bluuebunny/crossref_metadata_2025 huggingface dataset:
Potential of Prebiotic D-Tagatose for Prevention of Oral Disease
Authors: Mayumi Shota , Kuboniwa Masae , Sakanaka Akito , Hashino Ei , Ishikawa Asuka , Ijima Yura , Amano Atsuo
Published: November 2021

Recent studies have shown phenotypic and metabolic heterogeneity in related species including Streptococcus oralis, a typical oral commensal bacterium, Streptococcus mutans, a cariogenic bacterium, and Streptococcus gordonii, which functions as an accessory pathogen in periodontopathic biofilm. In this study, metabolites characteristically contained in the saliva of individuals with good oral hygiene were determined, after which the effects of an identified prebiotic candidate, D-tagatose, on phenotype, gene expression, and metabolic profiles of those three key bacterial species were investigated. Examinations of the saliva metabolome of 18 systemically healthy volunteers identified salivary D-tagatose as associated with lower dental biofilm abundance in the oral cavity (Spearman’s correlation coefficient; r = -0.603, p = 0.008), then the effects of D-tagatose on oral streptococci were analyzed in vitro. In chemically defined medium (CDM) containing D-tagatose as the sole carbohydrate source, S. mutans and S. gordonii each showed negligible biofilm formation, whereas significant biofilms were formed in cultures of S. oralis. Furthermore, even in the presence of glucose, S. mutans and S. gordonii showed growth suppression and decreases in the final viable cell count in a D-tagatose concentration-dependent manner. In contrast, no inhibitory effects of D-tagatose on the growth of S. oralis were observed. To investigate species-specific inhibition by D-tagatose, the metabolomic profiles of D-tagatose-treated S. mutans, S. gordonii, and S. oralis cells were examined. The intracellular amounts of pyruvate-derived amino acids in S. mutans and S. gordonii, but not in S. oralis, such as branched-chain amino acids and alanine, tended to decrease in the presence of D-tagatose. This phenomenon indicates that D-tagatose inhibits growth of those bacteria by affecting glycolysis and its downstream metabolism. In conclusion, the present study provides evidence that D-tagatose is abundant in saliva of individuals with good oral health. Additionally, experimental results demonstrated that D-tagatose selectively inhibits growth of the oral pathogens S. mutans and S. gordonii. In contrast, the oral commensal S. oralis seemed to be negligibly affected, thus highlighting the potential of administration of D-tagatose as an oral prebiotic for its ability to manipulate the metabolism of those targeted oral streptococci.
Codon Usage Bias in Autophagy-Related Gene 13 in Eukaryotes: Uncovering the Genetic Divergence by the Interplay Between Nucleotides and Codon Usages
Authors: Li Yicong , Wang Rui , Wang Huihui , Pu Feiyang , Feng Xili , Jin Li , Ma Zhongren , Ma Xiao-xia
Published: November 2021

Synonymous codon usage bias is a universal characteristic of genomes across various organisms. Autophagy-related gene 13 (atg13) is one essential gene for autophagy initiation, yet the evolutionary trends of the atg13 gene at the usages of nucleotide and synonymous codon remains unexplored. According to phylogenetic analyses for the atg13 gene of 226 eukaryotic organisms at the nucleotide and amino acid levels, it is clear that their nucleotide usages exhibit more genetic information than their amino acid usages. Specifically, the overall nucleotide usage bias quantified by information entropy reflected that the usage biases at the first and second codon positions were stronger than those at the third position of the atg13 genes. Furthermore, the bias level of nucleotide ‘G’ usage is highest, while that of nucleotide ‘C’ usage is lowest in the atg13 genes. On top of that, genetic features represented by synonymous codon usage exhibits a species-specific pattern on the evolution of the atg13 genes to some extent. Interestingly, the codon usages of atg13 genes in the ancestor animals (Latimeria chalumnae, Petromyzon marinus, and Rhinatrema bivittatum) are strongly influenced by mutation pressure from nucleotide composition constraint. However, the distributions of nucleotide composition at different codon positions in the atg13 gene display that natural selection still dominates atg13 codon usages during organisms’ evolution.
Deep Learning-based Sentiment Analysis and Topic Modeling on Tourism During Covid-19 Pandemic
Authors: Mishra Ram Krishn , Urolagin Siddhaling , Jothi J. Angel Arul , Neogi Ashwin Sanjay , Nawaz Nishad
Published: November 2021

The Covid-19 pandemic has disrupted the world economy and significantly influenced the tourism industry. Millions of people have shared their emotions, views, facts, and circumstances on numerous social media platforms, which has resulted in a massive flow of information. The high-density social media data has drawn many researchers to extract valuable information and understand the user’s emotions during the pandemic time. The research looks at the data collected from the micro-blogging site Twitter for the tourism sector, emphasizing sub-domains hospitality and healthcare. The sentiment of approximately 20,000 tweets have been calculated using Valence Aware Dictionary for Sentiment Reasoning (VADER) model. Furthermore, topic modeling was used to reveal certain hidden themes and determine the narrative and direction of the topics related to tourism healthcare, and hospitality. Topic modeling also helped us to identify inter-cluster similar terms and analyzing the flow of information from a group of a similar opinion. Finally, a cutting-edge deep learning classification model was used with different epoch sizes of the dataset to anticipate and classify the people’s feelings. The deep learning model has been tested with multiple parameters such as training set accuracy, test set accuracy, validation loss, validation accuracy, etc., and resulted in more than a 90% in training set accuracy tourism hospitality and healthcare reported 80.9 and 78.7% respectively on test set accuracy.
Diagnostic Accuracy and Generalizability of a Deep Learning-Based Fully Automated Algorithm for Coronary Artery Stenosis Detection on CCTA: A Multi-Centre Registry Study
Authors: Xu Lixue , He Yi , Luo Nan , Guo Ning , Hong Min , Jia Xibin , Wang Zhenchang , Yang Zhenghan
Published: November 2021

Aims: In this retrospective, multi-center study, we aimed to estimate the diagnostic accuracy and generalizability of an established deep learning (DL)-based fully automated algorithm in detecting coronary stenosis on coronary computed tomography angiography (CCTA).

Methods and results: A total of 527 patients (33.0% female, mean age: 62.2 ± 10.2 years) with suspected coronary artery disease (CAD) who underwent CCTA and invasive coronary angiography (ICA) were enrolled from 27 hospitals from January 2016 to August 2019. Using ICA as a standard reference, the diagnostic accuracy of the DL algorithm in the detection of ≥50% stenosis was compared to that of expert readers. In the vessel-based evaluation, the DL algorithm had a higher sensitivity (65.7%) and negative predictive value (NPV) (78.8%) and a significantly higher area under the curve (AUC) (0.83, p < 0.001). In the patient-based evaluation, the DL algorithm achieved a higher sensitivity (90.0%), NPV (52.2%) and AUC (0.81). Generalizability analysis of the DL algorithm was conducted by comparing its diagnostic performance in subgroups stratified by sex, age, geographic area and CT scanner type. The AUCs of the DL algorithm in the aforementioned subgroups ranged from 0.79 to 0.86 and from 0.75 to 0.93 in the vessel-based and patient-based evaluations, both without significant group differences (p > 0.05). The DL algorithm significantly reduced post-processing time (160 [IQR:139–192] seconds), in comparison to manual work (p < 0.001).

Conclusions: The DL algorithm performed no inferior to expert readers in CAD diagnosis on CCTA and had good generalizability and time efficiency.
The Association of Plant-Based Diet With Cardiovascular Disease and Mortality: A Meta-Analysis and Systematic Review of Prospect Cohort Studies
Authors: Quek Jingxuan , Lim Grace , Lim Wen Hui , Ng Cheng Han , So Wei Zheng , Toh Jonathan , Pan Xin Hui , Chin Yip Han , Muthiah Mark D. , Chan Siew Pang , Foo Roger S. Y. , Yip James , Neelakantan Nithya , Chong Mary F. F. , Loh Poay Huan , Chew Nicholas W. S.
Published: November 2021

Background: The association between plant-based diets and cardiovascular disease (CVD) remains poorly characterized. Given that diet represents an important and a modifiable risk factor, this study aimed to assess (1) the relationships between the impact of adherence to plant-based diets on cardiovascular mortality, incident CVD, and stroke; (2) if associations differed by adherence to healthful and less healthful plant-based diets.

Methods and Findings: MEDLINE and EMBASE databases were searched up to May 2021. Studies assessing CVD outcomes with relation to plant-based dietary patterns or according to plant-based dietary indices (PDI) were included. A meta-analysis of hazard ratios (HR) was conducted using DerSimonian and Laird random effects model. Thirteen studies involving 410,085 participants were included. Greater adherence to an overall plant-based dietary pattern was significantly associated with a lower risk of cardiovascular mortality (pooled HR: 0.92, 95% CI: 0.86–0.99 p = 0.0193, I2 = 88.5%, N = 124,501) and a lower risk of CVD incidence (pooled HR: 0.90, 95% CI: 0.82–0.98, p = 0.0173, I2 = 87.2%, N = 323,854). Among the studies that used PDI, unhealthful plant-based diets were associated with increased risk of cardiovascular mortality (pooled HR: 1.05, 95% CI: 1.01–1.09, p = 0.0123, I2 = 0.00%, N = 18,966), but not CVD incidence. Conversely, healthful plant-based diets were associated with decreased CVD incidence (pooled HR: 0.87, 95% CI: 0.80–0.95, p = 0.0011, I2 = 57.5%, N = 71,301), but not mortality. Vegetarians also had significantly lower CVD incidence (HR: 0.81, 95% CI: 0.72–0.91, p = 0.0004, I2 = 22.2%, N = 16,254), but similar CVD mortality or stroke risk when compared to the meat-eaters.

Conclusion: To date, this comprehensive study examines the effects of a plant-based diet on major clinical endpoints using more holistic PDIs. These findings highlight the favorable role of healthful plant-based foods in reducing cardiovascular mortality and CVD.
Gene Therapy for Cardiovascular Disease: Basic Research and Clinical Prospects
Authors: Cao Genmao , Xuan Xuezhen , Zhang Ruijing , Hu Jie , Dong Honglin
Published: November 2021

In recent years, the vital role of genetic factors in human diseases have been widely recognized by scholars with the deepening of life science research, accompanied by the rapid development of gene-editing technology. In early years, scientists used homologous recombination technology to establish gene knock-out and gene knock-in animal models, and then appeared the second-generation gene-editing technology zinc-finger nucleases (ZFNs) and transcription activator–like effector nucleases (TALENs) that relied on nucleic acid binding proteins and endonucleases and the third-generation gene-editing technology that functioned through protein–nucleic acids complexes—CRISPR/Cas9 system. This holds another promise for refractory diseases and genetic diseases. Cardiovascular disease (CVD) has always been the focus of clinical and basic research because of its high incidence and high disability rate, which seriously affects the long-term survival and quality of life of patients. Because some inherited cardiovascular diseases do not respond well to drug and surgical treatment, researchers are trying to use rapidly developing genetic techniques to develop initial attempts. However, significant obstacles to clinical application of gene therapy still exists, such as insufficient understanding of the nature of cardiovascular disease, limitations of genetic technology, or ethical concerns. This review mainly introduces the types and mechanisms of gene-editing techniques, ethical concerns of gene therapy, the application of gene therapy in atherosclerosis and inheritable cardiovascular diseases, in-stent restenosis, and delivering systems.
Advances in Amazonian Peatland Discrimination With Multi-Temporal PALSAR Refines Estimates of Peatland Distribution, C Stocks and Deforestation
Authors: Bourgeau-Chavez Laura L. , Grelik Sarah L. , Battaglia Michael J. , Leisman Dorthea J. , Chimner Rod A. , Hribljan John A. , Lilleskov Erik A. , Draper Freddie C. , Zutta Brian R. , Hergoualc’h Kristell , Bhomia Rupesh K. , Lähteenoja Outi
Published: November 2021

There is a data gap in our current knowledge of the geospatial distribution, type and extent of C rich peatlands across the globe. The Pastaza Marañón Foreland Basin (PMFB), within the Peruvian Amazon, is known to store large amounts of peat, but the remoteness of the region makes field data collection and mapping the distribution of peatland ecotypes challenging. Here we review methods for developing high accuracy peatland maps for the PMFB using a combination of multi-temporal synthetic aperture radar (SAR) and optical remote sensing in a machine learning classifier. The new map produced has 95% overall accuracy with low errors of commission (1–6%) and errors of omission (0–15%) for individual peatland classes. We attribute this improvement in map accuracy over previous maps of the region to the inclusion of high and low water season SAR images which provides information about seasonal hydrological dynamics. The new multi-date map showed an increase in area of more than 200% for pole forest peatland (6% error) compared to previous maps, which had high errors for that ecotype (20–36%). Likewise, estimates of C stocks were 35% greater than previously reported (3.238 Pg in Draper et al. (2014) to 4.360 Pg in our study). Most of the increase is attributed to pole forest peatland which contributed 58% (2.551 Pg) of total C, followed by palm swamp (34%, 1.476 Pg). In an assessment of deforestation from 2010 to 2018 in the PMFB, we found 89% of the deforestation was in seasonally flooded forest and 43% of deforestation was occurring within 1 km of a river or road. Peatlands were found the least affected by deforestation and there was not a noticeable trend over time. With development of improved transportation routes and population pressures, future land use change is likely to put South American tropical peatlands at risk, making continued monitoring a necessity. Accurate mapping of peatland ecotypes with high resolution (<30 m) sensors linked with field data are needed to reduce uncertainties in estimates of the distribution of C stocks, and to aid in deforestation monitoring.
The Main Controlling Factors and Evaluation Method of the Reservoir Stimulation Potential: A Case Study of the Changning Shale Gas Field, Southern Sichuan Basin, SW China
Authors: Shen Cheng , Zhao Jinzhou , Xie Jun , Fu Yongqiang , Wu Jianfa , Ren Lan
Published: November 2021

Based on logging, seismic, fracturing and production data from 301 productive wells in Longmaxi Formation in Changning shale gas field of southern Sichuan basin, the various influence factors of shale gas stimulated potential have been analyzed to carry out the correlation study with estimated ultimate recovery (EUR) of the same fracturing operation intensity to fully clarify the main controlling factors for shale gas stimulated potential. The results show that matrix brittleness, fracture propagation and reservoir properties are the 3 key secondary potentials that control shale gas stimulation potential. The matrix brittleness is controlled by elastic modulus, Poisson’s ratio, Type I and II fracture toughness, which reflects the uniformity of hydraulic fracture propagation. Fracture propagation is controlled by critical net pressure, which reflects the scale of hydraulic fracture propagation. Reservoir properties are controlled by porosity, total organic carbon content (TOC) and horizontal interval differences, which reflect the enrichment conditions and dynamic production capacity of reservoir resources. The matrix brittleness index, fracture propagation index, reservoir properties index and their combined stimulated potential index were formed by using the above 7 parameters to verify and apply the wells in Changning shale gas field. Results show that the matrix brittleness index and length-width ratio of hydraulic fracture was significantly negative correlation, the fracture propagation index and stimulated reservoir volume (SRV) were significantly positive correlation, stimulated potential index was developed taking into account enrichment & exploitation potential. In areas where the value is greater than 0.5, increasing the fracturing scale can effectively improve the well productivity; in areas less than 0.5, increasing the fracturing scale has an upper limit on the increase of productivity, so the physical properties of the reservoir itself play a significant role in controlling the production of shale gas wells.
Serum Calcitonin-Negative Medullary Thyroid Carcinoma: A Case Series of 19 Patients in a Single Center
Authors: Kim Sun Jung , Yun Hyeok Jun , Shin Su-Jin , Lee Yong Sang , Chang Hang-Seok
Published: November 2021

Introduction

Medullary thyroid carcinoma (MTC) is a rare cancer that accounts for 5% of thyroid cancers. Serum calcitonin is a good biomarker for MTC, which is used for diagnosis, prognosis, and monitoring of recurrence. Calcitonin-negative MTC (CNMTC) is rare but confounds diagnostic and prognostic directions. This study introduces 19 cases of CNMTC in a single center.

Method

From 2002 March to 2020 July, more than 76,500 patients had undergone thyroid surgery due to thyroid cancer at the Severance Hospital, and a total of 320 patients were diagnosed with MTC (0.4%). Serum calcitonin levels were obtained from every patient who was suspected with MTC. These patients had undergone either bilateral total thyroidectomy or unilateral thyroidectomy with central compartment lymph node dissection, and additional modified radical lymph node dissection if lateral lymph node metastasis was positive. Postoperative monitoring and out-patient clinic follow-up were performed with obtaining the serum calcitonin levels.

Result

Nineteen patients tested negative for calcitonin preoperatively (6%). The mean preoperative calcitonin level was 5.1pg/mL if undetectable level is regarded as 0pg/mL. Only two patients were males, and the female bias was significant (p = 0.017). No one except two patients with modified radical neck dissection showed central compartment lymph node metastasis. Every patient’s postoperative calcitonin level remained low. The median follow-up period was 71 months. There was no recurrence and only one fatality, and the overall survival rate was 95%.

Conclusion

Since incidence of CNMTC is not negligible, MTC should not be ruled out in the diagnostic phase even if serum calcitonin is negative in preoperative examination. We presented 19 cases of CNMTC whose prognosis in general were favorable. Markers of serum and immunohistochemical samples other than calcitonin should be actively examined.
CKD Stages, Bone Metabolism Markers, and Cortical Porosity Index: Associations and Mediation Effects Analysis
Authors: Xiong Yan , He Tongxiang , Wang Yanan , Liu Weiyin Vivian , Hu Shuang , Zhang Yao , Wen Donglin , Hou Bowen , Li Yitong , Zhang Peisen , Liu Jianyi , He Fan , Li Xiaoming
Published: November 2021

Chronic kidney disease (CKD) has a significant negative impact on bone health. However, the mechanisms of cortical bone deterioration and cortical porosity enlargement caused by CKD have not been fully described. We therefore examined the association of CKD stages with cortical porosity index (PI), and explored potential mediators of this association. Double-echo ultrashort echo-time magnetic resonance imaging (UTE MRI) provides the possibility of quantifying cortical porosity in vivo. A total of 95 patients with CKD stages 2-5 underwent 3D double-echo UTE-Cones MRI (3.0T) of the midshaft tibia to obtain the PI. PI was defined as the ratio of the image signal intensity of a sufficiently long echo time (TE) to the shortest achievable TE. Parathyroid hormone (PTH), β-CrossLaps (β-CTX), total procollagen type I amino-terminal propeptide (T-P1NP), osteocalcin (OC), 25-hydroxyvitamin D (25OHD), and lumbar bone mineral density (BMD) were measured within one week of the MRI. Partial correlation analysis was performed to address associations between PI, eGFR and potential mediators (PTH, β-CTX, T-P1NP, OC, 25OHD, BMD, and T-score). Multiple linear regression models were used to assess the association between CKD stages and PI value. Then, a separate exploratory mediation analysis was carried out to explore the impact of CKD stages and mediators on the PI value. The increasing CKD stages were associated with a higher PI value (Ptrend < 0.001). The association of CKD stages and PI mediated 34.4% and 30.8% of the total effect by increased PTH and β-CTX, respectively. Our study provides a new idea to monitor bone health in patients with CKD, and reveals the internal mechanism of bone deterioration caused by CKD to some extent.
Annelid Borings on Brachiopod Shells From the Upper Ordovician of Peru. A Long-Distance Co-migration of Biotic Partners
Authors: Villas Enrique , Mayoral Eduardo , Santos Ana , Colmenar Jorge , Gutiérrez-Marco Juan Carlos
Published: November 2021

The Recent planktonic larvae of the polychaete spionids are some of the most widespread and abundant group of coastal meroplankton worldwide. To study the possible co-migration of biotic partners and determine whether they were host-specific, the type of biotic relationship between hosts and borers of an Upper Ordovician Peruvian brachiopod collection from the Proto-Andean margin of Gondwana was re-exanimated and compared with material from Wales (Avalonia). The species list studied is composed of Colaptomena expansa (41%), Heterorthis retrorsistria (24%), Horderleyella chacaltanai (19%), Drabovinella minuscula (13%), and Dinorthis cf. flabellulum (3%) and coincides closely with that of the Dinorthis community described in the Caradoc series of North Wales. The borings attributed to these spionids have been identified as Palaeosabella prisca only present in the valves of Colaptomena expansa and Heterorthis retrorsistria. All the studied valves are disarticulated, with very low fragmentation and are randomly oriented in a context below the fair-weather wave base. The settling larvae would feed on their brachiopod host soft parts at an early stage, being the biotic interaction initially of the parasitic type. Since Palaeosabella borings from Peru and Wales are identical, as well as the species specificity of their producers with their brachiopod hosts, it can be concluded that the same spionid annelid species produced them. The Southern Westerlies current that connected the Proto-Andean margin of Gondwana with Avalonia must have been responsible for transporting the larvae of annelids and brachiopods in what had to be a successful biotic relationship over a great transoceanic distance.
Continuous Modeling of T CD4 Lymphocyte Activation and Function
Authors: Martínez-Méndez David , Mendoza Luis , Villarreal Carlos , Huerta Leonor
Published: November 2021

T CD4+ cells are central to the adaptive immune response against pathogens. Their activation is induced by the engagement of the T-cell receptor by antigens, and of co-stimulatory receptors by molecules also expressed on antigen presenting cells. Then, a complex network of intracellular events reinforce, diversify and regulate the initial signals, including dynamic metabolic processes that strongly influence both the activation state and the differentiation to effector cell phenotypes. The regulation of cell metabolism is controlled by the nutrient sensor adenosine monophosphate-activated protein kinase (AMPK), which drives the balance between oxidative phosphorylation (OXPHOS) and glycolysis. Herein, we put forward a 51-node continuous mathematical model that describes the temporal evolution of the early events of activation, integrating a circuit of metabolic regulation into the main routes of signaling. The model simulates the induction of anergy due to defective co-stimulation, the CTLA-4 checkpoint blockade, and the differentiation to effector phenotypes induced by external cytokines. It also describes the adjustment of the OXPHOS-glycolysis equilibrium by the action of AMPK as the effector function of the T cell develops. The development of a transient phase of increased OXPHOS before induction of a sustained glycolytic phase during differentiation to the Th1, Th2 and Th17 phenotypes is shown. In contrast, during Treg differentiation, glycolysis is subsequently reduced as cell metabolism is predominantly polarized towards OXPHOS. These observations are in agreement with experimental data suggesting that OXPHOS produces an ATP reservoir before glycolysis boosts the production of metabolites needed for protein synthesis, cell function, and growth.
The bZIP Transcription Factor ZIP-11 Is Required for the Innate Immune Regulation in Caenorhabditis elegans
Authors: Zheng Zhongfan , Aihemaiti Yilixiati , Liu Junqiang , Afridi Muhammad Irfan , Yang Shengmei , Zhang Xiumei , Xu Yongfu , Chen Chunhong , Tu Haijun
Published: November 2021

Innate immunity is the first line of host defense against pathogen infection in metazoans. However, the molecular mechanisms of the complex immune regulatory network are not fully understood. Based on a transcriptome profiling of the nematode Caenorhabditis elegans, we found that a bZIP transcription factor ZIP-11 was up-regulated upon Pseudomonas aeruginosa PA14 infection. The tissue specific RNAi knock-down and rescue data revealed that ZIP-11 acts in intestine to promote host resistance against P. aeruginosa PA14 infection. We further showed that intestinal ZIP-11 regulates innate immune response through constituting a feedback loop with the conserved PMK-1/p38 mitogen-activated protein signaling pathway. Intriguingly, ZIP-11 interacts with a CCAAT/enhancer-binding protein, CEBP-2, to mediate the transcriptional response to P. aeruginosa PA14 infection independently of PMK-1/p38 pathway. In addition, human homolog ATF4 can functionally substitute for ZIP-11 in innate immune regulation of C. elegans. Our findings indicate that the ZIP-11/ATF4 genetic program activates local innate immune response through conserved PMK-1/p38 and CEBP-2/C/EBPγ immune signals in C. elegans, raising the possibility that a similar process may occur in other organisms.
SARS-CoV-2 Exacerbates COVID-19 Pathology Through Activation of the Complement and Kinin Systems
Authors: Savitt Anne G. , Manimala Samantha , White Tiara , Fandaros Marina , Yin Wei , Duan Huiquan , Xu Xin , Geisbrecht Brian V. , Rubenstein David A. , Kaplan Allen P. , Peerschke Ellinor I. , Ghebrehiwet Berhane
Published: November 2021

Infection with SARS-CoV-2 triggers the simultaneous activation of innate inflammatory pathways including the complement system and the kallikrein-kinin system (KKS) generating in the process potent vasoactive peptides that contribute to severe acute respiratory syndrome (SARS) and multi-organ failure. The genome of SARS-CoV-2 encodes four major structural proteins – the spike (S) protein, nucleocapsid (N) protein, membrane (M) protein, and the envelope (E) protein. However, the role of these proteins in either binding to or activation of the complement system and/or the KKS is still incompletely understood. In these studies, we used: solid phase ELISA, hemolytic assay and surface plasmon resonance (SPR) techniques to examine if recombinant proteins corresponding to S1, N, M and E: (a) bind to C1q, gC1qR, FXII and high molecular weight kininogen (HK), and (b) activate complement and/or the KKS. Our data show that the viral proteins: (a) bind C1q and activate the classical pathway of complement, (b) bind FXII and HK, and activate the KKS in normal human plasma to generate bradykinin and (c) bind to gC1qR, the receptor for the globular heads of C1q (gC1q) which in turn could serve as a platform for the activation of both the complement system and KKS. Collectively, our data indicate that the SARS-CoV-2 viral particle can independently activate major innate inflammatory pathways for maximal damage and efficiency. Therefore, if efficient therapeutic modalities for the treatment of COVID-19 are to be designed, a strategy that includes blockade of the four major structural proteins may provide the best option.
FlowKit: A Python Toolkit for Integrated Manual and Automated Cytometry Analysis Workflows
Authors: White Scott , Quinn John , Enzor Jennifer , Staats Janet , Mosier Sarah M. , Almarode James , Denny Thomas N. , Weinhold Kent J. , Ferrari Guido , Chan Cliburn
Published: November 2021

An important challenge for primary or secondary analysis of cytometry data is how to facilitate productive collaboration between domain and quantitative experts. Domain experts in cytometry laboratories and core facilities increasingly recognize the need for automated workflows in the face of increasing data complexity, but by and large, still conduct all analysis using traditional applications, predominantly FlowJo. To a large extent, this cuts domain experts off from the rapidly growing library of Single Cell Data Science algorithms available, curtailing the potential contributions of these experts to the validation and interpretation of results. To address this challenge, we developed FlowKit, a Gating-ML 2.0-compliant Python package that can read and write FCS files and FlowJo workspaces. We present examples of the use of FlowKit for constructing reporting and analysis workflows, including round-tripping results to and from FlowJo for joint analysis by both domain and quantitative experts.
Serum Alpha-1-Acid Glycoprotein-1 and Urinary Extracellular Vesicle miR-21-5p as Potential Biomarkers of Primary Aldosteronism
Authors: Carvajal Cristian A. , Tapia-Castillo Alejandra , Pérez Jorge A. , Fardella Carlos E.
Published: November 2021

Primary aldosteronism (PA) is the most common cause of secondary hypertension and reaches a prevalence of 6-10%. PA is an endocrine disorder, currently identified as a broad-spectrum phenotype, spanning from normotension to hypertension. In this regard, several studies have made advances in the identification of mediators and novel biomarkers of PA as specific proteins, miRNAs, and lately, extracellular vesicles (EVs) and their cargo.

Aim

To evaluate lipocalins LCN2 and AGP1, and specific urinary EV miR-21-5p and Let-7i-5p as novel biomarkers for PA.

Subjects and Methods

A cross-sectional study was performed in 41 adult subjects classified as normotensive controls (CTL), essential hypertensives (EH), and primary aldosteronism (PA) subjects, who were similar in gender, age, and BMI. Systolic (SBP) and diastolic (DBP) blood pressure, aldosterone, plasma renin activity (PRA), and aldosterone to renin ratio (ARR) were determined. Inflammatory parameters were defined as hs-C-reactive protein (hs-CRP), PAI-1, MMP9, IL6, LCN2, LCN2-MMP9, and AGP1. We isolated urinary EVs (uEVs) and measured two miRNA cargo miR-21-5p and Let-7i-5p by Taqman-qPCR. Statistical analyses as group comparisons were performed by Kruskall-Wallis, and discriminatory analyses by ROC curves were performed with SPSS v21 and Graphpad-Prism v9.

Results

PA and EH subjects have significantly higher SBP and DBP (p <0.05) than the control group. PA subjects have similar hs-CRP, PAI-1, IL-6, MMP9, LCN2, and LCN2-MMP9 but have higher levels of AGP1 (p <0.05) than the CTL&EH group. The concentration and size of uEVs and miRNA Let-7i-5p did not show any difference between groups. In PA, we found significantly lower levels of miR-21-5p than controls (p <0.05). AGP1 was associated with aldosterone, PRA, and ARR. ROC curves detected AUC for AGP1 of 0.90 (IC 95 [0.79 – 1.00], p <0.001), and combination of AGP1 and EV-miR-21-5p showed an AUC of 0.94 (IC 95 [0.85 – 1.00], p<0.001) to discriminate the PA condition from EH and controls.

Conclusion

Serum AGP1 protein was found to be increased, and miR-21-5p in uEVs was decreased in subjects classified as PA. Association of AGP1 with aldosterone, renin activity, and ARR, besides the high discriminatory capacity of AGP1 and uEV-miR-21-5p to identify the PA condition, place both as potential biomarkers of PA.
Comprehensive Analysis of m6A RNA Methylation Regulators and the Immune Microenvironment to Aid Immunotherapy in Pancreatic Cancer
Authors: Guo Yongdong , Wang Ronglin , Li Junqiang , Song Yang , Min Jie , Zhao Ting , Hua Lei , Shi Jingjie , Zhang Chao , Ma Peixiang , Yang Cheng , Zhu Liaoliao , Gan Dongxue , Li Shanshan , Liu Xiaonan , Su Haichuan
Published: November 2021

Pancreatic cancer (PAAD) is one of the most malignant cancers and immune microenvironment has been proved to be involved in pathogenesis of PAAD. m6A modification, related to the expression of m6A regulators, participates in the development of multiple cancers. However, the correlation between m6A regulators and immune microenvironment was largely unknown in PAAD. And because of the small sample size of pancreatic cancer in the TCGA database, it is not enough to draw a convincing conclusion. In the present study, we downloaded seven pancreatic cancer datasets with survival data and removed batch effects among these datasets to be used as the PAAD cohort to analyze the immune landscape of PAAD and the expression pattern of m6A regulators and divided the integrated dataset into cluster 1 and cluster 2 by consensus clustering for m6A regulators. Lower m6A regulators were found to be related to higher immune cell infiltration and a better survival. Moreover, we identified six m6A regulators and constructed the prognostic signature of m6A regulators. Patients with low-risk score had a higher response to immune checkpoint inhibitor and a longer overall survival. To figure out the underlying mechanism, we analyzed the cancer immunity cycle, most altered genes, gene set enrichment analysis (GSEA) and gene set variation analysis (GSVA) in risk subtypes. In summary, the present study proved m6A regulators modulated the PAAD immune microenvironment. And risk scores served as predictive indicator for immunotherapy and played a prognostic role for PAAD patients. Our study provided novel therapeutic targets to improve immunotherapy efficacy.
Viral-Like Particles Are Associated With Endosymbiont Pathology in Florida Corals Affected by Stony Coral Tissue Loss Disease
Authors: Work Thierry M. , Weatherby Tina M. , Landsberg Jan H. , Kiryu Yasunari , Cook Samantha M. , Peters Esther C.
Published: November 2021

Stony coral tissue loss disease (SCTLD) was first documented in 2014 near the Port of Miami, Florida, and has since spread north and south along Florida’s Coral Reef, killing large numbers of more than 20 species of coral and leading to the functional extinction of at least one species, Dendrogyra cylindrus. SCTLD is assumed to be caused by bacteria based on presence of different molecular assemblages of bacteria in lesioned compared to apparently healthy tissues, its apparent spread among colonies, and cessation of spread of lesions in individual colonies treated with antibiotics. However, light microscopic examination of tissues of corals affected with SCTLD has not shown bacteria associated with tissue death. Rather, microscopy shows dead and dying coral cells and symbiotic dinoflagellates (endosymbionts) indicating a breakdown of host cell and endosymbiont symbiosis. It is unclear whether host cells die first leading to death of endosymbionts or vice versa. Based on microscopy, hypotheses as to possible causes of SCTLD include infectious agents not visible at the light microscopy level or toxicosis, perhaps originating from endosymbionts. To clarify this, we examined corals affected with SCTLD and apparently healthy corals using transmission electron microscopy. Endosymbionts in SCTLD-affected and apparently healthy corals consistently had varying degrees of pathology associated with elongated particles compatible in morphology with filamentous positive single-stranded RNA viruses of plants termed anisometric viral-like particles (AVLP). There was apparent progression from early to late replication of AVLP in the cytoplasm of endosymbionts adjacent to or at times within chloroplasts, with morphologic changes in chloroplasts consistent with those seen in plant cells infected by viruses. Coral host cell pathology appeared limited to massive proliferation and lysis of mucus cells. Based on these findings, we hypothesize that SCTLD is a viral disease of endosymbionts leading to coral host death. Efforts to confirm the presence of a virus associated with SCTLD through other means would be appropriate. These include showing the presence of a virus through molecular assays such as deep sequencing, attempts to grow this virus in the laboratory through culture of endosymbionts, localization of virus in tissue sections using immunohistochemistry or in situ hybridization, and experimental infection of known-virus-negative corals to replicate disease at the gross and microscopic level.
First Ecological Characterization of Whip Black Coral Assemblages (Hexacorallia: Antipatharia) in the Easter Island Ecoregion, Southeastern Pacific
Authors: Tapia-Guerra Jan M. , Asorey Cynthia M. , Easton Erin E. , Wagner Daniel , Gorny Matthias , Sellanes Javier
Published: November 2021

One of the main priorities of marine scientific research is to provide practical information and guidance for biodiversity conservation and management. In this context, the identification of key and fragile habitat-forming species is particularly important. Despite their ecological importance, whip corals in the order Antipatharia remain poorly studied around the world, and especially in the South Pacific. During recent expeditions to explore mesophotic and deep benthic habitats around Rapa Nui (Easter Island), dense assemblages of whip black corals were observed in situ. We here report the first detailed description of the distribution and abundance of these black coral assemblages and their associated fauna and habitat. These descriptions were based on analysis of video surveys collected on 67 remotely operated vehicle dives conducted in 2014 through 2019 at three sites (Pukao seamount, Apolo peak, and Rapa Nui Island shelf and slope) within the Easter Island Ecoregion at depths between 50 and 330 m. At least four morphotypes (yellow, red, white/orange, and Pukao) of unbranched black corals were detected. Each morphotype had polyps arranged in a single row on only one side of the corallum, a diagnostic morphological character currently assigned to the antipatharian genus Stichopathes. Samples of the yellow and red morphotypes were collected and studied using morphological and molecular techniques. These analyses indicate that the genus Stichopathes is not monophyletic and requires further revisions, a conclusion that is consistent with previous studies. Extensive fields of whip black corals, primarily of the yellow and red morphotype, were present at 28 sites from 60 to 245 m on rocky substrates, coarse sand, or rhodoliths. Densities of these assemblages per frame were up to 58.2 ± 5.2 colonies m–2 (average: 13.2 ± 0.8), which represent some of the highest reported densities for black corals to date. Numerous faunal groups, including ophiuroids, echinoids, and fishes, were associated with these whip black coral assemblages. Our observations should be considered in future management and conservation efforts around Rapa Nui, where a multi-use marine protected area was established in 2018, as well as in adjacent international waters that remain unprotected but likely harbor similar assemblages.
Gut Microbiota Interplay With COVID-19 Reveals Links to Host Lipid Metabolism Among Middle Eastern Populations
Authors: Al Bataineh Mohammad Tahseen , Henschel Andreas , Mousa Mira , Daou Marianne , Waasia Fathimathuz , Kannout Hussein , Khalili Mariam , Kayasseh Mohd Azzam , Alkhajeh Abdulmajeed , Uddin Maimunah , Alkaabi Nawal , Tay Guan K. , Feng Samuel F. , Yousef Ahmed F. , Alsafar Habiba S.
Published: November 2021

The interplay between the compositional changes in the gastrointestinal microbiome, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) susceptibility and severity, and host functions is complex and yet to be fully understood. This study performed 16S rRNA gene-based microbial profiling of 143 subjects. We observed structural and compositional alterations in the gut microbiota of the SARS-CoV-2-infected group in comparison to non-infected controls. The gut microbiota composition of the SARS-CoV-2-infected individuals showed an increase in anti-inflammatory bacteria such as Faecalibacterium (p-value = 1.72 × 10–6) and Bacteroides (p-value = 5.67 × 10–8). We also revealed a higher relative abundance of the highly beneficial butyrate producers such as Anaerostipes (p-value = 1.75 × 10–230), Lachnospiraceae (p-value = 7.14 × 10–65), and Blautia (p-value = 9.22 × 10–18) in the SARS-CoV-2-infected group in comparison to the control group. Moreover, phylogenetic investigation of communities by reconstructing unobserved state (PICRUSt) functional prediction analysis of the 16S rRNA gene abundance data showed substantial differences in the enrichment of metabolic pathways such as lipid, amino acid, carbohydrate, and xenobiotic metabolism, in comparison between both groups. We discovered an enrichment of linoleic acid, ether lipid, glycerolipid, and glycerophospholipid metabolism in the SARS-CoV-2-infected group, suggesting a link to SARS-CoV-2 entry and replication in host cells. We estimate the major contributing genera to the four pathways to be Parabacteroides, Streptococcus, Dorea, and Blautia, respectively. The identified differences provide a new insight to enrich our understanding of SARS-CoV-2-related changes in gut microbiota, their metabolic capabilities, and potential screening biomarkers linked to COVID-19 disease severity.
Influenza A Virus–Host Specificity: An Ongoing Cross-Talk Between Viral and Host Factors
Authors: Zhang Miaomiao , Liu Mingbin , Bai Shimeng , Zhao Chen , Li Zejun , Xu Jianqing , Zhang Xiaoyan
Published: November 2021

One big threat from influenza A viruses (IAVs) is that novel viruses emerge from mutation alongside reassortment. Some of them have gained the capability to transmit into human from the avian reservoir. Understanding the molecular events and the involved factors in breaking the cross-species barrier holds important implication for the surveillance and prevention of potential influenza outbreaks. In this review, we summarize recent progresses, including several ground-breaking findings, in how the interaction between host and viral factors, exemplified by the PB2 subunit of the influenza virus RNA polymerase co-opting host ANP32 protein to facilitate transcription and replication of the viral genome, shapes the evolution of IAVs from host specificity to cross-species infection.
NcRNAs in Vascular and Valvular Intercellular Communication
Authors: Bartsch Benedikt , Goody Philip Roger , Hosen Mohammed Rabiul , Nehl Denise , Mohammadi Neda , Zietzer Andreas , Düsing Philip , Pfeifer Alexander , Nickenig Georg , Jansen Felix
Published: November 2021

Non-coding RNAs have been shown to be important biomarkers and mediators of many different disease entities, including cardiovascular (CV) diseases like atherosclerosis, aneurysms, and valvulopathies. Growing evidence suggests a central role of ncRNAs as regulators of different pathological pathways involved in endothelial dysfunction, cardiovascular inflammation, cell differentiation, and calcification. This review will discuss the role of protein-bound and extracellular vesicular-bound ncRNAs as biomarkers of vascular and valvular diseases, their role as intercellular communicators, and regulators of disease pathways and also highlights possible treatment strategies.
Usability Assessment of Body Controlled Electric Hand Prostheses: A Pilot Study
Authors: Godfrey Sasha B. , Piazza Cristina , Felici Federica , Grioli Giorgio , Bicchi Antonio , Catalano Manuel G.
Published: November 2021

Poly-articulated hands, actuated by multiple motors and controlled by surface myoelectric technologies, represent the most advanced aids among commercial prostheses. However, simple hook-like body-powered solutions are still preferred for their robustness and control reliability, especially for challenging environments (such as those encountered in manual work or developing countries). This study presents the mechatronic implementation and the usability assessment of the SoftHand Pro-Hybrid, a family of poly-articulated, electrically-actuated, and body-controlled artificial hands, which combines the main advantages of both body-powered and myoelectric systems in a single device. An assessment of the proposed system is performed with individuals with and without limb loss, using as a benchmark the SoftHand Pro, which shares the same soft mechanical architecture, but is controlled using surface electromyographic sensors. Results indicate comparable task performance between the two control methods and suggest the potential of the SoftHand Pro-Hybrid configurations as a viable alternative to myoelectric control, especially in work and demanding environments.
De Novo Variants in the DYNC1H1 Gene Associated With Infantile Spasms
Authors: Yang Haipo , Gong Pan , Jiao Xianru , Niu Yue , Zhou Qiujun , Zhang Yuehua , Yang Zhixian
Published: November 2021

Objective: The DYNC1H1 gene is related to a variety of diseases, including spinal muscular atrophy with lower extremity–predominant 1, Charcot–Marie–Tooth disease type 2O, and mental retardation, autosomal dominant13 (MRD13). Some patients with DYNC1H1 variant also had epilepsy. This study aimed to detect DYNC1H1 variants in Chinese patients with infantile spasms (ISs).

Methods: We reviewed clinical information, video electroencephalogram (V-EEG), and neuroimaging of a newly identified cohort of five patients with de novo DYNC1H1gene variants.

Results: Five patients with four DYNC1H1variants from four families were included. All patients had epileptic spasms (ESs), the median age at seizure onset was 7.5 months (range from 5 months to 2 years 7 months), and the interictal V-EEG results were hypsarrhythmia. Four of five patients had brain magnetic resonance imaging (MRI) abnormalities. Four de novo DYNC1H1 variants were identified, including two novel variants (p.N1117K, p.M3405L) and two reported variants (p.R1962C, p.F1093S). As for the variant site, two variants are located in the tail domain, one variant is located in the motor domain, and one variant is located in the stalk domain. All patients had tried more than five kinds of antiepileptic drugs. One patient has been controlled well by vigabatrin (VGB) for 4 years, and another patient by VGB and steroids for 1.5 years. The other three patients still had frequent ESs. All patients had severe intellectual disability and development delays.

Significance: IS was one of the phenotypes of DYNC1H1 variants. Most patients had non-specific brain MRI abnormality. Two of four DYNC1H1 variants were novel, expanding the variant spectrum. The IS phenotype was related to the variant's domains of DYNC1H1 variant sites. All patients were drug-refractory and showed development delays.
Sensory Attenuation in the Auditory Modality as a Window Into Predictive Processing
Authors: Kiepe Fabian , Kraus Nils , Hesselmann Guido
Published: November 2021

Self-generated auditory input is perceived less loudly than the same sounds generated externally. The existence of this phenomenon, called Sensory Attenuation (SA), has been studied for decades and is often explained by motor-based forward models. Recent developments in the research of SA, however, challenge these models. We review the current state of knowledge regarding theoretical implications about the significance of Sensory Attenuation and its role in human behavior and functioning. Focusing on behavioral and electrophysiological results in the auditory domain, we provide an overview of the characteristics and limitations of existing SA paradigms and highlight the problem of isolating SA from other predictive mechanisms. Finally, we explore different hypotheses attempting to explain heterogeneous empirical findings, and the impact of the Predictive Coding Framework in this research area.