bluuebunny/crossref_metadata_2025 huggingface dataset:
Effect of Postoperative High-Concentration Oxygen on Recovery After Thyroid Surgery: A Prospective, Open, Randomized, Controlled Study
Authors: Zhou Qian , Cai Ming , Gou Juxiang , Ning Ning
Published: July 2021

Objective

To investigate the effectiveness of high-concentration oxygen on the improvement of throat symptoms and voice changes after thyroid surgery and its protection of the parathyroid function.

Methods

A total of 600 patients undergoing thyroid surgery who met the inclusion criteria were randomly divided into the experimental group (n = 300) and the control group (n = 300) by using a random number generator. The patients in the experimental group underwent high-oxygen treatment [FiO280 (8 L/min)] for 6 continuous hours after returning to the ward after surgery. The patients in the control group underwent low-oxygen treatment [FiO230 (2 L/min)] for 6 continuous hours after returning to the ward after surgery.

Results

The postoperative incision pain score of patients in the experimental group was significantly better than that in the control group at 6 h (1.07 ± 0.80 VS 1.23 ± 0.95, P=0.031) and 12 h (1.08 ± 0.64 VS 1.20 ± 0.73, P=0.041). The postoperative throat pain score of the patients in the experimental group was significantly better than that of the control group at 6 h (1.40 ± 0.85 VS 1.59 ± 0.97, P=0.011) and 12 h (1.40 ± 0.85 VS 1.59 ± 0.97, P=0.019). The PONV score of the patients in the experimental group was significantly better than that of the control group at 12 h (0.09 ± 0.19 VS 0.14 ± 0.37, P=0.024). The Voice Handicap Index score of the patients in the experimental group was significantly better than that of the control group at 24 h (2.89 ± 5.92 VS 4.10 ± 6.31, P=0.017), 36 h (2.46 ± 5.06 VS 3.43 ± 5.97, P=0.035), and 48 h (2.46 ± 5.06 VS 3.43 ± 5.97, P=0.032).

Conclusion

High-concentration oxygen can alleviate PONV and pain after thyroid surgery, with less severe voice changes potentially. However, its effects on swallowing function, and parathyroid function need to be further verified.

Clinical Trial Registration Number

ChiCTR-IOR-17012765 (China Clinical Trial Registry clinical trial registration center [http://www.chictr.org.cn/index.aspx)
Association of Soy and Exclusive Breastfeeding With Central Precocious Puberty: A Case-Control Study
Authors: Felício João Soares , de Alcântara Angélica Leite , Janaú Luísa Corrêa , de Moraes Lorena Vilhena , de Oliveira Maria Clara Neres Iunes , de Lemos Manuela Nascimento , de Souza Neto Norberto Jorge Kzan , Neto João Felício Abrahão , da Silva Wanderson Maia , de Souza Ícaro José Araújo , Said Nivin Mazen , de Lemos Gabriela Nascimento , Vieira Giovana Miranda , Khayat André Salim , Santos Ândrea Kely Campos Ribeiro dos , de Queiroz Natércia Neves Marques , de Sousa Ana Carolina Contente Braga , Santos Márcia Costa dos , de Melo Franciane Trindade Cunha , Piani Pedro Paulo Freire , Felício Karem Miléo
Published: July 2021

Introduction

While soy is suggested as a possible risk factor, exclusive breastfeeding (EBF) has a likely protective effect in precocious puberty. Our aim was to evaluate the association between both of these variables with central precocious puberty (CPP)

Methods

We performed a retrospective, case-control study. A total of 161 girls were divided into two groups: 84 patients diagnosed with CPP composed the case group and 77 patients without the diagnosis of CPP (had gone through normal onset of puberty) were the control group.

Results

Our control group had a higher presence of EBF >6 months, which was an important protective factor for CPP (OR: 0.5; IC 95%: 0.3–0.9, p = 0.05) and also correlated negatively with the presence of it (r = −0.2; p < 0.05). Oppositely, the use of soy was significantly higher in the CPP group, (OR: 3.8; IC 95%: 1.5–6, p < 0.05) and positively correlating (r = 0.2; p < 0.01) with the presence of CPP. Duration of soy intake (years) correlated with bone age (r = 0.415; p < 0.05). A logistic regression was performed to evaluate the effects of EBF duration and soy on CPP. The model was significant (x² (2) = 20,715, p = <0.001) and explained 12.2% (Nagelkerke R2) of the variance, correctly classifying 62.5% of cases. EBF was associated with a reduction of likelihood of having CPP [OR = 0,187 (CI = 0.055–0,635); Wald = 7,222, p = 0.007], while soy intake increased the risk [OR = 3.505 (CI) = 1,688–7,279, Wald = 11,319, p = 0.001].

Conclusion

Our data found the use of soy was associated with CPP. Additionally, EBF was pointed as a protective factor. However, future prospective studies are needed to clarify this issue.
Precious Data from Tiny Samples: Revealing the Correlation Between Energy Content and the Chemical Oxygen Demand of Municipal Wastewater by Micro-Bomb Combustion Calorimetry
Authors: Korth Benjamin , Heber Claudia , Normant-Saremba Monika , Maskow Thomas , Harnisch Falk
Published: July 2021

Wastewater treatment plants (WWTP) are aimed to be transformed from sinks into sources of energy and material. For fostering corresponding engineering efforts and economic assessments, comprehensive knowledge of the energy content of wastewater is required. We show in this proof-of-concept study that these data can be gathered by combining micro-bomb combustion calorimetry with freeze-drying. Thereby, the methodology for measuring the combustion enthalpy (ΔcH) of wastewater is significantly improved by decreasing the time demand for the drying process as only tiny amounts of samples are required. Here, the effluent of the primary clarifier of a wastewater treatment plant treating low-strength municipal wastewater was sampled on a weekly basis for 1 year, yielding 53 composite samples that were analyzed for ΔcH and standard wastewater parameters. A robust correlation between the chemical oxygen demand (COD) and ΔcH of −14.9 ± 3.5 kJ gCOD−1 (r = 0.51) was determined, verifying previous results obtained with more laborious and time-demanding methodologies. The global chemical energy potential of the sampled WWTP is presumably higher as the first treatment steps and losses during sample preparation reduced the amount of energy-rich compounds. A stronger correlation was observed between ΔcH and the biochemical oxygen demand (BOD5, r = 0.64), suggesting its usage for predicting the potential of wastewater as feedstock for biotechnological applications. This demonstrates that micro-bomb combustion calorimetry can be applied for deriving precious information on the energy content of wastewater from simple COD measurements.
Out of Africa: A New Afrotheria Lineage Rises From Extinct South American Mammals
Authors: Avilla Leonardo S. , Mothé Dimila
Published: July 2021

The South American native ungulates (SANUs) are usually overlooked in Eutherian phylogenetic studies. In the rare studies where they were included, the diversity of SANUs was underrated, keeping their evolutionary history poorly known. Some authors recognized the SANUs as a monophyletic lineage and formally named it Meridiungulata. Here, we recognized and defined a new supraordinal lineage of Eutheria, the Sudamericungulata, after performing morphological phylogenetic analyses including all lineages of SANUs and Eutheria. The SANUs resulted as non-monophyletic; thus, Meridiungulata is not a natural group; Litopterna and “Didolodontidae” are Panameriungulata and closer to Laurasiatheria than to other “Meridiungulata” (Astrapotheria, Notoungulata, Pyrotheria, and Xenungulata). The other “Meridiungulata” is grouped in the Sudamericungulata, as a new monophyletic lineage of Afrotheria Paenungulata, and shared a common ancestor with Hyracoidea. The divergence between the African and South American lineages is estimated to Early Paleocene, and their interrelationships support the Atlantogea biogeographic model. Shortly afterward, the Sudamericungulata explosively diversified in its four lineages. Confronting the Sudamericungulata evolutionary patterns and the Cenozoic natural events (such as tectonics and climatic and environmental changes, among others) helps to unveil a new chapter in the evolution of Gondwanan Eutheria, as well as the natural history of South America during the Cenozoic.
Identification and Validation of a Four-Long Non-coding RNA Signature Associated With Immune Infiltration and Prognosis in Colon Cancer
Authors: Wang Yanbo , Liu Jing , Ren Fenghai , Chu Yanjie , Cui Binbin
Published: July 2021

The emerging evidence has demonstrated the critical roles of long non-coding RNAs (lncRNAs) as regulators in the tumor immune microenvironment (TIME). However, the tumor immune infiltration-associated lncRNAs and their clinical significance in colon cancer have not yet been thoroughly investigated. This study performed an integrative analysis of lncRNA expression profiles and immune cell infiltration profiles and identified 258 immune infiltration-associated lncRNAs. Of them, four lncRNAs (AC008494.3, LINC00926, AC022034.1, and SNHG26) were significantly and independently associated with the patient’s overall survival. Finally, we developed a tumor immune infiltration-associated lncRNA signature (TIILncSig) comprising of these four lncRNAs, which can divide colon cancer patients of The Cancer Genome Atlas (TCGA) into high-risk and low-risk groups with a significantly different outcome [Hazard ratio (HR) = 2.718, 95% CI = 1.955–3.779,p< 0.001]. Prognostic performance of the TIILncSig was further validated in another independent colon cancer cohort (HR = 1.832, 95% CI = 1.045–3.21,p= 0.034). Results of multivariate Cox regression and stratification analysis demonstrated that the TIILncSig is an independent predictive factor from other clinical features (HR = 2.687, 95% CI = 1.912–3.776,p< 0.001 for TCGA cohort and HR = 1.837, 95% CI = 1.047–3.223,p= 0.034 for GSE17538 cohort). Literature analysis provided experimental evidence supporting roles of the TIILncSig in cancer carcinogenesis and progression and immune regulation. Summary, our study will help to understand the mechanisms of lncRNAs in immune regulation in the tumor microenvironment and provide novel biomarkers or targets for prognosis prediction and therapy decision-making for patients with colon cancer.
Identification and Validation of Immune-Related LncRNA Prognostic Signature for Lung Adenocarcinoma
Authors: Wu Guomin , Wang Qihao , Zhu Ting , Fu Linhai , Li Zhupeng , Wu Yuanlin , Zhang Chu
Published: July 2021

This study aimed to establish a prognostic risk model for lung adenocarcinoma (LUAD). We firstly divided 535 LUAD samples in TCGA-LUAD into high-, medium-, and low-immune infiltration groups by consensus clustering analysis according to immunological competence assessment by single-sample gene set enrichment analysis (ssGSEA). Profile of long non-coding RNAs (lncRNAs) in normal samples and LUAD samples in TCGA was used for a differential expression analysis in the high- and low-immune infiltration groups. A total of 1,570 immune-related differential lncRNAs in LUAD were obtained by intersecting the above results. Afterward, univariate COX regression analysis and multivariate stepwise COX regression analysis were conducted to screen prognosis-related lncRNAs, and an eight-immune-related-lncRNA prognostic signature was finally acquired (AL365181.2, AC012213.4, DRAIC, MRGPRG-AS1, AP002478.1, AC092168.2, FAM30A, and LINC02412). Kaplan–Meier analysis and ROC analysis indicated that the eight-lncRNA-based model was accurate to predict the prognosis of LUAD patients. Simultaneously, univariate COX regression analysis and multivariate COX regression analysis were undertaken on clinical features and risk scores. It was illustrated that the risk score was a prognostic factor independent from clinical features. Moreover, immune data of LUAD in the TIMER database were analyzed. The eight-immune-related-lncRNA prognostic signature was related to the infiltration of B cells, CD4+ T cells, and dendritic cells. GSEA enrichment analysis revealed significant differences in high- and low-risk groups in pathways like pentose phosphate pathway, ubiquitin mediated proteolysis, and P53 signaling pathway. This study helps to treat LUAD patients and explore molecules related to LUAD immune infiltration to deeply understand the specific mechanism.
Identification of Causal Genes of COVID-19 Using the SMR Method
Authors: Zong Yan , Li Xiaofei
Published: July 2021

Since the first report of COVID-19 in December 2019, more than 100 million people have been infected with SARS-CoV-2. Despite ongoing research, there is still limited knowledge about the genetic causes of COVID-19. To resolve this problem, we applied the SMR method to analyze the genes involved in COVID-19 pathogenesis by the integration of multiple omics data. Here, we assessed the SNPs associated with COVID-19 risk from the GWAS data of Spanish and Italian patients and lung eQTL data from the GTEx project. Then, GWAS and eQTL data were integrated by summary-data-based (SMR) methods using SNPs as instrumental variables (IVs). As a result, six protein-coding and five non-protein-coding genes regulated by nine SNPs were identified as significant risk factors for COVID-19. Functional analysis of these genes showed that UQCRH participates in cardiac muscle contraction, PPA2 is closely related to sudden cardiac failure (SCD), and OGT, as the interacting gene partner of PANO1, is associated with neurological disease. Observational studies show that myocardial damage, SCD, and neurological disease often occur in COVID-19 patients. Thus, our findings provide a potential molecular mechanism for understanding the complications of COVID-19.
Single-Cell Transcriptome Analysis in Melanoma Using Network Embedding
Authors: Wang Liming , Liu Fangfang , Du Longting , Qin Guimin
Published: July 2021

Single-cell sequencing technology provides insights into the pathology of complex diseases like cancer. Here, we proposed a novel computational framework to explore the molecular mechanisms of cancer called melanoma. We first constructed a disease-specific cell–cell interaction network after data preprocessing and dimensionality reduction. Second, the features of cells in the cell–cell interaction network were learned by node2vec which is a graph embedding technology proposed previously. Then, consensus clusters were identified by considering different clustering algorithms. Finally, cell markers and cancer-related genes were further analyzed by integrating gene regulation pairs. We exploited our model on two independent datasets, which showed interesting results that the differences between clusters obtained by consensus clustering based on network embedding (CCNE) were observed obviously through visualization. For the KEGG pathway analysis of clusters, we found that all clusters are extremely related to MicroRNAs in cancer and HTLV-I infection, and the hub genes in cluster specific regulatory networks, i.e.,ETS1,TP53,E2F1, andGATA3are highly associated with melanoma. Furthermore, our method can also be extended to other scRNA-seq data.
A Comprehensive Pan-Cancer Analysis of 33 Human Cancers Reveals the Immunotherapeutic Value of Aryl Hydrocarbon Receptor
Authors: Mo Zhuomao , Li Pan , Cao Zhirui , Zhang Shijun
Published: July 2021

Background

Previous studies have reported the potential of aryl hydrocarbon receptor (AhR) in cancer immunotherapy. However, the mechanisms underpinning its therapeutic value have yet to be comprehensively investigated. Thus, this research aimed to explore the underlying association between AhR and cancer immunotherapy in 33 human cancers.

Methods

The gene expression data and clinical characteristics of 33 cancers were retrieved from The Cancer Genome Atlas database. The immunotherapeutic cohorts included GSE67501 and GSE78220 as well as IMvigor210, which were obtained from the Gene Expression Omnibus database and included in a previously published study respectively. Clinical parameters, including patient age, gender, survival, and tumor stage were analyzed to assess the prognostic value of AhR. The activity of AhR was generated by single sample gene set enrichment analysis and used to evaluate the difference between the AhR transcriptome and protein expression level. To better understand the role of AhR in cancer immunotherapy, the correlation between AhR and tumor microenvironment, as well as its relation to immune processes/elements, such as immune cell infiltration, immune inhibitors and stimulators, and the major histocompatibility complex were analyzed. The relevant underlying pathways associated with AhR signaling in cancer were also explored. Furthermore, the correlation between AhR and two immunotherapeutic biomarkers (tumor mutational burden and microsatellite instability) was investigated. Finally, the relationship between AhR and immunotherapeutic response was explored using three independent immunotherapeutic cohorts.

Results

Although AhR was not closely associated with age (5/33), gender (3/33), or tumor stage (3/21) in any of the studied human cancers, it exhibited potential prognostic value for predicting patient survival. Consistency has been observed between AhR activity and expression in some cancers (7/33). Generally, AhR presented a robust correlation with immune cell infiltration, immune modulators, and immunotherapeutic markers. Moreover, high AhR expression was significantly related to immune-relevant pathways. However, no significant correlation was observed between AhR and the immunotherapeutic response.

Conclusions

This research investigated the immunotherapeutic value of AhR in 33 human cancers, providing evidence regarding the function of AhR and its role in clinical treatment. However, considering that a bioinformatics approach was adopted, the current results are preliminary and require further validation.
CCR2 Deficiency Impairs Ly6Clo and Ly6Chi Monocyte Responses in Orientia tsutsugamushi Infection
Authors: Petermann Michael , Orfanos Zacharias , Sellau Julie , Gharaibeh Mohammad , Lotter Hannelore , Fleischer Bernhard , Keller Christian
Published: July 2021

Orientia (O.) tsutsugamushi, the causative agent of scrub typhus, is a neglected, obligate intracellular bacterium that has a prominent tropism for monocytes and macrophages. Complications often involve the lung, where interstitial pneumonia is a typical finding. The severity of scrub typhus in humans has been linked to altered plasma concentrations of chemokines which are known to act as chemoattractants for myeloid cells. The trafficking and function of monocyte responses is critically regulated by interaction of the CC chemokine ligand 2 (CCL2) and its CC chemokine receptor CCR2. In a self-healing mouse model of intradermal infection with the human-pathogenic Karp strain of O. tsutsugamushi, we investigated the role of CCR2 on bacterial dissemination, development of symptoms, lung histology and monocyte subsets in blood and lungs. CCR2-deficient mice showed a delayed onset of disease and resolution of symptoms, higher concentrations and impaired clearance of bacteria in the lung and the liver, accompanied by a slow infiltration of interstitial macrophages into the lungs. In the blood, we found an induction of circulating monocytes that depended on CCR2, while only a small increase in Ly6Chi monocytes was observed in CCR2-/- mice. In the lung, significantly higher numbers of Ly6Chi and Ly6Clo monocytes were found in the C57BL/6 mice compared to CCR2-/- mice. Both wildtype and CCR2-deficient mice developed an inflammatory milieu as shown by cytokine and inos/arg1 mRNA induction in the lung, but with delayed kinetics in CCR2-deficient mice. Histopathology revealed that infiltration of macrophages to the parenchyma, but not into the peribronchial tissue, depended on CCR2. In sum, our data suggest that in Orientia infection, CCR2 drives blood monocytosis and the influx and activation of Ly6Chi and Ly6Clo monocytes into the lung, thereby accelerating bacterial replication and development of interstitial pulmonary inflammation.
A Biological Circuit Involving Mef2c, Mef2d, and Hdac9 Controls the Immunosuppressive Functions of CD4+Foxp3+ T-Regulatory Cells
Authors: Di Giorgio Eros , Wang Liqing , Xiong Yan , Christensen Lanette M. , Akimova Tatiana , Han Rongxiang , Samanta Arabinda , Trevisanut Matteo , Brancolini Claudio , Beier Ulf H. , Hancock Wayne W.
Published: July 2021

The Mads/Mef2 (Mef2a/b/c/d) family of transcription factors (TFs) regulates differentiation of muscle cells, neurons and hematopoietic cells. By functioning in physiological feedback loops, Mef2 TFs promote the transcription of their repressor, Hdac9, thereby providing temporal control of Mef2-driven differentiation. Disruption of this feedback is associated with the development of various pathologic states, including cancer. Beside their direct involvement in oncogenesis, Mef2 TFs indirectly control tumor progression by regulating antitumor immunity. We recently reported that in CD4+CD25+Foxp3+ T-regulatory (Treg) cells, Mef2d is required for the acquisition of an effector Treg (eTreg) phenotype and for the activation of an epigenetic program that suppresses the anti-tumor immune responses of conventional T and B cells. We now report that as with Mef2d, the deletion of Mef2c in Tregs switches off the expression of Il10 and Icos and leads to enhanced antitumor immunity in syngeneic models of lung cancer. Mechanistically, Mef2c does not directly bind the regulatory elements of Icos and Il10, but its loss-of-function in Tregs induces the expression of the transcriptional repressor, Hdac9. As a consequence, Mef2d, the more abundant member of the Mef2 family, is converted by Hdac9 into a transcriptional repressor on these loci. This leads to the impairment of Treg suppressive properties in vivo and to enhanced anti-cancer immunity. These data further highlight the central role played by the Mef2/Hdac9 axis in the regulation of CD4+Foxp3+ Treg function and adds a new level of complexity to the analysis and study of Treg biology.
Do Vaccines Need a Gender Perspective? Influenza Says Yes!
Authors: Sánchez-de Prada Laura , Ortiz de Lejarazu-Leonardo Raúl , Castrodeza-Sanz Javier , Tamayo-Gómez Eduardo , Eiros-Bouza José María , Sanz-Muñoz Iván
Published: July 2021

Background

Sex differences in immune responses are well known. However, the humoral response in males and females in the case of influenza vaccination is yet to be characterized since studies have shown uneven results.

Methods

A retrospective study was conducted in 2,243 individuals (46.9% males) divided by age (15–64 and ≥65 years old). A serological analysis was performed by hemagglutination inhibition assay (HI) just before and 28 days after annual vaccination against seasonal influenza viruses in people vaccinated during the 2006–2018 seasons. A comparison of the humoral responses against influenza A and B viruses contained in the vaccine, between male and female individuals in young adults and elderly was conducted.

Results

Significative higher humoral response against classical influenza A (H1N1), A(H1N1)pdm09 subtype and B/Victoria lineage in terms of seroconversion rate were found in elderly women. No significant differences were found in the case of A(H3N2) subtype.

Conclusions

Elderly women seem to display a greater humoral response against classical A(H1N1), pandemic A(H1N1)pmd09 and B/Victoria lineage than elderly men. Sex dimorphism does not affect young adults.
Phytoplankton Photophysiology Utilities: A Python Toolbox for the Standardization of Processing Active Chlorophyll-a Fluorescence Data
Authors: Ryan-Keogh Thomas J. , Robinson Charlotte M.
Published: July 2021

The uptake and application of single turnover chlorophyll fluorometers to the study of phytoplankton ecosystem status and microbial functions has grown considerably in the last two decades. However, standardization of measurement protocols, processing of fluorescence transients and quality control of derived photosynthetic parameters is still lacking and makes community goals of large global databases of high-quality data unrealistic. We introduce the Python package Phytoplankton Photophysiology Utilities (PPU), an adaptable and open-source interface between Fast Repetition Rate and Fluorescence Induction and Relaxation instruments and python. The PPU package includes a variety of functions for the loading, processing and quality control of single turnover fluorescence transients from many commercially available instruments. PPU provides the user with greater flexibility in the application of the Kolber-Prasil-Falkowski model; tools for plotting, quality control, correcting instrument biases and high-throughput processing with ease; and a greater appreciation for the uncertainties in derived photosynthetic parameters. Using data from three research cruises across different biogeochemical regimes, we provide example applications of PPU to fit raw active chlorophyll-a fluorescence data from three commercial instruments and demonstrate tools which help to reduce uncertainties in the final fitted parameters.
Contrasting Phylogeographic Patterns Among Northern and Southern Hemisphere Fin Whale Populations With New Data From the Southern Pacific
Authors: Pérez-Alvarez MJosé , Kraft Sebastián , Segovia Nicolás I. , Olavarría Carlos , Nigenda-Morales Sergio , Urbán R. Jorge , Viloria-Gómora Lorena , Archer Frederick , Moraga Rodrigo , Sepúlveda Maritza , Santos-Carvallo Macarena , Pavez Guido , Poulin Elie
Published: July 2021

Four fin whale sub-species are currently considered valid:Balaenoptera physalus physalusin the North Atlantic,B. p. veliferain the North Pacific,B. p. quoyiandB. p. patachonicain the Southern Hemisphere. The last, not genetically validated, was described as a pygmy-type sub-species, found in low to mid latitudes of the Southern Hemisphere. Genetic analyses across hemispheres show strong phylogeographic structure, yet low geographic coverage in middle latitudes of the Southern Hemisphere impeded an assessment within the area, as well as evaluating the validity ofB. p. patachonica. New mtDNA sequences from the Southeastern Pacific allowed an improved coverage of the species’ distribution. Our phylogenetic analyses showed three main lineages and contrasting phylogeographic patterns between Northern and Southern Hemispheres. Absence of recurrent female mediated gene flow between hemispheres was found; however, rare dispersal events revealing old migrations were noted. The absence of genetic structure suggests the existence of one single taxa within the Southern Hemisphere. Thus, until further evidence supporting this subspecies can be produced, such as genetic, ecological, behavioral, or morphological data, we propose that all fin whales from the Southern Hemisphere, including those from middle latitudes of the Southeastern Pacific belong toB. p. quoyisubspecies. This information is important for the current assessment of fin whales, contributing to the evaluation of the taxonomic classification and the conservation of the species.
Cyclic di-GMP Is Integrated Into a Hierarchal Quorum Sensing Network Regulating Antimicrobial Production and Biofilm Formation in Roseobacter Clade Member Rhodobacterales Strain Y4I
Authors: Armes April C. , Buchan Alison
Published: July 2021

Microbial biofilms associated with marine particulate organic matter carry out transformations that influence local and regional biogeochemical cycles. Early microbial colonizers are often hypothesized to “set the stage” for biofilm structure, dynamics, and function via N-acyl homoserine lactone (AHL)-mediated quorum sensing (QS). Production of AHLs, as well as antimicrobials, contributes to the colonization success of members of the Roseobacter clade. One member of this group of abundant marine bacteria, Rhodobacterales sp. Y4I, possesses two QS systems, phaRI (QS1) and pgaRI (QS2). Here, we characterize mutants in both QS systems to provide genetic evidence that the two systems work in hierarchical fashion to coordinate production of the antimicrobial indigoidine as well as biofilm formation. A mutation in pgaR (QS2) results in decreased expression of genes encoding both QS systems as well as those governing the biosynthesis of indigoidine. In contrast, mutations in QS1 did not significantly influence gene expression of QS2. Addition of exogenous AHLs to QS1 and QS2 mutants led to partial restoration of indigoidine production (45–60% of WT) for QS1 but not QS2. Mutational disruptions of QS1 had a more pronounced effect on biofilm development than those in QS2. Finally, we demonstrate that c-di-GMP levels are altered in QS and indigoidine biosynthesis Y4I mutants. Together, these results indicate that pgaRI (QS2) is at the top of a regulatory hierarchy governing indigoidine biosynthesis and that the global regulatory metabolite, c-di-GMP, is likely integrated into the QS circuitry of this strain. These findings provide mechanistic understanding of physiological processes that are important in elucidating factors driving competitiveness of Roseobacters in nature.
Indigenous Traditional Ecological Knowledge and Ocean Observing: A Review of Successful Partnerships
Authors: Proulx MaryJane , Ross Lydia , Macdonald Christina , Fitzsimmons Shayla , Smit Michael
Published: July 2021

Understanding and management of the marine environment requires respect for, and inclusion of, Indigenous knowledge, cultures, and traditional practices. The Aha Honua, an ocean observing declaration from Coastal Indigenous Peoples, calls on the ocean observing community to “formally recognize the traditional knowledge of Indigenous peoples,” and “to learn and respect each other’s ways of knowing.” Ocean observing systems typically adopt open data sharing as a core principle, often requiring that data be Findable, Accessible, Interoperable, and Reusable (FAIR). Without modification, this approach to Traditional Ecological Knowledge (TEK) would mean disregarding historical and ongoing injustices and imbalances in power, and information management principles designed to address these wrongs. Excluding TEK from global ocean observing is not equitable or desirable. Ocean observing systems tend to align with settler geography, but their chosen regions often include Indigenous coastal-dwelling communities that have acted as caretakers and stewards of the land and ocean for thousands of years. Achieving the call of Aha Honua will require building relationships that recognize Indigenous peoples play a special role in the area of ocean stewardship, care, and understanding. This review examines the current understanding of how Indigenous TEK can be successfully coordinated or utilized alongside western scientific systems, specifically the potential coordination of TEK with ocean observing systems. We identify relevant methods and collaborative projects, including cases where TEK has been collected, digitized and the meta(data) has been made open under some or all the FAIR principles. This review also highlights enabling factors that notably contribute to successful outcomes in digitization, and mitigation measures to avoid the decontextualization of TEK. Recommendations are primarily value- and process-based, rather than action-based, and acknowledge the key limitation that this review is based on extant written knowledge. In cases where examples are provided, or local context is necessary to be concrete, we refer to a motivating example of the nascent Atlantic Regional Association of the Canadian Integrated Ocean Observing System and their desire to build relationships with Indigenous communities.
Herpesviruses Serology Distinguishes Different Subgroups of Patients From the United Kingdom Myalgic Encephalomyelitis/Chronic Fatigue Syndrome Biobank
Authors: Domingues Tiago Dias , Grabowska Anna D. , Lee Ji-Sook , Ameijeiras-Alonso Jose , Westermeier Francisco , Scheibenbogen Carmen , Cliff Jacqueline M. , Nacul Luis , Lacerda Eliana M. , Mouriño Helena , Sepúlveda Nuno
Published: July 2021

The evidence of an association between Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) and chronic herpesviruses infections remains inconclusive. Two reasons for the lack of consistent evidence are the large heterogeneity of the patients' population with different disease triggers and the use of arbitrary cutoffs for defining seropositivity. In this work we re-analyzed previously published serological data related to 7 herpesvirus antigens. Patients with ME/CFS were subdivided into four subgroups related to the disease triggers: S0-42 patients who did not know their disease trigger; S1-43 patients who reported a non-infection trigger; S2-93 patients who reported an infection trigger, but that infection was not confirmed by a lab test; and S3-48 patients who reported an infection trigger and that infection was confirmed by a lab test. In accordance with a sensitivity analysis, the data were compared to those from 99 healthy controls allowing the seropositivity cutoffs to vary within a wide range of possible values. We found a negative association between S1 and seropositivity to Epstein-Barr virus (VCA and EBNA1 antigens) and Varicella-Zoster virus using specific seropositivity cutoff. However, this association was not significant when controlling for multiple testing. We also found that S3 had a lower seroprevalence to the human cytomegalovirus when compared to healthy controls for all cutoffs used for seropositivity and after adjusting for multiple testing using the Benjamini-Hochberg procedure. However, this association did not reach statistical significance when using Benjamini-Yekutieli procedure. In summary, herpesviruses serology could distinguish subgroups of ME/CFS patients according to their disease trigger, but this finding could be eventually affected by the problem of multiple testing.
Videofluoroscopic Swallowing Study Findings Associated With Subsequent Pneumonia in Patients With Dysphagia Due to Frailty
Authors: Chang Min Cheol , Kwak Soyoung
Published: July 2021

Dysphagia in frailty or deconditioning without specific diagnosis that may cause dysphagia such as stroke, traumatic brain injury, or laryngeal pathology, has been reported in previous studies; however, little is known about which findings of the videofluoroscopic swallowing study (VFSS) are associated with subsequent pneumonia and how many patients actually develop subsequent pneumonia in this population. In this study, we followed 190 patients with dysphagia due to frailty or deconditioning without specific diagnosis that may cause dysphagia for 3 months after VFSS and analyzed VFSS findings for the risk of developing pneumonia. During the study period, the incidence of subsequent pneumonia was 24.74%; regarding the VFSS findings, (1) airway penetration (PAS 3) and aspiration (PAS 7 and 8) were associated with increased risk of developing pneumonia, and (2) the functional dysphagia scale (FDS) scores of the patients who developed subsequent pneumonia were higher than those of the patients who did not develop subsequent pneumonia. Our study findings might assist clinicians in making clinical decisions based on the VFSS findings in this population.
Comparative Whole Genome Sequence Analysis and Biological Features of Clostridioides difficile Sequence Type 2‡
Authors: Xu Xingxing , Bian Qiao , Luo Yun , Song Xiaojun , Lin Shan , Chen Huan , Liang Qian , Wang Meixia , Ye Guangyong , Zhu Bo , Chen Liang , Tang Yi-Wei , Wang Xianjun , Jin Dazhi
Published: July 2021

Clostridioides difficile sequence type 2 (ST2) has been increasingly recognized as one of the major genotypes in China, while the genomic characteristics and biological phenotypes of Chinese ST2 strains remain to be determined. We used whole-genome sequencing and phylogenetic analysis to investigate the genomic features of 182 ST2 strains, isolated between 2011 and 2017. PCR ribotyping (RT) was performed, and antibiotic resistance, toxin concentration, and sporulation capacity were measured. The core genome Maximum-likelihood phylogenetic analysis showed that ST2 strains were distinctly segregated into two genetically diverse lineages [L1 (67.0% from Northern America) and L2], while L2 further divided into two sub-lineages, SL2a and SL2b (73.5% from China). The 36 virulence-related genes were widely distributed in ST2 genomes, but in which only 11 antibiotic resistance-associated genes were dispersedly found. Among the 25 SL2b sequenced isolates, RT014 (40.0%, n = 10) and RT020 (28.0%, n = 7) were two main genotypes with no significant difference on antibiotic resistance (χ2 = 0.024–2.667, P > 0.05). A non-synonymous amino acid substitution was found in tcdB (Y1975D) which was specific to SL2b. Although there was no significant difference in sporulation capacity between the two lineages, the average toxin B concentration (5.11 ± 3.20 ng/μL) in SL2b was significantly lower in comparison to those in L1 (10.49 ± 15.82 ng/μL) and SL2a (13.92 ± 2.39 ng/μL) (χ2 = 12.30, P < 0.05). This study described the genomic characteristics of C. difficile ST2, with many virulence loci and few antibiotic resistance elements. The Chinese ST2 strains with the mutation in codon 1975 of the tcdB gene clustering in SL2b circulating in China express low toxin B, which may be associated with mild or moderate C. difficile infection.
Whole Resistome Analysis in Campylobacter jejuni and C. coli Genomes Available in Public Repositories
Authors: Cobo-Díaz José F. , González del Río Paloma , Álvarez-Ordóñez Avelino
Published: July 2021

Campylobacter spp. are the most frequent agent of human gastroenteritis worldwide, and the spread of multidrug-resistant strains makes the clinical treatment difficult. The current study presents the resistome analysis of 39,798 Campylobacter jejuni and 11,920 Campylobacter coli genomes available in public repositories. Determinants of resistance to β-lactams (Be) and tetracyclines (Te) were the most frequent for both species, with resistance to quinolones (Qu) as the third most important on C. jejuni and to aminoglycosides (Am) on C. coli. Moreover, resistance to Te, Qu, and Am was frequently found in co-occurrence with resistance to other antibiotic families. Geographical differences on clonal complexes distribution were found for C. jejuni and on resistome genotypes for both C. jejuni and C. coli species. Attending to the resistome patterns by isolation source, three main clusters of genomes were found on C. jejuni genomes at antimicrobial resistance gene level. The first cluster was formed by genomes from human, food production animals (e.g., sheep, cow, and chicken), and food (e.g., dairy products) isolates. The higher incidence of tet(O), associated with tetracycline resistance, and the gyrA (T86I) single-nucleotide polymorphism (SNP), associated with quinolone resistance, among genomes from this cluster could be due to the intense use of these antibiotics in veterinary and human clinical settings. Similarly, a high incidence of tet(O) genes of C. coli genomes from pig, cow, and turkey was found. Moreover, the cluster based on resistome patterns formed by C. jejuni and C. coli genomes of human, turkey, and chicken origin is in agreement with previous observations reporting chicken or poultry-related environments as the main source of human campylobacteriosis infections. Most clonal complexes (CCs) associated with chicken host specialization (e.g., ST-354, ST-573, ST-464, and ST-446) were the CCs with the highest prevalence of determinants of resistance to Be, Qu, and Te. Finally, a clear trend toward an increase in the occurrence of Te and Qu resistance determinants on C. jejuni, linked to the spread of the co-occurrence of the blaOXA–61 and tet(O)-tet(O/W/O) genes and the gyrA (T86I) SNP, was found from 2001 to date in Europe.
Co-harboring of Novel blaKPC–2 Plasmid and Integrative and Conjugative Element Carrying Tn6203 in Multidrug-Resistant Pseudomonas aeruginosa
Authors: Cai Heng , Zhu Yiwei , Hu Dandan , Li Yue , Leptihn Sebastian , Loh Belinda , Hua Xiaoting , Yu Yunsong
Published: July 2021

Many strains of the opportunistic pathogen Pseudomonas aeruginosa have acquired resistance to multiple antibiotics. Carbapenem-resistant P. aeruginosa poses a global healthcare problem due to limited therapeutic options for the treatment of infections. Plasmids and integrative and conjugative elements (ICEs) are the major vectors of antibiotic-resistance gene transfer. In our study, four carbapenem-resistant strains of P. aeruginosa were isolated from the same patient in a tertiary referral hospital in China, one of these was resistant to gentamicin and tobramycin. In this strain P33, we observed a non-transferable plasmid, pP33-2, carrying a novel blaKPC−2 gene segment (ISKpn27-blaKPC−2-ISKpn6-korC-ORF-klcA-IS26), which we concluded to have been formed by IS26-mediated gene cluster translocation. In addition, by comparing the chromosomes of the P. aeruginosa strains that belong to the same sequence type, we identified an ICE, ICEP33, adjacent to a prophage. The attL site of ICEP33 is identical to the terminal part of the attR site of the prophage. The ICEP33 element contains the transposon Tn6203, which encodes antibiotic and metal resistance genes. The insertion of ICEP33 in the chromosome mediates resistance to multiple antibiotics. Our study contributes to the understanding of the acquisition of antibiotic resistance in P. aeruginosa facilitated by mobile genetic elements.
Geographical and Seasonal Thermal Sensitivity of Grazing Pressure by Microzooplankton in Contrasting Marine Ecosystems
Authors: Cabrerizo Marco J. , Marañón Emilio
Published: July 2021

Grazing pressure, estimated as the ratio between microzooplankton grazing and phytoplankton growth rates (g:μ), is a strong determinant of microbial food-web structure and element cycling in the upper ocean. It is generally accepted that g is more sensitive to temperature than μ, but it remains unknown how the thermal dependence (activation energy, Ea) of g:μ varies over spatial and temporal scales. To tackle this uncertainty, we used an extensive literature analysis obtaining 751 paired rate estimates of μ and g from dilution experiments performed throughout the world’s marine environments. On a geographical scale, we found a stimulatory effect of temperature in polar open-ocean (∼0.5 eV) and tropical coastal (∼0.2 eV) regions, and an inhibitory one in the remaining biomes (values between −0.1 and −0.4 eV). On a seasonal scale, the temperature effect on g:μ ratios was stimulatory, particularly in polar environments; however, the large variability existing between estimates resulted in non-significant differences among biomes. We observed that increases in nitrate availability stimulated the temperature dependence of grazing pressure (i.e., led to more positive Ea of g:μ) in open-ocean ecosystems and inhibited it in coastal ones, particularly in polar environments. The percentage of primary production grazed by microzooplankton (∼56%) was similar in all regions. Our results suggest that warming of surface ocean waters could exert a highly variable impact, in terms of both magnitude and direction (stimulation or inhibition), on microzooplankton grazing pressure in different ocean regions.
Staquorsin: A Novel Staphylococcus aureus Agr-Mediated Quorum Sensing Inhibitor Impairing Virulence in vivo Without Notable Resistance Development
Authors: Mahdally Norhan H. , George Riham F. , Kashef Mona T. , Al-Ghobashy Medhat , Murad Fathia E. , Attia Ahmed S.
Published: July 2021

The emergence of microbial resistance to the available antibiotics is a major public health concern, especially with the limited rate of developing new antibiotics. The utilization of anti-virulence agents is a non-conventional approach that can be used to combat microbial infection. In Staphylococcus aureus, many virulence factors are regulated by the Agr-mediated quorum sensing (QS). We developed a chemical compound that acts a potential Agr-inhibitor without reducing bacterial viability. The compound was designated staquorsin for Staphylococcus aureus QS inhibitor. In silico analyses confirmed the binding of staquorsin to the AgrA active site with an absolute binding score comparable to savirin, a previously described AgrA inhibitor. However, staquorsin turned out to be superior over savarin in not affecting the S. aureus viability in concentrations up to 600 μM. On the other hand, savirin inhibited S. aureus growth in concentrations as low as 25 μM. Moreover, staquorsin proved to be a potent inhibitor of the Agr system by inhibiting hemolysins, lipase production, and affecting biofilms formation and detachment. On the molecular level it significantly inhibited the effector transcript RNA III. In vivo testing, using the murine skin abscess model, confirmed the ability of staquorsin to modulate S. aureus virulence by effectively controlling the infection. Twenty passages of S. aureus in the presence of 40 μM staquorsin have not resulted in loss of activity as evidenced by maintaining its ability to reduce hemolysin production and RNA III transcript levels. In conclusion, we hereby describe a novel anti-virulence compound inhibiting the S. aureus Agr-system and its associated virulence factors. It is active both in vitro and in vivo, and its frequent use does not lead to the development of resistance. These findings model staquorsin as a promising drug candidate to join the fierce battle against the formidable pathogen S. aureus.
(S)-3-Hydroxybutyryl-CoA Dehydrogenase From the Autotrophic 3-Hydroxypropionate/4-Hydroxybutyrate Cycle in Nitrosopumilus maritimus
Authors: Liu Li , Schubert Daniel M. , Könneke Martin , Berg Ivan A.
Published: July 2021

Ammonia-oxidizing archaea of the phylum Thaumarchaeota are among the most abundant organisms that exert primary control of oceanic and soil nitrification and are responsible for a large part of dark ocean primary production. They assimilate inorganic carbon via an energetically efficient version of the 3-hydroxypropionate/4-hydroxybutyrate cycle. In this cycle, acetyl-CoA is carboxylated to succinyl-CoA, which is then converted to two acetyl-CoA molecules with 4-hydroxybutyrate as the key intermediate. This conversion includes the (S)-3-hydroxybutyryl-CoA dehydrogenase reaction. Here, we heterologously produced the protein Nmar_1028 catalyzing this reaction in thaumarchaeon Nitrosopumilus maritimus, characterized it biochemically and performed its phylogenetic analysis. This NAD-dependent dehydrogenase is highly active with its substrate, (S)-3-hydroxybutyryl-CoA, and its low Km value suggests that the protein is adapted to the functioning in the 3-hydroxypropionate/4-hydroxybutyrate cycle. Nmar_1028 is homologous to the dehydrogenase domain of crotonyl-CoA hydratase/(S)-3-hydroxybutyryl-CoA dehydrogenase that is present in many Archaea. Apparently, the loss of the dehydratase domain of the fusion protein in the course of evolution was accompanied by lateral gene transfer of 3-hydroxypropionyl-CoA dehydratase/crotonyl-CoA hydratase from Bacteria. Although (S)-3-hydroxybutyryl-CoA dehydrogenase studied here is neither unique nor characteristic for the HP/HB cycle, Nmar_1028 appears to be the only (S)-3-hydroxybutyryl-CoA dehydrogenase in N. maritimus and is thus essential for the functioning of the 3-hydroxypropionate/4-hydroxybutyrate cycle and for the biology of this important marine archaeon.