bluuebunny/crossref_metadata_2025 huggingface dataset:
Optimization of Spectral Wavelets for Persistence-Based Graph Classification
Authors: Yim Ka Man , Leygonie Jacob
Published: April 2021

A graph's spectral wavelet signature determines a filtration, and consequently an associated set of extended persistence diagrams. We propose a framework that optimizes the choice of wavelet for a dataset of graphs, such that their associated persistence diagrams capture features of the graphs that are best suited to a given data science problem. Since the spectral wavelet signature of a graph is derived from its Laplacian, our framework encodes geometric properties of graphs in their associated persistence diagrams and can be applied to graphs without a priori node attributes. We apply our framework to graph classification problems and obtain performances competitive with other persistence-based architectures. To provide the underlying theoretical foundations, we extend the differentiability result for ordinary persistent homology to extended persistent homology.
Influence of Sound on Empirical Brain Networks
Authors: Sawicki Jakub , Schöll Eckehard
Published: April 2021

We analyze the influence of an external sound source in a network of FitzHugh–Nagumo oscillators with empirical structural connectivity measured in healthy human subjects. We report synchronization patterns, induced by the frequency of the sound source. We show that the level of synchrony can be enhanced by choosing the frequency of the sound source and its amplitude as control parameters for synchronization patterns. We discuss a minimum model elucidating the modalities of the influence of music on the human brain.
Continuous Classification of Locomotion in Response to Task Complexity and Anticipatory State
Authors: Kazemimoghadam Mahdieh , Fey Nicholas P.
Published: April 2021

Objective

Intent recognition in lower-extremity assistive devices (e.g., prostheses and exoskeletons) is typically limited to either recognition of steady-state locomotion or changes of terrain (e.g., level ground to stair) occurring in a straight-line path and under anticipated condition. Stability is highly affected during non-steady changes of direction such as cuts especially when they are unanticipated, posing high risk of fall-related injuries. Here, we studied the influence of changes of direction and user anticipation on task recognition, and accordingly introduced classification schemes accommodating such effects.

Methods

A linear discriminant analysis (LDA) classifier continuously classified straight-line walking, sidestep/crossover cuts (single transitions), and cuts-to-stair locomotion (mixed transitions) performed under varied task anticipatory conditions. Training paradigms with varying levels of anticipated/unanticipated exposures and analysis windows of size 100–600 ms were examined.

Results

More accurate classification of anticipated relative to unanticipated tasks was observed. Including bouts of target task in the training data was necessary to improve generalization to unanticipated locomotion. Only up to two bouts of target task were sufficient to reduce errors to <20% in unanticipated mixed transitions, whereas, in single transitions and straight walking, substantial unanticipated information (i.e., five bouts) was necessary to achieve similar outcomes. Window size modifications did not have a significant influence on classification performance.

Conclusion

Adjusting the training paradigm helps to achieve classification schemes capable of adapting to changes of direction and task anticipatory state.

Significance

The findings could provide insight into developing classification schemes that can adapt to changes of direction and user anticipation. They could inform intent recognition strategies for controlling lower-limb assistive to robustly handle “unknown” circumstances, and thus deliver increased level of reliability and safety.
Colchicine Blocks Tubulin Heterodimer Recycling by Tubulin Cofactors TBCA, TBCB, and TBCE
Authors: Nolasco Sofia , Bellido Javier , Serna Marina , Carmona Bruno , Soares Helena , Zabala Juan Carlos
Published: April 2021

Colchicine has been used to treat gout and, more recently, to effectively prevent autoinflammatory diseases and both primary and recurrent episodes of pericarditis. The anti-inflammatory action of colchicine seems to result from irreversible inhibition of tubulin polymerization and microtubule (MT) assembly by binding to the tubulin heterodimer, avoiding the signal transduction required to the activation of the entire NLRP3 inflammasome. Emerging results show that the MT network is a potential regulator of cardiac mechanics. Here, we investigated how colchicine impacts in tubulin folding cofactors TBCA, TBCB, and TBCE activities. We show that TBCA is abundant in mouse heart insoluble protein extracts. Also, a decrease of the TBCA/β-tubulin complex followed by an increase of free TBCA is observed in human cells treated with colchicine. The presence of free TBCA is not observed in cells treated with other anti-mitotic agents such as nocodazole or cold shock, neither after translation inhibition by cycloheximide.In vitroassays show that colchicine inhibits tubulin heterodimer dissociation by TBCE/TBCB, probably by interfering with interactions of TBCE with tubulin dimers, leading to free TBCA. Manipulation of TBCA levels, either by RNAi or overexpression results in decreased levels of tubulin heterodimers. Together, these data strongly suggest that TBCA is mainly receiving β-tubulin from the dissociation of pre-existing heterodimers instead of newly synthesized tubulins. The TBCE/TBCB+TBCA system is crucial for controlling the critical concentration of free tubulin heterodimers and MT dynamics in the cells by recycling the tubulin heterodimers. It is conceivable that colchicine affects tubulin heterodimer recycling through the TBCE/TBCB+TBCA system producing the known benefits in the treatment of pericardium inflammation.
Macro and Trace Elements in Hemp (Cannabis sativa L.) Cultivated in Greece: Risk Assessment of Toxic Elements
Authors: Zafeiraki Effrosyni , Kasiotis Konstantinos M. , Nisianakis Paul , Machera Kyriaki
Published: April 2021

The accumulation of hazardous contaminants in Cannabis sativa L. raises warning signs regarding possible adverse effects on human health due to the consumption of herbal medicines and/or other herbal edible products made from cannabis. Thus, there is an urge to investigate the levels of hazardous contaminants, such as heavy metals, in cannabis plant. In the present study, 29 macro and trace elements, including both beneficial and toxic elements (heavy metals and metalloids), were investigated in 90 samples of Cannabis sativa L. collected from Greece. According to the results, the detected concentrations of macro elements in the leaves/flowers of cannabis ranged between 28 and 138,378 ppm, and of trace elements between 0.002 and 1352.904 ppm. Although the concentrations of elements varied among the samples, their accumulation pattern was found to be similar, with the contribution of toxic elements to the total concentration of trace elements being below 1%. The detected levels of the most toxic elements were below the prescribed limits established by the WHO, while the calculated THQ and CR values showed no risk (non-carcinogenic and carcinogenic) for the population exposed to the current cannabis samples. Positive correlation between the concentration of elements and cannabis geographical origin and variety was observed. Cannabis leaves/flowers were more contaminated with trace and macro elements than seeds.
Preliminary Experimental Study of Methane Adsorption Capacity in Shale After Brittle Deformation Under Uniaxial Compression
Authors: Liang Mingliang , Wang Zongxiu , Zheng Guodong , Zhang Xiaobao , Greenwell Hugh Christopher , Zhang Kaixun , Feng Xingqiang , Zhang Linyan , Li Huijun
Published: April 2021

This paper presents a preliminary experimental study on methane adsorption capacity in shales before and after artificial deformation. The experimental results are based on uniaxial compression and methane isothermal adsorption tests on different shale samples from the Silurian Longmaxi Formation, Daozhen County, South China. Two sets of similar cylindrical samples were drilled from the each same bulk sample, one set was subjected to a uniaxial compressive simulation test and then crushed as artificial deformed shale sample, the other set was directly crushed as the original undeformed shale sample. And then we conducted a comparative experimental study of the methane adsorption capacity of original undeformed and artificially deformed shales. The uniaxial compression simulation results show that the failure mode of all samples displayed brittle deformation. The methane isothermal adsorption results show that the organic matter content is the main controlling factor of shale methane adsorption capacity. However, the comparative results also show that the compression and deformation have an effect on methane adsorption capacity, with shale methane adsorption capacity decreasing by about 4.26–8.48% after uniaxial compression deformation for the all shale samples in this study.
A Rapid Intraoperative Parathyroid Hormone Assay Based on the Immune Colloidal Gold Technique for Parathyroid Identification in Thyroid Surgery
Authors: Xia Wenfei , Zhang Jinjun , Shen Wenzhuang , Zhu Zhi , Yang Zhifang , Li Xingrui
Published: April 2021

Objective

A novel immunochromatographic test strip method was developed to detect tissue parathyroid hormone (PTH) using the immune colloidal gold technique (ICGT). The accuracy and application value of this method for intraoperative parathyroid identification were evaluated.

Methods

Serum samples were collected to measure PTH by both ICGT and electrochemiluminescence immunoassay (ECLIA). Patients who underwent unilateral and total thyroidectomy were enrolled to evaluate the feasibility and clinical efficacy of rapid intraoperative identification of parathyroid glands via PTH determination using ICGT. Two sample preparation methods, fine needle aspiration (FNA) and tissue block homogenate (TBH), were used for PTH-ICGT analysis.

Results

Bablok analysis showed a linear relationship between the serum PTH measurements obtained by ICGT and ECLIA. Non-parathyroid tissues had much lower PTH concentrations (14.8 ± 2.1 pg/ml, n = 97) detected by ICGT, compared to the parathyroid gland tissues (955.3 ± 16.1 pg/ml, n = 79; P < 0.0001), With biopsy results as the standard, ICGT showed higher diagnosis rates as compared with direct visual inspection, for identifying both parathyroid glands (97.4 vs. 78.2%) and non-parathyroid tissues (100 vs. 68.9%). The cut-off values for parathyroid identification by FNA and TBH methods were 63.99 and 136.30 pg/ml, respectively. The detection time was 2 min by TBH method for in vitro tissue detection and 6 min by FNA method for in situ tissue detection, both of which were faster than traditional intraoperative cryopathological examination (usually >30 min). Intraoperative application of ICGT method was associated with higher postoperative serum calcium and blood PTH levels at 1 and 3 months as well as a lower incidence of postoperative transient hypocalcemia, as compared with direct visual inspection.

Conclusion

PTH-ICGT assay shows high potential as a rapid, novel alternative for intraoperative parathyroid identification.
Effect of Additional Amino Group to Improve the Performance of Immobilized Lipase From Aspergillus niger by Adsorption-Crosslinking Method
Authors: Nuraliyah Andi , Perdani Meka Saima , Putri Dwini Normayulisa , Sahlan Muhamad , Wijanarko Anondho , Hermansyah Heri
Published: April 2021

Adsorption-crosslinking is one of the immobilization methods to improve the reusability of lipase. It requires amino groups to reduce cross-link immobilization risk so that lipase–support interaction increases and the immobilization is attainable. Also, the amino group on the support is expected to increase lipase performance. This study aimed to analyze the effect of amino group addition on immobilized Aspergillus niger lipase by the adsorption-crosslinking using MP-64 macroporous anion resin and XAD-7HP macroporous nonionic resin that has been treated with chitosan. The chitosan-coated resin was characterized by Fourier transform infrared spectrometry (FTIR) and scanning electron microscope (SEM). Lipase immobilization was carried out by adding 10 ml lipase solution containing 0.75 g resins and shaken at 25°C for 150 rpm. Adsorption was achieved for 4 h, followed by cross-linking separately (adding 0.5% (v/v) glutaraldehyde and re-reacting for 20 min). Lipase activity was measured with the titrimetric of olive oil emulsion; mixed with Aspergillus niger lipase, emulsion, and a buffer solution (pH 6.5, ionic strength of 0.7); and incubated for 30 min at 37°C. The effect of amino-functional groups was investigated based on lipase loading and lipase activity. The best lipase loading and lipase activity of 83.79% and 29.41 U/g support were achieved in the adsorption-crosslinking using MP-64 resin coated with chitosan. After four cycles, biodiesel synthesis was maintained at 70.61% of the initial yield. These results indicated that chitosan as an affordable and readily available source of amino groups could be used to modify support for Aspergillus niger lipase immobilization.
Exploration of Prognostic Biomarkers for Lung Adenocarcinoma Through Bioinformatics Analysis
Authors: Tu Zhengliang , He Xiangfeng , Zeng Liping , Meng Di , Zhuang Runzhou , Zhao Jiangang , Dai Wanrong
Published: April 2021

With the development of computer technology, screening cancer biomarkers based on public databases has become a common research method. Here, an eight-gene prognostic model, which could be used to judge the prognosis of patients with lung adenocarcinoma (LUAD), was developed through bioinformatics methods. This study firstly used several gene datasets from GEO database to mine differentially expressed genes (DEGs) in LUAD tissue and healthy tissue via joint analysis. Later, enrichment analysis for the DEGs was performed, and it was found that the DEGs were mainly activated in pathways involved in extracellular matrix, cell adhesion, and leukocyte migration. Afterward, a TCGA cohort was used to perform univariate Cox, least absolute shrinkage and selection operator method, and multivariate Cox regression analyses for the DEGs, and a prognostic model consisting of eight genes (GPX3, TCN1, ASPM, PCP4, CAV2, S100P, COL1A1, and SPOK2) was established. Receiver operation characteristic (ROC) curve was then used to substantiate the diagnostic efficacy of the prognostic model. The survival significance of signature genes was verified through the GEPIA database, and the results exhibited that the risk coefficients of the eight genes were basically congruous with the effects of these genes on the prognosis in the GEPIA database, which suggested that the results were accurate. Finally, combined with clinical characteristics of patients, the diagnostic independence of the prognostic model was further validated through univariate and multivariate regression, and the results indicated that the model had independent prognostic value. The overall finding of the study manifested that the eight-gene prognostic model is closely related to the prognosis of LUAD patients, and can be used as an independent prognostic indicator. Additionally, the prognostic model in this study can help doctors make a better diagnosis in treatment and ultimately benefit LUAD patients.
A Novel Signature for Predicting Prognosis of Smoking-Related Squamous Cell Carcinoma
Authors: Chen Chang , Cheng Xiaoqing , Li Shuyan , Chen Huanghui , Cui Mengjing , Bian Linlin , Jin Hui
Published: April 2021

Tobacco smoking is an established risk factor for squamous cell carcinoma (SCC). We obtained smoking-related SCC, including cervical SCC (CSCC), esophageal SCC (ESCC), head and neck SCC (HNSC), and lung SCC (LUSC), from The Cancer Genome Atlas (TCGA) database to investigate the association between smoking status (reformed and current smoking) and prognosis. We found that reformed smokers had a better prognosis than current smokers in CSCC (p = 0.003), HNSC (p = 0.019), and LUSC (p < 0.01) cohorts. Then, we selected LUSC cohorts as the training cohort and other SCC cohorts as the test cohorts. Function analysis revealed that homologous recombination (HR) was the most significant pathway involved in smoking-induced LUSC. Moreover, the effect of cross-talk between the smoking status and HR deficiency (HRD) on the prognosis was further evaluated, revealing that quitting smoking with high HRD scores could significantly improve patients’ prognosis (p < 0.01). To improve prognosis prediction and more effectively screen suitable populations for platinum drugs and poly-ADP-ribose polymerase (PARP) inhibitors, we constructed a risk score model using smoking- and HRD-related genes in LUSC. The risk score model had high power for predicting 2-, 3-, and 5-year survival (p < 0.01, AUC = 0.67, 0.66, and 0.66). In addition, the risk scores were an independent risk factor for LUSC (HR = 2.34, 95%CI = 1.70–3.23). The practical nomogram was also built using the risk score, smoking status, and other clinical information with a good c-index (0.72, 95%CI = 0.70–0.74). Finally, we used other TCGA SCC cohorts to confirm the reliability and validity of the risk score model (p < 0.01 and AUC > 0.6 at 2, 3, and 5 years in CSCC and HNSC cohorts). In conclusion, the present study suggested that smoking cessation should be a part of smoking-related SCC treatment, and also provided a risk score model to predict prognosis and improve the effectiveness of screening the platinum/PARP population.
Role of CCR2+ Myeloid Cells in Inflammation Responses Driven by Expression of a Surfactant Protein-C Mutant in the Alveolar Epithelium
Authors: Venosa Alessandro , Cowman Sophie , Katzen Jeremy , Tomer Yaniv , Armstrong Brittnie S. , Mulugeta Surafel , Beers Michael F.
Published: April 2021

Acute inflammatory exacerbations (AIE) represent precipitous deteriorations of a number of chronic lung conditions, including pulmonary fibrosis (PF), chronic obstructive pulmonary disease and asthma. AIEs are marked by diffuse and persistent polycellular alveolitis that profoundly accelerate lung function decline and mortality. In particular, excess monocyte mobilization during AIE and their persistence in the lung have been linked to poor disease outcome. The etiology of AIEs remains quite uncertain, but environmental exposure and genetic predisposition/mutations have been identified as two contributing factors. Guided by clinical evidence, we have developed a mutant model of pulmonary fibrosis leveraging the PF-linked missense isoleucine to threonine substitution at position 73 [I73T] in the alveolar type-2 cell-restricted Surfactant Protein-C [SP-C] gene [SFTPC]. With this toolbox at hand, the present work investigates the role of peripheral monocytes during the initiation and progression of AIE-PF. Genetic ablation of CCR2+ monocytes (SP-CI73TCCR2KO) resulted in improved lung histology, mouse survival, and reduced inflammation compared to SP-CI73TCCR2WT cohorts. FACS analysis of CD11b+CD64-Ly6Chi monocytes isolated 3 d and 14 d after SP-CI73T induced injury reveals dynamic transcriptional changes associated with “Innate Immunity’ and ‘Extracellular Matrix Organization’ signaling. While immunohistochemical and in situ hybridization analysis revealed comparable levels of tgfb1 mRNA expression localized primarily in parenchymal cells found nearby foci of injury we found reduced effector cell activation (C1q, iNOS, Arg1) in SP-CI73TCCR2KO lungs as well as partial colocalization of tgfb1 mRNA expression in Arg1+ cells. These results provide a detailed picture of the role of resident macrophages and recruited monocytes in the context of AIE-PF driven by alveolar epithelial dysfunction.
Influence of Specimen Size on Autogenous Volume Deformation of Long-Aged MgO-Admixed Concrete
Authors: Chen Changli , Chen Rongfei , Zhao Zhenhua , Li Weiwei , Yan Shaolian , Du Xiangqin , Yang Huashan
Published: April 2021

The transformation law of autogenous volume deformation of MgO-admixed concrete with specimen size was revealed through continuous observation on standard-size (Φ200 mm × 500 mm), medium-size (Φ250 mm × 500 mm), and large-size specimens (Φ250 mm × 600 mm) over 6 years. Besides, the pore parameters of concrete core samples obtained from autogenous volume deformation specimens in the 1st, 3rd, and 6th years of age were investigated. The results show that the autogenous volume deformation of MgO-admixed concrete increases with the increase in the MgO content or age. The expansion rate of the concrete specimen decreases after the age of 360 days, and the autogenous volume expansion deformation of the specimen tends to be stable after about 2 years. When the size of the specimen changes, the autogenous volume deformation of MgO-admixed concrete decreases with the increase of specimen size. During the age of 2–6 years, the expansion of medium- and large-size specimens is reduced by 6–10 and 15–20%, respectively, compared with the standard-size specimens under the same MgO content. With the condition of an appropriate MgO content, regardless of the size of the specimen, the pore structure of the concrete becomes better and better with the growth of age, the concrete becomes denser and denser, and the expansion caused by MgO hydration will not cause damage to concrete structures.
Phased-Array Transducer for Intracardiac Echocardiography Based on 1–3 Piezocomposite
Authors: Han Zhile , Wang Ninghao , Li Zhangjian , Zhu Xinle , Chen Youwei , Jian Xiaohua , Cui Yaoyao
Published: April 2021

In this study, an ultrasonic phased-array transducer was proposed, which could effectively improve the imaging performance by using 1–3 piezocomposite. The piezocomposite consists of PZT and epoxy, with a pitch of 70 μm, kerf of 20 μm, and thickness of 170 μm. The phased-array transducer has 64 elements; the size of each element is 85 μm × 1.3 mm; the pitch of the transducer is 100 μm; and the kerf between the elements is only 15 μm. To minimize the transducer size, the 1–3 composite uses an encase structure, which connects the upper surface of the composite directly to the flexible circuit board bonded to the lower surface as the ground electrode. The size of the final fabricated transducer is 2 mm × 7.4 mm, and the transducer is mounted on a 9 F (3 mm diameter) catheter, which can bend in four directions and is primarily used for intracardiac echocardiography (ICE). The acoustic and electrical properties of the transducer were tested, including impedance, echo sensitivity, center frequency (9 MHz), bandwidth (BW) (55%), and consistency. Finally, the wire phantom experiments were carried out to demonstrate the spatial resolutions and imaging performance. This study shows that this transducer with compact design and construction can bring higher performance for the single-use disposable ICE catheter.
Single-Cell RNA-seq Reveals Angiotensin-Converting Enzyme 2 and Transmembrane Serine Protease 2 Expression in TROP2+ Liver Progenitor Cells: Implications in Coronavirus Disease 2019-Associated Liver Dysfunction
Authors: Seow Justine Jia Wen , Pai Rhea , Mishra Archita , Shepherdson Edwin , Lim Tony Kiat Hon , Goh Brian K. P. , Chan Jerry K. Y. , Chow Pierce K. H. , Ginhoux Florent , DasGupta Ramanuj , Sharma Ankur
Published: April 2021

The recent coronavirus disease 2019 (COVID-19) pandemic is caused by severe acute respiratory syndrome coronavirus 2. COVID-19 was first reported in China (December 2019) and is now prevalent across the globe. Entry of severe acute respiratory syndrome coronavirus 2 into mammalian cells requires the binding of viral Spike (S) proteins to the angiotensin-converting enzyme 2 receptor. Once entered, the S protein is primed by a specialized serine protease, transmembrane serine protease 2 in the host cell. Importantly, besides the respiratory symptoms that are consistent with other common respiratory virus infections when patients become viremic, a significant number of COVID-19 patients also develop liver comorbidities. We explored whether a specific target cell-type in the mammalian liver could be implicated in disease pathophysiology other than the general deleterious response to cytokine storms. Here, we used single-cell RNA-seq to survey the human liver and identified potentially implicated liver cell-type for viral ingress. We analyzed ~300,000 single cells across five different (i.e., human fetal, healthy, cirrhotic, tumor, and adjacent normal) liver tissue types. This study reports on the co-expression of angiotensin-converting enzyme 2 and transmembrane serine protease 2 in a TROP2+ liver progenitor population. Importantly, we detected enrichment of this cell population in the cirrhotic liver when compared with tumor tissue. These results indicated that in COVID-19-associated liver dysfunction and cell death, a viral infection of TROP2+ progenitors in the liver might significantly impair liver regeneration in patients with liver cirrhosis.
Oral Mucosa, Saliva, and COVID-19 Infection in Oral Health Care
Authors: Atukorallaya Devi Sewvandini , Ratnayake Ravindra K.
Published: April 2021

The SARS-CoV-2 virus has shaken the globe with an ongoing pandemic of COVID-19 and has set challenges to every corner of the modern health care setting. The oral mucosa and saliva are high risk sites for higher viral loads and dental health care professionals are considered a high risk group. COVID-19-induced oral lesions and loss of taste and smell are common clinical complaints in the dental health care setting. The SARS-CoV-2 virus has been found to cause a wide range of non-specific oral mucosal lesions, but the specific diagnosis of these mucocutaneous lesions as COVID-19 lesions will facilitate the prevention of SARS-CoV-2 in dental health care settings and aid in proper patient management. The reported loss of taste and smell needs further investigation at the receptor level as it will give new insights into SARS-CoV-2 pathogenicity. The high yield of virus in the salivary secretion is a common finding in this infection and ongoing research is focusing on developing saliva as a rapid diagnostic fluid in COVID-19. In this review, we discuss the significance of oral mucosa, saliva and the relevance of the COVID-19 pandemic in dentistry.
Construction of Mycoplasma hyopneumoniae P97 Null Mutants
Authors: Clampitt Jeannett M. , Madsen Melissa L. , Minion F. Chris
Published: April 2021

Mycoplasma hyopneumoniaeis the causative agent of enzootic pneumonia, a world-wide problem in the pig industry. This disease is characterized by a dry, non-productive cough, labored breathing, and pneumonia. Despite years of research, vaccines are marginally effective, and none fully protect pigs in a production environment. A better understanding of the host-pathogen interactions of theM. hyopneumoniae-pig disease, which are complex and involve both host and pathogen components, is required. Among the surface proteins involved in virulence are members of two gene families called P97 and P102. These proteins are the adhesins directing attachment of the organism to the swine respiratory epithelium. P97 is the major ciliary binding adhesin and has been studied extensively. Monoclonal antibodies that block its binding to swine cilia have contributed extensively to its characterization. In this study we use recombination to construct null mutants of P97 inM. hyopneumoniaeand characterize the resulting mutants in terms of loss of protein by immunoblot using monoclonal antibodies, ability to bind purified swine cilia, and adherence to PK15 cells. Various approaches to recombination with this fastidious mycoplasma were tested including intact plasmid DNA, single-stranded DNA, and linear DNA with and without a heterologous RecA protein. Our results indicate that recombination can be used to generate site-specific mutants inM. hyopneumoniae.P97 mutants are deficient in cilia binding and PK15 cell adherence, and lack the characteristic banding pattern seen in immunoblots developed with the anti-P97 monoclonal antibody.
Effect of Lactic Acid Bacteria Strains on the Growth and Aflatoxin Production Potential of Aspergillus parasiticus, and Their Ability to Bind Aflatoxin B1, Ochratoxin A, and Zearalenone in vitro
Authors: Møller Cleide Oliveira de Almeida , Freire Luisa , Rosim Roice Eliana , Margalho Larissa Pereira , Balthazar Celso Fasura , Franco Larissa Tuanny , Sant’Ana Anderson de Souza , Corassin Carlos Humberto , Rattray Fergal Patrick , Oliveira Carlos Augusto Fernandes de
Published: April 2021

The increased consumption of plant-based foods has intensified the concern related to mycotoxin intoxication. This study aimed to investigate the effect of selected lactic acid bacteria (LAB) strains on the growth of Aspergillus parasiticus NRRL 2999 and its production of aflatoxin (AF). The ability of the heat-killed (100°C for 1 h) LAB strains to bind aflatoxin M1 (AFM1) in milk and aflatoxin B1 (AFB1), ochratoxin A (OTA), and zearalenone (ZEN) in potassium phosphate buffer (PPB) was also evaluated in vitro. Ten LAB strains were tested individually, by inoculating them simultaneously with the fungus or after incubation of the fungus for 24 or 48 h at 25°C. Double layer yeast extract sucrose (YES) agar, de Man Rogosa and Sharpe (MRS) agar, and YES broth were incubated for 7 days at 25°C to follow the development of the fungus. Levilactobacillus spp. 3QB398 and Levilactobacillus brevis 2QB422 strains were able to delay the growth of A. parasiticus in YES broth, even when these strains were inoculated 24 h after the fungus. The inhibitory effect of these LAB strains was confirmed by the reduction of fungus colony size, suggesting dominance of LAB by competition (a Lotka-Voltera effect). The production of AFB1 by A. parasiticus was inhibited when the fungus was inoculated simultaneously with Lactiplantibacillus plantarum 3QB361 or L. plantarum 3QB350. No AFB1 was found when Levilactobacillus spp. 2QB383 was present, even when the LAB was inoculated 48 h after the fungus. In binding studies, seven inactivated LAB strains were able to promote a reduction of at least 50% the level of AFB1, OTA, and ZEN. This reduction varied depending on the pH of the PPB. In milk, however, only two inactivated LAB strains were able to reduce AFM1, with a reduction of 33 and 45% for Levilactobacillus spp. 3QB398 (Levilactobacillus spp.) and L. brevis 2QB422, respectively. Nevertheless, these results clearly indicate the potential of using LAB for mycotoxin reduction.
Pan-Cancer Analysis of FURIN as a Potential Prognostic and Immunological Biomarker
Authors: Zhou Bolun , Gao Shugeng
Published: April 2021

Background

Furin is a calcium-dependent protease that processes various precursor proteins through diverse secretory pathways. The deregulation of FURIN correlated with the prognosis of patients in numerous diseases. However, the role of FURIN in human pan-cancer is still largely unknown.

Methods

Multiple bioinformatic methods were employed to comprehensively analyze the correlation of FURIN expression with prognosis, mismatch repair (MMR), microsatellite instability (MSI), tumor mutational burden (TMB), DNA methylation, tumor immune infiltration, and common immune checkpoint inhibitors (ICIs) from the public database, and aim to evaluate the potential prognostic value of FURIN across cancers.

Results

FURIN was aberrantly expressed and was strongly correlated with MMR, MSI, TMB, and DNA methylation in multiple types of cancer. Moreover, survival analysis across cancers revealed that FURIN expression was correlated with overall survival (OS) in four cancers, disease-specific survival (DSS) in five cancers, progression-free interval (PFI) in seven cancers, and disease-free interval (DFI) in two cancers. Also, FURIN expression was related to immune cell infiltration in 6 cancers and ImmuneScore/StromalScore in 10 cancers, respectively. In addition, FURIN expression also showed strong association between expression levels and immune checkpoint markers in three cancers.

Conclusion

FURIN can serve as a significant prognostic biomarker and correlate with tumor immunity in human pan-cancer.
The Role of ClpB in Bacterial Stress Responses and Virulence
Authors: Alam Athar , Bröms Jeanette E. , Kumar Rajender , Sjöstedt Anders
Published: April 2021

Bacterial survival within a mammalian host is contingent upon sensing environmental perturbations and initiating an appropriate counter-response. To achieve this, sophisticated molecular machineries are used, where bacterial chaperone systems play key roles. The chaperones are a prerequisite for bacterial survival during normal physiological conditions as well as under stressful situations, e.g., infection or inflammation. Specific stress factors include, but are not limited to, high temperature, osmolarity, pH, reactive oxidative species, or bactericidal molecules. ClpB, a member of class 1 AAA+ proteins, is a key chaperone that via its disaggregase activity plays a crucial role for bacterial survival under various forms of stress, in particular heat shock. Recently, it has been reported that ClpB also regulates secretion of bacterial effector molecules related to type VI secretion systems. In this review, the roles of ClpB in stress responses and the mechanisms by which it promotes survival of pathogenic bacteria are discussed.
Antibodies and Vaccines Target RBD of SARS-CoV-2
Authors: Min Long , Sun Qiu
Published: April 2021

The novel human coronavirus, severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), which gives rise to the coronavirus disease 2019 (COVID-19), has caused a serious threat to global public health. On March 11, 2020, the WHO had officially announced COVID-19 as a pandemic. Therefore, it is vital to find effective and safe neutralizing antibodies and vaccines for COVID-19. The critical neutralizing domain (CND) that is contained in the receptor-binding domain (RBD) of the spike protein (S protein) could lead to a highly potent neutralizing antibody response as well as the cross-protection of other strains of SARS. By using RBD as an antigen, many neutralizing antibodies are isolated that are essential to the therapeutics of COVID-19. Furthermore, a subunit vaccine, which is based on the RBD, is expected to be safer than others, thus the RBD in the S protein is a more important target for vaccine development. In this review, we focus on neutralizing antibodies that are targeting RBD as well as the vaccine based on RBD under current development.
For Better or for Worse: A Look Into Neutrophils in Traumatic Spinal Cord Injury
Authors: Zivkovic Sandra , Ayazi Maryam , Hammel Grace , Ren Yi
Published: April 2021

Neutrophils are short-lived cells of the innate immune system and the first line of defense at the site of an infection and tissue injury. Pattern recognition receptors on neutrophils recognize pathogen-associated molecular patterns or danger-associated molecular patterns, which recruit them to the destined site. Neutrophils are professional phagocytes with efficient granular constituents that aid in the neutralization of pathogens. In addition to phagocytosis and degranulation, neutrophils are proficient in creating neutrophil extracellular traps (NETs) that immobilize pathogens to prevent their spread. Because of the cytotoxicity of the associated granular proteins within NETs, the microbes can be directly killed once immobilized by the NETs. The role of neutrophils in infection is well studied; however, there is less emphasis placed on the role of neutrophils in tissue injury, such as traumatic spinal cord injury. Upon the initial mechanical injury, the innate immune system is activated in response to the molecules produced by the resident cells of the injured spinal cord initiating the inflammatory cascade. This review provides an overview of the essential role of neutrophils and explores the contribution of neutrophils to the pathologic changes in the injured spinal cord.
Multicenter Interventional Phase IV Study for the Assessment of the Effects on Patient's Satisfaction of Peg IFN Beta-1a (Pre-filled Pen) in Subjects With Relapsing–Remitting Multiple Sclerosis Unsatisfied With Other Injectable Subcutaneous Interferons (PLATINUM Study)
Authors: Centonze Diego , Fantozzi Roberta , Buttari Fabio , Grimaldi Luigi Maria Edoardo , Totaro Rocco , Corea Francesco , Marrosu Maria Giovanna , Confalonieri Paolo , Cottone Salvatore , Trojano Maria , Zipoli Valentina
Published: April 2021

Subcutaneous (SC) interferons beta (IFN-beta) are effective therapies for the treatment of relapsing–remitting multiple sclerosis (RRMS). Factors such as dosing schedule, needle intolerance/fatigue, and side effects may impact patient satisfaction with treatment. Improvement of patient satisfaction may increase the adherence to treatment and the patient quality of life. This study was aimed at evaluating the impact of switching to “Peginterferon beta-1a (Peg-IFN beta-1a)” in patients with RRMS unsatisfied with other SC interferons. The multicenter, open-label, phase IV PLATINUM study was conducted in 32 Italian centers. The primary endpoint was changes from baseline in the score of a convenience satisfaction domain of the TSQM-9 questionnaire at 12 weeks. The secondary endpoints were patients' global satisfaction, short-term adherence to treatment, satisfaction with the injection system, effect on fatigue, disease activity, and patient inability score. A total of 193 patients were enrolled and 166 (86%) completed the study, receiving Peg-IFN beta-1a for 24 weeks. Patients switching to Peg-IFN beta-1a from other SC interferons reported a significant improvement (p < 0.001) of Convenience Score and all other scores of the TSQM-9 questionnaire at 12 and 24 weeks (p < 0.001). Peg IFN beta-1a attained very high adherence to the treatment (92 and 86% at 12 and 24 weeks, respectively) with a stable annualized relapse rate (ARR). At 24 weeks, 94% of the participants were relapse free. Adverse events (AEs), recorded on 82 patients (42%), were mild or moderate. The most common AE was flu-like syndrome (29.2%). Patients switching from SC IFN beta therapy to Peg IFN beta-1a showed high treatment satisfaction with a positive safety profile, comparable with that of other currently approved first-line injectable SC interferons. This study suggests that Peg IFN beta-1a might represent a treatment choice to improve adherence in RRMS patients unsatisfied with other SC interferons.
A Methodological Review of fNIRS in Driving Research: Relevance to the Future of Autonomous Vehicles
Authors: Balters Stephanie , Baker Joseph M. , Geeseman Joseph W. , Reiss Allan L.
Published: April 2021

As automobile manufacturers have begun to design, engineer, and test autonomous driving systems of the future, brain imaging with functional near-infrared spectroscopy (fNIRS) can provide unique insights about cognitive processes associated with evolving levels of autonomy implemented in the automobile. Modern fNIRS devices provide a portable, relatively affordable, and robust form of functional neuroimaging that allows researchers to investigate brain function in real-world environments. The trend toward “naturalistic neuroscience” is evident in the growing number of studies that leverage the methodological flexibility of fNIRS, and in doing so, significantly expand the scope of cognitive function that is accessible to observation via functional brain imaging (i.e., from the simulator to on-road scenarios). While more than a decade’s worth of study in this field of fNIRS driving research has led to many interesting findings, the number of studies applying fNIRS during autonomous modes of operation is limited. To support future research that directly addresses this lack in autonomous driving research with fNIRS, we argue that a cogent distillation of the methods used to date will help facilitate and streamline this research of tomorrow. To that end, here we provide a methodological review of the existing fNIRS driving research, with the overarching goal of highlighting the current diversity in methodological approaches. We argue that standardization of these approaches will facilitate greater overlap of methods by researchers from all disciplines, which will, in-turn, allow for meta-analysis of future results. We conclude by providing recommendations for advancing the use of such fNIRS technology in furthering understanding the adoption of safe autonomous vehicle technology.
QDECR: A Flexible, Extensible Vertex-Wise Analysis Framework in R
Authors: Lamballais Sander , Muetzel Ryan L.
Published: April 2021

The cerebral cortex is fundamental to the functioning of the mind and body. In vivo cortical morphology can be studied through magnetic resonance imaging in several ways, including reconstructing surface-based models of the cortex. However, existing software for surface-based statistical analyses cannot accommodate “big data” or commonly used statistical methods such as the imputation of missing data, extensive bias correction, and non-linear modeling. To address these shortcomings, we developed the QDECR package, a flexible and extensible R package for group-level statistical analysis of cortical morphology. QDECR was written with large population-based epidemiological studies in mind and was designed to fully utilize the extensive modeling options in R. QDECR currently supports vertex-wise linear regression. Design matrix generation can be done through simple, familiar R formula specification, and includes user-friendly extensions for R options such as polynomials, splines, interactions and other terms. QDECR can handle unimputed and imputed datasets with thousands of participants. QDECR has a modular design, and new statistical models can be implemented which utilize several aspects from other generic modules which comprise QDECR. In summary, QDECR provides a framework for vertex-wise surface-based analyses that enables flexible statistical modeling and features commonly used in population-based and clinical studies, which have until now been largely absent from neuroimaging research.
ID4 Is Required for Normal Ependymal Cell Development
Authors: Rocamonde Brenda , Herranz-Pérez Vicente , Garcia-Verdugo Jose Manuel , Huillard Emmanuelle
Published: April 2021

Ependymal cells are radial glia-derived multiciliated cells lining the lateral ventricles of the brain and spinal cord. Correct development and coordinated cilia beating is essential for proper cerebrospinal fluid (CSF) flow and neurogenesis modulation. Dysfunctions of ependymal cells were associated with transcription factor deregulation. Here we provide evidence that the transcriptional regulator ID4 is involved in ependymal cell development and maturation. We observed that Id4-deficient mice display altered ventricular cell cytoarchitecture, decreased ependymal cell number and enlarged ventricles. In addition, absence of ID4 during embryonic development resulted in decreased ependymal cell number and delayed maturation. Our findings open the way for a potential role of ID4 in ependymal cell development and motor cilia function.
Long Noncoding RNA MLK7-AS1 Promotes Non-Small-Cell Lung Cancer Migration and Invasion via the miR-375-3p/YWHAZ Axis
Authors: Jia Jingzhou , Sun Jiwei , Wang Wenbo , Yong Hongmei
Published: April 2021

Long noncoding RNAs act essential regulators in lung cancer tumorigenesis. Our research aimed to investigate the potential function and molecular mechanisms of MLK7-AS1 in NSCLC (non-small-cell lung cancer). QRT-PCR results indicated that the MLK7-AS1 expression level was upregulated in NSCLC cells and tissues. MLK7-AS1 strengthened cell migration and invasion in H1299 and A549 cells. Luciferase reporter assay found that MLK7-AS1 functioned as an endogenous sponge for miR-375-3p. Transwell assay results showed that miR-375-3p suppressed cell migration and invasion in H1299 and A549 cells. YWHAZ was confirmed as a target gene of miR-375-3p by Targetscan. YWHAZ overexpression promoted the invasion of H1299 and A549 cells. MLK7-AS1 upregulated YWHAZ expression and enhanced H1299 and A549 cell invasion by sponging miR-375-3p. MLK7-AS1 improved the metastasis ability of A549 in vivo. In conclusion, MLK7-AS1 was identified as a novel oncogenic RNA in NSCLC and can function as a potential therapeutic target for NSCLC treatment.
TRIM68, PIKFYVE, and DYNLL2: The Possible Novel Autophagy- and Immunity-Associated Gene Biomarkers for Osteosarcoma Prognosis
Authors: Jiang Jie , Liu Dachang , Xu Guoyong , Liang Tuo , Yu Chaojie , Liao Shian , Chen Liyi , Huang Shengsheng , Sun Xuhua , Yi Ming , Zhang Zide , Lu Zhaojun , Wang Zequn , Chen Jiarui , Chen Tianyou , Li Hao , Yao Yuanlin , Chen Wuhua , Guo Hao , Liu Chong , Zhan Xinli
Published: April 2021

Introduction

Osteosarcoma is among the most common orthopedic neoplasms, and currently, there are no adequate biomarkers to predict its prognosis. Therefore, the present study was aimed to identify the prognostic biomarkers for autophagy-and immune-related osteosarcoma using bioinformatics tools for guiding the clinical diagnosis and treatment of this disease.

Materials and Methods

The gene expression and clinical information data were downloaded from the Public database. The genes associated with autophagy were extracted, followed by the development of a logistic regression model for predicting the prognosis of osteosarcoma using univariate and multivariate COX regression analysis and LASSO regression analysis. The accuracy of the constructed model was verified through the ROC curves, calibration plots, and Nomogram plots. Next, immune cell typing was performed using CIBERSORT to analyze the expression of the immune cells in each sample. For the results obtained from the analysis, we used qRT-PCR validation in two strains of human osteosarcoma cells.

Results

The screening process identified a total of three genes that fulfilled all the screening criteria. The survival curves of the constructed prognostic model revealed that patients with the high risk presented significantly lower survival than the patients with low risk. Finally, the immune cell component analysis revealed that all three genes were significantly associated with the immune cells. The expressions of TRIM68, PIKFYVE, and DYNLL2 were higher in the osteosarcoma cells compared to the control cells. Finally, we used human pathological tissue sections to validate the expression of the genes modeled in osteosarcoma and paracancerous tissue.

Conclusion

The TRIM68, PIKFYVE, and DYNLL2 genes can be used as biomarkers for predicting the prognosis of osteosarcoma.