bluuebunny/crossref_metadata_2025 huggingface dataset:
Clinical Significance of Serum-Derived Exosomal LINC00917 in Patients With Non-Small Cell Lung Cancer
Authors: Xiong Dani , Wang Chuanlin , Yang Zhaohui , Han Fusen , Zhan Huaibing
Published: December 2021

Background: In this study, we aimed to explore the diagnostic potential of serum-based exosomal long intergenic noncoding RNA 917 (LINC00917) in non-small cell lung cancer (NSCLC).

Methods: Exosomes were extracted from NSCLC patients’ serum samples. Exosomal LINC00917 expression levels were compared, by qRT-PCR, between cancer patients and healthy controls, as well as sub-populations of cancer patients. The association between exosomal LINC00917 expression and NSCLC patients’ clinicopathologic factors were investigated, and receiver operating characteristic (ROC) curves were drawn. In addition, NSCLC patients’ overall survivals (OSs) was examined based on exosomal LINC00917 expression and further evaluated by the cox regression analysis.

Results: Serum-derived exosomal LINC00917 was highly expressed in NSCLC patients, and further upregulated in stage III/IV cancer patients. Exosomal LINC00917 yielded modestly good under the curve (AUC) values. Upregulated exosomal LINC00917 expression was closely associated with cancer patients’ advanced stages and shorter OSs.

Conclusion: Serum-derived exosomal LINC00917 may hold diagnostic potential for patients with non-small cell lung cancer.
Differentially Expressed lncRNAs Related to the Development of Abdominal Fat in Gushi Chickens and Their Interaction Regulatory Network
Authors: Zhai Bin , Zhao Yinli , Fan Shengxin , Yuan Pengtao , Li Hongtai , Li Shuaihao , Li Yuanfang , Zhang Yanhua , Huang Hetian , Li Hong , Kang Xiangtao , Li Guoxi
Published: December 2021

Chickens are one of the most important sources of meat worldwide, and the growth status of abdominal fat is closely related to production efficiency. Long noncoding RNAs (lncRNAs) play an important role in lipid metabolism and deposition regulation. However, research on the expression profile of lncRNAs related to the development of abdominal fat in chickens after hatching and their interaction regulatory networks is still lacking. To characterize the lncRNA expression profile during the development of chicken abdominal fat, abdominal adipose tissues from 6-, 14-, 22-, and 30-week-old Chinese Gushi chickens were herein used to construct 12 cDNA libraries, and a total of 3,827 new lncRNAs and 5,466 previously annotated lncRNAs were revealed. At the same time, based on the comparative analysis of five combinations, 276 differentially expressed lncRNAs (DE-lncRNAs) were screened. Functional enrichment analysis showed that the predicted target genes of these DE-lncRNAs were significantly enriched in pathways related to the posttranscriptional regulation of gene expression, negative regulation of cell proliferation, cell adhesion and other biological processes, glycosphingolipid biosynthesis, PPAR signaling, fatty acid degradation, fatty acid synthesis and others. In addition, association analysis of the lncRNA transcriptome profile was performed, and DE-lncRNA-related lncRNA-mRNA, lncRNA-miRNA and lncRNA-miRNA-mRNA interaction regulatory networks were constructed. The results showed that DE-lncRNA formed a complex network with PPAR pathway components, including PPARD, ACOX1, ADIPOQ, CPT1A, FABP5, ASBG2, LPL, PLIN2 and related miRNAs, including mir-200b-3p, mir-130b-3p, mir-215-5p, mir-122-5p, mir-223 and mir-125b-5p, and played an important regulatory role in biological processes such as lipid metabolism, adipocyte proliferation and differentiation. This study described the dynamic expression profile of lncRNAs in the abdominal fat of Gushi chickens for the first time and constructed the DE-lncRNA interaction regulatory network. The results expand the number of known lncRNAs in chicken abdominal fat and provide valuable resources for further elucidating the posttranscriptional regulatory mechanism of chicken abdominal fat development or deposition.
Network Analyses Based on Machine Learning Methods to Quantify Effects of Peptide–Protein Complexes as Drug Targets Using Cinnamon in Cardiovascular Diseases and Metabolic Syndrome as a Case Study
Authors: Wang Yingying , Wang Lili , Liu Yinhe , Li Keshen , Zhao Honglei
Published: December 2021

Peptide–protein complexes play important roles in multiple diseases such as cardiovascular diseases (CVDs) and metabolic syndrome (MetS). The peptides may be the key molecules in the designing of inhibitors or drug targets. Many Chinese traditional drugs are shown to play various roles in different diseases, and comprehensive analyses should be performed using networks which could offer more information than results generated from a single level. In this study, a network analysis pipeline was designed based on machine learning methods to quantify the effects of peptide–protein complexes as drug targets. Three steps, namely, pathway filter, combined network construction, and biomarker prediction and validation based on peptides, were performed using cinnamon (CA) in CVDs and MetS as a case. Results showed that 17 peptide–protein complexes including six peptides and four proteins were identified as CA targets. The expressions of AKT1, AKT2, and ENOS were tested using qRT-PCR in a mouse model that was constructed. AKT2 was shown to be a CA-indicating biomarker, while E2F1 and ENOS were CA treatment targets. AKT1 was considered a diabetic responsive biomarker because it was down-regulated in diabetic but not related to CA. Taken together, the pipeline could identify new drug targets based on biological function analyses. This may provide a deep understanding of the drugs’ roles in different diseases which may foster the development of peptide–protein complex–based therapeutic approaches.
Landscape and Clinical Significance of Immune Checkpoint in Cutaneous Melanoma
Authors: Mao Rui , Yang Fan , Zhang Tongtong , Li Ji
Published: December 2021

Background

The incidence of cutaneous melanoma (CM) is increasing, and its prognosis is not optimistic. Although immune checkpoint (ICP) inhibitors are effective in the treatment of CM patients, they are not effective for all CM patients. There is an urgent need for a marker to predict both the prognosis and the immunotherapy effect in patients with CM.

Approaches

Two groups of patients with greatly different prognosis and response to immunotherapy were identified by unwatched cluster exploration of TCGA on the basis of 34 ICPs. The prognosis and immunotherapy effect of CM were predicted by developing a precise and given signature on the basis of ICPs, and a multivariate Cox risk regression model was established from the TCGA cohort consisting of 454 CM samples. The model was validated in 210 and 231 samples in the test and verification cohorts, respectively.

Results

The prognosis in clinical subgroups was predicted by the classification system. High-risk patients had poorer responses to chemotherapy and immunotherapy. Finally, the signature was recognized as an independent prognostic factor. Based on checkpoint-based signature (ICPBS) and clinical characteristics, we constructed a nomogram for the prognosis in patients with CM, which was superior to ICPBS in efficacy than ICPBS alone.

Conclusion

As a useful prognostic tool to further improve cancer immunotherapy, the signature can accurately predict recurrence and overall survival among patients with CM.
Physical Interactions With Bacteria and Protozoan Parasites Establish the Scavenger Receptor SSC4D as a Broad-Spectrum Pattern Recognition Receptor
Authors: Cardoso Marcos S. , Santos Rita F. , Almeida Sarah , Sá Mónica , Pérez-Cabezas Begoña , Oliveira Liliana , Tavares Joana , Carmo Alexandre M.
Published: December 2021

Since the pioneering discoveries, by the Nobel laureates Jules Hoffmann and Bruce Beutler, that Toll and Toll-like receptors can sense pathogenic microorganisms and initiate, in vertebrates and invertebrates, innate immune responses against microbial infections, many other families of pattern recognition receptors (PRRs) have been described. One of such receptor clusters is composed by, if not all, at least several members of the scavenger receptor cysteine-rich (SRCR) superfamily. Many SRCR proteins are plasma membrane receptors of immune cells; however, a small subset consists of secreted receptors that are therefore in circulation. We here describe the first characterization of biological and functional roles of the circulating human protein SSC4D, one of the least scrutinized members of the family. Within leukocyte populations, SSC4D was found to be expressed by monocytes/macrophages, neutrophils, and B cells, but its production was particularly evident in epithelial cells of several organs and tissues, namely, in the kidney, thyroid, lung, placenta, intestinal tract, and liver. Similar to other SRCR proteins, SSC4D shows the capacity of physically binding to different species of bacteria, and this opsonization can increase the phagocytic capacity of monocytes. Importantly, we have uncovered the capacity of SSC4D of binding to several protozoan parasites, a singular feature seldom described for PRRs in general and here demonstrated for the first time for an SRCR family member. Overall, our study is pioneer in assigning a PRR role to SSC4D.
Vulnerability to Meningococcal Disease in Immunodeficiency Due to a Novel Pathogenic Missense Variant in NFKB1
Authors: Anim Manfred , Sogkas Georgios , Schmidt Gunnar , Dubrowinskaja Natalia , Witte Torsten , Schmidt Reinhold Ernst , Atschekzei Faranaz
Published: December 2021

NF-κB1 deficiency is suggested to be the most common cause of common variable immunodeficiency (CVID). NFKB1 encodes for the p105 precursor protein of NF-κB1, which is converted into the active transcriptional subunit p50 through proteasomal processing of its C-terminal half upon stimulation and is implicated in the canonical NF-kB pathway. Rare monoallelic NFKB1 variants have been shown to cause (haplo) insufficiency. Our report describes a novel NFKB1 missense variant (c.691C>T, p.R230C; allele frequency 0.00004953) in a family vulnerable to meningitis, sepsis, and late-onset hypogammaglobulinemia. We investigated the pathogenic relevance of this variant by lymphocyte stimulation, immunophenotyping, overexpression study and immunoblotting. The ectopic expression of p50 for c.691 C>T restricted transcriptionally active p50 in the cytoplasm, and immunoblotting revealed reduced p105/50 expression. This study shows that the deleterious missense variant in NFKB1 adversely affects the transcriptional and translational activity of NFκB1, impairing its function. Patients immunological parameters show a progressive course of hypogammaglobulinemia, which may partially account for the incomplete disease penetrance and suggest the need for closer immunological monitoring of those mutation carriers.
Molecular Subtypes Based on Cell Differentiation Trajectories in Head and Neck Squamous Cell Carcinoma: Differential Prognosis and Immunotherapeutic Responses
Authors: Huang Zhen-Dong , Liu Zi-Zhen , Liu Yan-Yi , Fu Yong-Cheng , Lin Lu-Lu , Hu Chao , Gu Hui-Yun , Wei Ren-Xiong
Published: December 2021

Objective

Head and neck squamous cell carcinoma (HNSCC) is one of the most common and lethal malignant tumors. We aimed to investigate the HNSCC cell differentiation trajectories and the corresponding clinical relevance.

Methods

Based on HNSCC cell differentiation-related genes (HDRGs) identified by single-cell sequencing analysis, the molecular subtypes and corresponding immunity, metabolism, and stemness characteristics of 866 HNSCC cases were comprehensively analyzed. Machine-learning strategies were used to develop a HNSCC cell differentiation score (HCDscore) in order to quantify the unique heterogeneity of individual samples. We also assessed the prognostic value and biological characteristics of HCDscore using the multi-omics data.

Results

HNSCCs were stratified into three distinct molecular subtypes based on HDRGs: active stroma (Cluster-A), active metabolism (Cluster-B), and active immune (Cluster-C) types. The three molecular subtypes had different characteristics in terms of biological phenotype, genome and epigenetics, prognosis, immunotherapy and chemotherapy responses. We then demonstrated the correlations between HCDscore and the immune microenvironment, subtypes, carcinogenic biological processes, genetic variation, and prognosis. The low-HCDscore group was characterized by activation of immunity, enhanced response to anti-PD-1/PD-L1 immunotherapy, and better survival compared to the high-HCDscore group. Finally, by integrating the HCDscore with prognostic clinicopathological characteristics, a nomogram with strong predictive performance and high accuracy was constructed.

Conclusions

This study revealed that the cell differentiation trajectories in HNSCC played a nonnegligible role in patient prognosis, biological characteristics, and immune responses. Evaluating cancer cell differentiation will help to develop more effective immunotherapy, metabolic therapy, and chemotherapy strategies.
Gut Microbiota and Acute Central Nervous System Injury: A New Target for Therapeutic Intervention
Authors: Yuan Bin , Lu Xiao-jie , Wu Qi
Published: December 2021

Acute central nervous system (CNS) injuries, including stroke, traumatic brain injury (TBI), and spinal cord injury (SCI), are the common causes of death or lifelong disabilities. Research into the role of the gut microbiota in modulating CNS function has been rapidly increasing in the past few decades, particularly in animal models. Growing preclinical and clinical evidence suggests that gut microbiota is involved in the modulation of multiple cellular and molecular mechanisms fundamental to the progression of acute CNS injury-induced pathophysiological processes. The altered composition of gut microbiota after acute CNS injury damages the equilibrium of the bidirectional gut-brain axis, aggravating secondary brain injury, cognitive impairments, and motor dysfunctions, which leads to poor prognosis by triggering pro-inflammatory responses in both peripheral circulation and CNS. This review summarizes the studies concerning gut microbiota and acute CNS injuries. Experimental models identify a bidirectional communication between the gut and CNS in post-injury gut dysbiosis, intestinal lymphatic tissue-mediated neuroinflammation, and bacterial-metabolite-associated neurotransmission. Additionally, fecal microbiota transplantation, probiotics, and prebiotics manipulating the gut microbiota can be used as effective therapeutic agents to alleviate secondary brain injury and facilitate functional outcomes. The role of gut microbiota in acute CNS injury would be an exciting frontier in clinical and experimental medicine.
Kinetics and Size Effects on Adsorption of Cu(II), Cr(III), and Pb(II) Onto Polyethylene, Polypropylene, and Polyethylene Terephthalate Microplastic Particles
Authors: Han Xiaoxin , Wang Shiyu , Yu Xue , Vogt Rolf D. , Feng Jianfeng , Zhai Lifang , Ma Weiqi , Zhu Lin , Lu Xueqiang
Published: December 2021

Due to its small size, large specific surface area and hydrophobicity, microplastics, and the adsorbed contaminants may together cause potential negative effects on ecosystems and human beings. In this study, kinetics and size effects on adsorption of Cu(II), Cr(III), and Pb(II) onto PE, PP and PET microplastic particles were explored. Results indicated that the PE and PET microplastics have the higher adsorption capacity for Cu(II), Cr(III), and Pb(II) than that for PP microplastic. The adsorption capacity was affected by microplastic types and metal species. Among the three metals, Pb(II) had the largest adsorption amount on microplastic particles, especially on PET particles. Moreover, the adsorption capacities of microplastics increase with the decrease of particle size. The metal adsorption capacity of <0.9 mm microplastics is greater than that of 0.9–2 mm and 2–5 mm microplastics. The size effect on metal adsorption was largest for PE microplastic. More attention should be paid in case of the coexistence of heavy metals and tiny PE and PET microplastics in the environment.
Therapeutic Plateletpheresis in Patients With Thrombocytosis: Gender, Hemoglobin Before Apheresis Significantly Affect Collection Efficiency
Authors: Jiang Hongqiang , Jin Yanxia , Shang Yufeng , Yuan Guolin , Liu Dandan , Li Jianfang , Wang Cong , Ding Lu , Tong Xiqin , Guo Shishang , Gong Fayun , Zhou Fuling
Published: December 2021

Background: Thrombocytosis is a common symptom in myeloproliferative neoplasms (MPN), and excessive proliferation may deteriorate into thrombosis, bleeding, myelofibrosis, and may ultimately convert to acute leukemia. This study aimed to investigate the collection efficiency of plateletpheresis (CEPP) and factors influencing its efficacy in patients with thrombocytosis.

Materials and Methods: From September 2010 to December 2016, 81 patients from two institutions in China with myeloproliferative neoplasms and thrombocytosis accompanied by severe symptoms were treated with plateletpheresis by Fresenius COM. TEC machine.

Results: After apheresis, the median CEPP was 20.71% (IQR: 9.99–36.69%) and median PLT reduction rate was 25.87% (IQR: 21.78–36.23%). Further analysis showed that no significant difference was observed between PLT count with 800–1,000 × 109/L and > 1,000 × 109/L. The PLT counts significantly decreased (P < 0.001) after plateletpheresis, the red blood cell (RBC), white blood cell (WBC), hemoglobin (HGB), and hematocrit (HCT) levels showed no significant differences before- or after- plateletpheresis. Multivariate analysis showed that female sex (P = 0.009) and HGB (P = 0.010) before apheresis were associated with CEPP. Female (P = 0.022), HCT (P = 0.001) and blood volume (P = 0.015) were associated with the PLT reduction rate. Furthermore, symptoms were relieved after apheresis in patients whose PLT count was 800–1,000 × 109/L accompanied with symptoms.

Conclusions: It is reasonable to perform plateletpheresis when the PLT count is over 800 × 109/L and patients are complicated by clinical symptoms such as dizziness, headache, somnolence, and stupor. Plateletpheresis is effective in removing PLTs especially in females with high HGB.
Efficacy and Safety of Anticoagulation Treatment in COVID-19 Patient Subgroups Identified by Clinical-Based Stratification and Unsupervised Machine Learning: A Matched Cohort Study
Authors: Bian Yi , Le Yue , Du Han , Chen Junfang , Zhang Ping , He Zhigang , Wang Ye , Yu Shanshan , Fang Yu , Yu Gang , Ling Jianmin , Feng Yikuan , Wei Sheng , Huang Jiao , Xiao Liuniu , Zheng Yingfang , Yu Zhen , Li Shusheng
Published: December 2021

Objective: To explore the efficacy of anticoagulation in improving outcomes and safety of Coronavirus disease 2019 (COVID-19) patients in subgroups identified by clinical-based stratification and unsupervised machine learning.

Methods: This single-center retrospective cohort study unselectively reviewed 2,272 patients with COVID-19 admitted to the Tongji Hospital between Jan 25 and Mar 23, 2020. The association between AC treatment and outcomes was investigated in the propensity score (PS) matched cohort and the full cohort by inverse probability of treatment weighting (IPTW) analysis. Subgroup analysis, identified by clinical-based stratification or unsupervised machine learning, was used to identify sub-phenotypes with meaningful clinical features and the target patients benefiting most from AC.

Results: AC treatment was associated with lower in-hospital death risk either in the PS matched cohort or by IPTW analysis in the full cohort. A higher incidence of clinically relevant non-major bleeding (CRNMB) was observed in the AC group, but not major bleeding. Clinical subgroup analysis showed that, at admission, severe cases of COVID-19 clinical classification, mild acute respiratory distress syndrome (ARDS) cases, and patients with a D-dimer level ≥0.5 μg/mL, may benefit from AC. During the hospital stay, critical cases and severe ARDS cases may benefit from AC. Unsupervised machine learning analysis established a four-class clustering model. Clusters 1 and 2 were non-critical cases and might not benefit from AC, while clusters 3 and 4 were critical patients. Patients in cluster 3 might benefit from AC with no increase in bleeding events. While patients in cluster 4, who were characterized by multiple organ dysfunction (neurologic, circulation, coagulation, kidney and liver dysfunction) and elevated inflammation biomarkers, did not benefit from AC.

Conclusions: AC treatment was associated with lower in-hospital death risk, especially in critically ill COVID-19 patients. Unsupervised learning analysis revealed that the most critically ill patients with multiple organ dysfunction and excessive inflammation might not benefit from AC. More attention should be paid to bleeding events (especially CRNMB) when using AC.
Efficacy and Safety of Mucopolysaccharide Polysulfate Cream for Non-Exudative Eczema: A Systematic Review and Meta-Analysis
Authors: Li Ming , Li Yan , Xiang Lujing , Li Linfeng
Published: December 2021

Background: Mucopolysaccharide polysulfate (MPS) cream as a moisturizer is widely applied to treat eczema, and a lot of clinical trials have demonstrated its efficacy and safety. However, there is no further research to collect and analyze these studies.

Objective: This meta-analysis aimed to assess the efficacy and safety of MPS cream as monotherapy or add-on therapy for non-exudative eczema.

Methods: Ten databases were searched to identify the eligible randomized controlled trials (RCTs) from their inception to July 31, 2021. Revman 5.3 software was used for the meta-analysis.

Results: A total of eligible 20 studies were included. Among the 20 studies, 2 studies compared MPS cream with other moisturizers, 14 compared MPS cream plus topical corticosteroids (TCS) with TCS alone, and 4 compared with MPS cream plus tacrolimus ointment with tacrolimus ointment alone. The pooled results demonstrated that MPS cream had a higher total efficacy rate [Risk ratio (RR) 1.21, 95% CI: 1.12 to 1.30, P < 0.00001], a lower recurrence rate (RR 0.44, 95% CI: 0.26 to 0.74, P = 0.002) and a lower pruritus score [mean difference (MD) −1.78, 95% CI: −2.16 to −1.40, P < 0.00001] than urea cream or vaseline ointment. Moreover, in comparison with TCS or tacrolimus ointment alone, the combination treatment performed better in terms of total efficacy rate, total symptom score, recurrence rate, and pruritus score. For safety, the skin adverse events were mild, and MPS cream as monotherapy or add-on therapy did not increase the risk of skin adverse events.

Conclusions: MPS cream as monotherapy or add-on therapy could provide a good effect for treating non-exudative eczema with mild and tolerable skin adverse events. However, due to the suboptimal quality of the included studies, high-quality and large-sample RCTs are needed in the future for update or validation.

Systematic Review Registration: PROSPERO (https://www.crd.york.ac.uk/PROSPERO/), identifier: CRD42021265735.
Posterior Reversible Encephalopathy Syndrome in a Patient With Microscopic Polyangiitis: A Case Report and Literature Review
Authors: Xu Jing , Ding Ying , Qu Zhen , Yu Feng
Published: December 2021

Central nervous system (CNS) is rarely involved in microscopic polyangiitis (MPA). Here, we report a 14-year-old girl with MPA who developed new-onset seizures with deterioration of renal function. Her brain CT scan and MRI showed concurrent complications of intracerebral hemorrhage and posterior reversible encephalopathy syndrome (PRES). She got remission with combinations of methylprednisolone pulse, plasma exchange, regular hemodialysis, antiseizure and antihypertension medications. Furthermore, it is crucial to exclude the adverse effect of medications such as corticosteroid and biological therapy. We searched the literatures, retrieved 6 cases of MPA with PRES and summarized their clinical characteristics.
Mortality and Respiratory-Related Hospitalizations in Idiopathic Pulmonary Fibrosis Not Treated With Antifibrotics
Authors: Cottin Vincent , Spagnolo Paolo , Bonniaud Philippe , Nolin Maëva , Dalon Faustine , Kirchgässler Klaus-Uwe , Kamath Tripthi V. , Van Ganse Eric , Belhassen Manon
Published: December 2021

Background: Real-world data regarding outcomes of idiopathic pulmonary fibrosis (IPF) are scarce, outside of registries. The claims data from the French National Health System (SNDS) were used to describe outcomes in patients diagnosed with IPF in 2015–2016 but who did not receive antifibrotic therapies.

Method: Patients aged <50 years were excluded, as were patients with pulmonary fibrosis other than IPF, patients who had previously received a lung transplant, and those who had received antifibrotic therapies at any time between 2010 and 2016. Patients were followed-up until their last health record, lung transplantation, initiation of antifibrotic therapies, death, or the end of the study period (31 December 2017), whichever occurred first.

Results: A total of 5,360 patients (43.2%) not treated with antifibrotic therapies were included. The mean age was 75.5 years, and 57.9% were males. In the year before inclusion, 47.3% of patients had a Charlson score ≥5. During follow-up, 41.2% of patients died. The unadjusted incidence rate was 29.9 per 100 person-years (95%CI = [28.7–31.2]), and the cumulative incidence of death at 3 years was 50.2% (95% CI = [48.3–52.1%]). In the study population, 35.3% of patients experienced an acute respiratory-related hospitalization. The unadjusted incidence rate was 32.1 per 100 person-years (95%CI = [30.6–33.5]) and the cumulative incidence of the event at 3 years was 41.5% (95% CI = [39.7–43.2%]).

Interpretation: This observational study showed that, if untreated with antifibrotics, IPF is associated with a 50% all-cause mortality at 3 years. These figures can serve as a historical control of the natural course of the disease.
Patient and Citizen Participation in the Identification of Ethical Considerations Aiming to Address Uncertainty in the Evaluation of Promising Interventions in a Pandemic Context
Authors: Olivier Catherine , Ganache Isabelle , Demers-Payette Olivier , Lochhead Louis , Pelaez Sandra , de Guise Michèle , Pomey Marie-Pascale
Published: December 2021

Since the beginning of the COVID-19 pandemic, numerous studies have been conducted to identify interventions that could contribute to alleviating the burden it has caused. The Institut national d'excellence en santé et en services sociaux (INESSS) has played a key role in informing the government of Québec regarding the evaluation of specific pandemic-related interventions. This process took place in a context characterized by a sense of urgency to assess and recommend potential interventions that could save lives and reduce the effects of the disease on populations and healthcare systems, which increased the pressure on the regulatory agencies leading these evaluations. While some of the interventions examined were considered promising, results from COVID-19 studies often led to uncertainty regarding their efficacy or safety. Regulatory agencies evaluating the value of promising interventions thus face challenges in deciding whether these should be made available to the population, particularly when assessing their benefit-risk balance. To shed light on these challenges, we identified underlying ethical considerations that can influence such an assessment. A rapid literature review was conducted in February 2021, to identify the main challenges associated with the benefit-risk balance assessment of promising interventions. To reinforce our understanding of the underlying ethical considerations, we initiated a discussion among various social actors involved in critical thinking surrounding the evaluation of promising interventions, including ethicists, clinicians and researchers involved in clinical or public health practice, as well as patients and citizens. This discussion allowed us to create a space for exchange and mutual understanding among these various actors who contributed equally to the identification of ethical considerations. The knowledge and perspectives stemming from the scientific literature and those consulted were integrated in a common reflection on these ethical considerations. This allowed patients and citizens, directly affected by the evaluation of pandemic-related interventions and the resulting social choices, to contribute to the identification of the relevant ethical considerations. It also allowed for reflection on the responsibilities of the various actors involved in the development, evaluation, and distribution of promising interventions in a setting of urgency and uncertainty, such as that brought about by the COVID-19 pandemic.
Deinococcus radiodurans Exopolysaccharide Inhibits Staphylococcus aureus Biofilm Formation
Authors: Chen Fengjia , Zhang Jing , Ji Hyun Jung , Kim Min-Kyu , Kim Kyoung Whun , Choi Jong-Il , Han Seung Hyun , Lim Sangyong , Seo Ho Seong , Ahn Ki Bum
Published: December 2021

Deinococcus radiodurans is an extremely resistant bacterium against extracellular stress owing to on its unique physiological functions and the structure of its cellular constituents. Interestingly, it has been reported that the pattern of alteration in Deinococcus proportion on the skin is negatively correlated with skin inflammatory diseases, whereas the proportion of Staphylococcus aureus was increased in patients with chronic skin inflammatory diseases. However, the biological mechanisms of deinococcal interactions with other skin commensal bacteria have not been studied. In this study, we hypothesized that deinococcal cellular constituents play a pivotal role in preventing S. aureus colonization by inhibiting biofilm formation. To prove this, we first isolated cellular constituents, such as exopolysaccharide (DeinoPol), cell wall (DeinoWall), and cell membrane (DeinoMem), from D. radiodurans and investigated their inhibitory effects on S. aureus colonization and biofilm formation in vitro and in vivo. Among them, only DeinoPol exhibited an anti-biofilm effect without affecting bacterial growth and inhibiting staphylococcal colonization and inflammation in a mouse skin infection model. Moreover, the inhibitory effect was impaired in the Δdra0033 strain, a mutant that cannot produce DeinoPol. Remarkably, DeinoPol not only interfered with S. aureus biofilm formation at early and late stages but also disrupted a preexisting biofilm by inhibiting the production of poly-N-acetylglucosamine (PNAG), a key molecule required for S. aureus biofilm formation. Taken together, the present study suggests that DeinoPol is a key molecule in the negative regulation of S. aureus biofilm formation by D. radiodurans. Therefore, DeinoPol could be applied to prevent and/or treat infections or inflammatory diseases associated with S. aureus biofilms.
Yeast and Filamentous Fungi Microbial Communities in Organic Red Grape Juice: Effect of Vintage, Maturity Stage, SO2, and Bioprotection
Authors: Windholtz Sara , Vinsonneau Emmanuel , Farris Laura , Thibon Cécile , Masneuf-Pomarède Isabelle
Published: December 2021

Changes are currently being made to winemaking processes to reduce chemical inputs [particularly sulfur dioxide (SO2)] and adapt to consumer demand. In this study, yeast growth and fungal diversity were investigated in merlot during the prefermentary stages of a winemaking process without addition of SO2. Different factors were considered, in a two-year study: vintage, maturity level and bioprotection by the adding yeast as an alternative to SO2. The population of the target species was monitored by quantitative-PCR, and yeast and filamentous fungi diversity was determined by 18S rDNA metabarcoding. A gradual decrease of the α-diversity during the maceration process was highlighted. Maturity level played a significant role in yeast and fungal abundance, which was lower at advanced maturity, while vintage had a strong impact onHanseniasporaspp. population level and abundance. The presence of SO2altered the abundance of yeast and filamentous fungi, but not their nature. The absence of sulfiting led to an unexpected reduction in diversity compared to the presence of SO2, which might result from the occupation of the niche by certain dominant species, namelyHanseniasporaspp. Inoculation of the grape juice with non-Saccharomycesyeast resulted in a decrease in the abundance of filamentous fungi generally associated with a decline in grape must quality. Lower abundance and niche occupation by bioprotection agents were observed at the overripened stage, thus suggesting that doses applied should be reconsidered at advanced maturity. Our study confirmed the bioprotective role ofMetschnikowia pulcherrimaandTorulaspora delbrueckiiin a context of vinification without sulfites.
Microbial Eukaryotes Associated With Sediments in Deep-Sea Cold Seeps
Authors: Zhang Yue , Huang Ning , Wang Minxiao , Liu Hongbin , Jing Hongmei
Published: December 2021

Microbial eukaryotes are key components of the marine food web, but their distribution in deep-sea chemosynthetic ecosystems has not been well studied. Here, high-throughput sequencing of the 18S rRNA gene and network analysis were applied to investigate the diversity, distribution and potential relationships between microbial eukaryotes in samples collected from two cold seeps and one trough in the northern South China Sea. SAR (i.e., Stramenopiles, Alveolata, and Rhizaria) was the predominant group in all the samples, and it was highly affiliated to genotypes with potential symbiotic and parasitic strategies identified from other deep-sea extreme environments (e.g., oxygen deficient zones, bathypelagic waters, and hydrothermal vents). Our findings indicated that specialized lineages of deep-sea microbial eukaryotes exist in chemosynthetic cold seeps, where microbial eukaryotes affiliated with parasitic/symbiotic taxa were prevalent in the community. The biogeographic pattern of the total community was best represented by the intermediate operational taxonomic unit (OTU) category, whose relative abundance ranged 0.01–1% within a sample, and the communities of the two cold seeps were distinct from the trough, which suggests that geographical proximity has no critical impact on the distribution of deep-sea microbial eukaryotes. Overall, this study has laid the foundations for future investigations regarding the ecological function and in situ trophic relationships of microbial eukaryotes in deep-sea ecosystems.
The Distribution and Turnover of Bacterial Communities in the Root Zone of Seven Stipa Species Across an Arid and Semi-arid Steppe
Authors: Ma Xiaodan , Chao Lumeng , Li Jingpeng , Ding Zhiying , Wang Siyu , Li Fansheng , Bao Yuying
Published: December 2021

The bacterial communities of the root-zone soil are capable of regulating vital biogeochemical cycles and the succession of plant growth. Stipa as grassland constructive species is restricted by the difference features of east–west humidity and north–south heat, which shows the population substituting distribution. The distribution, turnover, and potential driving factors and ecological significance of the root-zone bacterial community along broad spatial gradients of Stipa taxa transition remain unclear. This paper investigated seven Stipa species root-zone soils based on high-throughput sequencing combined with the measurements of multiple environmental parameters in arid and semi-arid steppe. The communities of soil bacteria in root zone had considerable turnover, and some regular variations in structure along the Stipa taxa transition are largely determined by climatic factors, vegetation coverage, and pH at a regional scale. Bacterial communities had a clear Stipa population specificity, but they were more strongly affected by the main annual precipitation, which resulted in a biogeographical distribution pattern along precipitation gradient, among which Actinobacteria, Acidobacteria, Proteobacteria, and Chloroflexi were the phyla that were most abundant. During the transformation of Stipa taxa from east to west, the trend of diversity shown by bacterial community in the root zone decreased first, and then increased sharply at S. breviflora, which was followed by continuous decreasing toward northwest afterwards. However, the richness and evenness showed an opposite trend, and α diversity had close association with altitude and pH. There would be specific and different bacterial taxa interactions in different Stipa species, in which S. krylovii had the simplest and most stable interaction network with the strongest resistance to the environment and S. breviflora had most complex and erratic. Moreover, the bacterial community was mainly affected by dispersal limitation at a certain period. These results are conducive to the prediction of sustainable ecosystem services and protection of microbial resources in a semi-arid grassland ecosystem.
Implications of RNA Viruses in the Male Reproductive Tract: An Outlook on SARS-CoV-2
Authors: Zafar Mohammad Ishraq , Yu Jiangyu , Li Honggang
Published: December 2021

Emerging viral infections continuously pose a threat to human wellbeing. Several RNA viruses have managed to establish access to the male reproductive tract and persist in human semen. The sexual transmission of the virus is of critical public concern. The epidemiological inferences are essential to understand its complexity, particularly the probability of viral transmission from asymptomatic patients or those in the incubation period or from the patient who was previously infected and now fully recovered. From the clinical perspective, negative impacts in the male reproductive tract associated with RNA virus infection have been described, including orchitis, epididymitis, impaired spermatogenesis, and a decrease in sperm quality, which can affect male fertility at different time intervals. The disruption of anatomical barriers due to inflammatory responses might enable the viral invasion into the testis, and the immune privilege status of testes might facilitate a sustained persistence of the virus in the semen. In this review, the current knowledge about other RNA viruses that affect male reproductive health provides the framework to discuss the impact of the SARS-CoV-2 pandemic. The molecular mechanisms, sexual transmission, and viral impacts for mumps, HIV, Zika, and Ebola viruses are explored. We discuss the currently available information on the impact of SARS-CoV-2 and its sequelae in the male reproductive tract, particularly regarding presence in semen, its impact on sexual organs, and sperm quality. To date, no sexual transmission of SARS-CoV-2 has been reported, whereas the identification of viral particles in semen remains conflicting. In the purview of the earlier conducted analyses, it is essential to investigate further the long-term health impacts of SARS-CoV-2 on the male reproductive tract.
The Succession of Bacterial Community Attached on Biodegradable Plastic Mulches During the Degradation in Soil
Authors: Ju Zhicheng , Du Xiongfeng , Feng Kai , Li Shuzhen , Gu Songsong , Jin Decai , Deng Ye
Published: December 2021

Despite the increasing application of biodegradable plastic mulches (BDMs) in agriculture, the colonization and succession of the attached microbial community on BDMs during their degradation processes remain poorly characterized. Here, we buried four types of commonly used BDMs, including pure polylactic acid (PLA), pure polybutylene adipate terephthalate (PBAT), and two mixtures of PLA and PBAT (85:15 and 15:85 w/w), and one classic polyethylene (PE) mulch in soil for 5 months. Both plastic components and incubation time significantly shaped the β-diversities of microbiota on the plastic mulches (p < 0.001). Meanwhile, the microbial compositions and community structures on BDMs were significantly different from PE mulch, and when excluding PE mulch, the microbiota varied more with time than by the composition of the four BDMs. The orders Burkholderiales and Pseudonocardiales were dominant on most BDMs across different time points. The genus Ramlibacter was revealed as a common biomarker for both PLA and PBAT by random-forest model, and all biomarkers for the BDMs belonged to the dominant order Burkholderiales. In addition, degradation-related and pathogen-related functional taxa were enriched in all mulches among all 40 functional groups, while surprisingly, potential pathogens were detected at higher levels on BDMs than PE. For community assembly on all mulches, the drift and dispersal processes played more important roles than selection, and in particular, the contribution of stochastic drift increased during the degradation process of BDMs while selection decreased, while the opposite trend was observed with PE mulch. Overall, our results demonstrated some degradation species and pathogens were specifically enriched on BDMs, though stochastic processes also had important impacts on the community assembly. It suggested that, similar to conventional plastic mulch, the increased usage of BDMs could lead to potential hazards to crops and human health.
Prevalence, Risk Factors, and Genetic Characterization of Extended-Spectrum Beta-Lactamase Escherichia coli Isolated From Healthy Pregnant Women in Madagascar
Authors: Milenkov Milen , Rasoanandrasana Saida , Rahajamanana Lalaina Vonintsoa , Rakotomalala Rivo Solo , Razafindrakoto Catherine Ainamalala , Rafalimanana Christian , Ravelomandranto Emile , Ravaoarisaina Zakasoa , Westeel Emilie , Petitjean Marie , Mullaert Jimmy , Clermont Olivier , Raskine Laurent , Samison Luc Hervé , Endtz Hubert , Andremont Antoine , Denamur Erick , Komurian-Pradel Florence , Armand-Lefevre Laurence
Published: December 2021

Antimicrobial resistance is a major public health concern worldwide affecting humans, animals and the environment. However, data is lacking especially in developing countries. Thus, the World Health Organization developed a One-Health surveillance project called Tricycle focusing on the prevalence of ESBL-producing Escherichia coli in humans, animals, and the environment. Here we present the first results of the human community component of Tricycle in Madagascar. From July 2018 to April 2019, rectal swabs from 492 pregnant women from Antananarivo, Mahajanga, Ambatondrazaka, and Toamasina were tested for ESBL-E. coli carriage. Demographic, sociological and environmental risk factors were investigated, and E. coli isolates were characterized (antibiotic susceptibility, resistance and virulence genes, plasmids, and genomic diversity). ESBL-E. coli prevalence carriage in pregnant women was 34% varying from 12% (Toamasina) to 65% (Ambatondrazaka). The main risk factor associated with ESBL-E. coli carriage was the rainy season (OR = 2.9, 95% CI 1.3–5.6, p = 0.009). Whole genome sequencing was performed on 168 isolates from 144 participants. blaCTX–M–15 was the most frequent ESBL gene (86%). One isolate was resistant to carbapenems and carried the blaNDM–5 gene. Most isolates belonged to commensalism associated phylogenetic groups A, B1, and C (90%) and marginally to extra-intestinal virulence associated phylogenetic groups B2, D and F (10%). Multi locus sequence typing showed 67 different sequence types gathered in 17 clonal complexes (STc), the most frequent being STc10/phylogroup A (35%), followed distantly by the emerging STc155/phylogroup B1 (7%), STc38/phylogroup D (4%) and STc131/phylogroup B2 (3%). While a wide diversity of clones has been observed, SNP analysis revealed several genetically close isolates (n = 34/168) which suggests human-to-human transmissions. IncY plasmids were found with an unusual prevalence (23%), all carrying a blaCTX–M–15. Most of them (85%) showed substantial homology (≥85%) suggesting a dissemination of IncY ESBL plasmids in Madagascar. This large-scale study reveals a high prevalence of ESBL-E. coli among pregnant women in four cities in Madagascar associated with warmth and rainfall. It shows the great diversity of E. coli disseminating throughout the country but also transmission of specific clones and spread of plasmids. This highlights the urgent need of public-health interventions to control antibiotic resistance in the country.
Effect of Chinese Herbal Medicine Mixture 919 Syrup on Regulation of the Ghrelin Pathway and Intestinal Microbiota in Rats With Non-alcoholic Fatty Liver Disease
Authors: Chen Manman , Xing Jingwei , Pan Danqing , Gao Pengfei
Published: December 2021

As a manifestation of metabolic syndrome in the liver, non-alcoholic fatty liver disease (NAFLD) has become the top cause of liver disease in many countries. Recent studies have shown that intestinal microbiota disorder plays an important role in the occurrence and development of NAFLD and that regulating intestinal microbiota provides a new option for NAFLD treatment. In addition, research indicates that risk of NAFLD increases as body mass index rises, and interventions that reduce body weight and change diet can help to lower the incidence of NAFLD. Studies have found that 919 syrup may effectively treat NAFLD in rats by improving liver function and lipid metabolism and regulating body weight and feed intake, however, its potential toxicity and the specific mechanism by which it controls this disease require further exploration. This study assesses both the toxicity of 919 syrup and its regulatory effect on the appetite-related Ghrelin pathway and intestinal microbiota of rats with NAFLD. Results indicate that 919 syrup has no obvious side-effects on body weight, feed intake, blood glucose level, hepatorenal function, and liver tissue structure of normal rats. Moreover, 919 syrup can reverse abnormal changes to expression of Ghrelin pathway genes related to appetite in both the brain and stomach and repair alterations to the intestinal microbiota in rats with NAFLD. This herbal medicine is a safe and promising therapeutic drug for the treatment of NAFLD.