bluuebunny/crossref_metadata_2025_split huggingface dataset:
Metagenomic sequencing, molecular characterization, and Bayesian phylogenetics of imported type 2 vaccine-derived poliovirus, Spain, 2021
Authors: Fernandez-Garcia Maria Dolores , Faye Martin , Diez-Fuertes Francisco , Moreno-Docón Antonio , Chirlaque-López Maria Dolores , Faye Ousmane , Cabrerizo Maria 
Published: May 2023

IntroductionIn 2021, a type 2 vaccine-derived poliovirus (VDPV2) was isolated from the stool of a patient with acute flaccid paralysis (AFP) admitted to Spain from Senegal. A virological investigation was conducted to characterize and trace the origin of VDPV2.MethodsWe used an unbiased metagenomic approach for the whole-genome sequencing of VDPV2 from the stool (pre-treated with chloroform) and from the poliovirus-positive supernatant. Phylogenetic analyses and molecular epidemiological analyses relying on the Bayesian Markov Chain Monte Carlo methodology were used to determine the geographical origin and estimate the date of the initiating dose of the oral poliovirus vaccine for the imported VDPV2.ResultsWe obtained a high percentage of viral reads per total reads mapped to the poliovirus genome (69.5% for pre-treated stool and 75.8% for isolate) with a great depth of sequencing coverage (5,931 and 11,581, respectively) and complete genome coverage (100%). The two key attenuating mutations in the Sabin 2 strain had reverted (A481G in the 5’UTR and Ile143Thr in VP1). In addition, the genome had a recombinant structure between type-2 poliovirus and an unidentified non-polio enterovirus-C (NPEV-C) strain with a crossover point in the protease-2A genomic region. VP1 phylogenetic analysis revealed that this strain is closely related to VDPV2 strains circulating in Senegal in 2021. According to Bayesian phylogenetics, the most recent common ancestor of the imported VDPV2 could date back 2.6 years (95% HPD: 1.7–3.7) in Senegal. We suggest that all VDPV2s circulating in 2020–21 in Senegal, Guinea, Gambia, and Mauritania have an ancestral origin in Senegal estimated around 2015. All 50 stool samples from healthy case contacts collected in Spain (n = 25) and Senegal (n = 25) and four wastewater samples collected in Spain were poliovirus negative.DiscussionBy using a whole-genome sequencing protocol with unbiased metagenomics from the clinical sample and viral isolate with high sequence coverage, efficiency, and throughput, we confirmed the classification of VDPV as a circulating type. The close genomic linkage with strains from Senegal was consistent with their classification as imported. Given the scarce number of complete genome sequences for NPEV-C in public databases, this protocol could help expand poliovirus and NPEV-C sequencing capacity worldwide.
Causal effects between gut microbiota and IgA nephropathy: a bidirectional Mendelian randomization study
Authors: Ren Feihong , Jin Qiubai , Liu Tongtong , Ren Xuelei , Zhan Yongli 
Published: May 2023

BackgroundTherapeutic approaches that target the gut microbiota (GM) may be helpful in the potential prevention and treatment of IgA nephropathy (IgAN). Meanwhile, relevant studies demonstrated a correlation between GM and IgAN, however, these confounding evidence cannot prove a causal relationship between GM and IgAN.MethodsBased on the data from the GM genome-wide association study (GWAS) of MiBioGen and the IgAN GWAS data from the FinnGen research. A bi-directional Mendelian randomization (MR) study was performed to explore the causal relationship between GM and IgAN. We used inverse variance weighted (IVW) method as the primary method to determine the causal relationship between exposure and outcome in our MR study. Besides, we used additional analysis (MR-Egger, weighted median) and sensitivity analysis (Cochrane’s Q test, MR-Egger and MR-PRESSO) to select significant results, followed by Bayesian model averaging (MR-BMA) to test the results of MR study. Finally, a reverse MR analysis was conducted to estimate the probability of reverse causality.ResultsAt the locus-wide significance level, the results of IVW method and additional analysis showed that Genus Enterorhabdus was a protective factor for IgAN [OR: 0.456, 95% CI: 0.238-0.875, p=0.023], while Genus butyricicoccus was a risk factor for IgAN [OR: 3.471, 95% CI: 1.671-7.209, p=0.0008]. In the sensitivity analysis, no significant pleiotropy or heterogeneity of the results was found.ConclusionOur study revealed the causal relationship between GM and IgAN, and expanded the variety of bacterial taxa causally related to IgAN. These bacterial taxa could become novel biomarkers to facilitate the development of targeted therapies for IgAN, developing our understanding of the “gut-kidney axis”.
Intestinal loads of extended-spectrum beta-lactamase and Carbapenemase genes in critically ill pediatric patients
Authors: Dahdouh Elias , Cendejas-Bueno Emilio , Ruiz-Carrascoso Guillermo , Schüffelmann Cristina , Lázaro-Perona Fernando , Castro-Martínez Mercedes , Moreno-Ramos Francisco , Escosa-García Luis , Alguacil-Guillén Marina , Mingorance Jesús 
Published: May 2023

IntroductionIntestinal colonization by Multi-Drug Resistant Organisms (MDROs) can pose a threat on the health of critically ill patients. The extent of colonization by these organisms is related to previous antibiotic treatments and their ability to cause infections among adult patients. The aim of this study is to determine the relationship between the intestinal Relative Loads (RLs) of selected antibiotic resistance genes, antibiotic consumption and extra-intestinal spread among critically ill pediatric patients.MethodsRLs of blaCTX-M-1-Family, blaOXA-1, blaOXA-48 and blaVIM were determined in 382 rectal swabs obtained from 90 pediatric critically ill patients using qPCRs. The RLs were compared to the patients’ demographics, antibiotic consumption, and detection of MDROs from extra-intestinal sites. 16SrDNA metagenomic sequencing was performed for 40 samples and clonality analyses were done for representative isolates.Results and discussion76 (74.45%) patients from which 340 (89.01%) rectal swabs were collected had at least one swab that was positive for one of the tested genes. Routine cultures did not identify carbapenemases in 32 (45.1%) and 78 (58.2%) swabs that were positive by PCR for blaOXA-48 and blaVIM, respectively. RLs of above 6.5% were associated with extra-intestinal spread of blaOXA-48-harboring MDROs. Consumption of carbapenems, non-carbapenem β-lactams, and glycopeptides were statistically associated with testing negative for blaCTX-M-1-Family and blaOXA-1 while the consumption of trimethoprim/sulfamethoxazole and aminoglycosides was associated with testing negative for blaOXA-48 (P&lt;0.05). In conclusion, targeted qPCRs can be used to determine the extent of intestinal dominance by antibiotic resistant opportunistic pathogens and their potential to cause extra-intestinal infections among a critically ill pediatric population.
Treatment of pure aortic regurgitation using surgical or transcatheter aortic valve replacement between 2018 and 2020 in Germany
Authors: Oettinger Vera , Hilgendorf Ingo , Wolf Dennis , Stachon Peter , Heidenreich Adrian , Zehender Manfred , Westermann Dirk , Kaier Klaus , von zur Mühlen Constantin 
Published: May 2023

BackgroundIn pure aortic regurgitation, transcatheter aortic valve replacement (TAVR) is not yet used on a regular base. Due to constant development of TAVR, it is necessary to analyze current data.MethodsBy use of health records, we analyzed all isolated TAVR or surgical aortic valve replacements (SAVR) for pure aortic regurgitation between 2018 and 2020 in Germany.Results4,861 procedures—4,025 SAVR and 836 TAVR—for aortic regurgitation were identified. Patients treated with TAVR were older, showed a higher logistic EuroSCORE, and had more pre-existing diseases. While results indicate a slightly higher unadjusted in-hospital mortality for transapical TAVR (6.00%) vs. SAVR (5.71%), transfemoral TAVR showed better outcomes, with self-expanding compared to balloon-expandable transfemoral TAVR having significantly lower in-hospital mortality (2.41% vs. 5.17%; p = 0.039). After risk adjustment, balloon-expandable as well as self-expanding transfemoral TAVR were associated with a significantly lower mortality vs. SAVR (balloon-expandable: risk adjusted OR = 0.50 [95% CI 0.27; 0.94], p = 0.031; self-expanding: OR = 0.20 [0.10; 0.41], p &lt; 0.001). Furthermore, the observed in-hospital outcomes of stroke, major bleeding, delirium, and mechanical ventilation &gt;48 h were significantly in favor of TAVR. In addition, TAVR showed a significantly shorter length of hospital stay compared to SAVR (transapical: risk adjusted Coefficient = −4.75d [−7.05d; −2.46d], p &lt; 0.001; balloon-expandable: Coefficient = −6.88d [−9.06d; −4.69d], p &lt; 0.001; self-expanding: Coefficient = −7.22 [−8.95; −5.49], p &lt; 0.001).ConclusionsTAVR is a viable alternative to SAVR in the treatment of pure aortic regurgitation for selected patients, showing overall low in-hospital mortality and complication rates, especially with regard to self-expanding transfemoral TAVR.
The role of proteasome activators PA28αβ and PA200 in brown adipocyte differentiation and function
Authors: Koçberber Zeynep , Willemsen Nienke , Bartelt Alexander 
Published: May 2023

IntroductionBrown adipocytes produce heat through non shivering thermogenesis (NST). To adapt to temperature cues, they possess a remarkably dynamic metabolism and undergo substantial cellular remodeling. The proteasome plays a central role in proteostasis and adaptive proteasome activity is required for sustained NST. Proteasome activators (PAs) are a class of proteasome regulators but the role of PAs in brown adipocytes is unknown. Here, we studied the roles of PA28α (encoded by Psme1) and PA200 (encoded by Psme4) in brown adipocyte differentiation and function.MethodsWe measured gene expression in mouse brown adipose tissue. In cultured brown adipocytes, we silenced Psme1 and/or Psme4 expression through siRNA transfection. We then assessed impact on the ubiquitin proteasome system, brown adipocyte differentiation and function.ResultsWe found that Psme1 and Psme4 are expressed in brown adipocytes in vivo and in vitro. Through silencing of Psme1 and/or Psme4 expression in cultured brown adipocytes, we found that loss of PAs did not impair proteasome assembly or activity, and that PAs were not required for proteostasis in this model. Loss of Psme1 and/or Psme4 did not impair brown adipocyte development or activation, suggesting that PAs are neither required for brown adipogenesis nor NST.DiscussionIn summary, we found no role for Psme1 and Psme4 in brown adipocyte proteostasis, differentiation, or function. These findings contribute to our basic understanding of proteasome biology and the roles of proteasome activators in brown adipocytes.
Identification and validation of a novel stress granules-related prognostic model in colorectal cancer
Authors: Liu Zhihao , Zhao Enen , Li Huali , Lin Dagui , Huang Chengmei , Zhou Yi , Zhang Yaxin , Pan Xingyan , Liao Wenting , Li Fengtian 
Published: May 2023

Aims: A growing body of evidence demonstrates that Stress granules (SGs), a non-membrane cytoplasmic compartments, are important to colorectal development and chemoresistance. However, the clinical and pathological significance of SGs in colorectal cancer (CRC) patients is unclear. The aim of this study is to propose a new prognostic model related to SGs for CRC on the basis of transcriptional expression.Main methods: Differentially expressed SGs-related genes (DESGGs) were identified in CRC patients from TCGA dataset by limma R package. The univariate and Multivariate Cox regression model was used to construct a SGs-related prognostic prediction gene signature (SGPPGS). The CIBERSORT algorithm was used to assess cellular immune components between the two different risk groups. The mRNA expression levels of the predictive signature from 3 partial response (PR) and 6 stable disease (SD) or progress disease (PD) after neoadjuvant therapy CRC patients’ specimen were examined.Key findings: By screening and identification, SGPPGS comprised of four genes (CPT2, NRG1, GAP43, and CDKN2A) from DESGGs is established. Furthermore, we find that the risk score of SGPPGS is an independent prognostic factor to overall survival. Notably, the abundance of immune response inhibitory components in tumor tissues is upregulated in the group with a high-risk score of SGPPGS. Importantly, the risk score of SGPPGS is associated with the chemotherapy response in metastatic colorectal cancer.Significance: This study reveals the association between SGs related genes and CRC prognosis and provides a novel SGs related gene signature for CRC prognosis prediction.
A self-binding immune complex vaccine elicits strong neutralizing responses against herpes simplex virus in mice
Authors: Diamos Andrew G. , Pardhe Mary D. , Bergeman Melissa H. , Kamzina Aigerim S. , DiPalma Michelle P. , Aman Sara , Chaves Artemio , Lowe Kenneth , Kilbourne Jacquelyn , Hogue Ian B. , Mason Hugh S. 
Published: May 2023

IntroductionIt has been known for over half a century that mixing an antigen with its cognate antibody in an immune complex (IC) can enhance antigen immunogenicity. However, many ICs produce inconsistent immune responses, and the use of ICs in the development new vaccines has been limited despite the otherwise widespread success of antibody-based therapeutics. To address this problem, we designed a self-binding recombinant immune complex (RIC) vaccine which mimics the larger ICs generated during natural infection.Materials and methodsIn this study, we created two novel vaccine candidates: 1) a traditional IC targeting herpes simplex virus 2 (HSV-2) by mixing glycoprotein D (gD) with a neutralizing antibody (gD-IC); and 2) an RIC consisting of gD fused to an immunoglobulin heavy chain and then tagged with its own binding site, allowing self-binding (gD-RIC). We characterized the complex size and immune receptor binding characteristics in vitro for each preparation. Then, the in vivo immunogenicity and virus neutralization of each vaccine were compared in mice.ResultsgD-RIC formed larger complexes which enhanced C1q receptor binding 25-fold compared to gD-IC. After immunization of mice, gD-RIC elicited up to 1,000-fold higher gD-specific antibody titers compared to traditional IC, reaching endpoint titers of 1:500,000 after two doses without adjuvant. The RIC construct also elicited stronger virus-specific neutralization against HSV-2, as well as stronger cross-neutralization against HSV-1, although the proportion of neutralizing antibodies to total antibodies was somewhat reduced in the RIC group.DiscussionThis work demonstrates that the RIC system overcomes many of the pitfalls of traditional IC, providing potent immune responses against HSV-2 gD. Based on these findings, further improvements to the RIC system are discussed. RIC have now been shown to be capable of inducing potent immune responses to a variety of viral antigens, underscoring their broad potential as a vaccine platform.
Atractylodes macrocephala Koidz. volatile oil relieves acute ulcerative colitis via regulating gut microbiota and gut microbiota metabolism
Authors: Cheng Hao , Zhang Dandan , Wu Jing , Liu Juan , Tan Yuzhu , Feng Wuwen , Peng Cheng 
Published: May 2023

BackgroundAtractylodes macrocephala Koidz. (AM) is a functional food with strong ant-colitis activity. AM volatile oil (AVO) is the main active ingredient of AM. However, no study has investigated the improvement effect of AVO on ulcerative colitis (UC) and the bioactivity mechanism also remains unknown. Here, we investigated whether AVO has ameliorative activity on acute colitis mice and its mechanism from the perspective of gut microbiota.MethodsAcute UC was induced in C57BL/6 mice by dextran sulfate sodium and treated with the AVO. Body weight, colon length, colon tissue pathology, and so on were assessed. The gut microbiota composition was profiled using 16s rRNA sequencing and global metabolomic profiling of the feces was performed. The results showed that AVO can alleviate bloody diarrhea, colon damage, and colon inflammation in colitis mice. In addition, AVO decreased potentially harmful bacteria (Turicibacter, Parasutterella, and Erysipelatoclostridium) and enriched potentially beneficial bacteria (Enterorhabdus, Parvibacter, and Akkermansia). Metabolomics disclosed that AVO altered gut microbiota metabolism by regulating 56 gut microbiota metabolites involved in 102 KEGG pathways. Among these KEGG pathways, many metabolism pathways play an important role in maintaining intestine homeostasis, such as amino acid metabolism (especially tryptophan metabolism), bile acids metabolism, and retinol metabolism.ConclusionIn conclusion, our study indicated that AVO can be expected as novel prebiotics to treat ulcerative colitis, and modulating the composition and metabolism of gut microbiota may be its pharmacological mechanism.
Inhibition of the intracellular domain of Notch1 results in vascular endothelial cell dysfunction in sepsis
Authors: Liu Tingyan , Zhang Caiyan , Ying Jiayun , Wang Yaodong , Yan Gangfeng , Zhou Yufeng , Lu Guoping 
Published: May 2023

BackgroundNotch signaling is critical for regulating the function of vascular endothelial cells (ECs). However, the effect of the intracellular domain of Notch1 (NICD) on EC injury in sepsis remains unclear.MethodsWe established a cell model of vascular endothelial dysfunction and induced sepsis in a mouse model via lipopolysaccharide (LPS) injection and cecal ligation and puncture (CLP). Endothelial barrier function and expression of endothelial-related proteins were determined using CCK-8, permeability, flow cytometry, immunoblot, and immunoprecipitation assays. The effect of NICD inhibition or activation on endothelial barrier function was evaluated in vitro. Melatonin was used for NICD activation in sepsis mice. The survival rate, Evans blue dye of organs, vessel relaxation assay, immunohistochemistry, ELISA, immunoblot were used to explore the specific role of melatonin for sepsis induced vascular dysfunction in vivo.ResultsWe found that LPS, interleukin 6, and serum collected from septic children could inhibit the expression of NICD and its downstream regulator Hes1, which impaired endothelial barrier function and led to EC apoptosis through the AKT pathway. Mechanistically, LPS decreased the stability of NICD by inhibiting the expression of a deubiquitylating enzyme, ubiquitin-specific proteases 8 (USP8). Melatonin, however, upregulated USP8 expression, thus maintaining the stability of NICD and Notch signaling, which ultimately reduced EC injury in our sepsis model and elevated the survival rate of septic mice.ConclusionsWe found a previously uncharacterized role of Notch1 in mediating vascular permeability during sepsis, and we showed that inhibition of NICD resulted in vascular EC dysfunction in sepsis, which was reversed by melatonin. Thus, the Notch1 signaling pathway is a potential target for the treatment of sepsis.
Aquatic species shows asymmetric distribution range shifts in native and non-native areas
Authors: Costa Eudriano F. S. , Encarnação João , Teodósio Maria Alexandra , Morais Pedro 
Published: May 2023

IntroductionClimate change is reshaping the geographical distribution of species across the globe. In marine ecosystems, climate change creates novel challenges to an environment impacted by numerous anthropogenic stressors. Forecasting shifts in species distribution, including the expansion of non-indigenous species under climate change scenarios, is a management challenge for today’s world.MethodsWe applied Bayesian Additive Regression Tree (BART) models to investigate the environmental factors modulating the occurrence and habitat preferences of the Atlantic blue crab Callinectes sapidus Rathbun, 1896 in native and non-native areas. With BART models, we also aimed to predict its current and future distributions under two climate change scenarios (RCPs 4.5 and 8.5). BART models were performed using global occurrences of the Atlantic blue crab – recorded from 1830 to 2022 – and several environmental covariates (i.e., water temperature, salinity, current velocity, and rugosity). Model accuracy was assessed with the Area Under the Curve (AUC) and True Skill Statistics (TSS) criteria. Cross-validation experiments were made to balance accuracy prediction and uncertainty model prediction intervals.Results and discussionAUC and TSS values indicated that data validation was successful for the BART model. Water temperature was the most critical variable affecting the presence probability of the Atlantic blue crab. The BART model predicts asymmetric distribution range shifts on both sides of the Atlantic Ocean. The non-native populations will experience broader shifts in their distribution range than in the native range, and the RCP 8.5 scenario model outputs predict a wider distribution range by the end of the century. Overall, we anticipate significant ecological changes in native and non-native areas. The range expansion in native areas is often equivalent to the ecological shifts induced by invasive species, so lessons learned by ecologists and managers in non-native areas will provide actionable insights to managers in native areas.
Risk factors accounting for anal incontinence during the first year after vaginal delivery—A case control study in China
Authors: Jia Yang , Liu Qingao , Zeng Lin , Wang Yan 
Published: May 2023

Introduction and hypothesisAnal incontinence (AI) is a prevalent postpartum disorder. This study aims to investigate and quantify the risk factors for AI in the Chinese population during the first year following vaginal delivery.MethodsThe case control study was conducted at Peking University Third Hospital, including all women who delivered vaginally between January 1, 2014, and June 30, 2018. Participants were followed up by telephone interviews 1 year after delivery. AI was defined as the involuntary loss of flatus or feces using a retrospective Jorge and Wexner score above 0. Clinical data were retrieved from the medical record system. Univariate and multivariate analyses were applied to identify potential risk factors accounting for AI. Based on the logistic regression model, a nomogram was constructed to predict the probability of AI postpartum. Restricted cubic spline was utilized to explore potential non-linear relationships between birth weight and AI postpartum.ResultsAmong the 140 AI and 421 none AI cases, we observed antepartum factors like every 100 g of birth weight gain (OR 1.39, 95% CI 1.30–1.49), while intrapartum factors like forceps-assisted vaginal delivery (OR 7.11, 95% CI 2.60–19.45), midline episiotomy (OR 13.11, 95% CI 1.71–100.89), second-degree perineal tear (OR 6.51, 95% CI 1.16–36.68), and third to fourth-degree perineal tear were independent risk factors for postpartum AI. Significantly, infant weighing over 3,400 g at birth increased the risk of AI postpartum. Based on logistic regression model, we constructed a nomogram to estimate the risk of AI 1 year after vaginal delivery.ConclusionOur findings indicated that during the first year following vaginal delivery, infant with birth weight of 3,400 g or more, forceps-assisted vaginal delivery, midline episiotomy, and second to fourth-degree perineal tear increased the risk of AI. As a result, it is essential to limit the routine use of forceps and midline episiotomy and to monitor fetal weight during prenatal care.