Ureteroscopic lithotripsy for ureteral stones in children using holmium: yag laser energy: results of a multicentric survey

BACKGROUND: Holmium:YAG (Ho:YAG) laser lithotripsy has broadened the indications for ureteroscopic stone managements in adults, but few evidence are currently available in the pediatric population. OBJECTIVE: This article aimed to assess the outcome of Ho:YAG laser lithotripsy during retrograde ureteroscopic management of ureteral stones in different locations in children. STUDY DESIGN: The medical records of 149 patients (71 boys and 78 girls; median age 9.2 years) treated with Ho:YAG laser ureteroscopic lithotripsy in five international pediatric urology units over the last 5 years were retrospectively reviewed. Exclusion criteria included patients with renal calculi and/or with a history of ipsilateral stricture, renal failure, active urinary tract infection, or coagulation disorder. RESULTS: Stones were treated with dusting technique in all cases. The median stone size was 10.3 mm (range 5-17). Stones were located in the distal ureter in 77 cases (51.7%), in the middle ureter in 23 cases (15.4%), and in the proximal ureter in 49 cases (32.9%). The median operative time was 29.8 min (range 20-95). Intra-operative complications included five bleedings (3.3%) and seven stone retropulsions (4.7%). Overall stone-free rate was 97.3%. Overall postoperative complications rate was 4.0% and included two cases of stent migration (1.3%) (Clavien II) and four residual stone fragments (2.7%) that were successfully treated using the same technique (Clavien IIIb). On multivariate analysis, re-operation rate was significantly dependent on the proximal stone location and presence of residual fragments >2 mm (P = 0.001). DISCUSSION: This study is one of the largest pediatric series among those published until now. The study series reported a shorter operative time, a higher success rate, and a lower postoperative complications rate compared with previous series. A limitation of this study is that stone-free rates may be somewhat inaccurate using ultrasonography and plain X-ray compared with computed tomography (CT); the study's 97.3% success rate may be overestimated because no CT scan was done postoperatively to check the stone-free rate. Other limitations of this article include its retrospective nature, the multi-institutional participation, and the heterogeneous patient collective. CONCLUSION: The Ho:YAG laser ureteroscopic lithotripsy seems to be an excellent first-line treatment for children with ureteral stones, independently from primary location and size. However, patients with proximal ureteral stones and residual fragments >2 mm reported a higher risk to require a secondary procedure to become stone-free. Combination of techniques as well as appropriate endourologic tools are key points for the success of the procedure regardless of stones' size and location

SBML2LaTEX: Conversion of SBML files into human-readable reports

Summary: The XML-based Systems Biology Markup Language (SBML) has emerged as a standard for storage, communication and interchange of models in systems biology. As a machine-readable format XML is difficult for humans to read and understand. Many tools are available that visualize the reaction pathways stored in SBML files, but many components, e.g. unit declarations, complex kinetic equations or links to MIRIAM resources, are often not made visible in these diagrams. For a broader understanding of the models, support in scientific writing and error detection, a human-readable report of the complete model is needed. We present SBML2LaTEX, a Java-based stand-alone program to fill this gap. A convenient web service allows users to directly convert SBML to various formats, including DVI, LaTEX and PDF, and provides many settings for customization

Whole genome sequencing,molecular typing and in vivovirulence of OXA-48-producingEscherichia coli isolates includingST131 H30-Rx, H22 and H41subclones

Carbapenem-resistant Enterobacteriaceae, including the increasingly reported OXA-48 Escherichia coli producers, are an emerging public health threat worldwide. Due to their alarming detection in our healthcare setting and their possible presence in the community, seven OXA-48-producing, extraintestinal pathogenic E. coli were analysed by whole genome sequencing as well as conventional tools, and tested for in vivo virulence. As a result, five E. coli OXA-48-producing subclones were detected (O25:H4-ST131/PST43-fimH30-virotype E; O25:H4-ST131/PST9-fimH22-virotype D5, O16:H5-ST131/ PST506-fimH41; O25:H5-ST83/PST207 and O9:H25-ST58/PST24). Four ST131 and one ST83 isolates satisfied the ExPEC status, and all except the O16:H5 ST131 isolate were UPEC. All isolates exhibited local inflammatory response with extensive subcutaneous necrosis but low lethality when tested in a mouse sepsis model. The blaOXA-48 gene was located in MOBP131/IncL plasmids (four isolates) or within the chromosome (three ST131 H30-Rx isolates), carried by Tn1999-like elements. All, except the ST83 isolate, were multidrug-resistant, with additional plasmids acting as vehicles for the spread of various resistance genes. This is the first study to analyse the whole genome sequences of blaOXA-48-positive ST131, ST58 and ST83 E. coli isolates in conjunction with experimental data, and to evaluate the in vivo virulence of blaOXA-48 isolates, which pose an important challenge to patient management

Complete Sequencing of pNDM-HK Encoding NDM-1 Carbapenemase from a Multidrug-Resistant Escherichia coli Strain Isolated in Hong Kong

BACKGROUND: The emergence of plasmid-mediated carbapenemases, such as NDM-1 in Enterobacteriaceae is a major public health issue. Since they mediate resistance to virtually all β-lactam antibiotics and there is often co-resistance to other antibiotic classes, the therapeutic options for infections caused by these organisms are very limited. METHODOLOGY: We characterized the first NDM-1 producing E. coli isolate recovered in Hong Kong. The plasmid encoding the metallo-β-lactamase gene was sequenced. PRINCIPAL FINDINGS: The plasmid, pNDM-HK readily transferred to E. coli J53 at high frequencies. It belongs to the broad host range IncL/M incompatibility group and is 88803 bp in size. Sequence alignment showed that pNDM-HK has a 55 kb backbone which shared 97% homology with pEL60 originating from the plant pathogen, Erwina amylovora in Lebanon and a 28.9 kb variable region. The plasmid backbone includes the mucAB genes mediating ultraviolet light resistance. The 28.9 kb region has a composite transposon-like structure which includes intact or truncated genes associated with resistance to β-lactams (bla(TEM-1), bla(NDM-1), Δbla(DHA-1)), aminoglycosides (aacC2, armA), sulphonamides (sul1) and macrolides (mel, mph2). It also harbors the following mobile elements: IS26, ISCR1, tnpU, tnpAcp2, tnpD, ΔtnpATn1 and insL. Certain blocks within the 28.9 kb variable region had homology with the corresponding sequences in the widely disseminated plasmids, pCTX-M3, pMUR050 and pKP048 originating from bacteria in Poland in 1996, in Spain in 2002 and in China in 2006, respectively. SIGNIFICANCE: The genetic support of NDM-1 gene suggests that it has evolved through complex pathways. The association with broad host range plasmid and multiple mobile genetic elements explain its observed horizontal mobility in multiple bacterial taxa

The dynamic stability and nonlinear resonance of a flexible connecting rod: Continuous parameter model

The transverse vibrations of a flexible connecting rod in an otherwise rigid slider-crank mechanism are considered. An analytical approach using the method of multiple scales is adopted and particular emphasis is placed on nonlinear effects which arise from finite deformations. Several nonlinear resonances and instabilities are investigated, and the influences of important system parameters on these resonances are examined in detail.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/43330/1/11071_2004_Article_BF00162233.pd

Drug-target identification in COVID-19 disease mechanisms using computational systems biology approaches

IntroductionThe COVID-19 Disease Map project is a large-scale community effort uniting 277 scientists from 130 Institutions around the globe. We use high-quality, mechanistic content describing SARS-CoV-2-host interactions and develop interoperable bioinformatic pipelines for novel target identification and drug repurposing. MethodsExtensive community work allowed an impressive step forward in building interfaces between Systems Biology tools and platforms. Our framework can link biomolecules from omics data analysis and computational modelling to dysregulated pathways in a cell-, tissue- or patient-specific manner. Drug repurposing using text mining and AI-assisted analysis identified potential drugs, chemicals and microRNAs that could target the identified key factors.ResultsResults revealed drugs already tested for anti-COVID-19 efficacy, providing a mechanistic context for their mode of action, and drugs already in clinical trials for treating other diseases, never tested against COVID-19. DiscussionThe key advance is that the proposed framework is versatile and expandable, offering a significant upgrade in the arsenal for virus-host interactions and other complex pathologies

SBML Level 3: an extensible format for the exchange and reuse of biological models

Systems biology has experienced dramatic growth in the number, size, and complexity of computational models. To reproduce simulation results and reuse models, researchers must exchange unambiguous model descriptions. We review the latest edition of the Systems Biology Markup Language (SBML), a format designed for this purpose. A community of modelers and software authors developed SBML Level 3 over the past decade. Its modular form consists of a core suited to representing reaction-based models and packages that extend the core with features suited to other model types including constraint-based models, reaction-diffusion models, logical network models, and rule-based models. The format leverages two decades of SBML and a rich software ecosystem that transformed how systems biologists build and interact with models. More recently, the rise of multiscale models of whole cells and organs, and new data sources such as single-cell measurements and live imaging, has precipitated new ways of integrating data with models. We provide our perspectives on the challenges presented by these developments and how SBML Level 3 provides the foundation needed to support this evolution

The first 10 years of the international coordination network for standards in systems and synthetic biology (COMBINE)

This paper presents a report on outcomes of the 10th Computational Modeling in Biology Network (COMBINE) meeting that was held in Heidelberg, Germany, in July of 2019. The annual event brings together researchers, biocurators and software engineers to present recent results and discuss future work in the area of standards for systems and synthetic biology. The COMBINE initiative coordinates the development of various community standards and formats for computational models in the life sciences. Over the past 10 years, COMBINE has brought together standard communities that have further developed and harmonized their standards for better interoperability of models and data. COMBINE 2019 was co-located with a stakeholder workshop of the European EU-STANDS4PM initiative that aims at harmonized data and model standardization for in silico models in the field of personalized medicine, as well as with the FAIRDOM PALs meeting to discuss findable, accessible, interoperable and reusable (FAIR) data sharing. This report briefly describes the work discussed in invited and contributed talks as well as during breakout sessions. It also highlights recent advancements in data, model, and annotation standardization efforts. Finally, this report concludes with some challenges and opportunities that this community will face during the next 10 years.publishe