Regulation on Food Habit Transition and Metamorphosis of Veined Rapa Whelk Rapana venosa (Valenciennes, 1846)
Authors: Yang Mei-Jie , Feng Jie , Song Hao , Yu Zheng-Lin , Shi Pu , Liang Jian , Hu Zhi , Zhou Cong , Wang Xiao-Lin , Zhang Tao
Published: July 2021

Metamorphosis is a critical developmental event in mollusks, and neuroendocrine system plays an essential role in this process. Rapana venosa is an economically important shellfish in China, but the artificial technology of R. venosa aquaculture is limited by metamorphosis. As a carnivorous gastropod, food habit transition makes the mechanism of R. venosa metamorphosis more complex. To investigate the changes in the neuroendocrine system and to reveal its role in regulating the food habit transition and metamorphosis of R. venosa, we cloned the cDNA sequences encoding 5-hydroxytryptamine receptor (Rv-5HTR), nitric oxide synthetase (Rv-NOS) and cholecystokinin receptor (Rv-CCKR), and investigated their expression by quantitative real-time PCR analysis, and explore the spatio-temporal changes of 5-HT protein expression using Immunohistochemical (IHC) analysis. The expression of the three geens was significantly increased in the early intramembrane veliger stage, which indicates that the three genes are related to the development of digestive system. Additionally, expression of the three genes was decreased after metamorphosis, while Rv-NOS and Rv-CCKR were increasingly expressed in competent larvae, which may help the larvae find suitable environments and promote digestive system development for metamorphosis, and the result of 5-HT IHC analysis also reflects the development of neuroendocrine system. Furthermore, results show that CCK can effect the expression of digestive enzyme, NOS and 5-HT receptor. Finally, based on the present results, we hypothesized that CCK and CCK receptor may be critical regulatory factors of food habit transition and metamorphosis. These results might provide information on the development of neuroendocrine system of R. venosa, and new insight into the regulation of the food habit transition and metamorphosis of gastropods.
Antimicrobial Defensin and DNA Traps in Manila Clam Ruditapes philippinarum: Implications for Their Roles in Immune Responses
Authors: Han Yijing , Hu Gege , Chen Yuying , Chen Lizhu , Yu Daode , Zhang Qianqian , Yang Dinglong
Published: July 2021

Although defensins have been isolated from a variety of metazoan, their role in cellular immunity has not been answered. In the study, we found that the hemocytes of the Manila clams Ruditapes philippinarum release defensin (designated as Rpdef3) in response to Vibrio parahaemolyticus challenge. The antimicrobial Rpdef3 was proved to be involved in the extracellular traps (ETs) that hemocytes released in response to Vibrio challenge. Scanning electron microscopy observation proved the patterns how ETs eliminate invading bacteria. Furthermore, Rpdef3 involved in ETs had broad-spectrum antimicrobial effect on both Gram-negative bacteria and Gram-positive bacteria. ELISA assay revealed that Rpdef3 could bind lipopolysaccharides and peptidoglycan in a dose-dependent manner. As concerned to the antibacterial mechanisms, Rpdef3 can cause bacterial membrane permeabilization, leading to cell death. As a result, Rpdef3 might contribute to the trap and the elimination of invading Vibrio in clam ETs. Taken together, our study suggest that the formation of ETs is a defense mechanism triggered by bacterial stimulation, coupled with antibacterial defensin.
Exploring the Clinical Characteristics of COVID-19 Clusters Identified Using Factor Analysis of Mixed Data-Based Cluster Analysis
Authors: Han Liang , Shen Pan , Yan Jiahui , Huang Yao , Ba Xin , Lin Weiji , Wang Hui , Huang Ying , Qin Kai , Wang Yu , Chen Zhe , Tu Shenghao
Published: July 2021

The COVID-19 outbreak has brought great challenges to healthcare resources around the world. Patients with COVID-19 exhibit a broad spectrum of clinical characteristics. In this study, the Factor Analysis of Mixed Data (FAMD)-based cluster analysis was applied to demographic information, laboratory indicators at the time of admission, and symptoms presented before admission. Three COVID-19 clusters with distinct clinical features were identified by FAMD-based cluster analysis. The FAMD-based cluster analysis results indicated that the symptoms of COVID-19 were roughly consistent with the laboratory findings of COVID-19 patients. Furthermore, symptoms for mild patients were atypical. Different hospital stay durations and survival differences among the three clusters were also found, and the more severe the clinical characteristics were, the worse the prognosis. Our aims were to describe COVID-19 clusters with different clinical characteristics, and a classifier model according to the results of FAMD-based cluster analysis was constructed to help provide better individualized treatments for numerous COVID-19 patients in the future.
Subthreshold Micropulse Laser vs. Conventional Laser for Central Serous Chorioretinopathy: A Randomized Controlled Clinical Trial
Authors: Zhou Lijun , Lai Kunbei , Jin Ling , Huang Chuangxin , Xu Fabao , Gong Yajun , Li Longhui , Zhu Zhe , Lu Lin , Jin Chenjin
Published: July 2021

Purpose: To investigate the effectiveness and safety of 577-nm subthreshold micropulse laser (SML) on acute central serous chorioretinopathy (CSC).

Methods: One hundred and ten patients with acute CSC were randomized to receive SML or 577-nm conventional laser (CL) treatment. Optical coherence tomography and best-corrected visual acuity (BCVA) were performed before and after treatment.

Results: At 3 months, the complete resolution of subretinal fluid (SRF) in 577-nm SML group (72.7%) was lower than that in CL group (89.1%) (Unadjusted RR, 0.82; P = 0.029), but it was 85.5 vs. 92.7% at 6 months (unadjusted RR, 0.92; P = 0.221). The mean LogMAR BCVA significantly improved, and the mean central foveal thickness (CFT) significantly decreased in the SML group and CL group (all P < 0.001) at 6 months. But there was no statistical difference between the two groups (all P > 0.05). In the SML group, obvious retinal pigment epithelium (RPE) damage was shown only in 3.64% at 1 month but 92.7% in the CL group (P < 0.001).

Conclusions: Although 577-nm SML has a lower complete absorption of SRF compared with 577-nm CL for acute CSC at 3 months, it is similarly effective as 577-nm CL on improving retinal anatomy and function at 6 months. Importantly, 577-nm SML causes less damage to the retina.
Treatment of COVID-19 in Patients With Sarcoidosis
Authors: Kondle Shreya , Hou Titus , Manansala Michael , Ascoli Christian , Novak Richard M. , Sweiss Nadera
Published: July 2021

Recent case reports and studies on treating COVID-19 in patients with chronic sarcoidosis describe different treatment modalities ranging from glucocorticoids to biologic medications. This review article summarizes seven case series and reports totaling 46 patients. While one case report suggested that sarcoidosis medications such as glucocorticoids may lengthen the COVID-19 disease course, another study with a larger registry suggests they do not. More studies are needed to elucidate an improvement in outcomes. It is possible that addition of TNF-alpha inhibitors at COVID-19 diagnosis decreases hospitalization rate. Overall, it is difficult to make firm conclusions regarding treatment given the heterogeneity of treatment modalities in the current literature. Our summarized findings are outlined with the opinions of sarcoidosis, pulmonary, and infectious disease experts in a flow chart that provides clinicians with our proposed management algorithm for sarcoidosis patients who develop COVID-19. We emphasize a need for exchange of information regarding management of COVID-19 in the setting of sarcoidosis to further improve treatment in this vulnerable population of patients.
Endophytic Fungal Community of Tobacco Leaves and Their Potential Role in the Formation of “Cherry-Red” Tobacco
Authors: Jiang Yonglei , Chen Xing , Zhao Gaokun , Liu Jiahong , Xie Yan , Li Yong , Gu Huaguo , Zou Congming
Published: July 2021

“Cherry-red” tobacco is the superior variant of tobacco, appearing with the apperance of red dapples on cured leaves due to the demethylation of nicotine to nornicotine during maturation and curing. Fungi are known to have the capacity to convert nicotine to nornicotine. However, an endophytic fungal community of “cherry-red” tobacco has never been reported to our best knowledge. Here, we sampled mature leaves from both “cherry-red” and ordinary tobacco at lower, center, and upper plant sections, and we analyzed the ITS diversity using high-throughput sequencing. Results revealed a significantly different fungal community of foliar endophyte in “cherry-red” and ordinary tobacco. In comparison to the ordinary control, higher diversity and a co-occurrence network complex were found in “cherry-red” samples, especially in the center and upper leaves, where the red dapples mainly emerged. More taxa were enriched in the “cherry-red” than ordinary tobacco leaves at all plant sections. In particular, Aspergillus, some strains of which are reported capable of converting nicotine to nornicotine, was specifically enriched in upper “cherry-red” tobacco leaves, which showed most red dapples after curing. A less robust network structure was detected in the “cherry-red” tobacco compared to ordinary tobacco. The nearest taxon index (NTI) and β NTI indicated that the local community structuration of tobacco endophytic fungi mainly driven by deterministic process, while the community turnover among plant sections was stochastic. In conclusion, our study provides the earliest information of endophytic fungal community in “cherry-red” tobacco leaf, and the community diversity, composition, and network features are synchronously varied with the appearance of red dapples, which is suggestive of their relationship to the formation of “cherry-red” tobacco.
Intestinal Fibrosis and Gut Microbiota: Clues From Other Organs
Authors: Zhan Shukai , Li Na , Liu Caiguang , Mao Ren , Wu Dongxuan , Li Tong , Chen Minhu , Zhuang Xiaojun , Zeng Zhirong
Published: July 2021

Fibrosis is a complex and difficult to elucidate pathological process with no available therapies. Growing evidence implicates intestinal microbiota in the occurrence and development of fibrosis, and the potential mechanisms involved in different organs have been explored in several studies. In this review, we summarize the causative and preventive effects of gut microbiota on intestinal fibrosis, as well as the relationships between gut microbiota and fibrosis in other organs. Interestingly, several colonized microbes are associated with fibrosis via their structural components and metabolic products. They may also play essential roles in regulating inflammation and fibroblast activation or differentiation, which modulates extracellular matrix formation. While the relationships between intestinal fibrosis and gut microbiota remain unclear, lessons can be drawn from the effects of gut microbiota on hepatic, cardiac, nephritic, and pulmonary fibrosis. Various intestinal microbes alterations have been detected in different fibrotic organs; however, the results were heterogeneous. Mechanisms by which the intestinal microbiota regulate fibrotic processes in other organs, such as novel metabolic products or specific microbes, are also discussed. The specific microbiota associated with fibrosis in other organs could instruct future studies aiming to discover prospective mechanisms regulating intestinal fibrosis.
Management Based on Multimodal Brain Monitoring May Improve Functional Connectivity and Post-operative Neurocognition in Elderly Patients Undergoing Spinal Surgery
Authors: Yang Shuyi , Xiao Wei , Wu Hao , Liu Yang , Feng Shuai , Lu Jie , Wang Tianlong
Published: July 2021

Perioperative neurocognitive disorder (PND) is a common condition in elderly patients undergoing surgery. Sedation, analgesia, regional cerebral oxygen saturation (rSO2), and body temperature are known to be associated with PND, but few studies have examined the contribution of these factors combined in detail. This prospective, randomized, controlled, double-blinded study investigated whether anesthesia management based on multimodal brain monitoring—an anesthesia management algorithm designed by our group—could improve the post-operative cognitive function and brain functional connectivity (FC) in elderly patients undergoing elective spinal surgery with general anesthesia. The patients (aged ≥65 years) were randomized into two groups [control (Group C), n = 12 and intervention (Group I), n = 14]. Patients in Group I were managed with multimodal brain monitoring (patient state index, spectral edge frequency, analgesia nociception index, rSO2, and temperature), and those in Group C were managed with routine anesthesia management. All patients were pre- and post-operatively evaluated (7 days after surgery) with the Montreal Cognitive Assessment (MoCA). Amplitude of low-frequency fluctuation (ALFF) and FC were analyzed after resting-state functional MRI. Serum C-reactive protein (CRP) and lipopolysaccharide levels were measured, and the correlation between FC and changes in inflammatory marker levels was analyzed. Mean post-operative MoCA score was higher in Group I (24.80 ± 2.09) than in Group C (22.56 ± 2.24) (p = 0.04), with no difference in PND incidence between groups (28.57 vs. 16.67%; p = 0.47). Group I also showed significantly increased ALFF values in several brain regions after surgery (p < 0.05), and FC between the left hippocampus and left orbital inferior frontal gyrus (FG), left middle FG, left superior temporal gyrus, and left precentral gyrus was enhanced (p < 0.05), which was negatively correlated with the change in serum CRP (pre vs. post-intervention) (R = −0.58, p = 0.01). These results suggest that management of elderly patients undergoing surgery by multimodal brain monitoring may improve post-operative neurocognition and FC by reducing systemic inflammation.

Clinical Trial Registration:http://www.chictr.org.cn/index.aspx, identifier: ChiCTR1900028024.
An Inexpensive, High-Precision, Modular Spherical Treadmill Setup Optimized for Drosophila Experiments
Authors: Loesche Frank , Reiser Michael B.
Published: July 2021

To pursue a more mechanistic understanding of the neural control of behavior, many neuroethologists study animal behavior in controlled laboratory environments. One popular approach is to measure the movements of restrained animals while presenting controlled sensory stimulation. This approach is especially powerful when applied to genetic model organisms, such as Drosophila melanogaster, where modern genetic tools enable unprecedented access to the nervous system for activity monitoring or targeted manipulation. While there is a long history of measuring the behavior of body- and head-fixed insects walking on an air-supported ball, the methods typically require complex setups with many custom components. Here we present a compact, simplified setup for these experiments that achieves high-performance at low cost. The simplified setup integrates existing hardware and software solutions with new component designs. We replaced expensive optomechanical and custom machined components with off-the-shelf and 3D-printed parts, and built the system around a low-cost camera that achieves 180 Hz imaging and an inexpensive tablet computer to present view-angle-corrected stimuli updated through a local network. We quantify the performance of the integrated system and characterize the visually guided behavior of flies in response to a range of visual stimuli. In this paper, we thoroughly document the improved system; the accompanying repository incorporates CAD files, parts lists, source code, and detailed instructions. We detail a complete ~$300 system, including a cold-anesthesia tethering stage, that is ideal for hands-on teaching laboratories. This represents a nearly 50-fold cost reduction as compared to a typical system used in research laboratories, yet is fully featured and yields excellent performance. We report the current state of this system, which started with a 1-day teaching lab for which we built seven parallel setups and continues toward a setup in our lab for larger-scale analysis of visual-motor behavior in flies. Because of the simplicity, compactness, and low cost of this system, we believe that high-performance measurements of tethered insect behavior should now be widely accessible and suitable for integration into many systems. This access enables broad opportunities for comparative work across labs, species, and behavioral paradigms.
High-Dose Fluorescein Reveals Unusual Confocal Endomicroscope Imaging of Low-Grade Glioma
Authors: Belykh Evgenii , Onaka Naomi R. , Zhao Xiaochun , Abramov Irakliy , Eschbacher Jennifer M. , Nakaji Peter , Preul Mark C.
Published: July 2021

Background: Fluorescence-guided brain tumor surgery using fluorescein sodium (FNa) for contrast is effective in high-grade gliomas. However, the effectiveness of this technique for visualizing noncontrast-enhancing and low-grade gliomas is unknown. This report is the first documented case of the concurrent use of wide-field fluorescence-guided surgery and confocal laser endomicroscopy (CLE) with high-dose FNa (40 mg/kg) for intraoperative visualization of tumor tissue cellularity in a nonenhancing glioma.

Case Description: A patient underwent fluorescence-guided surgery for a left frontal lobe mass without contrast enhancement on magnetic resonance imaging. The patient received 40 mg/kg FNa intravenously at the induction of anesthesia. Surgery was performed under visualization with a Yellow 560 filter and white-light wide-field imaging. Intraoperative CLE produced high-quality images of the lesion 1.5 h after FNa injection. Frozen-section analysis demonstrated findings comparable to those of intraoperative CLE visualization and consistent with World Health Organization (WHO) glioma grades II–III. The patient recovered without complications. Analysis of the permanent histologic sections identified the tumor as an anaplastic oligodendroglioma, IDH-mutant, 1p/19q co-deleted, consistent with WHO grade III because of discrete foci of hypercellularity and increased mitotic figures, but large regions of the lesion were low grade.

Conclusions: The use of high-dose FNa in this patient with a nonenhancing borderline low-grade/high-grade glioma produced actionable wide-field fluorescence imaging using the operating microscope and improved CLE visualization of tumor cellularity. Higher doses of FNa for intraoperative CLE imaging and possible simultaneous wide-field fluorescence surgical guidance in nonenhancing gliomas merit further investigation.
Epileptic Seizures After Allogeneic Hematopoietic Stem Cell Transplantation
Authors: Wang Zhuo , Zhao Munan , Gao Sujun
Published: July 2021

Technique in allogeneic hematopoietic stem cell transplantation has greatly advanced over the past decades, which has led to an increase in the number of patients receiving transplantation, but the complex procedure places these transplant recipients at high risk of a large spectrum of complications including neurologic involvement. As a common manifestation of neurological disorders, epileptic seizures after transplantation have been of great concern to clinicians because it seriously affects the survival rate and living quality of those recipients. The aim of this review is to elucidate the incidence of seizures after allogeneic hematopoietic stem cell transplantation, and to further summarize in detail its etiologies, possible mechanisms, clinical manifestations, therapeutic schedule, and prognosis, hoping to improve doctors' understandings of concurrent seizures following transplantation, so they can prevent, process, and eventually improve the survival and outlook for patients in a timely manner and correctly.
Spin in Published Reports of Tinnitus Randomized Controlled Trials: Evidence of Overinterpretation of Results
Authors: Velde Hedwig M. , van Heteren Jan A. A. , Smit Adriana L. , Stegeman Inge
Published: July 2021

Background: Spin refers to reporting practices that could distort the interpretation and mislead readers by being more optimistic than the results justify, thereby possibly changing the perception of clinicians and influence their decisions. Because of the clinical importance of accurate interpretation of results and the evidence of spin in other research fields, we aim to identify the nature and frequency of spin in published reports of tinnitus randomized controlled trials (RCTs) and to assess possible determinants and effects of spin.

Methods: We searched PubMed systematically for RCTs with tinnitus-related outcomes published from 2015 to 2019. All eligible articles were assessed on actual and potential spin using prespecified criteria.

Results: Our search identified 628 studies, of which 87 were eligible for evaluation. A total of 95% of the studies contained actual or potential spin. Actual spin was found mostly in the conclusion of articles, which reflected something else than the reported point estimate (or CI) of the outcome (n = 34, 39%) or which was selectively focused (n = 49, 56%). Linguistic spin (“trend,” “marginally significant,” or “tendency toward an effect”) was found in 17% of the studies. We were not able to assess the association between study characteristics and the occurrence of spin due to the low number of trials for some categories of the study characteristics. We found no effect of spin on type of journal [odds ratio (OR) −0.13, 95% CI −0.56–0.31], journal impact factor (OR 0.17, 95% CI −0.18–0.51), or number of citations (OR 1.95, CI −2.74–6.65).

Conclusion: There is a large amount of spin in tinnitus RCTs. Our findings show that there is room for improvement in reporting and interpretation of results. Awareness of different forms of spin must be raised to improve research quality and reduce research waste.
Prediction of Second Language Proficiency Based on Electroencephalographic Signals Measured While Listening to Natural Speech
Authors: Ihara Aya S. , Matsumoto Atsushi , Ojima Shiro , Katayama Jun’ichi , Nakamura Keita , Yokota Yusuke , Watanabe Hiroki , Naruse Yasushi
Published: July 2021

This study had two goals: to clarify the relationship between electroencephalographic (EEG) features estimated while non-native speakers listened to a second language (L2) and their proficiency in L2 determined by a conventional paper test and to provide a predictive model for L2 proficiency based on EEG features. We measured EEG signals from 205 native Japanese speakers, who varied widely in English proficiency while they listened to natural speech in English. Following the EEG measurement, they completed a conventional English listening test for Japanese speakers. We estimated multivariate temporal response functions separately for word class, speech rate, word position, and parts of speech. We found significant negative correlations between listening score and 17 EEG features, which included peak latency of early components (corresponding to N1 and P2) for both open and closed class words and peak latency and amplitude of a late component (corresponding to N400) for open class words. On the basis of the EEG features, we generated a predictive model for Japanese speakers’ English listening proficiency. The correlation coefficient between the true and predicted listening scores was 0.51. Our results suggest that L2 or foreign language ability can be assessed using neural signatures measured while listening to natural speech, without the need of a conventional paper test.
Efficacy and Prognostic Factors of Trans-Arterial Chemoembolization Combined With Stereotactic Body Radiation Therapy for BCLC Stage B Hepatocellular Carcinoma
Authors: Jiang Changchen , Jing Shenghua , Zhou Han , Li Aomei , Qiu Xiangnan , Zhu Xixu , Shen Zetian
Published: July 2021

Purpose

This study aimed to evaluate the efficacy and safety of trans-arterial chemoembolization (TACE) followed by stereotactic body radiation therapy (SBRT) in treating Barcelona Clinic Liver Cancer (BCLC) stage B hepatocellular carcinoma (HCC) not amenable to resection and radiofrequency ablation (RFA).

Methods

From February 2012 to January 2017, a total of 57 BCLC stage B HCC patients who were unsuitable candidates for resection and RFA treated with TACE combined with CyberKnife SBRT were included in this retrospective study. Patients underwent TACE for a median of two times (1–5 times) before SBRT. SBRT prescription doses ranged from 30 Gy to 50 Gy in 3–5 fractions.

Results

The median follow-up time was 42 months. The objective response rate (CR + PR) was 85.9%, and the disease control rate (CR + PR + SD) was 96.5%. The local control (LC) rates were 91.1% and 84.3% at 1 and 2 years, respectively. The 1-, 2-, 3-year overall survival (OS) and the median survival time were 73.2%, 51.4%, 32.4% and 26.6 months, respectively. The 1-, 2-, and 3-year progression-free survival (PFS) were 34.2%, 21.6%, and 9%, respectively, with a median PFS time of 9.7 months. A subgroup analysis was conducted in 32 patients with AFP ≥ 200 ng/ml before TACE. OS was significantly prolonged in those with AFP that decreased by more than 75% than those with AFP that decreased by less than 75% (P = 0.018) after SBRT. The treatment was well tolerated with only one patient (1.8%) developed grade 3 gastrointestinal toxicity, and another patient developed non-classical RILD. In multivariate analysis, tumor length ≥ 10 cm and AFP ≥ 200 ng/ml were independent poor prognostic factors for OS.

Conclusion

The combination of TACE and Cyberknife SBRT showed optimal efficacy with acceptable toxicity for BCLC stage B HCC.