bluuebunny/crossref_metadata_2025 huggingface dataset:
The Presence of Circulating Nucleated Red Blood Cells Is Associated With Disease Severity in Patients of Hemorrhagic Fever With Renal Syndrome
Authors: Zhang Jingang , Tang Kang , Zhang Yun , Ma Ying , Zhang Chunmei , Hu Haifeng , Jia Xiaozhou , Zhuang Ran , Jin Boquan , Wang Meng , Zhang Xiyue , Liu Dalu , Zhang Yusi
Published: May 2021

Hemorrhagic fever with renal syndrome (HFRS) is a regional infectious disease of epidemic potential caused by the Hantaan virus (HTNV). Red blood cells (RBCs) are the major components of peripheral blood. However, pathological changes in RBCs and the underlying mechanisms during HTNV infection remain largely unclear. Therefore, this study sought to explore changes in RBCs in the peripheral blood of HFRS patients. We isolated PBMCs from HFRS patients and performed single-cell RNA sequencing. The results showed that clusters of RBCs in the peripheral blood of HFRS could be classified as nucleated red blood cells (NRBC) based on their cellular components, gene expression profiles and cell surface markers. In addition, it was shown that the higher the count of NRBC in peripheral blood, the more severe the disease status was. Moreover, hematological indices related to RBCs were analyzed and the results showed that impairment in the folate pathway might be the possible reason behind the presence of NRBCs. This study, for the first time showed that the presence of NRBCs in the peripheral blood of HFRS patients was associated with disease severity. This was also the first study to show that infection with the HTNV virus hindered the maturation of RBCs. Therefore, this work provides further insights on the role of and pathological changes in RBCs during HTNV infection.
Cellulolytic and Xylanolytic Microbial Communities Associated With Lignocellulose-Rich Wheat Straw Degradation in Anaerobic Digestion
Authors: Jensen Mads Borgbjerg , de Jonge Nadieh , Dolriis Maja Duus , Kragelund Caroline , Fischer Christian Holst , Eskesen Martin Rosenørn , Noer Karoline , Møller Henrik Bjarne , Ottosen Lars Ditlev Mørck , Nielsen Jeppe Lund , Kofoed Michael Vedel Wegener
Published: May 2021

The enzymatic hydrolysis of lignocellulosic polymers is generally considered the rate-limiting step to methane production in anaerobic digestion of lignocellulosic biomass. The present study aimed to investigate how the hydrolytic microbial communities of three different types of anaerobic digesters adapted to lignocellulose-rich wheat straw in continuous stirred tank reactors operated for 134 days. Cellulase and xylanase activities were monitored weekly using fluorescently-labeled model substrates and the enzymatic profiles were correlated with changes in microbial community compositions based on 16S rRNA gene amplicon sequencing to identify key species involved in lignocellulose degradation. The enzymatic activity profiles and microbial community changes revealed reactor-specific adaption of phylogenetically different hydrolytic communities. The enzymatic activities correlated significantly with changes in specific taxonomic groups, including representatives of Ruminiclostridium, Caldicoprobacter, Ruminofilibacter, Ruminococcaceae, Treponema, and Clostridia order MBA03, all of which have been linked to cellulolytic and xylanolytic activity in the literature. By identifying microorganisms with similar development as the cellulase and xylanase activities, the proposed correlation method constitutes a promising approach for deciphering essential cellulolytic and xylanolytic microbial groups for anaerobic digestion of lignocellulosic biomass.
Archaea: A Gold Mine for Topoisomerase Diversity
Authors: Garnier Florence , Couturier Mohea , Débat Hélène , Nadal Marc
Published: May 2021

The control of DNA topology is a prerequisite for all the DNA transactions such as DNA replication, repair, recombination, and transcription. This global control is carried out by essential enzymes, named DNA-topoisomerases, that are mandatory for the genome stability. Since many decades, the Archaea provide a significant panel of new types of topoisomerases such as the reverse gyrase, the type IIB or the type IC. These more or less recent discoveries largely contributed to change the understanding of the role of the DNA topoisomerases in all the living world. Despite their very different life styles, Archaea share a quasi-homogeneous set of DNA-topoisomerases, except thermophilic organisms that possess at least one reverse gyrase that is considered a marker of the thermophily. Here, we discuss the effect of the life style of Archaea on DNA structure and topology and then we review the content of these essential enzymes within all the archaeal diversity based on complete sequenced genomes available. Finally, we discuss their roles, in particular in the processes involved in both the archaeal adaptation and the preservation of the genome stability.
Characterization of a Novel Bacteriophage swi2 Harboring Two Lysins Can Naturally Lyse Escherichia coli
Authors: Sui Bingrui , Qi Xin , Wang Xiaoxue , Ren Huiying , Liu Wenhua , Zhang Can
Published: May 2021

The novel virulent Siphoviridae bacteriophage swi2 was isolated from a pig farm, and its biological characteristics, genome architecture, and infection-related properties were characterized. Phage swi2 has a high titer of 1.01 × 1012 PFU/mL with good tolerance to UV rays and remains stable in the pH range of 6–10 and at temperatures less than 50°C. One-step growth analysis revealed that phage swi2 had a 25 min latent period with a large burst size (1,000 PFU/cell). The biological characteristics indicated that swi2 had good host infectivity and effective lytic activities. The genome of phage swi2 is composed of 47,611 bp with a G + C content of 46.50%. Eighty-nine orfs were predicted, and only 18 of them have known functions. No virulence genes or drug resistance genes were found in the genome. Genome sequence comparison of phage swi2 showed that there were a total of 10 homologous phages in the database with low similarity (less than 92.51% nucleotide identity and 66% query coverage). The predicted host lysis-related genes of phage swi2 consist of one holin, two endolysins, and Rz/Rz1 equivalents. Antibacterial activity assays showed that both endolysins could naturally reduce the host Escherichia coli 51 titers by -1 log unit both in vitro and in vivo, EDTA showed no obvious synergistic action, and holin had no lytic effects on the host cell. These results provide necessary information for the development of antibiotic alternatives for the treatment of multidrug-resistant Escherichia coli infection.
The Borrelia burgdorferi Adenylate Cyclase, CyaB, Is Important for Virulence Factor Production and Mammalian Infection
Authors: Ante Vanessa M. , Farris Lauren C. , Saputra Elizabeth P. , Hall Allie J. , O’Bier Nathaniel S. , Oliva Chávez Adela S. , Marconi Richard T. , Lybecker Meghan C. , Hyde Jenny A.
Published: May 2021

Borrelia burgdorferi, the causative agent of Lyme disease, traverses through vastly distinct environments between the tick vector and the multiple phases of the mammalian infection that requires genetic adaptation for the progression of pathogenesis. Borrelial gene expression is highly responsive to changes in specific environmental signals that initiate the RpoS regulon for mammalian adaptation, but the mechanism(s) for direct detection of environmental cues has yet to be identified. Secondary messenger cyclic adenosine monophosphate (cAMP) produced by adenylate cyclase is responsive to environmental signals, such as carbon source and pH, in many bacterial pathogens to promote virulence by altering gene regulation. B. burgdorferi encodes a single non-toxin class IV adenylate cyclase (bb0723, cyaB). This study investigates cyaB expression along with its influence on borrelial virulence regulation and mammalian infectivity. Expression of cyaB was specifically induced with co-incubation of mammalian host cells that was not observed with cultivated tick cells suggesting that cyaB expression is influenced by cellular factor(s) unique to mammalian cell lines. The 3′ end of cyaB also encodes a small RNA, SR0623, in the same orientation that overlaps with bb0722. The differential processing of cyaB and SR0623 transcripts may alter the ability to influence function in the form of virulence determinant regulation and infectivity. Two independent cyaB deletion B31 strains were generated in 5A4-NP1 and ML23 backgrounds and complemented with the cyaB ORF alone that truncates SR0623, cyaB with intact SR0623, or cyaB with a mutagenized full-length SR0623 to evaluate the influence on transcriptional and posttranscriptional regulation of borrelial virulence factors and infectivity. In the absence of cyaB, the expression and production of ospC was significantly reduced, while the protein levels for BosR and DbpA were substantially lower than parental strains. Infectivity studies with both independent cyaB mutants demonstrated an attenuated phenotype with reduced colonization of tissues during early disseminated infection. This work suggests that B. burgdorferi utilizes cyaB and potentially cAMP as a regulatory pathway to modulate borrelial gene expression and protein production to promote borrelial virulence and dissemination in the mammalian host.
Novel Long Non-coding RNA and LASSO Prediction Model to Better Identify Pulmonary Tuberculosis: A Case-Control Study in China
Authors: Meng Zirui , Wang Minjin , Guo Shuo , Zhou Yanbing , Lyu Mengyuan , Hu Xuejiao , Bai Hao , Wu Qian , Tao Chuanmin , Ying Binwu
Published: May 2021

Introduction

The insufficient understanding and misdiagnosis of clinically diagnosed pulmonary tuberculosis (PTB) without an aetiological evidence is a major problem in the diagnosis of tuberculosis (TB). This study aims to confirm the value of Long non-coding RNA (lncRNA) n344917 in the diagnosis of PTB and construct a rapid, accurate, and universal prediction model.

Methods

A total of 536 patients were prospectively and consecutively recruited, including clinically diagnosed PTB, PTB with an aetiological evidence and non-TB disease controls, who were admitted to West China hospital from Dec 2014 to Dec 2017. The expression levels of lncRNA n344917 of all patients were analyzed using reverse transcriptase quantitative real-time PCR. Then, the laboratory findings, electronic health record (EHR) information and expression levels of n344917 were used to construct a prediction model through the Least Absolute Shrinkage and Selection Operator algorithm and multivariate logistic regression.

Results

The factors of n344917, age, CT calcification, cough, TBIGRA, low-grade fever and weight loss were included in the prediction model. It had good discrimination (area under the curve = 0.88, cutoff = 0.657, sensitivity = 88.98%, specificity = 86.43%, positive predictive value = 85.61%, and negative predictive value = 89.63%), consistency and clinical availability. It also showed a good replicability in the validation cohort. Finally, it was encapsulated as an open-source and free web-based application for clinical use and is available online at https://ziruinptb.shinyapps.io/shiny/.

Conclusion

Combining the novel potential molecular biomarker n344917, laboratory and EHR variables, this web-based prediction model could serve as a user-friendly, accurate platform to improve the clinical diagnosis of PTB.
Noncanonical Functions and Cellular Dynamics of the Mammalian Signal Recognition Particle Components
Authors: Faoro Camilla , Ataide Sandro F.
Published: May 2021

The signal recognition particle (SRP) is a ribonucleoprotein complex fundamental for co-translational delivery of proteins to their proper membrane localization and secretory pathways. Literature of the past two decades has suggested new roles for individual SRP components, 7SL RNA and proteins SRP9, SRP14, SRP19, SRP54, SRP68 and SRP72, outside the SRP cycle. These noncanonical functions interconnect SRP with a multitude of cellular and molecular pathways, including virus-host interactions, stress response, transcriptional regulation and modulation of apoptosis in autoimmune diseases. Uncovered novel properties of the SRP components present a new perspective for the mammalian SRP as a biological modulator of multiple cellular processes. As a consequence of these findings, SRP components have been correlated with a growing list of diseases, such as cancer progression, myopathies and bone marrow genetic diseases, suggesting a potential for development of SRP-target therapies of each individual component. For the first time, here we present the current knowledge on the SRP noncanonical functions and raise the need of a deeper understanding of the molecular interactions between SRP and accessory cellular components. We examine diseases associated with SRP components and discuss the development and feasibility of therapeutics targeting individual SRP noncanonical functions.
Mechanisms of Cotranslational Protein Maturation in Bacteria
Authors: Koubek Jiří , Schmitt Jaro , Galmozzi Carla Veronica , Kramer Günter
Published: May 2021

Growing cells invest a significant part of their biosynthetic capacity into the production of proteins. To become functional, newly-synthesized proteins must be N-terminally processed, folded and often translocated to other cellular compartments. A general strategy is to integrate these protein maturation processes with translation, by cotranslationally engaging processing enzymes, chaperones and targeting factors with the nascent polypeptide. Precise coordination of all factors involved is critical for the efficiency and accuracy of protein synthesis and cellular homeostasis. This review provides an overview of the current knowledge on cotranslational protein maturation, with a focus on the production of cytosolic proteins in bacteria. We describe the role of the ribosome and the chaperone network in protein folding and how the dynamic interplay of all cotranslationally acting factors guides the sequence of cotranslational events. Finally, we discuss recent data demonstrating the coupling of protein synthesis with the assembly of protein complexes and end with a brief discussion of outstanding questions and emerging concepts in the field of cotranslational protein maturation.
Carotid Atherosclerotic Calcification Characteristics Relate to Post-stroke Cognitive Impairment
Authors: Wang Yingzhe , Li Chanchan , Ding Mengyuan , Lin Luyi , Li Peixi , Wang Yizhe , Dong Qiang , Yang Yanmei , Cui Mei
Published: May 2021

Background: Together with cerebral small vessel disease (CSVD), large vessel atherosclerosis is considered to be an equally important risk factor in the progression of vascular cognitive impairment. This article aims to investigate whether carotid atherosclerotic calcification is associated with the increased risk of post-stroke cognitive impairment (PSCI).

Methods: A total of 128 patients (mean age: 62.1 ± 12.2 years, 37 women) suffering from ischemic stroke underwent brain/neck computer tomography angiography examination. The presence and characteristic of carotid calcification (size, number and location) were analyzed on computer tomography angiography. White matter hyperintensity (WMH) was assessed using Fazekas scales. PSCI was diagnosed based on a battery of neuropsychological assessments implemented 6−12 months after stroke.

Results: Among 128 patients, 26 developed post-stroke dementia and 96 had carotid calcification. Logistic regression found carotid calcification (odds ratio [OR] = 7.15, 95% confidence interval [CI]: 1.07–47.69) and carotid artery stenosis (OR = 6.42, 95% CI: 1.03–40.15) both significantly increased the risk for post-stroke dementia. Moreover, multiple, thick/mixed, and surface calcifications exhibited an increasing trend in PSCI (Ptrend = 0.004, 0.016, 0.045, respectively). The prediction model for post-stroke dementia including carotid calcification (area under curve = 0.67), WMH (area under curve = 0.67) and other covariates yielded an area under curve (AUC) of 0.90 (95% CI: 0.82–0.99).

Conclusion: Our findings demonstrated that the quantity and location of carotid calcifications were independent indicators for PSCI. The significant role of large vessel atherosclerosis in PSCI should be concerned in future study.
Improving NKCC1 Function Increases the Excitability of DRG Neurons Exacerbating Pain Induced After TRPV1 Activation of Primary Sensory Neurons
Authors: Deng Shi-Yu , Tang Xue-Chun , Chang Yue-Chen , Xu Zhen-Zhen , Chen Qin-Yi , Cao Nan , Kong Liang-Jing-Yuan , Wang Yang , Ma Ke-Tao , Li Li , Si Jun-Qiang
Published: May 2021

Background Our aim was to investigate the effects of the protein expression and the function of sodium, potassium, and chloride co-transporter (NKCC1) in the dorsal root ganglion (DRG) after activation of transient receptor potential vanilloid 1 receptor (TRPV1) in capsaicin-induced acute inflammatory pain and the possible mechanism of action.

Methods Male Sprague–Dawley rats were randomly divided into control, capsaicin, and inhibitor groups. The expression and distribution of TRPV1 and NKCC1 in rat DRG were observed by immunofluorescence. Thermal radiation and acetone test were used to detect the pain threshold of heat and cold noxious stimulation in each group. The expressions of NKCC1 mRNA, NKCC1 protein, and p-NKCC1 in the DRG were detected by PCR and western blotting (WB). Patch clamp and chloride fluorescent probe were used to observe the changes of GABA activation current and intracellular chloride concentration. After intrathecal injection of protein kinase C (PKC) inhibitor (GF109203X) or MEK/extracellular signal-regulated kinase (ERK) inhibitor (U0126), the behavioral changes and the expression of NKCC1 and p-ERK protein in L4–6 DRG were observed.

Result: TRPV1 and NKCC1 were co-expressed in the DRG. Compared with the control group, the immunofluorescence intensity of NKCC1 and p-NKCC1 in the capsaicin group was significantly higher, and the expression of NKCC1 in the nuclear membrane was significantly higher than that in the control group. The expression of NKCC1 mRNA and protein of NKCC1 and p-NKCC1 in the capsaicin group were higher than those in the control group. After capsaicin injection, GF109203X inhibited the protein expression of NKCC1 and p-ERK, while U0126 inhibited the protein expression of NKCC1. In the capsaicin group, paw withdrawal thermal latency (WTL) was decreased, while cold withdrawal latency (CWL) was prolonged. Bumetanide, GF109203X, or U0126 could reverse the effect. GABA activation current significantly increased in the DRG cells of the capsaicin group, which could be reversed by bumetanide. The concentration of chloride in the DRG cells of the capsaicin group increased, but decreased after bumetanide, GF109203X, and U0126 were administered.

Conclusion Activation of TRPV1 by exogenous agonists can increase the expression and function of NKCC1 protein in DRG, which is mediated by activation of PKC/p-ERK signaling pathway. These results suggest that DRG NKCC1 may participate in the inflammatory pain induced by TRPV1.
Cortical and Subcortical Circuits for Cross-Modal Plasticity Induced by Loss of Vision
Authors: Ewall Gabrielle , Parkins Samuel , Lin Amy , Jaoui Yanis , Lee Hey-Kyoung
Published: May 2021

Cortical areas are highly interconnected both via cortical and subcortical pathways, and primary sensory cortices are not isolated from this general structure. In primary sensory cortical areas, these pre-existing functional connections serve to provide contextual information for sensory processing and can mediate adaptation when a sensory modality is lost. Cross-modal plasticity in broad terms refers to widespread plasticity across the brain in response to losing a sensory modality, and largely involves two distinct changes: cross-modal recruitment and compensatory plasticity. The former involves recruitment of the deprived sensory area, which includes the deprived primary sensory cortex, for processing the remaining senses. Compensatory plasticity refers to plasticity in the remaining sensory areas, including the spared primary sensory cortices, to enhance the processing of its own sensory inputs. Here, we will summarize potential cellular plasticity mechanisms involved in cross-modal recruitment and compensatory plasticity, and review cortical and subcortical circuits to the primary sensory cortices which can mediate cross-modal plasticity upon loss of vision.
Outcomes of Traumatic Brain-Injured Patients With Glasgow Coma Scale < 5 and Bilateral Dilated Pupils Undergoing Decompressive Craniectomy
Authors: Tang Zhiji , Yang Ruijin , Zhang Jinshi , Huang Qianliang , Zhou Xiaoping , Wei Wenjin , Jiang Qiuhua
Published: May 2021

Objective: Decompressive craniectomy (DC) plays an important role in the treatment of patients with severe traumatic brain injury (sTBI) with mass lesions and intractably elevated intracranial hypertension (ICP). However, whether DC should be performed in patients with bilateral dilated pupils and a low Glasgow Coma Scale (GCS) score is still controversial. This retrospective study explored the clinical outcomes and risk factors for an unfavorable prognosis in sTBI patients undergoing emergency DC with bilateral dilated pupils and a GCS score <5.

Methods: The authors reviewed the data from patients who underwent emergency DC from January 2012 to March 2019 in a medical center in China. All data, such as patient demographics, radiological findings, clinical parameters, and preoperative laboratory variables, were extracted. Multivariate logistic regression analysis was performed to determine the factors associated with 30-day mortality and 6-month negative neurological outcome {defined as death or vegetative state [Glasgow Outcome Scale (GOS) score 1–2]}.

Results: A total of 94 sTBI patients with bilateral dilated pupils and a GCS score lower than five who underwent emergency DC were enrolled. In total, 74 patients (78.7%) died within 30 days, and 84 (89.4%) had a poor 6-month outcome (GOS 1–2). In multivariate analysis, advanced age (OR: 7.741, CI: 2.288–26.189), prolonged preoperative activated partial thromboplastin time (aPTT) (OR: 7.263, CI: 1.323–39.890), and low GCS (OR: 6.162, CI: 1.478–25.684) were associated with a higher risk of 30-day mortality, while advanced age (OR: 8.812, CI: 1.817–42.729) was the only independent predictor of a poor 6-month prognosis in patients undergoing DC with preoperative bilateral dilated pupils and a GCS score <5.

Conclusions: The mortality and disability rates are extremely high in severe TBI patients undergoing emergency DC with bilateral fixed pupils and a GCS score <5. DC is more valuable for younger patients.
What Tinnitus Therapy Outcome Measures Are Important for Patients?– A Discrete Choice Experiment
Authors: Rademaker Maaike M. , Essers Brigitte A. B. , Stokroos Robert J. , Smit Adriana L. , Stegeman Inge
Published: May 2021

Introduction: The therapeutic rationale varies among tinnitus therapies. A recent study identified which outcome measures should be used for different types of interventions. What patients consider the most important outcome measure in tinnitus therapy is unclear.

Objectives: To study the preference of the tinnitus patient for different outcome measures in tinnitus therapy.

Methods: A discrete choice experiment was conducted. Participants were provided with two alternatives per choice set (nine choice sets total). Each choice-set consisted of four attributes (tinnitus loudness, tinnitus acceptance, quality of sleep and concentration). With a difference in one of three levels (increased, similar or decreased after treatment) between the alternatives. Results were analyzed with a mixed logit model. Preference heterogeneity was explored with covariates, correlating attributes and a latent class analysis.

Results: One hundred and twenty-seven participants took part. In the mixed logit models we found that the choice for a tinnitus therapy was significantly affected by all levels of the outcomes, except for a similar level in concentration and tinnitus acceptance. Tinnitus loudness was considered the most important outcome measure relative to the other attributes. Preference heterogeneity was not explained by correlating attributes. The latent class analysis identified two classes. The first class was similar to the mixed logit analysis, except for a non-significance of similar quality of sleep and tinnitus acceptance. The second class showed a statistical significant preference only for increased tinnitus acceptance and similar quality of sleep.

Conclusion: Based on this study, tinnitus patients consider loudness the most important outcome measure. However, there is a variance in preference as indicated by the latent class analysis. This study underlines the importance of research into tinnitus heterogeneity. Next, this study highlights the need for research into tinnitus therapies that focus on diminishing tinnitus loudness.
Brain Networks Underlying Strategy Execution and Feedback Processing in an Efficient Functional Magnetic Resonance Imaging Neurofeedback Training Performed in a Parallel or a Serial Paradigm
Authors: Dewiputri Wan Ilma , Schweizer Renate , Auer Tibor
Published: May 2021

Neurofeedback (NF) is a complex learning scenario, as the task consists of trying out mental strategies while processing a feedback signal that signifies activation in the brain area to be self-regulated and acts as a potential reward signal. In an attempt to dissect these subcomponents, we obtained whole-brain networks associated with efficient self-regulation in two paradigms: parallel, where the task was performed concurrently, combining feedback with strategy execution; and serial, where the task was performed consecutively, separating feedback processing from strategy execution. Twenty participants attempted to control their anterior midcingulate cortex (aMCC) using functional magnetic resonance imaging (fMRI) NF in 18 sessions over 2 weeks, using cognitive and emotional mental strategies. We analyzed whole-brain fMRI activations in the NF training runs with the largest aMCC activation for the serial and parallel paradigms. The equal length of the strategy execution and the feedback processing periods in the serial paradigm allows a description of the two task subcomponents with equal power. The resulting activation maps were spatially correlated with functionally annotated intrinsic connectivity brain maps (BMs). Brain activation in the parallel condition correlates with the basal ganglia (BG) network, the cingulo-opercular network (CON), and the frontoparietal control network (FPCN); brain activation in the serial strategy execution condition with the default mode network (DMN), the FPCN, and the visual processing network; while brain activation in the serial feedback processing condition predominantly with the CON, the DMN, and the FPCN. Additional comparisons indicate that BG activation is characteristic to the parallel paradigm, while supramarginal gyrus (SMG) and superior temporal gyrus (STG) activations are characteristic to the serial paradigm. The multifaceted view of the subcomponents allows describing the cognitive processes associated with strategy execution and feedback processing independently in the serial feedback task and as combined processes in the multitasking scenario of the conventional parallel feedback task.
Children ASD Evaluation Through Joint Analysis of EEG and Eye-Tracking Recordings With Graph Convolution Network
Authors: Zhang Shasha , Chen Dan , Tang Yunbo , Zhang Lei
Published: May 2021

Recent advances in neuroscience indicate that analysis of bio-signals such as rest state electroencephalogram (EEG) and eye-tracking data can provide more reliable evaluation of children autism spectrum disorder (ASD) than traditional methods of behavior measurement relying on scales do. However, the effectiveness of the new approaches still lags behind the increasing requirement in clinical or educational practices as the “bio-marker” information carried by the bio-signal of a single-modality is likely insufficient or distorted. This study proposes an approach to joint analysis of EEG and eye-tracking for children ASD evaluation. The approach focuses on deep fusion of the features in two modalities as no explicit correlations between the original bio-signals are available, which also limits the performance of existing methods along this direction. First, the synchronization measures, information entropy, and time-frequency features of the multi-channel EEG are derived. Then a random forest applies to the eye-tracking recordings of the same subjects to single out the most significant features. A graph convolutional network (GCN) model then naturally fuses the two group of features to differentiate the children with ASD from the typically developed (TD) subjects. Experiments have been carried out on the two types of the bio-signals collected from 42 children (21 ASD and 21 TD subjects, 3–6 years old). The results indicate that (1) the proposed approach can achieve an accuracy of 95% in ASD detection, and (2) strong correlations exist between the two bio-signals collected even asynchronously, in particular the EEG synchronization against the face related/joint attentions in terms of covariance.
CAR T Cell-Based Immunotherapy for the Treatment of Glioblastoma
Authors: Maggs Luke , Cattaneo Giulia , Dal Ali Emre , Moghaddam Ali Sanjari , Ferrone Soldano
Published: May 2021

Glioblastoma multiforme (GBM) is the most common and aggressive malignant primary brain tumor in adults. Current treatment options typically consist of surgery followed by chemotherapy or more frequently radiotherapy, however, median patient survival remains at just over 1 year. Therefore, the need for novel curative therapies for GBM is vital. Characterization of GBM cells has contributed to identify several molecules as targets for immunotherapy-based treatments such as EGFR/EGFRvIII, IL13Rα2, B7-H3, and CSPG4. Cytotoxic T lymphocytes collected from a patient can be genetically modified to express a chimeric antigen receptor (CAR) specific for an identified tumor antigen (TA). These CAR T cells can then be re-administered to the patient to identify and eliminate cancer cells. The impressive clinical responses to TA-specific CAR T cell-based therapies in patients with hematological malignancies have generated a lot of interest in the application of this strategy with solid tumors including GBM. Several clinical trials are evaluating TA-specific CAR T cells to treat GBM. Unfortunately, the efficacy of CAR T cells against solid tumors has been limited due to several factors. These include the immunosuppressive tumor microenvironment, inadequate trafficking and infiltration of CAR T cells and their lack of persistence and activity. In particular, GBM has specific limitations to overcome including acquired resistance to therapy, limited diffusion across the blood brain barrier and risks of central nervous system toxicity. Here we review current CAR T cell-based approaches for the treatment of GBM and summarize the mechanisms being explored in pre-clinical, as well as clinical studies to improve their anti-tumor activity.
Future Land Use for Insect Meat Production Among Countries: A Global Classification
Authors: Doi Hideyuki , Mulia Randy Nathaniel
Published: May 2021

A potentially suitable alternative to reduce land use by livestock production is insect meat production. However, land use predictions for insect meat production, which are important in the planning of food production strategies in each country, have not been well-performed. To consider the strategy of insect meat production with regard to land use, the categorical perspectives of countries would be highly useful. Here, using previous simulation results, we used random forest machine learning to classify the potential land use of 157 countries for insect meat production under future climate change. From the categorical maps, we showed the global distribution of five different country categories and found that the land area of the countries may be an important factor in considering the future increase in insect meat production. Our classification could be used to help formulate future food policies by considering the increase in insect meat production in each country, as well as regionally and/or globally.
A Correlation Study of Prognostic Risk Prediction for Colorectal Cancer Based on Autophagy Signature Genes
Authors: Zhao Haibi , Huang Chengzhi , Luo Yuwen , Yao Xiaoya , Hu Yong , Wang Muqing , Chen Xin , Zeng Jun , Hu Weixian , Wang Junjiang , Li Rongjiang , Yao Xueqing
Published: May 2021

Autophagy plays a complex role in tumors, sometimes promoting cancer cell survival and sometimes inducing apoptosis, and its role in the colorectal tumor microenvironment is controversial. The purpose of this study was to investigate the prognostic value of autophagy-related genes (ARGs) in colorectal cancer. We identified 37 differentially expressed autophagy-related genes by collecting TCGA colorectal tumor transcriptome data. A single-factor COX regression equation was used to identify 11 key prognostic genes, and a prognostic risk prediction model was constructed based on multifactor COX analysis. We classified patients into high and low risk groups according to prognostic risk parameters (p <0.001) and determined the prognostic value they possessed by survival analysis and the receiver operating characteristic (ROC) curve in the training and test sets of internal tests. In a multifactorial independent prognostic analysis, this risk value could be used as an independent prognostic indicator (HR=1.167, 95% CI=1.078-1.264, P<0.001) and was a robust predictor without any staging interference. To make it more applicable to clinical procedures, we constructed nomogram based on risk parameters and parameters of key clinical characteristics. The area under ROC curve for 3-year and 5-year survival rates were 0.735 and 0.718, respectively. These will better enable us to monitor patient prognosis, thus improve patient outcomes.
DCTPP1, an Oncogene Regulated by miR-378a-3p, Promotes Proliferation of Breast Cancer via DNA Repair Signaling Pathway
Authors: Niu Ming , Shan Ming , Liu Yang , Song Yanni , Han Ji-guang , Sun Shanshan , Liang Xiao-shuan , Zhang Guo-qiang
Published: May 2021

Breast cancer (BRCA) is one of the most deadly cancers worldwide, with poor survival rates that could be due to its high proliferation. Human all-alpha dCTP pyrophosphatase 1 (DCTPP1) is implicated in numerous diseases, including cancers. However, its role in BRCA is unclear. In this study, we used bioinformatic analyses of the ONCOMINE, UALCAN, and GEPIA databases to determine the expression pattern of DCTPP1 in BRCA. We found that elevated DCTPP1 levels correlate with poor BRCA prognosis. DCTPP1 silencing inhibited BRCA cell proliferation and induced apoptosis in vitro, as well as in vivo. Our data show that this tumorigenic effect depends on DNA repair signaling. Moreover, we found that DCTPP1 is directly modulated by miR-378a-3p, whose downregulation is linked to BRCA progression. Our results showed down-regulation of miR-378a-3p in BRCA. Upregulation of miR-378a-3p, on the other hand, can inhibit BRCA cell growth and proliferation. This study shows that reduced miR-378a-3p level enhances DCTPP1 expression in BRCA, which promotes proliferation by activating DNA repair signaling in BRCA.
Vitamin D: Possible Therapeutic Roles in Hepatocellular Carcinoma
Authors: Adelani Isaacson B. , Rotimi Oluwakemi A. , Maduagwu Emmanuel N. , Rotimi Solomon O.
Published: May 2021

Hepatocellular carcinoma (HCC) is a unique type of liver cancer instigated by underlying liver diseases. Pre-clinical evidence suggests that HCC progression, like other cancers, could be aided by vitamin D deficiency. Vitamin D is a lipid-soluble hormone usually obtained through sunlight. Vitamin D elucidates its biological responses by binding the vitamin D receptor; thus, promoting skeletal mineralization, and maintain calcium homeostasis. Other reported Vitamin D functions include specific roles in proliferation, angiogenesis, apoptosis, inflammation, and cell differentiation. This review highlighted studies on vitamin D’s functional roles in HCC and discussed the specific therapeutic targets from various in vivo, in vitro and clinical studies over the years. Furthermore, it described recent advancements in vitamin D’s anticancer effects and its metabolizing enzymes’ roles in HCC development. In summary, the review elucidated specific vitamin D-associated target genes that play critical functions in the inhibition of tumorigenesis through inflammation, oxidative stress, invasion, and apoptosis in HCC progression.
Expression Profiling of Glioblastoma Cell Lines Reveals Novel Extracellular Matrix-Receptor Genes Correlated With the Responsiveness of Glioma Patients to Ionizing Radiation
Authors: Serafim Rodolfo Bortolozo , da Silva Patrick , Cardoso Cibele , Di Cristofaro Luis Fernando Macedo , Netto Renato Petitto , de Almeida Rodrigo , Navegante Geovana , Storti Camila Baldin , de Sousa Juliana Ferreira , de Souza Felipe Canto , Panepucci Rodrigo , Moreira Cristiano Gallina , Penna Larissa Siqueira , Silva Wilson Araujo , Valente Valeria
Published: May 2021

Glioblastoma (GBM) is the most lethal and frequent type of brain tumor, leading patients to death in approximately 14 months after diagnosis. GBM treatment consists in surgical removal followed by radio and chemotherapy. However, tumors commonly relapse and the treatment promotes only a slight increase in patient survival. Thus, uncovering the cellular mechanisms involved in GBM resistance is of utmost interest, and the use of cell lines has been shown to be an extremely important tool. In this work, the exploration of RNAseq data from different GBM cell lines revealed different expression signatures, distinctly correlated with the behavior of GBM cell lines regarding proliferation indexes and radio-resistance. U87MG and U138MG cells, which presented expressively reduced proliferation and increased radio-resistance, showed a particular expression signature encompassing enrichment in many extracellular matrix (ECM) and receptor genes. Contrasting, U251MG and T98G cells, that presented higher proliferation and sensibility to radiation, exhibited distinct signatures revealing consistent enrichments for DNA repair processes and although several genes from the ECM-receptor pathway showed up-regulation, enrichments for this pathway were not detected. The ECM-receptor is a master regulatory pathway that is known to impact several cellular processes including: survival, proliferation, migration, invasion, and DNA damage signaling and repair, corroborating the associations we found. Furthermore, searches to The Cancer Genome Atlas (TCGA) repository revealed prognostic correlations with glioma patients for the majority of genes highlighted in the signatures and led to the identification of 31 ECM-receptor genes individually correlated with radiation responsiveness. Interestingly, we observed an association between the number of upregulated genes and survivability greater than 5 years after diagnosis, where almost all the patients that presented 21 or more upregulated genes were deceased before 5 years. Altogether our findings suggest the clinical relevance of ECM-receptor genes signature found here for radiotherapy decision and as biomarkers of glioma prognosis.
A Pan-Cancer Analysis of the Oncogenic Role of Twinfilin Actin Binding Protein 1 in Human Tumors
Authors: Huo Gengwei , Wang Yali , Chen Jinliang , Song Ying , Zhang Cuicui , Guo Hua , Zuo Ran , Zhu Fuyi , Cui Jinfang , Chen Weidong , Chen Wenming , Chen Peng
Published: May 2021

Background

Understanding common and unique mechanisms driving oncogenic processes in human tumors is indispensable to develop efficient therapies. Recent studies have proposed Twinfilin Actin Binding Protein 1 (TWF1) as a putative driver gene in lung cancer, pancreatic cancer and breast cancer, however a systematic pan-cancer analysis has not been carried out.

Methods

Here, we set out to explore the role of TWF1 in 33 tumor types using TCGA (The Cancer Genome Atlas), GEO (Gene Expression Omnibus) dataset, Human Protein Atlas (HPA), and several bioinformatic tools.

Results

As part of our analysis, we have assessed TWF1 expression across tumors. We found that over-expression of TWF1 generally predicted poor OS for patients with tumors with high TWF1 expression, such as mesothelioma, lung adenocarcinoma, cervical cancer and pancreatic adenocarcinoma. We also assessed the mutation burden of TWF1 in cancer and the TWF1-associated survival of cancer patients, compared the phosphorylation of TWF1 between normal and primary tumor tissues and explored putative functional mechanisms in TWF1-mediated oncogenesis.

Conclusions

Our pan-cancer analysis provides a comprehensive overview of the oncogenic roles of TWF1 in multiple human cancers.
The Efficacy and Medium to Long-Term Follow-Up of Transcatheter Retrograde Closure of Perimembranous Ventricular Septal Defects via the Femoral Artery With Amplatzer Duct Occluder II in Children
Authors: Jiang Diandong , Zhang Jianjun , Fan Youfei , Han Bo , Zhao Lijian , Yi Yingchun , Lv Jianli , Wang Jing
Published: May 2021

Objective: The aim of this study was to assess the efficacy and safety of transcatheter retrograde closure of perimembranous ventricular septal defect (pmVSD) via the femoral artery with an Amplatzer Duct Occluder II (ADO II) in children.

Methods: The clinical and follow-up data of 102 children who had successfully undergone transcatheter retrograde closure of pmVSD via the femoral artery with Amplatzer Duct Occluder II (ADO II) from February 2012 to June 2019 in our center were retrospectively reviewed.

Results: In 102 of 103 patients, the defects were successfully closed (99.0%). The average age was 4.03 ± 1.84 years and the mean weight was 17.50 ± 5.58 kg. The mean diameter of the defects was 2.58 ± 0.63 mm. Hundred of the occluders had a waist length of 4 mm. The complete closure rate was 89.2% 24 h after the procedure and 98% at the last follow-up. The follow-up period ranged from 6 to 92 months, with a median of 36 months. One child developed new mild aortic regurgitation (AR), and 9 patients developed new mild tricuspid regurgitation (TR). During follow-up, TR disappeared in 5 patients and decreased in 4 patients, and AR relieved in one patient. One patient developed intermittent complete left bundle branch block 4 days after the procedure and recovered sinus rhythm 2 days later. No serious complications occurred.

Conclusion: Transcatheter retrograde closure of pmVSD via the femoral artery with ADO II in children is safe, feasible, and effective in selected patients.
Antimicrobial Resistance Analysis of Clinical Escherichia coli Isolates in Neonatal Ward
Authors: Wu Dan , Ding Yijun , Yao Kaihu , Gao Wei , Wang Yajuan
Published: May 2021

Background:Escherichia coli (E. coli) column for one of the most common pathogens causing neonatal infections. The emergence of antibiotic-resistant bacteria is a major cause of treatment failure in infected newborns. The purpose of this study was to describe antibiotic and multidrug resistance of E. coli strains isolated from neonates with infection throughout the years 2009–2011.

Methods: The antimicrobial susceptibility testing of E. coli strains to selected antibiotics was assessed using the E-test technique on the Mueller-Hinton agar. The antimicrobial tests included ceftazidime, cefuroxime, cefatriaxone, amoxicillin, amoxicillin-clavulanic acid, cefoperazone- sulbactam, meropenem, gentamicin, ciprofloxacin, and sulfonamides.

Results: A total of 100 E. coli strains were isolated from sputum (n = 78), blood (n = 10), cerebrospinal fluid (n = 5), and umbilical discharge (n = 7) samples of hospitalized neonates at the Beijing Children's Hospital. The highest rate of E. coli resistance was found in amoxicillin (85%), followed by cefuroxime (65%), and cefatriaxone (60%), respectively. A total of 6 and 5% of all isolates were only resistant to amoxicillin/clavulanic acid and cefoperazone -sulbactam. The rates of resistance to ceftazidime, gentamicin, ciprofloxacin, and sulfonamides were 31, 20, 33, and 47%, respectively. All isolates were susceptible to meropenem. Approximately 26% of all E. coli isolates were multidrug-resistant. The detection rate of ESBL-Producing E. coli was 55%.

Conclusions: Multi-drug-resistant E. coli has become an important and complex problem in clinical treatment, and it is thus essential to monitor E. coli resistance in neonates.
Interactive Effects of Glucocorticoids and Cytochrome P450 Polymorphisms on the Plasma Trough Concentrations of Voriconazole
Authors: Jia Su-jie , Gao Ke-qin , Huang Pan-hao , Guo Ren , Zuo Xiao-cong , Xia Qing , Hu Shuang-yao , Yu Zhen , Xie Yue-liang
Published: May 2021

Aims: To explore the interactive influence of glucocorticoids and cytochrome P450 (CYP450) polymorphisms on voriconazole (VRC) plasma trough concentrations (Cmin) and provide a reliable basis for reasonable application of VRC.

Methods: A total of 918 VRC Cmin from 231 patients was collected and quantified using high-performance liquid chromatography in this study. The genotypes of CYP2C19, CYP3A4, and CYP3A5 were detected by DNA sequencing assay. The effects of different genotypes and the coadministration of glucocorticoids on VRC Cmin were investigated. Furthermore, the interactive effects of glucocorticoids with CYP450s on VRC Cmin were also analyzed.

Results: The median Cmin of oral administration was lower than that of intravenous administration (1.51 vs. 4.0 mg l−1). Coadministration of glucocorticoids (including dexamethasone, prednisone, prednisolone, and methylprednisolone) reduced the VRC Cmin/dose, respectively, among which dexamethasone make the median of the VRC Cmin/dose ratio lower. As a result, when VRC was coadministrated with glucocorticoids, the proportion of VRC Cmin/dose in the subtherapeutic window was increased. Different CYP450 genotypes have different effects on the Cmin/dose of VRC. Mutations of CYP2C19*2 and *3 increased Cmin/dose of VRC, while CYP2C19*17 and CYP3A4 rs4646437 polymorphisms decreased Cmin/dose of VRC. The mutation of CYP3A5 has no significant effect. Furthermore, CYP2C19*17 mutants could strengthen the effects of glucocorticoids and decrease VRC Cmin/dose to a larger extent.

Conclusion: Our study revealed that glucocorticoids reduced the Cmin/dose levels of VRC and different SNPs of CYP450 have different effects on the Cmin/dose ratio of VRC. Glucocorticoids and CYP2C19*17 mutants had a synergistic effect on reducing VRC Cmin/dose. The present results suggested that when VRC is combined with glucocorticoids, we should pay more attention to the clinical efficacy of VRC, especially when CYP2C19*17 mutants exist.