30 research outputs found

    Optimal input potential functions in the interacting particle system method

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    The assessment of the probability of a rare event with a naive Monte-Carlo method is computationally intensive, so faster estimation methods, such as variance reduction methods, are needed. We focus on one of these methods which is the interacting particle (IPS) system method. The method requires to specify a set of potential functions. The choice of these functions is crucial, because it determines the magnitude of the variance reduction. So far, little information was available on how to choose the potential functions. To remedy this, we provide the expression of the optimal potential functions minimizing the asymptotic variance of the estimator of the IPS method

    High prevalence of a globally disseminated hypervirulent clone, Staphylococcus aureus CC121, with reduced vancomycin susceptibility in community settings in China

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    Objectives: Most vancomycin-intermediate Staphylococcus aureus (VISA) and heterogeneous VISA (hVISA) are derived from hospital-associated MRSA due to treatment failure; however, the prevalence of hVISA/VISA in community settings remains unclear. Methods: Four hundred and seventy-six community-associated isolates were collected between 2010 and 2011 during national surveillance for antimicrobial resistance in 31 county hospitals across China. Drug susceptibility evaluation and mecA detection were performed by using broth microdilution and PCR analysis, respectively. hVISA/VISA were identified by using macro-Etest and a modified population analysis profile (PAP)-AUC method. The genetic features of all hVISA/VISA isolates were genotyped. Results: Among 476 isolates, MRSA and MSSA accounted for 19.7% (n = 94) and 80.3% (n = 382), respectively. Two VISA and 36 hVISA isolates were identified by PAP-AUC testing. The VISA isolates and 29 of the hVISA isolates were MRSA. The proportion of hVISA/VISA was significantly higher in MRSA (30.9%) than in MSSA (1.8%). The hVISA/VISA isolates were assigned to 18 STs classified into seven clonal complexes (CCs). CC121 (n = 12) followed by ST239 (n = 11) was the most prevalent hVISA/VISA clone. All ST239-hVISA/VISA were MRSA, while 12 CC121-hVISA isolates included 6 MSSA and 6 MRSA isolates. SCCmec III was predominant among MRSA-hVISA/VISA isolates. agr I and agr IV were detected in ST239 and CC121, respectively. All except two strains were positive for Panton-Valentine leucocidin genes. Conclusions: To the best of our knowledge, this is the first report of CC121 as a prevalent hVISA clone in community settings, highlighting the necessity of surveillance and stricter infection control measures for this globally disseminated lineage

    Novel Subclone of Carbapenem-Resistant Klebsiella pneumoniae Sequence Type 11 with Enhanced Virulence and Transmissibility, China.

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    We aimed to clarify the epidemiologic and clinical importance of evolutionary events that occurred in carbapenem-resistant Klebsiella pneumoniae (CRKP). We collected 203 CRKP causing bloodstream infections in a tertiary hospital in China during 2013-2017. We detected a subclonal shift in the dominant clone sequence type (ST) 11 CRKP in which the previously prevalent capsular loci (KL) 47 had been replaced by KL64 since 2016. Patients infected with ST11-KL64 CRKP had a significantly higher 30-day mortality rate than other CRKP-infected patients. Enhanced virulence was further evidenced by phenotypic tests. Phylogenetic reconstruction demonstrated that ST11-KL64 is derived from an ST11-KL47-like ancestor through recombination. We identified a pLVPK-like virulence plasmid carrying rmpA and peg-344 in ST11-KL64 exclusively from 2016 onward. The pLVPK-like-positive ST11-KL64 isolates exhibited enhanced environmental survival. Retrospective screening of a national collection identified ST11-KL64 in multiple regions. Targeted surveillance of this high-risk CRKP clone is urgently needed

    Variety-driven rhizosphere microbiome bestows differential salt tolerance to alfalfa for coping with salinity stress

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    Soil salinization is a global environmental issue and a significant abiotic stress that threatens crop production. Root-associated rhizosphere microbiota play a pivotal role in enhancing plant tolerance to abiotic stresses. However, limited information is available concerning the specific variations in rhizosphere microbiota driven by different plant genotypes (varieties) in response to varying levels of salinity stress. In this study, we compared the growth performance of three alfalfa varieties with varying salt tolerance levels in soils with different degrees of salinization. High-throughput 16S rRNA and ITS sequencing were employed to analyze the rhizosphere microbial communities. Undoubtedly, the increasing salinity significantly inhibited alfalfa growth and reduced rhizosphere microbial diversity. However, intriguingly, salt-tolerant varieties exhibited relatively lower susceptibility to salinity, maintaining more stable rhizosphere bacterial community structure, whereas the reverse was observed for salt-sensitive varieties. Bacillus emerged as the dominant species in alfalfa's adaptation to salinity stress, constituting 21.20% of the shared bacterial genera among the three varieties. The higher abundance of Bacillus, Ensifer, and Pseudomonas in the rhizosphere of salt-tolerant alfalfa varieties is crucial in determining their elevated salt tolerance. As salinity levels increased, salt-sensitive varieties gradually accumulated a substantial population of pathogenic fungi, such as Fusarium and Rhizoctonia. Furthermore, rhizosphere bacteria of salt-tolerant varieties exhibited increased activity in various metabolic pathways, including biosynthesis of secondary metabolites, carbon metabolism, and biosynthesis of amino acids. It is suggested that salt-tolerant alfalfa varieties can provide more carbon sources to the rhizosphere, enriching more effective plant growth-promoting bacteria (PGPB) such as Pseudomonas to mitigate salinity stress. In conclusion, our results highlight the variety-mediated enrichment of rhizosphere microbiota in response to salinity stress, confirming that the high-abundance enrichment of specific dominant rhizosphere microbes and their vital roles play a significant role in conferring high salt adaptability to these varieties

    APT Weighted MRI as an Effective Imaging Protocol to Predict Clinical Outcome After Acute Ischemic Stroke

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    To explore the capability of the amide-proton-transfer weighted (APTW) magnetic resonance imaging (MRI) in the evaluation of clinical neurological deficit at the time of hospitalization and assessment of long-term daily functional outcome for patients with acute ischemic stroke (AIS). We recruited 55 AIS patients with brain MRI acquired within 24–48 h of symptom onset and followed up with their 90-day modified Rankin Scale (mRS) score. APT weighted MRI was performed for all the study subjects to measure APTW signal quantitatively in the acute ischemic area (APTWipsi) and the contralateral side (APTWcont). Change of the APT signal between the acute ischemic region and the contralateral side (ΔAPTW) was calculated. Maximum APTW signal (APTWmax) and minimal APTW signal (APTWmin) were also acquired to demonstrate APTW signals heterogeneity (APTWmax−min). In addition, all the patients were divided into 2 groups according to their 90-day mRS score (good prognosis group with mRS score <2 and poor prognosis group with mRS score ≥2). In the meantime, ΔAPTW of these groups was compared. We found that ΔAPTW was in good correlation with National Institutes of Health Stroke Scale (NIHSS) score (R2 = 0.578, p < 0.001) and 90-day mRS score (R2 = 0.55, p < 0.001). There was significant difference of ΔAPTW between patients with good prognosis and patients with poor prognosis. Plus, APTWmax−min was significantly different between two groups. These results suggested that APT weighted MRI could be used as an effective tool to assess the stroke severity and prognosis for patients with AIS, with APTW signal heterogeneity as a possible biomarker

    APPLICATION OF A NOVEL WHOLE-GENOME HPV SEQUENCING APPROACH TO CLARIFY THE EPIDEMIOLOGY AND MOLECULAR PATHOGENESIS OF CERVICAL ADENOCARCINOMA

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    Cervical screening has not effectively controlled cervical adenocarcinoma (ADC), which now accounts for one-third of cervical cancer cases in the US. ADC has poorly-defined precursors, and its rarity compared to the precursors of the most common subtype of cervical cancer, squamous cell carcinoma (SCC), has made it challenging to study. The overarching research goal of this dissertation is to clarify the pathogenesis of ADC and possibly improve cervical cancer screening effectiveness as a result. By combining large-scale epidemiology cohort study with next-generation whole-genome sequence HPV data, this dissertation will explore the pathogenesis of ADC from three different level: 1) HPV type level, 2) HPV lineage/sublineage level, and 3) HPV variant level
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