bluuebunny/crossref_metadata_2025 huggingface dataset:
The Transcription Factor FRA-1/AP-1 Controls Lipocalin-2 Expression and Inflammation in Sepsis Model
Authors: Cao Shan , Schnelzer Anne , Hannemann Nicole , Schett Georg , Soulat Didier , Bozec Aline
Published: October 2021

Sepsis is a life-threatening condition characterized by excessive inflammation in its early phase. This is followed by an aberrant resolution phase associated to a prolonged period of immune suppression that can ultimately lead to multiple organ dysfunctions. This immunosuppression can be mediated by the functional reprogramming of gene transcription in monocytes/macrophages in response to prolonged lipopolysaccharide (LPS) exposure. Surprisingly, there is no report on the role of AP-1 transcription factors in this reprogramming process. Herein, we used the endotoxin tolerance model on murine bone marrow-derived macrophages in which tolerant cells stimulated twice with LPS were compared to naïve cells stimulated once. Out of all AP-1 transcription factors tested, Fosl1 gene stood out because of its unique regulation in tolerized cells. Moreover, we could correlate FRA-1 expression to the expression of an essential anti-inflammatory molecule involved in sepsis response, Lipocalin 2 aka NGAL. Identical results were obtained in human PBMC following the endotoxin tolerance model. When using FRA-1 deficient macrophages, we could confirm that FRA-1 regulates NGAL expression during the tolerant state. Interestingly, ChIP-seq and ChIP-qPCR revealed the binding of FRA-1 on Lcn2 promoter after LPS stimulation in these cells. Finally, we used an in vivo septic model of consecutive injection of LPS, in which the second stimulation is performed before the resolution of inflammation, in wild type and FRA-1 deficient mice. NGAL secretion was elevated in lung, spleen and serum of wild type tolerant mice, whereas it was significantly lower in tolerant FRA-1 deficient mice. Moreover, an increased inflammatory state likely dependent of the low level of NGAL was observed in these FRA-1 deficient mice. This was characterized by an increase of neutrophil infiltration in lung and an increase of apoptotic follicular cells in spleen. This suggests that FRA-1 expression supports resolution of inflammation in this model. Collectively, our data indicate that FRA-1 is involved in myeloid cell tolerance responses by mediating the functional reprogramming of Lcn2 transcription in response to prolonged LPS exposure. In conclusion, FRA-1 may have a protective role in the tolerance response of sepsis through the regulation of NGAL, leading to resolution of inflammation.
Expression Analysis of NF-κB-Related lncRNAs in Parkinson’s Disease
Authors: Ghafouri-Fard Soudeh , Gholipour Mahdi , Abak Atefe , Mazdeh Mehrdokht , Taheri Mohammad , Sayad Arezou
Published: October 2021

Parkinson’s disease (PD) has been shown to affect approximately 1% of the persons aged more than 65 years. This multifactorial disorder has been associated with abnormal function of NF-κB signals. In this research, we have evaluated expressions of NF-κB-related long non-coding RNAs in the circulation of PD patients compared with healthy controls. Expression of PACER was lower in total PD patients compared with healthy persons (Ratio of mean expressions (RME)=0.32, P value<0.001). This pattern was also evident among males (RME=0.25, P value<0.001). Expression of DILC was higher in total PD patients (RME=4.07, P value<0.001), and in both sex-based subgroups (RME=3.77, P value=0.01 and RME=4.25, P value<0.001, for females and males, respectively). Similarly, CEBPA was significantly over-expressed in total PD patients (RME=14.76, P value<0.001), and in both sex-based subgroups (RME=12.42, P value<0.001 and RME=15.80, P value<0.001, for females and males, respectively). ATG5 had a similar expression pattern (RME=2.6, P value=1E-08, RME=1.73, P value=0.03 and RME=3.09, P value=1E-07, for total cases, females and males, respectively). H19 was up-regulated in total cases and male cases compared with corresponding controls (RME=2.19, P value<0.001, RME=2.68, P value=0.01, respectively). Finally, HNFA1-AS was down-regulated in all comparisons (RME=0.10, P value=2E-06, RME=0.08, P value<0.001 and RME=0.12, P value<0.001, for total cases, females and males, respectively). Among PD patients, expressions of NKILA and ADINR were robustly correlated with each other (r=0.75, P value=2.40E-10). In addition, expression levels of DICER1-AS were significantly correlated with those of ADINR, PACER and H19 in these patients (r=0.73, P value=1.76E-9; r=0.72, P value=5.15E-09 and r=0.72, P value=3.09E-09, respectively). Correlation analyses among healthy controls revealed robust correlations between CHAST and CEBPA (r=0.84, P value=3.09E-09), NKILA and ADINR (r=0.80, P value=4.24E-12) as well as between DILC and CHAST (r=0.76, P value=1.70E-10). CEBPA had the best parameters among all assessed genes (AUC=0.96, Sensitivity=0.90 and specificity=0.97). DILC and ATG5 were the most appropriate markers after CEBPA with AUC values of 0.82 and 0.80, respectively. Most notably, combination of all genes improved AUC, sensitivity and specificity parameters to 1, 0.97 and 0.99, respectively. Cumulatively, the current study provides evidence for participation of NF-κB-related lncRNAs in the pathoetiology of PD.
Obesity Correlates With Pronounced Aberrant Innate Immune Responses in Hospitalized Aged COVID-19 Patients
Authors: Zulu Michael Z. , Sureshchandra Suhas , Pinski Amanda N. , Doratt Brianna , Shen Weining , Messaoudi Ilhem
Published: October 2021

Both age and obesity are leading risk factors for severe coronavirus disease 2019 (COVID-19), which is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Specifically, although most infections occur in individuals under the age of 55 years, 95% of hospitalizations, admissions to the intensive care unit, and deaths occur in those over the age of 55 years. Moreover, hospitalized COVID-19 patients have a higher prevalence of obesity. It is generally believed that chronic low-grade inflammation and dysregulated innate and adaptive immune responses that are associated with aging and obesity are responsible for this elevated risk of severe disease. However, the impact of advanced age and obesity on the host response to SARS-CoV-2 infection remains poorly defined. In this study, we assessed changes in the concentration of soluble immune mediators, IgG antibody titers, frequency of circulating immune cells, and cytokine responses to mitogen stimulation as a function of BMI and age. We detected significant negative correlations between BMI and myeloid immune cell subsets that were more pronounced in aged patients. Similarly, inflammatory cytokine production by monocytes was also negatively correlated with BMI in aged patients. These data suggest that the BMI-dependent impact on host response to SARS-CoV-2 is more pronounced on innate responses of aged patients.
Using Citizen Science Within an Integrated Knowledge Translation (IKT) Approach to Explore Cardiovascular Disease Risk Perception in Rwanda
Authors: Niyibizi Jean Berchmans , Nganabashaka Jean Pierre , Ntawuyirushintege Seleman , Tumusiime David , Umwali Ghislaine , Rulisa Stephen , Nyandwi Alypio , Okop Kufre Joseph , Ntaganda Evariste , Sell Kerstin , Levitt Naomi , Jessani Nasreen S. , Bavuma Charlotte M.
Published: October 2021

Background

Collaborative approaches to generating knowledge between knowledge users (KUs) and researchers as a means of enhancing evidence-informed decision making have been gaining ground over the last few years. The principal study targeted rural and urban communities within the catchment areas of Cyanika health centre (Burera district, Northern Province) and Kacyiru health centre (Gasabo district, in City of Kigali), respectively to understand perceptions and preferences of communication with respect to cardiovascular disease (CVD) risk in Rwanda. This paper describes the integration of citizen science within an integrated knowledge translation (IKT) approach for this study.

Methods

The citizen science approach included deliberate, selective and targeted engagement of KUs at various steps throughout the study. It incorporated national and district levels stakeholders, primary health care stakeholders, local community leaders and influencers, and local community members (selected and trained to be termed citizen scientists) in the process of implementation. Data for this paper included minutes, reports and notes from meetings and workshops which were perused to report the immediate outcomes and challenges of citizen science within an IKT approach for a study such as described for Rwanda.

Results

As a result of a deliberate IKT strategy, key national stakeholders attended and contributed to all phases of citizen science implementation. Project-based and relationship-based immediate outcomes were documented. In line with local community health issues reported by the citizen scientists, the local community stakeholders pledged home grown solutions. These included enhancement of compliance to implement the “kitchen garden per household” policy, teaching local residents on preparation of healthy diet from locally available food items, organizing collective physical activity, fighting against locally made substandard beverages and teaching local residents on CVD (risk factors). As an indicator of the probable uptake of research evidence, district officials appreciated citizen scientists’ work and decided to consider presented results in their next fiscal year action plan.

Conclusion

Citizen science proved to be an important strategy for research co-production in Rwanda. While this strategy falls within the remit of a larger IKT approach it focuses on the role and ownership of research by local community residents. This study demonstrated that to improve the relevance and impact of research in local community a deliberate IKT approach that incorporates citizen science can be invaluable.
Survival and Metabolic Modulation of Swimming Crab Portunus trituberculatus During Live Transport
Authors: Shi Ce , Ye Yangfang , Pei Feng , Mu Changkao , Wang Chunlin
Published: October 2021

Demand from consumers for small quantities of live swimming crab Portunus trituberculatus is rising with the development of e-commerce. However, it is challenging to keep P. trituberculatus alive post-capture. In this study, a transport bag containing oxygen and seawater (24 ppt) was used to investigate the survival and metabolic changes of P. trituberculatus during transport. The results showed that more than 80% P. trituberculatus could survive at least 24 h in the transport bag. The ability of the crabs to survive may be attributed to adaptive metabolism, as suggested by the switch from an aerobic to an anaerobic pathway for energy generation and a decline in amino acid metabolism, nucleic acid metabolism, and osmoregulation. Our findings suggest that the transport bag could effectively extend the post-capture survival time of P. trituberculatus. Metabolic adaptation – especially energy homeostasis – is crucial for crab survival during transport. Our study provides a promising method for the transport of live P. trituberculatus.
Abundance and Characteristics of Microplastics in Seawater and Corals From Reef Region of Sanya Bay, China
Authors: Lei Xinming , Cheng Hao , Luo Yong , Zhang Yuyang , Jiang Lei , Sun Youfang , Zhou Guowei , Huang Hui
Published: October 2021

Microplastics (MPs) contamination is widespread in the coral reef ecosystems leading to the exposure of both corals and other biotas. Knowledge gaps still exist concerning patterns in MPs abundance spatially. This work quantified the MPs abundance and characteristics in the seawater and corals in the Sanya Bay, Hainan Island. MPs abundance was detected in the seawater and coral samples ranging from 15.50 to 22.14 items L–1, and 0.01 to 3.60 items polyp–1, respectively. We found the predominant size and type of MPs in seawater and corals were smaller than 2 mm and fiber. Further analysis revealed that the characteristics of MPs in the corals were significantly different from those in the seawater environment, indicating that the MPs are selectively enriched in corals. Furthermore, the MPs particles ingested and retained in coral tissue may be related to the polyp size. This study shows that MPs are present in the whole coral reef region and the coral community structure would be potentially harmed by these contaminants.
Seagrass Depth Distribution Mirrors Coastal Development in the Mexican Caribbean – An Automated Analysis of 800 Satellite Images
Authors: Hedley John D. , Velázquez-Ochoa Roberto , Enríquez Susana
Published: October 2021

The seagrass Thalassia testudinum is the dominant habitat-builder in coastal reef lagoons of the Caribbean, and provides vital ecosystem services including coastal protection and carbon storage. We used a remote sensing methodology to map T. testudinum canopies over 400 km of coastline of the eastern Yucatán Peninsula, comparing the depth distribution of canopy density, in terms of leaf area index (LAI), to a previously established ecological model of depth and LAI for this species in oligotrophic conditions. The full archive of Sentinel-2 imagery from 2016 to 2020 was applied in an automated model inversion method to simultaneously estimate depth and LAI, covering ∼900 km2 of lagoon with approximately 800 images. Data redundancy allowed for statistical tests of change detection. Achieved accuracy was sufficient for the objectives: LAI estimates compared to field data had mean absolute error of 0.59, systematic error of 0.04 and r2 > 0.67 over a range of 0–5. Bathymetry compared to 46,000 ICESat-2 data points had a mean absolute error of 1 m, systematic error less than 0.5 m, and r2 > 0.88 over a range of 0–15 m. The estimated total area of seagrass canopy was consistent with previously published estimates of ∼580 km2, but dense canopies (LAI > 3), which are the primary contributors to below-ground carbon storage, comprise only ∼40 km2. Within the year-to-year variation there was no change in overall seagrass abundance 2017–2020, but localised statistically significant (p < 0.01) patches of canopy extension and retraction occurred. 2018 and 2019 were affected by beaching of pelagic Sargassum and dispersion as organic matter into the lagoon. The multi-year analysis enabled excluding this influence and provided an estimate of its extent along the coast. Finally, the distribution of LAI with depth was consistent with the ecological model and showed a gradient from north to south which mirrored a well-established gradient in anthropogenic pressure due to touristic development. Denser canopies were more abundant in developed areas, the expected growth response to nutrient enrichment. This increase in canopy density may be a useful early bio-indicator of environmental eutrophication, detectable by remote sensing before habitat deterioration is observed.
Numerical Study of Thermal Shock Damage Mechanism of Polycrystalline Ceramics
Authors: Gong Zhenyuan , Guan Kang , Rao Pinggen , Zeng Qingfeng , Liu Jiantao , Feng Zhiqiang
Published: October 2021

A dual-scale model is proposed to study the effect of microstructure parameters (grain size and grain boundary fracture energy) on the thermal shock damage mechanism on an example of alumina. At microscale, representative volume element (RVE) models generated by Voronoi tessellation are simulated to obtain the mechanical parameters for macro models. At macroscale, a coupled thermomechanical model based on the finite–discrete element method (FDEM) is applied to simulate the crack nucleation and propagation. Energy dissipation (ALLDMD) is introduced to investigate the thermal shock cracking mechanism by combining crack patterns and crack density, which indicates that decreasing grain size and increasing grain boundary fracture energy have a positive effect on thermal shock resistance. The proposed models not only predict the critical stress temperature which is well consistent to the theoretical thermal shock resistance factor, but also quantify the two previously unconsidered stages (crack nucleation and crack instability stage). Our models suggest the crack nucleation and instability will not occur immediately when the model reaches critical stress, but the models can sustain for higher temperature difference. The thermal shock damage mechanism and the influence of microstructural parameters on thermal shock resistance have also been discussed in detail.
An Experimental Study Into the Effects of Cumulative Energy Damage on the Mechanical Properties of Coal
Authors: Guo Shuai , Huang Peng , Spearing A.J.S. (Sam) , Wang Zhaojun , Dong Xiangjian
Published: October 2021

The accumulated damage of the surrounding rocks induced by the existing coal mining activities (such as excavation and extraction) is the initial mechanical background of the rock and coal for the further mining operations. An energy-based Cumulative Initial Damage (CID) variable was proposed to account for such existing damage. With the MTS815 electro-hydraulic servo-controlled system, coal samples with different CID value were prepared by cyclic pre-loading and unloading process, and a novel experimental framework was presented to investigate the effect of CID on the further mechanical properties of the CID coal samples. The deformation characteristics, peak strength, peak strain, dilatancy characteristics, brittle-ductile transformation behavior, and microscopic structure of the CID coal samples were investigated in detail. The triaxial compression tests showed that with the increased of CID value, the compaction part of the coal samples was shorter and the strain softening stage became longer. When the CID value was increased from 0 to 0.521, the deviation stress and peak strain of the coal decreased by 31.4 and 37.7%, respectively and the main characteristic of the fracture morphology changed from cleavage steps to dimpling.
Case Report: Severe Immune-Related Cholestatic Hepatitis and Subsequent Pneumonia After Pembrolizumab Therapy in a Geriatic Patient With Metastic Gastric Cancer
Authors: Yang Hui , Zhou Chenfei , Yuan Fei , Guo Liting , Yang Liu , Shi Yan , Zhang Jun
Published: October 2021

Background: Immune checkpoint inhibitors have provided significant clinical benefits to many patients with advanced cancer; however, severe immune-related adverse events (irAEs) have occurred. Detecting and treating irAEs early could improve patient prognoses. Therefore, clinicians and patients should understand that these irAEs exist, especially those that are rare and serious.

Case Presentation: In this report, an 86-year-old male patient, diagnosed with metastatic gastric cancer involving the peritoneum and retroperitoneal lymph nodes was treated with 5-cycle pembrolizumab therapy (100 mg q 2 weeks), achieving a partial response. However, the patient developed Grade 3 cholestatic hepatitis and delayed pneumonia 10 days and 2 months after the final pembrolizumab dose, respectively. After discontinuing the pembrolizumab therapy and excluding obstructive jaundice with imaging studies, the patient received steroid therapy, with a gradual symptom improvement. However, the patient developed delayed pneumonia with type 1 respiratory failure 1-month post-discharge. Several microbiologic tests were negative, and immune-associated pneumonia was suspected, but we could not exclude an opportunistic infection. The patient recovered with steroids and antibiotics and remained in partial remission 5 months after pembrolizumab withdrawal.

Conclusions: Cholestatic hepatitis is a rarely reported toxicity of immune checkpoint inhibitors, which should be suspected and addressed once obstructive jaundice is ruled out. In addition, clinicians should be aware that irAEs can occur at any time in patients treated with immune checkpoint inhibitors and that a timely diagnosis should be made.
Effect of Poor Nutritional Status and Comorbidities on the Occurrence and Outcome of Pneumonia in Elderly Adults
Authors: Chen Bo , Liu Wen , Chen Yanbing , She Quan , Li Min , Zhao HongYe , Zhao Weihong , Peng Zhihang , Wu Jianqing
Published: October 2021

Background: Malnutrition and comorbidity are two common geriatric syndromes. The pathology of pneumonia is multifactorial, making its diagnosis and management a great challenge. Hospital-acquired pneumonia (HAP) and community-acquired pneumonia (CAP) are two main types of pneumonia. However, the effect of geriatric syndromes on pneumonia and its prognosis have not been clearly explored.

Methods: We collected the relevant electronic data of inpatients aged over 65 years and diagnosed with pneumonia in the Geriatrics Department Building of the First Affiliated Hospital with Nanjing Medical University between December 2018 and December 2019, and further divided them into HAP group and CAP group. The correlations of age, age-adjusted Charlson Comorbidity Index (aCCI), basic diseases and nutritional indexes (i.e., albumin, electrolyte, hemoglobin) with pneumonia and prognosis were analyzed. We analyzed the associations between infection prognosis/infection level and age, nutritional status, aCCI and underlying diseases, using linear regression model. The box plot was applied to present infection outcome, and the nomogram was built for predicting infection outcomes. We utilized the heat map to show the associations between nutritional status and infection level/outcome in all infected patients, HAP, and CAP.

Results: The final study comprised samples of 669 pneumonia patients divided into HAP group (n = 517) and CAP group (n = 152). In all patients, the infection outcome was negatively correlated with age (P = 0.013). The level of albumin was negatively correlated with infection prognosis in all patients (P = 0.03), and negatively correlated with neutrophil count and CRP (P = 0.008, P < 0.001). ACCI was positively correlated with CRP (P = 0.003). The prognosis was negatively associated with age and albumin level. In the patients with basic dementia/Alzheimer's disease and chronic obstructive pulmonary disease/asthma, the prognosis was worse.

Conclusion: There was a correlation between poor nutritional status-related indexes and inflammatory indexes. A poor nutritional status might predict a high risk of pneumonia in elderly adults. Advanced age and comorbidities were risk factors for the occurrence and poor prognosis of pneumonia. Therefore, comorbidities should be well-treated in the elderly with pneumonia.
Terbium Medical Radioisotope Production: Laser Resonance Ionization Scheme Development
Authors: Gadelshin Vadim Maratovich , Formento Cavaier Roberto , Haddad Ferid , Heinke Reinhard , Stora Thierry , Studer Dominik , Weber Felix , Wendt Klaus
Published: October 2021

Terbium (Tb) is a promising element for the theranostic approach in nuclear medicine. The new CERN-MEDICIS facility aims for production of its medical radioisotopes to support related R&D projects in biomedicine. The use of laser resonance ionization is essential to provide radioisotopic yields of highest quantity and quality, specifically regarding purity. This paper presents the results of preparation and characterization of a suitable two-step laser resonance ionization process for Tb. By resonance excitation via an auto-ionizing level, the high ionization efficiency of 53% was achieved. To simulate realistic production conditions for Tb radioisotopes, the influence of a surplus of Gd atoms, which is a typical target material for Tb generation, was considered, showing the necessity of radiochemical purification procedures before mass separation. Nevertheless, a 10-fold enhancement of the Tb ion beam using laser resonance ionization was observed even with Gd:Tb atomic ratio of 100:1.
Efficacy and Safety of 12-week Monotherapy With Once Daily 5 mg Tadalafil for Lower Urinary Tract Symptoms of Benign Prostatic Hyperplasia: Evidence-based Analysis
Authors: Cui Jianwei , Cao Dehong , Bai Yunjin , Wang Jiahao , Yin Shan , Wei Wuran , Xiao Yunfei , Wang Jia , Wei Qiang
Published: October 2021

Background: Tadalafil has been approved for the treatment of benign prostatic hyperplasia (BPH) for nearly 10 years. However, there are insufficient evidence-based studies of the efficacy and safety of tadalafil in treating lower urinary tract symptoms of BPH (LUTS/BPH).

Objective: To evaluate the therapeutic effect and clinical safety of tadalafil monotherapy (5 mg once daily for 12 weeks) for LUTS/BPH.

Methods: A total of 13 studies (15 randomized clinical trials [RCTs]) were extracted from the following databases: PubMed, Cochrane Central Register of Controlled Trials, Embase, and Web of Science for the period up to July 2021. The quality of the included RCTs was evaluated independently by two authors, who, respectively, extracted data according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses principles. Conflicts were settled by a discussion with two-third of senior authors. All data analyses were conducted by the Review Manager, version 5.4.

Results: Regarding efficacy, 12-week trials indicated that 5 mg once daily tadalafil showed a significantly lower and, consequently, better total International Prostate Symptom Score (IPSS) than the placebo did (mean difference [MD]: −1.97, 95% CI: −2.24 to −1.70; P < 0.00001). In addition, significant differences were found between the tadalafil regimen and the placebo in the IPSS voiding subscore (MD: −1.30, 95% CI: −1.48 to −1.11; P < 0.00001), the IPSS storage subscore (MD: −0.70, 95% CI: −0.82 to −0.58; P < 0.00001), the IPSS quality of life (MD: −0.29, 95% CI: −0.35 to −0.22; P < 0.00001), and BPH impact index (MD: −0.58, 95% CI: −0.76 to −0.40; P < 0.00001). The safety analysis did not show a significant difference in serious adverse events between the two groups (risk ratio: 1.27, 95% CI: 0.80–2.01; P = 0.31), although the adverse events occurred at a higher incidence in the tadalafil group than in the placebo.

Conclusions: This study demonstrates that once daily 5 mg tadalafil is a potentially effective and safe treatment choice with excellent tolerability for patients with LUTS/BPH.

Systematic Review Registration: Identifier (CRD42021228840).
Early Alterations of Lymphocyte Subsets in Acute Respiratory Distress Syndrome Caused by Acinetobacter baumannii Pneumonia: A Prospective Observational Study
Authors: Cheng Wei , Zhang Jiahui , Li Dongkai , Bai Guangxu , Han Wen , Chen Jianwei , Wang Hao , Cui Na
Published: October 2021

Background: To prospectively observe the early alterations of lymphocyte subsets in ARDS caused by Acinetobacter baumannii.

Methods: ARDS patients admitted to our ICU between January 1, 2017 and May 30, 2020 were selected. We enrolled all the pulmonary ARDS caused by Acinetobacter baumannii pneumonia who required mechanical ventilation or vasopressors. All the available clinical data, follow up information and lymphocyte subsets were recorded.

Results: Eighty-seven of all the 576 ARDS patients were enrolled. The 28-day mortality of the enrolled patients was 20.7% (18/87). The T lymphocyte count (452 vs. 729 cells/ul, P = 0.004), especially the CD8+ T lymphocyte count (104 vs. 253 cells/ul, P = 0.002) was significantly lower in non-survivors, as were counts of the activated T cell subsets (CD8+CD28+ and CD8+CD38+). The CD8+ T cell count was an independent risk factor for 28-day mortality, and a cutoff value of 123 cells/ul was a good indicator to predict the prognosis of ARDS caused by Acinetobacter baumannii pneumonia, with sensitivity of 74.6% and specificity of 83.3% (AUC 0.812, P < 0.0001).

Conclusions: Lower CD8+ T cell count was associated with higher severity and early mortality in ARDS patients caused by Acinetobacter baumannii pneumonia, which could be valuable for outcome prediction.
The Potential Effects on Microbiota and Silage Fermentation of Alfalfa Under Salt Stress
Authors: Lu Qiang , Wang Zhen , Sa Duowen , Hou Meiling , Ge Gentu , Wang ZhiJun , Jia Yushan
Published: October 2021

This study investigated the fermentation quality of alfalfa grown in different salt stress regions in China. Following the production of silage from the natural fermentation of alfalfa, the interplay between the chemical composition, fermentation characteristics, and microbiome was examined to understand the influence of these factors on the fermentation quality of silage. The alfalfa was cultivated under salt stress with the following: (a) soil content of <1%0 (CK); (b) 1–2%0 (LS); (c) 2–3%0 (MS); (d) 3–4%0 (HS). The pH of the silage was high (4.9–5.3), and lactic acid content was high (26.3–51.0 g/kg DM). As the salt stress increases, the NA+ of the silages was higher (2.2–5.4 g/kg DM). The bacterial alpha diversities of the alfalfa silages were distinct. There was a predominance of desirable genera including Lactococcus and Lactobacillus in silage produced from alfalfa under salt stress, and this led to better fermentation quality. The chemical composition and fermentation characteristics of the silage were closely correlated with the composition of the bacterial community. Furthermore, NA+ was found to significantly influence the microbiome of the silage. The results confirmed that salt stress has a great impact on the quality and bacterial community of fresh alfalfa and silage. The salt stress and plant ions were thus most responsible for their different fermentation modes in alfalfa silage. The results of the study indicate that exogenous epiphytic microbiota of alfalfa under salt stress could be used as a potential bioresource to improve the fermentation quality.
Microbial Diversity Under the Influence of Natural Gas Storage in a Deep Aquifer
Authors: Ranchou-Peyruse Magali , Guignard Marion , Casteran Franck , Abadie Maïder , Defois Clémence , Peyret Pierre , Dequidt David , Caumette Guilhem , Chiquet Pierre , Cézac Pierre , Ranchou-Peyruse Anthony
Published: October 2021

Deep aquifers (up to 2km deep) contain massive volumes of water harboring large and diverse microbial communities at high pressure. Aquifers are home to microbial ecosystems that participate in physicochemical balances. These microorganisms can positively or negatively interfere with subsurface (i) energy storage (CH4 and H2), (ii) CO2 sequestration; and (iii) resource (water, rare metals) exploitation. The aquifer studied here (720m deep, 37°C, 88bar) is naturally oligotrophic, with a total organic carbon content of <1mg.L−1 and a phosphate content of 0.02mg.L−1. The influence of natural gas storage locally generates different pressures and formation water displacements, but it also releases organic molecules such as monoaromatic hydrocarbons at the gas/water interface. The hydrocarbon biodegradation ability of the indigenous microbial community was evaluated in this work. The in situ microbial community was dominated by sulfate-reducing (e.g., Sva0485 lineage, Thermodesulfovibriona, Desulfotomaculum, Desulfomonile, and Desulfovibrio), fermentative (e.g., Peptococcaceae SCADC1_2_3, Anaerolineae lineage and Pelotomaculum), and homoacetogenic bacteria (“Candidatus Acetothermia”) with a few archaeal representatives (e.g., Methanomassiliicoccaceae, Methanobacteriaceae, and members of the Bathyarcheia class), suggesting a role of H2 in microenvironment functioning. Monoaromatic hydrocarbon biodegradation is carried out by sulfate reducers and favored by concentrated biomass and slightly acidic conditions, which suggests that biodegradation should preferably occur in biofilms present on the surfaces of aquifer rock, rather than by planktonic bacteria. A simplified bacterial community, which was able to degrade monoaromatic hydrocarbons at atmospheric pressure over several months, was selected for incubation experiments at in situ pressure (i.e., 90bar). These showed that the abundance of various bacterial genera was altered, while taxonomic diversity was mostly unchanged. The candidate phylum Acetothermia was characteristic of the community incubated at 90bar. This work suggests that even if pressures on the order of 90bar do not seem to select for obligate piezophilic organisms, modifications of the thermodynamic equilibria could favor different microbial assemblages from those observed at atmospheric pressure.
Microbiome Profiling Using Shotgun Metagenomic Sequencing Identified Unique Microorganisms in COVID-19 Patients With Altered Gut Microbiota
Authors: Li Sijia , Yang Siyuan , Zhou Yuzheng , Disoma Cyrollah , Dong Zijun , Du Ashuai , Zhang Yongxing , Chen Yong , Huang Weiliang , Chen Junru , Song Deqiang , Chen Zongpeng , Liu Pinjia , Li Shiqin , Zheng Rong , Liu Sixu , Razzaq Aroona , Chen Xuan , Tao Siyi , Yu Chengping , Feng Tianxu , Liao Wenyan , Peng Yousong , Jiang Taijiao , Huang Jufang , Wu Wei , Hu Liqiang , Wang Linghang , Li Shanni , Xia Zanxian
Published: October 2021

COVID-19 is mainly associated with respiratory distress syndrome, but a subset of patients often present gastrointestinal (GI) symptoms. Imbalances of gut microbiota have been previously linked to respiratory virus infection. Understanding how the gut–lung axis affects the progression of COVID-19 can provide a novel framework for therapies and management. In this study, we examined the gut microbiota of patients with COVID-19 (n = 47) and compared it to healthy controls (n = 19). Using shotgun metagenomic sequencing, we have identified four microorganisms unique in COVID-19 patients, namely Streptococcus thermophilus, Bacteroides oleiciplenus, Fusobacterium ulcerans, and Prevotella bivia. The abundances of Bacteroides stercoris, B. vulgatus, B. massiliensis, Bifidobacterium longum, Streptococcus thermophilus, Lachnospiraceae bacterium 5163FAA, Prevotella bivia, Erysipelotrichaceae bacterium 6145, and Erysipelotrichaceae bacterium 2244A were enriched in COVID-19 patients, whereas the abundances of Clostridium nexile, Streptococcus salivarius, Coprococcus catus, Eubacterium hallii, Enterobacter aerogenes, and Adlercreutzia equolifaciens were decreased (p < 0.05). The relative abundance of butyrate-producing Roseburia inulinivorans is evidently depleted in COVID-19 patients, while the relative abundances of Paraprevotella sp. and the probiotic Streptococcus thermophilus were increased. We further identified 30 KEGG orthology (KO) modules overrepresented, with 7 increasing and 23 decreasing modules. Notably, 15 optimal microbial markers were identified using the random forest model to have strong diagnostic potential in distinguishing COVID-19. Based on Spearman’s correlation, eight species were associated with eight clinical indices. Moreover, the increased abundance of Bacteroidetes and decreased abundance of Firmicutes were also found across clinical types of COVID-19. Our findings suggest that the alterations of gut microbiota in patients with COVID-19 may influence disease severity. Our COVID-19 classifier, which was cross-regionally verified, provides a proof of concept that a set of microbial species markers can distinguish the presence of COVID-19.
In vitro Prebiotic Effect of Bread-Making Process in Inflammatory Bowel Disease Microbiome
Authors: Lluansí Aleix , Llirós Marc , Oliver Lia , Bahí Anna , Elias-Masiques Núria , Gonzalez Marina , Benejam Patrícia , Cueva Emilio , Termes Miquel , Ramió-Pujol Sara , Malagón Marta , Amoedo Joan , Serrano Marta , Busquets David , Torreabla Leyanira , Sabat Miriam , Buxó Maria , Cambra Maria , Serra-Pagès Mariona , Delgado-Aros Sílvia , García-Gil Liberado Jesús , Elias Isidre , Aldeguer Xavier
Published: October 2021

Inflammatory bowel disease (IBD), including its two main categories (Crohn's disease and ulcerative colitis), has been linked both to gut microbiota and to diet. Bread is a daily food that has a potential capacity as a prebiotic. Our aim was to evaluate different bread-making processes and their effect on fecal colonic microbiota in IBD patients. The microbial composition of several sourdoughs and dough samples was analyzed by high-throughput sequencing of 16S and 18S rRNA genes. Three types of bread, which followed different bread-making processes, were in vitro digested and incubated with feces from IBD patients. Changes in gut microbiota were assessed by a quantitative polymerase chain reaction using specific bacterial sequence targets. Short-chain fatty acid production was also analyzed by gas chromatography. Lactobacillus sanfranciscensis was the dominant lactic acid bacteria species found in sourdough and bread doughs prepared using sourdough, whereas Saccharomyces cerevisiae was the most dominant yeast in all groups, especially in bread doughs before baking. Differences in microbial composition in raw bread doughs were more related to the type of dough and elaboration than to fermentation time lengths. The analysis of in vitro fecal incubations with bread conditions revealed an increase in most bacterial groups analyzed and short-chain fatty acid production, both in Crohn's disease and ulcerative colitis samples. Most remarkable increases in short-chain fatty acid production mirrored higher abundances of Roseburia species. The potential prebiotic properties observed were mainly obtained when using a high quantity of bread, regardless of bread type. Overall, this study highlights the bacterial dynamics within the bread-making process and the potential prebiotic effect in IBD patients.
Multipotential Alkaline Protease From a Novel Pyxidicoccus sp. 252: Ecofriendly Replacement to Various Chemical Processes
Authors: Sharma Sonia , Kumar Shiv , Kaur Rajinder , Kaur Ramandeep
Published: October 2021

A newly isolated alkaline protease-producing myxobacterium was isolated from soil. The strain was identified as Pyxidicoccus sp. S252 on the basis of 16S rRNA sequence analysis. The extracellular alkaline proteases produced by isolate S252 (PyCP) was optimally active in the pH range of 11.0–12.0 and temperature range of 40–50°C The zymogram of PyCP showed six caseinolytic protease bands. The proteases were stable in the pH range of 8.0–10.0 and temperature range of 40–50°C. The activity of PyCP was enhanced in the presence of Na+, Mg2+, Cu2+, Tween-20, and hydrogen peroxide (H2O2) (hydrogen peroxide), whereas in Triton X-100, glycerol, ethylenediaminetetraacetic acid (EDTA), and Co2+, it was stable. PyCP showed a potential in various applications. The addition of PyCP in the commercial detergent enhanced the wash performance of the detergent by efficiently removing the stains of tomato ketchup and coffee. PyCP efficiently hydrolyzed the gelatin layer on X-ray film to release the embedded silver. PyCP also showed potent dehairing of goat skin and also efficiently deproteinized sea shell waste indicating its application in chitin extraction. Thus, the results of the present study indicate that Pyxidicoccus sp. S252 proteases have the potential to be used as an ecofriendly replacement of chemicals in several industrial processes.
Development of the in vitro Cecal Chicken ALIMEntary tRact mOdel-2 to Study Microbiota Composition and Function
Authors: Oost Miriam J. , Velkers Francisca C. , Kraneveld Aletta D. , Venema Koen
Published: October 2021

The digestive system of the chicken plays an important role in metabolism, immunity, and chicken health and production performance. The chicken ceca harbor a diverse microbial community and play a crucial role in the microbial fermentation and production of energy-rich short-chain fatty acids (SCFA). For humans, dogs, and piglets in vitro digestive system models have been developed and are used to study the microbiota composition and metabolism after intervention studies. For chickens, most research on the cecal microbiota has been performed in in vivo experiments or in static in vitro models that may not accurately resemble the in vivo situations. This paper introduces an optimized digestive system model that simulates the conditions in the ceca of the chicken, i.e., the Chicken ALIMEntary tRact mOdel-2 (CALIMERO-2). The system is based on the well-validated TNO in vitro model of the colon-2 (TIM-2) and is the first dynamic in vitro digestion model for chickens species. To validate this model, the pH, temperature, and different types of microbial feeding were compared and analyzed, to best mimic the conditions in the chicken ceca. The bacterial composition, as well as the metabolite production at 72 h, showed no significant difference between the different microbial feedings. Moreover, we compared the CALIMERO-2 digestive samples to the original inoculum and found some significant shifts in bacterial composition after the fermentation started. Over time the bacterial diversity increased and became more similar to the original inoculum. We can conclude that CALIMERO-2 is reproducible and can be used as a digestive system model for the chicken ceca, in which the microbial composition and activity can be maintained and shows similar results to the in vivo cecum. CALIMERO-2 can be used to study effects on composition and activity of the chicken cecum microbiota in response to in-feed interventions.
Strategy and Performance Evaluation of Low-Frequency Variant Calling for SARS-CoV-2 Using Targeted Deep Illumina Sequencing
Authors: Van Poelvoorde Laura A. E. , Delcourt Thomas , Coucke Wim , Herman Philippe , De Keersmaecker Sigrid C. J. , Saelens Xavier , Roosens Nancy H. C. , Vanneste Kevin
Published: October 2021

The ongoing COVID-19 pandemic, caused by SARS-CoV-2, constitutes a tremendous global health issue. Continuous monitoring of the virus has become a cornerstone to make rational decisions on implementing societal and sanitary measures to curtail the virus spread. Additionally, emerging SARS-CoV-2 variants have increased the need for genomic surveillance to detect particular strains because of their potentially increased transmissibility, pathogenicity and immune escape. Targeted SARS-CoV-2 sequencing of diagnostic and wastewater samples has been explored as an epidemiological surveillance method for the competent authorities. Currently, only the consensus genome sequence of the most abundant strain is taken into consideration for analysis, but multiple variant strains are now circulating in the population. Consequently, in diagnostic samples, potential co-infection(s) by several different variants can occur or quasispecies can develop during an infection in an individual. In wastewater samples, multiple variant strains will often be simultaneously present. Currently, quality criteria are mainly available for constructing the consensus genome sequence, and some guidelines exist for the detection of co-infections and quasispecies in diagnostic samples. The performance of detection and quantification of low-frequency variants using whole genome sequencing (WGS) of SARS-CoV-2 remains largely unknown. Here, we evaluated the detection and quantification of mutations present at low abundances using the mutations defining the SARS-CoV-2 lineage B.1.1.7 (alpha variant) as a case study. Real sequencing data were in silico modified by introducing mutations of interest into raw wild-type sequencing data, or by mixing wild-type and mutant raw sequencing data, to construct mixed samples subjected to WGS using a tiling amplicon-based targeted metagenomics approach and Illumina sequencing. As anticipated, higher variation and lower sensitivity were observed at lower coverages and allelic frequencies. We found that detection of all low-frequency variants at an abundance of 10, 5, 3, and 1%, requires at least a sequencing coverage of 250, 500, 1500, and 10,000×, respectively. Although increasing variability of estimated allelic frequencies at decreasing coverages and lower allelic frequencies was observed, its impact on reliable quantification was limited. This study provides a highly sensitive low-frequency variant detection approach, which is publicly available at https://galaxy.sciensano.be, and specific recommendations for minimum sequencing coverages to detect clade-defining mutations at certain allelic frequencies. This approach will be useful to detect and quantify low-frequency variants in both diagnostic (e.g., co-infections and quasispecies) and wastewater [e.g., multiple variants of concern (VOCs)] samples.
Autophagy Regulates the Survival of Hair Cells and Spiral Ganglion Neurons in Cases of Noise, Ototoxic Drug, and Age-Induced Sensorineural Hearing Loss
Authors: Guo Lingna , Cao Wei , Niu Yuguang , He Shuangba , Chai Renjie , Yang Jianming
Published: October 2021

Inner ear hair cells (HCs) and spiral ganglion neurons (SGNs) are the core components of the auditory system. However, they are vulnerable to genetic defects, noise exposure, ototoxic drugs and aging, and loss or damage of HCs and SGNs results in permanent hearing loss due to their limited capacity for spontaneous regeneration in mammals. Many efforts have been made to combat hearing loss including cochlear implants, HC regeneration, gene therapy, and antioxidant drugs. Here we review the role of autophagy in sensorineural hearing loss and the potential targets related to autophagy for the treatment of hearing loss.
Factors Influencing the Degree of Disability in Patients With Multiple Sclerosis
Authors: Xue Huiru , Yang Zhenzhen , Wang Li , Jiang Yayun , Li Jiayang , Wu Minghui , Wang Guilian , Zhang Yuanyuan , Zhang Meini
Published: October 2021

Objective: To explore the factors influencing the degree of disability in patients with multiple sclerosis (MS), and to provide evidence for its early diagnosis, prognostic evaluation and clinical intervention.

Methods: This retrospective observational study included 72 patients with relapsing-remitting multiple sclerosis (RRMS) at the First Hospital of Shanxi Medical University. All patients completed craniocerebral and spinal cord MRI (with or without Gd enhancement) and were evaluated for Expanded Disability Status Score (EDSS) scores before receiving treatment.

Results: Among 72 patients with RRMS, 45 (62.5%) had an EDSS score ≤3; A total of 27 patients (37.5%) had an EDSS score >3 points. Univariate analysis showed that age, annual recurrence rate (ARR), drug use, albumin (ALB), triglycerides (TG), and total number of lesions in groups with EDSS score ≤3 were significantly different from those with an EDSS score > 3 points (P < 0.05). Multivariate logistic regression analysis showed that ALB, total number of lesions, and drug use were independent influencing factors of the degree of disability in patients with MS, and the difference was statistically significant (P < 0.05). An ROC curve was constructed using ALB and the total number of lesions. The AUC of ALB was 0.681, P < 0.05, and the best cut-off value was 44.2 g/L. Its sensitivity to predict the degree of disability in patients with multiple sclerosis was 85.2%, while its specificity was 51.1%. The AUC of the total number of lesions was 0.665 (P < 0.05) and the best cut-off value was 5.5. Its sensitivity to predict the degree of disability in patients with multiple sclerosis was 70.4%, while its specificity was 64.4%. The AUC of the combined ALB, total number of lesions, and drug use was 0.795 (P < 0.05), sensitivity was 77.8, and specificity was 73.3%. The optimal diagnostic cut-off value of the regression equation for the EDSS score of patients with multiple sclerosis was 0.420.

Conclusion: Serum ALB, total number of lesions, and drug use in patients with multiple sclerosis were independent factors influencing the degree of disability. These findings provide clinical evidence for the prognostic evaluation and early intervention of patients with multiple sclerosis.