bluuebunny/crossref_metadata_2025 huggingface dataset:
Identification of Potential ceRNA Network and Patterns of Immune Cell Infiltration in Systemic Sclerosis-Associated Interstitial Lung Disease
Authors: Wu Qiuhong , Liu Yang , Xie Yan , Wei Shixiong , Liu Yi
Published: June 2021

Purpose

Systemic sclerosis-associated interstitial lung disease (SSc-ILD) is one of the most severe complications of systemic sclerosis (SSc) and is the leading cause of SSc-related deaths. However, the precise pathogenesis of pulmonary fibrosis in SSc-ILD remains unknown. This study aimed to evaluate the competing endogenous RNA (ceRNA) regulatory network and immune cell infiltration patterns in SSc-ILD.

Methods

One microRNA (miRNA) and three messenger RNA (mRNA) microarray datasets were obtained from the Gene Expression Omnibus (GEO) database. Then, the differentially expressed miRNAs (DEmiRs) and mRNAs (DEMs) between SSc-ILD patients and normal controls were identified, respectively, followed by the prediction of the target genes and target lncRNAs of DEmiRs. The overlapping genes between DEmiRs target genes and DEMs were identified as core mRNAs to construct the ceRNA network. In addition, the “Cell Type Identification by Estimating Relative Subsets of Known RNA Transcripts (CIBERSORT)” algorithm was used to analyze the composition of infiltrating immune cells in lung tissues of SSc-ILD patients and controls, and differentially expressed immune cells were recognized. The correlation between immune cells and core mRNAs was evaluated by Pearson correlation analysis.

Results

Totally, 42 SSc-ILD lung tissues and 18 normal lung tissues were included in this study. We identified 35 DEmiRs and 142 DEMs and predicted 1,265 target genes of DEmiRs. Then, 9 core mRNAs related to SSc-ILD were recognized, which were the overlapping genes between DEmiRs target genes and DEMs. Meanwhile, 9 DEmiRs related to core mRNAs were identified reversely, and their target lncRNAs were predicted. In total, 9 DEmiRs, 9 core mRNAs, and 51 predicted lncRNAs were integrated to construct the ceRNA regulatory network of SSc-ILD. In addition, 9 types of immune cells were differentially expressed in lung tissues between SSc-ILD patients and controls. Some core mRNAs, such as COL1A1, FOS, and EDN1, were positively or negatively correlated with the number of infiltrating immune cells.

Conclusion

This is the first comprehensive study to construct the potential ceRNA regulatory network and analyze the composition of infiltrating immune cells in lung tissues of SSc-ILD patients, which improves our understanding of the pathogenesis of SSc-ILD.
Structure and Function of Oral Microbial Community in Periodontitis Based on Integrated Data
Authors: Cai Zhengwen , Lin Shulan , Hu Shoushan , Zhao Lei
Published: June 2021

Objective

Microorganisms play a key role in the initiation and progression of periodontal disease. Research studies have focused on seeking specific microorganisms for diagnosing and monitoring the outcome of periodontitis treatment. Large samples may help to discover novel potential biomarkers and capture the common characteristics among different periodontitis patients. This study examines how to screen and merge high-quality periodontitis-related sequence datasets from several similar projects to analyze and mine the potential information comprehensively.

Methods

In all, 943 subgingival samples from nine publications were included based on predetermined screening criteria. A uniform pipeline (QIIME2) was applied to clean the raw sequence datasets and merge them together. Microbial structure, biomarkers, and correlation network were explored between periodontitis and healthy individuals. The microbiota patterns at different periodontal pocket depths were described. Additionally, potential microbial functions and metabolic pathways were predicted using PICRUSt to assess the differences between health and periodontitis.

Results

The subgingival microbial communities and functions in subjects with periodontitis were significantly different from those in healthy subjects. Treponema, TG5, Desulfobulbus, Catonella, Bacteroides, Aggregatibacter, Peptostreptococcus, and Eikenella were periodontitis biomarkers, while Veillonella, Corynebacterium, Neisseria, Rothia, Paludibacter, Capnocytophaga, and Kingella were signature of healthy periodontium. With the variation of pocket depth from shallow to deep pocket, the proportion of Spirochaetes, Bacteroidetes, TM7, and Fusobacteria increased, whereas that of Proteobacteria and Actinobacteria decreased. Synergistic relationships were observed among different pathobionts and negative relationships were noted between periodontal pathobionts and healthy microbiota.

Conclusion

This study shows significant differences in the oral microbial community and potential metabolic pathways between the periodontitis and healthy groups. Our integrated analysis provides potential biomarkers and directions for in-depth research. Moreover, a new method for integrating similar sequence data is shown here that can be applied to other microbial-related areas.
Clostridium butyricum Induces the Production and Glycosylation of Mucins in HT-29 Cells
Authors: Lili Qi , Xiaohui Lu , Haiguang Mao , Jinbo Wang
Published: June 2021

C. butyricum is a common gut commensal bacterium, which has many positive functions in human intestine. In this study, we investigated the effects of monosaccharide and its derivatives on the adhesion of C. butyricum to the mucus of HT-29 cells. RNA interference was performed to assess the roles of MUC2 and glycan in the adhesion of C. butyricum to HT-29 cells. The effects of C. butyricum on the glycosylation of mucins were assayed with fluorescence microscope. The expression levels of mucins and glycotransferases were also determined. The results showed that C. butyricum could adhere to the mucins secreted by HT-29 cells. Several kinds of monosaccharides inhibited the adhesion of C. butyricum to HT-29 cells, which suggested that the mucus glycan was the attaching sites of this bacterium. Knockdown of MUC2, FUT2 or GALNT7 significantly decreased the numbers of the bacteria adhering to HT-29 cells. When colonizing on the surface of HT-29 cells, C. butyricum could increase the production of mucins, promote the expression of glycotransferase, and induce the glycosylation of mucins. These results demonstrated that the glycan of mucus played important roles in the adhesion of C. butyricum to HT-29 cells. This study indicates for the first time that C. butyricum possesses the ability to modulate the glycosylation profile of mucus secreted by HT-29 cells. These findings contribute to understanding the mechanism of interaction between colonic epithelial cells and commensal bacteria.
Uncertainty Quantification and Bayesian Inference of Cloud Parameterization in the NCAR Single Column Community Atmosphere Model (SCAM6)
Authors: Pathak Raju , Dasari Hari Prasad , El Mohtar Samah , Subramanian Aneesh C. , Sahany Sandeep , Mishra Saroj Kanta , Knio Omar , Hoteit Ibrahim
Published: June 2021

Uncertainty quantification (UQ) in weather and climate models is required to assess the sensitivity of their outputs to various parameterization schemes and thereby improve their consistency with observations. Herein, we present an efficient UQ and Bayesian inference for the cloud parameters of the NCAR Single Column Atmosphere Model (SCAM6) using surrogate models based on a polynomial chaos expansion. The use of a surrogate model enables to efficiently propagate uncertainties in parameters into uncertainties in model outputs. We investigated eight uncertain parameters: the auto-conversion size threshold for ice to snow (dcs), the fall speed parameter for stratiform cloud ice (ai), the fall speed parameter for stratiform snow (as), the fall speed parameter for cloud water (ac), the collection efficiency of aggregation ice (eii), the efficiency factor of the Bergeron effect (berg_eff), the threshold maximum relative humidity for ice clouds (rhmaxi), and the threshold minimum relative humidity for ice clouds (rhmini). We built two surrogate models using two non-intrusive methods: spectral projection (SP) and basis pursuit denoising (BPDN). Our results suggest that BPDN performs better than SP as it enables to filter out internal noise during the process of fitting the surrogate model. Five out of the eight parameters (namely dcs, ai, rhmaxi, rhmini, and eii) account for most of the variance in predicted climate variables (e.g., total precipitation, cloud distribution, shortwave and longwave cloud radiative effect, ice, and liquid water path). A first-order sensitivity analysis reveals that dcs contributes ~40–80% of the total variance of the climate variables, ai around 15–30%, and rhmaxi, rhmini, and eii around 5–15%. The second- and higher-order effects contribute ~7 and 20%, respectively. The sensitivity of the model to these parameters was further explored using response curves. A Markov chain Monte Carlo (MCMC) sampling algorithm was also implemented for the Bayesian inference of dcs, ai, as, rhmini, and berg_eff using cloud distribution data collected at the Southern Great Plains (USA). The inferred parameters suggest improvements in the global Climate Earth System Model (CESM2) simulations of the tropics and sub-tropics.
Circulating Soluble Suppression of Tumorigenicity 2 Predicts Recurrence After Radiofrequency Ablation of Persistent Atrial Fibrillation
Authors: Tan Ruopeng , Yu Haixu , Han Xu , Liu Yang , Yang Xiaolei , Xia Yun-Long , Yin Xiaomeng
Published: June 2021

Objective: A more extensively fibrotic left atrium contributes to atrial fibrillation (AF) occurrence, persistence, and recurrence. The soluble suppression of tumorigenicity 2 (sST2) has emerged as a ventricular fibrotic biomarker for patients with heart failure. The present study is to investigate associations between circulating sST2 and risk of recurrence after ablation in AF patients.

Methods: We measured the baseline plasma level of sST2 from patients with persistent AF (n = 117) and paroxysmal AF (n = 93) patients. Patients were followed up for 15 months after ablation. The relationship between circulating sST2 and recurrence was assessed by multivariable Cox regression. The cutoff value of sST2 was determined by receiver operating characteristic curve. The relationship between baseline sST2 level and left atrial volume index (LAVI) was assessed by multivariate linear regression analysis. Serial sST2 measurements were also conducted after 24 h, 6 months, and 15 months of ablation. ST2 localization was examined in left atrial appendages of persistent AF patients by immunohistochemistry and Western blot.

Results: Baseline sST2 positively associated with LAVI in the persistent AF group, and elevated sST2 (≥39.25 ng/ml) independently increased the risk of recurrence after ablation (area under the curve = 0.748), with hazard ratio of 1.038 (95% confidence interval 1.017–1.060, P < 0.001) when adjusted for co-variables. In contrast, elevated sST2 cannot predict recurrence in paroxysmal AF.

Conclusions: In persistent AF patients, increased sST2 serves as a marker of recurrence after radiofrequency ablation. Patients with sST2 ≥ 39.25 ng/ml are more likely to develop recurrence within a year.
Comparative Effectiveness of Exercise Training for Patients With Chronic Thromboembolic Pulmonary Hypertension After Pulmonary Endarterectomy: A Systematic Review and Meta-Analysis
Authors: Zhao Ya-Lin , Yuan Ping , Zhao Qin-Hua , Gong Su-Gang , Zhang Rui , He Jing , Luo Ci-Jun , Qiu Hong-Ling , Liu Jin-Ming , Wang Lan , Jiang Rong
Published: June 2021

Background: Patients with chronic thromboembolic pulmonary hypertension (CTEPH) still experience reduced exercise capacity despite pulmonary endarterectomy (PEA). Exercise training improves the exercise capacity and quality of life (QoL) in patients with PH, but data on the effects of exercise training on these patients are scarce. The aim of this meta-analysis and systematic review was to evaluate the effectiveness and safety of exercise training in CTEPH after PEA.

Methods: We searched the relevant literature published before January 2020 for the systematic review and meta-analysis using the PubMed, EMBASE, and Cochrane Library databases. The primary outcome was a change in the 6-min walking distance (6 MWD). We also assessed the effect of exercise on the peak oxygen uptake (VO2) or peak VO2/kg, oxygen uptake anaerobic threshold, workload, oxygen pulse, hemodynamics, arterial blood gases, oxygen saturation, N-terminal pro-brain-type natriuretic peptide (NT-proBNP), quality of life (QoL) and pulmonary function tests.

Results: We included 4 studies with 208 exercise-training participants. In the pooled analysis, short-term exercise training can improve the 6 MWD of 58.89 m (95% CI: 46.26–71.52 m, P < 0.0001). There was a significant increase in the peak VO2/kg or peak VO2 after exercise training (3.15 ml/min/kg, 95% CI: 0.82–5.48, P = 0.008; 292.69 ml/min, 95% CI: 24.62–560.75, P = 0.032, respectively). After exercise training, the maximal workload and O2 pulse significantly improved. Three months of exercise training increased the right ventricular ejection fraction by 3.53% (95% CI: 6.31–11.94, P < 0.00001, I2 = 0) independently of PEA surgery. In addition, NT-proBNP plasma levels significantly improved with exercise training after PEA [weighted mean difference (WMD): −524.79 ng/L, 95% CI: 705.16 to −344.42, P < 0.0001, I2 = 0]. The partial pressure of oxygen and pH improved progressively over 12 weeks of exercise training (WMD: 4 mmHg, 95% CI: 1.01–8.33, P = 0.01; WMD: 0.03, 95% CI: 0.02–0.04, P < 0.0001, respectively). Subscales of the QoL measured by the SF-36 questionnaire had also improved. In addition, exercise training was well-tolerated with a low dropout rate, and no major adverse events occurred during exercise training.

Conclusion: Exercise training may be associated with a significant improvement in the exercise capacity and QoL among CTEPH patients after PEA and was proven to be safe. However, more large-scale multicentre studies are needed to confirm the effectiveness and safety of exercise training in CTEPH patients after PEA.

PROSPERO registration number:CRD42021235275.
Modest Gains After an 8-Week Exercise Program Correlate With Reductions in Non-traditional Markers of Cardiovascular Risk
Authors: Liang Grace , Huang Xianxi , Hirsch James , Mehmi Sanjeev , Fonda Holly , Chan Khin , Huang Ngan F. , Aalami Oliver , Froelicher Victor F. , Lee David P. , Myers Jonathan , Lee Andrew S. , Nguyen Patricia K.
Published: June 2021

Background: Although engaging in physical exercise has been shown to reduce the incidence of cardiovascular events, the molecular mechanisms by which exercise mediates these benefits remain unclear. Based on epidemiological evidence, reductions in traditional risk factors only accounts for 50% of the protective effects of exercise, leaving the remaining mechanisms unexplained. The objective of this study was to determine whether engaging in a regular exercise program in a real world clinical setting mediates cardiovascular protection via modulation of non-traditional risk factors, such as those involved in coagulation, inflammation and metabolic regulation.

Methods and Results: We performed a prospective, cohort study in 52 sedentary patients with cardiovascular disease or cardiovascular risk factors at two tertiary medical centers between January 1, 2016 and December 31, 2019. Prior to and at the completion of an 8-week exercise program, we collected information on traditional cardiovascular risk factors, exercise capacity, and physical activity and performed plasma analysis to measure levels of fibrinolytic, inflammatory and metabolic biomarkers to assess changes in non-traditional cardiovascular risk factors. The median weight change, improvement in physical fitness, and change in physical activity for the entire cohort were: −4.6 pounds (IQR: +2 pounds, −11.8 pounds), 0.37 METs (IQR: −0.076 METs, 1.06 METs), and 252.7 kcals/week (IQR: −119, 921.2 kcals/week). In addition to improvement in blood pressure and cholesterol, patients who lost at least 5 pounds, expended at least 1,000 additional kcals/week, and/or achieved ≥0.5 MET increase in fitness had a significant reduction in plasminogen activator inhibitor-1 [9.07 ng/mL (95% CI: 2.78–15.35 ng/mL); P = 0.026], platelet derived growth factor beta [376.077 pg/mL (95% CI: 44.69–707.46 pg/mL); P = 0.026); and angiopoietin-1 [(1104.11 pg/mL (95% CI: 2.92–2205.30 pg/mL); P = 0.049)].

Conclusion: Modest improvements in physical fitness, physical activity, and/or weight loss through a short-term exercise program was associated with decreased plasma levels of plasminogen activator inhibitor, platelet derived growth factor beta, and angiopoietin, which have been associated with impaired fibrinolysis and inflammation.
The OMZ and Its Influence on POC in the Tropical Western Pacific Ocean: Based on the Survey in March 2018
Authors: Ma Jun , Song Jinming , Li Xuegang , Wang Qidong , Zhong Guorong , Yuan Huamao , Li Ning , Duan Liqin
Published: June 2021

The hypoxia problem in the ocean is worsening, and the oxygen minimum zone (OMZ) continues to expand. The Tropical Western Pacific Ocean is one of the most sensitive areas in response to climate change and human activities, and the OMZ in this area has also expanded significantly. Based on a survey conducted in March 2018, the characteristics of OMZ in the Kocebu seamount area of the Tropical Western Pacific Ocean and its biogeochemical effects are discussed. The results showed that DO in the Kocebu seamount area first decreased and then increased, and the lowest value was 2.49 mg/L at a water depth of 750 m. Based on the oxycline and the threshold of 3.20 mg/L, OMZ in this area was located in the water column of 590–1,350 m. With the increase in water depth, the POC concentration decreased gradually and remained stable in the water column deeper than 1,000 m. The presence of OMZ reduced the decomposition rate of POC, causing more POC to sink into deeper waters. 38.77% of POC was decomposed in the water column of 150–300 m, whereas only 16.25% of POC was decomposed in the OMZ. In contrast to the vertical distribution of POC, δ13C-POC decreased rapidly in the water columns of 100–150 and 300–500 m, indicating the rapid decomposition of POC. This result suggests that POC and δ13C-POC should be combined in the evaluation of POC decomposition.
Plume Versus Slab-Pull: Example from the Arabian Plate
Authors: Aldaajani Thamer Z. , Almalki Khalid A. , Betts Peter G.
Published: June 2021

Mantle convection and the interaction of buoyant plumes with the lithosphere have been a significant influence on plate tectonics. Plume-lithosphere interactions have been regarded as a major driver of continental rifting, and have been linked to triple junction development and major supercontinent break-up events. There are also many extensional tectonic settings that lack evidence for a mantle plume and associated magmatism, indicating far-field plate stresses also drive plate fragmentation. The Arabian Plate is a spectacular active example where both a mantle plume and far-field plate stresses interact to drive continental break-up. Despite more than 80 years of geological research, there remains significant conjecture concerning the geodynamic processes responsible for the plate motion and the nature or onset of extension/deformation of the Arabian Plate. Complex structural patterns within the Arabian Plate have been interpreted in the context of tectonic plate movements and reorganization related to the subduction of the Tethys Oceanic plate, collision between Arabian and Eurasian plates, and the superposition of Afar plume. These interactions have accordingly resulted in different explanations or understanding of the geodynamic of the Afro-Arabian rift system. We assess the relative influence of plume vs. far field influences by reviewing the current views on the concept and models of these forces and highlighting their significance and implications on Arabia. Our synthesis shows that most of the geodynamical models proposed so far are not applicable to the entire Arabian Plate and its surrounding boundaries.
Development of a Novel Multi-Epitope Vaccine Against Crimean-Congo Hemorrhagic Fever Virus: An Integrated Reverse Vaccinology, Vaccine Informatics and Biophysics Approach
Authors: Tahir Ul Qamar Muhammad , Ismail Saba , Ahmad Sajjad , Mirza Muhammad Usman , Abbasi Sumra Wajid , Ashfaq Usman Ali , Chen Ling-Ling
Published: June 2021

Crimean-Congo hemorrhagic fever (CCHF) is a highly severe and virulent viral disease of zoonotic origin, caused by a tick-born CCHF virus (CCHFV). The virus is endemic in many countries and has a mortality rate between 10% and 40%. As there is no licensed vaccine or therapeutic options available to treat CCHF, the present study was designed to focus on application of modern computational approaches to propose a multi-epitope vaccine (MEV) expressing antigenic determinants prioritized from the CCHFV genome. Integrated computational analyses revealed the presence of 9 immunodominant epitopes from Nucleoprotein (N), RNA dependent RNA polymerase (RdRp), Glycoprotein N (Gn/G2), and Glycoprotein C (Gc/G1). Together these epitopes were observed to cover 99.74% of the world populations. The epitopes demonstrated excellent binding affinity for the B- and T-cell reference set of alleles, the high antigenic potential, non-allergenic nature, excellent solubility, zero percent toxicity and interferon-gamma induction potential. The epitopes were engineered into an MEV through suitable linkers and adjuvating with an appropriate adjuvant molecule. The recombinant vaccine sequence revealed all favorable physicochemical properties allowing the ease of experimental analysis in vivo and in vitro. The vaccine 3D structure was established ab initio. Furthermore, the vaccine displayed excellent binding affinity for critical innate immune receptors: TLR2 (−14.33 kcal/mol) and TLR3 (−6.95 kcal/mol). Vaccine binding with these receptors was dynamically analyzed in terms of complex stability and interaction energetics. Finally, we speculate the vaccine sequence reported here has excellent potential to evoke protective and specific immune responses subject to evaluation of downstream experimental analysis.
Consumption Trends of Antibiotic for Veterinary Use in Tanzania: A Longitudinal Retrospective Survey From 2010-2017
Authors: Sangeda Raphael Z. , Baha Andrea , Erick Alexander , Mkumbwa Sonia , Bitegeko Adonis , Sillo Hiiti B. , Fimbo Adam M. , Chambuso Mhina , Mbugi Erasto V.
Published: June 2021

Background

With increased livestock keeping, multiple prevailing infections, antimicrobial agents’ use and pattern in Tanzania, the development of antimicrobial resistance (AMR) becomes inevitable. Antibiotic-resistant pathogens have increasingly become a major challenge in human and animal medicine. Although inappropriate use of antibiotics in humans is the principal cause of resistance, antibiotic-resistant bacteria originating from animals contribute to the emergence and spread of these bacteria. Antibiotics help control a multitude of bacterial infections that are major causes of diseases in both animals and humans. Rational use in animals is crucial to control any development and transfer of AMR to humans. This study aimed to create quantitative evidence of animal antimicrobial usage patterns in Tanzania to serve as a baseline for surveillance of antimicrobial use and antimicrobial resistance control.

Methodology

This descriptive longitudinal retrospective study was conducted to explore the trend of veterinary-antibiotics consumed in the eight years, from 1st January 2010 to 31st December 2017 in Tanzania mainland. The data source was records of all antibiotics imported for veterinary use into Tanzania’s mainland according to the Tanzania Medicines and Medical Devices Authority (TMDA) records. The analysis employed the World Health Organization (WHO) Collaborating Centre for Drug Statistics Methodology using Anatomical Therapeutic and Chemical (ATC) classification. Regression and time series analysis was used to establish trends in antibiotics consumption.

Results

A total of 12,147,491 kg of antibiotics were consumed in Tanzania from 2010 to 2017. Tetracycline, sulfonamides and trimethoprim, quinolones, aminoglycosides, beta-lactams and antibacterial combinations were the most commonly used antibacterial agents in Tanzania. Tetracycline class topped the list with about 8,090,798 kg (66.6%) out of 12,147,491 kg total quantity of antimicrobials consumed. Non-significant, linear curve estimations and time series analysis indicate a decline in the quantities of veterinary antibiotics used in the eight years from 2010 to 2017.

Conclusions

This study suggests that tetracycline is the most used antibiotic class for veterinary medicine in Tanzania. The trend of antimicrobial use is generally decreasing compared to other countries in Africa. Even though some antibiotics have the lowest consumption rate, they are also prone to AMR, prompting follow-up by the relevant regulatory authorities.
Offshore Windfarm Footprint of Sediment Organic Matter Mineralization Processes
Authors: De Borger Emil , Ivanov Evgeny , Capet Arthur , Braeckman Ulrike , Vanaverbeke Jan , Grégoire Marilaure , Soetaert Karline
Published: June 2021

Offshore windfarms (OWFs) offer part of the solution for the energy transition which is urgently needed to mitigate effects of climate change. Marine life has rapidly exploited the new habitat offered by windfarm structures, resulting in increased opportunities for filter- and suspension feeding organisms. In this study, we investigated the effects of organic matter (OM) deposition in the form of fecal pellets expelled by filtering epifauna in OWFs, on mineralization processes in the sediment. OM deposition fluxes produced in a 3D hydrodynamic model of the Southern Bight of the North Sea were used as input in a model of early diagenesis. Two scenarios of OWF development in the Belgian Part of the North Sea (BPNS) and its surrounding waters were calculated and compared to a no-OWF baseline simulation. The first including constructed OWFs as of 2021, the second containing additional planned OWFs by 2026. Our results show increased total mineralization rates within OWFs (27–30%) in correspondence with increased deposition of reactive organic carbon (OC) encapsulated in the OM. This leads to a buildup of OC in the upper sediment layers (increase by ∼10%) and an increase of anoxic mineralization processes. Similarly, denitrification rates within the OWFs increased, depending on the scenario, by 2–3%. Effects were not limited to the OWF itself: clear changes were noticed in sediments outside of the OWFs, which were mostly opposite to the “within-OWF” effects. This contrast generated relatively small changes when averaging values over the full modeling domain, however, certain changes, such as for example the increased storage of OC in sediments, may be of significant value for national / regional carbon management inventories. Our results add to expectations of ecosystem-wide effects of windfarms in the marine environments, which need to be researched further given the rapid rate of expansion of OWFs.
Comorbidities of Patients With Idiopathic Pulmonary Fibrosis in Four Latin American Countries. Are There Differences by Country and Altitude?
Authors: Gonzalez-Garcia Mauricio , Rincon-Alvarez Emily , Alberti Maria Laura , Duran Mauricio , Caro Fabian , Venero Maria del Carmen , Liberato Yuri Edison , Buendia-Roldan Ivette
Published: June 2021

Background:Comorbidities in idiopathic pulmonary fibrosis (IPF) affect quality of life, symptoms, disease progression and survival. It is unknown what are the comorbidities in patients with IPF in Latin America (LA) and if there are differences between countries. Our objective was to compare IPF comorbidities in four countries and analyze possible differences by altitude.

Methods:Patients with IPF according 2012 ATS/ERS/JRS/ALAT guidelines, from two cities with an altitude of ≥2,250 m: Mexico City (Mexico) and Bogotá (Colombia) and from three at sea level: Buenos Aires (Argentina) and Lima and Trujillo (Peru). Comorbidities and pulmonary function tests were taken from clinical records. Possible pulmonary hypertension (PH) was defined by findings in the transthoracic echocardiogram of systolic pulmonary arterial pressure (sPAP) >36 mmHg or indirect signs of PH in the absence of other causes of PH. Emphysema as the concomitant finding of IPF criteria on chest tomography plus emphysema in the upper lobes. ANOVA or Kruskal Wallis and χ2-tests were used for comparison.

Results:Two hundred and seventy-six patients were included, 50 from Argentina, 86 from Colombia, 91 from Mexico and 49 from Peru. There prevalence of PH was higher in Colombia and Mexico (p< 0.001), systemic arterial hypertension in Argentina (p< 0.015), gastro-esophageal reflux and dyslipidemia in Colombia and Argentina (p< 0.001) and diabetes mellitus in Mexico (p< 0.007). Other comorbidities were obesity (28.4%), coronary artery disease (15.2%) and emphysema (14.9%), with no differences between countries. There was more PH in the altitude cities than those at sea level (51.7 vs. 15.3%,p< 0.001). In patients from Bogotá and Mexico City, arterial oxygen pressure, saturation (p< 0.001) and carbon monoxide diffusing capacity (p= 0.004) were significantly lower than in cities at sea level.

Conclusions:In this study with a significant number of patients, we were able to describe and compare the comorbidities of IPF in four LA countries, which contributes to the epidemiological data of this disease in the region. The main results were the differences in comorbidities between the countries and more PH in the subjects residing in the cities of higher altitude, a finding that should be validated in future studies.
Effects and Mechanisms of Symbiotic Microbial Combination Agents to Control Tomato Fusarium Crown and Root Rot Disease
Authors: Cai Xinyue , Zhao Honghai , Liang Chen , Li Min , Liu Runjin
Published: June 2021

This study evaluated the effects and underlying mechanisms of different combinations of plant symbiotic microbes, comprising arbuscular mycorrhizal fungi (AMF), plant growth-promoting rhizobacteria (PGPR), and Trichoderma spp., on tomato Fusarium crown and root rot (TFCRR) resistance. A total of 54 treatments were applied in a greenhouse pot experiment to tomato (Solanum lycopersicum) seedlings inoculated with or without Funneliformis mosseae (Fm), Rhizophagus intraradices (Ri), Trichoderma virens l40012 (Tv), Trichoderma harzianum l40015 (Th), Bacillus subtilis PS1-3 (Bs), Pseudomonas fluorescens PS2-6 (Pf), and Fusarium oxysporum f. sp. radicis-lycopersici (Fo). The symbioses on the tomato root system were well developed, and the composite symbiont generated by AMF + Trichoderma spp. was observed for the first time. Compared with other treatments, Ri + Bs + Tv and Fm + Pf + Tv stimulated the greatest improvements in tomato growth and yield. The combination Ri + Pf + Th + Fo resulted in the strongest biocontrol effects on TFCRR, followed by the treatments Th + Pf + Fo and Ri + Th + Fo. Compared with the Fo treatment, most inoculation treatments improved photosynthetic performance and significantly increased defense enzyme activity in tomato plants, of which the treatment Ri + Pf + Th + Fo showed the highest enzyme activity. Metabolome analysis detected changes in a total of 1,266 metabolites. The number of up-regulated metabolites in tomato plants inoculated with Ri + Pf + Th and Ri + Pf + Th + Fo exceeded that of the Fo treatment, whereas the number of down-regulated metabolites showed the opposite trend. It is concluded that AMF + Trichoderma + PGPR is the most effective combination to promote resistance to TFCRR in tomato. The up-regulation and down-regulation of metabolites regulated by symbiotic microbial genes may be an important mechanism by which root symbiotic microorganisms promote plant growth, increase yield, and improve disease resistance.
Long-Term Increase in Cholesterol Is Associated With Better Cognitive Function: Evidence From a Longitudinal Study
Authors: Liu Huamin , Zou Lianwu , Zhou Rui , Zhang Minyi , Gu Shanyuan , Zheng Jiazhen , Hukportie Daniel Nyarko , Wu Keyi , Huang Zhiwei , Yuan Zelin , Wu Xianbo
Published: June 2021

Background: Higher visit-to-visit cholesterol has been associated with cognitive decline. However, the association between long-term increase or decrease in cholesterol and cognitive decline remains unclear.

Methods: A total of 4,915 participants aged ≥45 years with normal cognition in baseline were included. The participants were divided into four groups, namely low–low, low–high, high–low, and high–high, according to the diagnostic thresholds of total cholesterol (TC), non-high-density lipoprotein cholesterol (NHDL-C), low-density lipoprotein cholesterol, and high-density lipoprotein cholesterol (HDL-C) after 4 years of follow-up. Cognitive function was assessed by episodic memory and mental intactness. Binary logistic regression was used to analyse the association of cholesterol variation with cognitive decline.

Results: Among the participants, 979 (19.9%) experienced global cognitive decline. The odds ratio (OR) of global cognitive and memory function decline were remarkably lower in participants in the low–high NHDL-C group than those in the low–low group [OR and 95% confidence interval (CI): 0.50 [0.26–0.95] for global cognitive decline, 0.45 [0.25–0.82] for memory function decline]. The lower OR was also significant in females (OR [95% CI]: 0.38 [0.17–0.87] for global cognitive decline; 0.44 [0.19–0.97] for memory function decline) and participants without cardiovascular disease (OR [95% CI]: 0.31 [0.11–0.87] for global cognitive decline; 0.34 [0.14–0.83] for memory function decline). The increases in other cholesterol were also negatively associated with the risk of cognitive decline although not significantly.

Conclusions: A longitudinal increase in NHDL-C may be protective for cognition in females or individuals without cardiovascular disease.
Use of EP3533-Enhanced Magnetic Resonance Imaging as a Measure of Disease Progression in Skeletal Muscle of mdx Mice
Authors: Murphy Alexander Peter , Greally Elizabeth , O'Hogain Dara , Blamire Andrew , Caravan Peter , Straub Volker
Published: June 2021

As putative treatments are developed for Duchenne muscular dystrophy (DMD), sensitive, non-invasive measures are increasingly important to quantify disease progression. Fibrosis is one of the histological hallmarks of muscular dystrophy and has been directly linked to prognosis. EP3533 is a novel contrast agent with an affinity to collagen 1 that has demonstrated a significant and high correlation to ex vivo fibrosis quantification. Halofuginone is an established anti-fibrotic compound shown to reduce collagen skeletal muscle fibrosis in murine models of DMD. This experiment explored whether EP3533 could be used to detect signal change in skeletal muscle of mdx mice before and after a 12 week course of halofuginone compared to controls. Four age-matched groups of treated and untreated mice were evaluated: 2 groups of mdx (n = 8 and n = 13, respectively), and 2 groups of BL10 mice (n = 5 and n = 3, respectively). Treated mice received an intraperitoneal injection with halofuginone three times per week for 12 weeks, with the remaining mice being given vehicle. Both mdx groups and the untreated BL10 were scanned at baseline, then all groups were scanned on week 13. All subjects were scanned using a 7T Varian scanner before and after administration of EP3533 using a T1 mapping technique. Mice underwent grip testing in week 13 prior to dissection. Skeletal muscle was used for Masson's trichrome quantification, hydroxyproline assay, and immunofluorescent antibody staining. Untreated mdx mice demonstrated a significant increase in R1 signal from pre- to post-treatment scan in three out of four muscles (gastrocnemius p = 0.04, hamstrings p = 0.009, and tibialis anterior p = 0.01), which was not seen in either the treated mdx or the BL10 groups. Histological quantification of fibrosis also demonstrated significantly higher levels in the untreated mdx mice with significant correlation seen between histology and EP3533 signal change. Forelimb weight adjusted-grip strength was significantly lower in the untreated mdx group, compared to the treated group. EP3533 can be used over time as an outcome measure to quantify treatment effect of an established anti-fibrotic drug. Further studies are needed to evaluate the use of this contrast agent in humans.
The Fundamental Need for Sleep in Neurocritical Care Units: Time for a Paradigm Shift
Authors: Kishore Kislay , Cusimano Michael D.
Published: June 2021

Intensive neurological assessments in neurocritical care settings for unduly prolonged period result in profound sleep deprivation in those patients that confounds the true neurological status of these patients, and the mounting apprehension in providers can beget a vicious cycle of even more intensive neurological assessments resulting in further sleep deprivation from being constantly woken up to be “assessed.” This iatrogenic state drives these patients into deep sleep stages that impact spontaneous breathing trials, weaken immunity, and lead to unwarranted investigations and interventions. There is dwindling value of prolonged frequent neurochecks beyond the initial 24–48 h of an intracranial event. We insist that sleep must be considered on at least an equal par to other functions that are routinely assessed. We reason that therapeutic sleep must be allowed to these patients in suitable amounts especially beyond the first 36–48 h to achieve ideal and swift recovery. This merits a paradigm shift.
Differences Changes in Cerebellar Functional Connectivity Between Mild Cognitive Impairment and Alzheimer's Disease: A Seed-Based Approach
Authors: Tang Fanyu , Zhu Donglin , Ma Wenying , Yao Qun , Li Qian , Shi Jingping
Published: June 2021

Background: Recent studies have discovered that functional connections are impaired among patients with Alzheimer's disease (AD), even at the preclinical stage. The cerebellum has been implicated as playing a role in cognitive processes. However, functional connectivity (FC) among cognitive sub-regions of the cerebellum in patients with AD and mild cognitive impairment (MCI) remains to be further elucidated.

Objective: Our study aims to investigate the FC changes of the cerebellum among patients with AD and MCI, compared to healthy controls (HC). Additionally, we explored the role of cerebellum FC changes in the cognitive performance of all subjects.

Materials: Resting-state functional magnetic resonance imaging (rs-fMRI) data from three different groups (28 AD patients, 26 MCI patients, and 30 HC) was collected. We defined cerebellar crus II and lobule IX as seed regions to assess the intragroup differences of cortico-cerebellar connectivity. Bias correlational analysis was performed to investigate the relationship between changes in FC and neuropsychological performance.

Results: Compared to HC, AD patients had decreased FC within the caudate, limbic lobe, medial frontal gyrus (MFG), middle temporal gyrus, superior frontal gyrus, parietal lobe/precuneus, inferior temporal gyrus, and posterior cingulate gyrus. Interestingly, MCI patients demonstrated increased FC within inferior parietal lobe, and MFG, while they had decreased FC in the thalamus, inferior frontal gyrus, and superior frontal gyrus. Further analysis indicated that FC changes between the left crus II and the right thalamus, as well as between left lobule IX and the right parietal lobe, were both associated with cognitive decline in AD. Disrupted FC between left crus II and right thalamus, as well as between left lobule IX and right parietal lobe, was associated with attention deficit among subjects with MCI.

Conclusion: These findings indicate that cortico-cerebellar FC in MCI and AD patients was significantly disrupted with different distributions, particularly in the default mode networks (DMN) and fronto-parietal networks (FPN) region. Increased activity within the fronto-parietal areas of MCI patients indicated a possible compensatory role for the cerebellum in cognitive impairment. Therefore, alterations in the cortico-cerebellar FC represent a novel approach for early diagnosis and a potential therapeutic target for early intervention.
Recurrent Vestibular Symptoms Not Otherwise Specified: Clinical Characteristics Compared With Vestibular Migraine and Menière's Disease
Authors: Dlugaiczyk Julia , Lempert Thomas , Lopez-Escamez Jose Antonio , Teggi Roberto , von Brevern Michael , Bisdorff Alexandre
Published: June 2021

Despite the huge progress in the definition and classification of vestibular disorders within the last decade, there are still patients whose recurrent vestibular symptoms cannot be attributed to any of the recognized episodic vestibular syndromes, such as Menière's disease (MD), vestibular migraine (VM), benign paroxysmal positional vertigo (BPPV), vestibular paroxysmia, orthostatic vertigo or transient ischemic attack (TIA). The aim of the present international, multi-center, cross-sectional study was to systematically characterize the clinical picture of recurrent vestibular symptoms not otherwise specified (RVS-NOS) and to compare it to MD and VM. Thirty-five patients with RVS-NOS, 150 patients with VM or probable VM and 119 patients with MD were included in the study. The symptoms of RVS-NOS had been present for 5.4 years on average before inclusion, similar to VM and MD in this study, suggesting that RVS-NOS is not a transitory state before converting into another diagnosis. Overall, the profile of RVS-NOS vestibular symptoms was more similar to VM than MD. In particular, the spectrum of vestibular symptom types was larger in VM and RVS-NOS than in MD, both at group comparison and the individual level. However, in contrast to VM, no female preponderance was observed for RVS-NOS. Positional, head-motion and orthostatic vertigo were reported more frequently by patients with RVS-NOS than MD, while external vertigo was more prevalent in the MD group. At group level, the spectrum of attack durations from minutes to 3 days was evenly distributed for VM, while a small peak for short and long attacks in RVS-NOS and a big single peak of hours in MD were discernible. In general, vertigo attacks and associated vegetative symptoms (nausea and vomiting) were milder in RVS-NOS than in the other two disorders. Some patients with RVS-NOS described accompanying auditory symptoms (tinnitus: 2.9%, aural fullness and hearing loss: 5.7% each), migrainous symptoms (photophobia, phonophobia or visual aura in 5.7% each) or non-migrainous headaches (14%), but did not fulfill the diagnostic criteria for MD or VM. Absence of a life time diagnosis of migraine headache and attack duration of <5 min were further reasons not to qualify for VM. In some RVS-NOS patients with accompanying ear symptoms, attack durations of <20 min excluded them from being diagnosed with MD. These findings suggest that RVS-NOS is a stable diagnosis over time whose overall clinical presentation is more similar to VM than to MD. It is more likely to be composed of several disorders including a spectrum of mild or incomplete variants of known vestibular disorders, such as VM and MD, rather than a single disease entity with distinct pathognomonic features.
Changes of Regional Neural Activity Homogeneity in Preclinical Alzheimer’s Disease: Compensation and Dysfunction
Authors: Zhang Zhen , Cui Liang , Huang Yanlu , Chen Yu , Li Yuehua , Guo Qihao
Published: June 2021

Introduction

Subjective cognitive decline (SCD) is the preclinical stage of Alzheimer’s disease and may develop into amnestic mild cognitive impairment (aMCI). Finding suitable biomarkers is the key to accurately identifying SCD. Previous resting-state functional magnetic resonance imaging (rs-fMRI) studies on SCD patients showed functional connectivity disorders. Our goal was to explore whether local neurological homogeneity changes in SCD patients, the relationship between these changes and cognitive function, and similarities of neurological homogeneity changes between SCD and aMCI patients.

Materials and Methods

37 cases of the healthy control (HC) group, 39 cases of the SCD group, and 28 cases of the aMCI group were included. Participants underwent rs-fMRI examination and a set of neuropsychological test batteries. Regional homogeneity (ReHo) was calculated and compared between groups. ReHo values were extracted from meaningful regions in the SCD group, and the correlation between ReHo values with the performance of neuropsychological tests was analyzed.

Results

Our results showed significant changes in the ReHo among groups. In the SCD group compared with the HC group, part of the parietal lobe, frontal lobe, and occipital lobe showed decreased ReHo, and the temporal lobe, part of the parietal lobe and the frontal lobe showed increased ReHo. The increased area of ReHo was negatively correlated with the decreased area, and was related to decrease on multiple neuropsychological tests performance. Simultaneously, the changed areas of ReHo in SCD patients are similar to aMCI patients, while aMCI group’s neuropsychological test performance was significantly lower than that of the SCD group.

Conclusion

There are significant changes in local neurological homogeneity in SCD patients, and related to the decline of cognitive function. The increase of neurological homogeneity in the temporal lobe and adjacent area is negatively correlated with cognitive function, reflecting compensation for local neural damage. These changes in local neurological homogeneity in SCD patients are similar to aMCI patients, suggesting similar neuropathy in these two stages. However, the aMCI group’s cognitive function was significantly worse than that of the SCD group, suggesting that this compensation is limited. In summary, regional neural activity homogeneity may be a potential biomarker for identifying SCD and measuring the disease severity.
Food Containing Bioactive Flavonoids and Other Phenolic or Sulfur Phytochemicals With Antiviral Effect: Can We Design a Promising Diet Against COVID-19?
Authors: Ghidoli Martina , Colombo Federico , Sangiorgio Stefano , Landoni Michela , Giupponi Luca , Nielsen Erik , Pilu Roberto
Published: June 2021

Since in late 2019, when the coronavirus 2 (SARS-CoV-2) pathogen of coronavirus disease 2019 (COVID-19) started to spread all over the world, causing the awful global pandemic we are still experiencing, an impressive number of biologists, infectious disease scientists, virologists, pharmacologists, molecular biologists, immunologists, and other researchers working in laboratories of all the advanced countries focused their research on the setting up of biotechnological tools, namely vaccines and monoclonal antibodies, as well as of rational design of drugs for therapeutic approaches. While vaccines have been quickly obtained, no satisfactory anti-Covid-19 preventive, or therapeutic approach has so far been discovered and approved. However, among the possible ways to achieve the goal of COVID-19 prevention or mitigation, there is one route, i.e., the diet, which until now has had little consideration. In fact, in the edible parts of plants supplying our food, there are a fair number of secondary metabolites mainly belonging to the large class of the flavonoids, endowed with antiviral or other health beneficial activities such as immunostimulating or anti-inflammatory action that could play a role in contributing to some extent to prevent or alleviate the viral infection and/or counteract the development of SARS induced by the novel coronavirus. In this review, a number of bioactive phytochemicals, in particular flavonoids, proven to be capable of providing some degree of protection against COVID-19, are browsed, illustrating their beneficial properties and mechanisms of action as well as their distribution in cultivated plant species which supply food for the human diet. Furthermore, room is also given to information regarding the amount in food, the resistance to cooking processes and, as a very important feature, the degree of bioavailability of these compounds. Concluding, remarks and perspectives for future studies aimed at increasing and improving knowledge and the possibility of using this natural complementary therapy to counteract COVID-19 and other viral pathologies are discussed.