Distinct Genomic Features Characterize Two Clades of <i>Corynebacterium diphtheriae</i>: Proposal of <i>Corynebacterium diphtheriae</i> Subsp. <i>diphtheriae</i> Subsp. nov. and <i>Corynebacterium diphtheriae</i> Subsp. <i>lausannense</i> Subsp. nov.

&lt;i&gt;Corynebacterium diphtheriae&lt;/i&gt; is the etiological agent of diphtheria, a disease caused by the presence of the diphtheria toxin. However, an increasing number of records report non-toxigenic &lt;i&gt;C. diphtheriae&lt;/i&gt; infections. Here, a &lt;i&gt;C. diphtheriae&lt;/i&gt; strain was recovered from a patient with a past history of bronchiectasis who developed a severe tracheo-bronchitis with multiple whitish lesions of the distal trachea and the mainstem bronchi. Whole-genome sequencing (WGS), performed in parallel with PCR targeting the toxin gene and the Elek test, provided clinically relevant results in a short turnaround time, showing that the isolate was non-toxigenic. A comparative genomic analysis of the new strain (CHUV2995) with 56 other publicly available genomes of &lt;i&gt;C. diphtheriae&lt;/i&gt; revealed that the strains CHUV2995, CCUG 5865 and CMCNS703 share a lower average nucleotide identity (ANI) (95.24 to 95.39%) with the &lt;i&gt;C. diphtheriae&lt;/i&gt; NCTC 11397 &lt;sup&gt;T&lt;/sup&gt; reference genome than all other &lt;i&gt;C. diphtheriae&lt;/i&gt; genomes (&gt;98.15%). Core genome phylogeny confirmed the presence of two monophyletic clades. Based on these findings, we propose here two new &lt;i&gt;C. diphtheriae&lt;/i&gt; subspecies to replace the lineage denomination used in previous multilocus sequence typing studies: &lt;i&gt;C. diphtheriae&lt;/i&gt; subsp. &lt;i&gt;lausannense&lt;/i&gt; subsp. nov. (instead of lineage-2), regrouping strains CHUV2995, CCUG 5865, and CMCNS703, and &lt;i&gt;C. diphtheriae&lt;/i&gt; subsp. &lt;i&gt;diphtheriae&lt;/i&gt; subsp. nov, regrouping all other &lt;i&gt;C. diphtheriae&lt;/i&gt; in the dataset (instead of lineage-1). Interestingly, members of subspecies &lt;i&gt;lausannense&lt;/i&gt; displayed a larger genome size than subspecies &lt;i&gt;diphtheriae&lt;/i&gt; and were enriched in COG categories related to transport and metabolism of lipids (I) and inorganic ion (P). Conversely, they lacked all genes involved in the synthesis of pili (SpaA-type, SpaD-type and SpaH-type), molybdenum cofactor and of the nitrate reductase. Finally, the CHUV2995 genome is particularly enriched in mobility genes and harbors several prophages. The genome encodes a type II-C CRISPR-Cas locus with 2 spacers that lacks &lt;i&gt;csn2&lt;/i&gt; or &lt;i&gt;cas4&lt;/i&gt; , which could hamper the acquisition of new spacers and render strain CHUV2995 more susceptible to bacteriophage infections and gene acquisition through various mechanisms of horizontal gene transfer

Human Bronchial Epithelial Cells Induce CD141/CD123/DC-SIGN/FLT3 Monocytes That Promote Allogeneic Th17 Differentiation.

Little is known about monocyte differentiation in the lung mucosal environment and about how the epithelium shapes monocyte function. We studied the role of the soluble component of bronchial epithelial cells (BECs) obtained under basal culture conditions in innate and adaptive monocyte responses. Monocytes cultured in bronchial epithelial cell-conditioned media (BEC-CM) specifically upregulate CD141, CD123, and DC-SIGN surface levels and FLT3 expression, as well as the release of IL-1β, IL-6, and IL-10. BEC-conditioned monocytes stimulate naive T cells to produce IL-17 through IL-1β mechanism and also trigger IL-10 production by memory T cells. Furthermore, monocytes cultured in an inflammatory environment induced by the cytokines IL-6, IL-8, IL-1β, IL-15, TNF-α, and GM-CSF also upregulate CD123 and DC-SIGN expression. However, only inflammatory cytokines in the epithelial environment boost the expression of CD141. Interestingly, we identified a CD141/CD123/DC-SIGN triple positive population in the bronchoalveolar lavage fluid (BALF) from patients with different inflammatory conditions, demonstrating that this monocyte population exists in vivo. The frequency of this monocyte population was significantly increased in patients with sarcoidosis, suggesting a role in inflammatory mechanisms. Overall, these data highlight the specific role that the epithelium plays in shaping monocyte responses. Therefore, the unraveling of these mechanisms contributes to the understanding of the function that the epithelium may play in vivo

MR Volumetry of Lung Nodules: A Pilot Study

Introduction: Computed tomography (CT) is currently the reference modality for the detection and follow-up of pulmonary nodules. While 2D measurements are commonly used in clinical practice to assess growth, increasingly 3D volume measurements are being recommended. The goal of this pilot study was to evaluate preliminarily the capabilities of 3D MRI using ultra-short echo time for lung nodule volumetry, as it would provide a radiation-free modality for this task.Material and Methods: Artificial nodules were manufactured out of Agar and measured using an ultra-short echo time MRI sequence. CT data were also acquired as a reference. Image segmentation was carried out using an algorithm based on signal intensity thresholding (SIT). For comparison purposes, we also performed manual slice by slice segmentation. Volumes obtained with MRI and CT were compared. Finally, the volumetry of a lung nodule was evaluated in one human subject in comparison with CT.Results: Using the SIT technique, minimal bias was observed between CT and MRI across the entire range of volumes (2%) with limits of agreement below 14%. Comparison of manually segmented MRI and CT resulted in a larger bias (8%) and wider limits of agreement (−23% to 40%). In vivo, nodule volume differed of &lt;16% between modalities with the SIT technique.Conclusion: This pilot study showed very good concordance between CT and UTE-MRI to quantify lung nodule volumes, in both a phantom and human setting. Our results enhance the potential of MRI to quantify pulmonary nodule volume with similar performance to CT

The Swiss Approach - feasibility of a national low-dose CT lung cancer screening program.

BACKGROUND Lung cancer is the leading cause of cancer-related deaths in Switzerland. Despite this, there is no lung cancer screening program in the country. In the United States, low-dose computed tomography (LDCT) lung cancer screening is partially established and endorsed by guidelines. Moreover, evidence is growing that screening reduces lung cancer-related mortality and this was recently shown in a large European randomized controlled trial. Implementation of a lung cancer screening program, however, is challenging and depends on many country-specific factors. The goal of this article is to outline a potential Swiss lung cancer screening program. FRAMEWORK An exhaustive literature review on international screening models as well as interviews and site visits with international experts were initiated. Furthermore, workshops and interviews with national experts and stakeholders were conducted to share experiences and to establish the basis for a national Swiss lung cancer screening program. SCREENING APPROACH General practitioners, pulmonologists and the media should be part of the recruitment process. Decentralisation of the screening might lead to a higher adherence rate. To reduce stigmatisation, the screening should be integrated in a "lung health check". Standardisation and a common quality level are mandatory. The PLCOm2012 risk calculation model with a threshold of 1.5% risk for developing cancer in the next six years should be used in addition to established inclusion criteria. Biennial screening is preferred. LUNG RADS and NELSON+ are applied as classification models for lung nodules. CONCLUSION Based on data from recent studies, literature research, a health technology assessment, the information gained from this project and a pilot study the Swiss Interest Group for lung cancer screening (CH-LSIG) recommends the timely introduction of a systematic lung cancer screening program in Switzerland. The final decision is for the Swiss Cancer Screening Committee to make

The Swiss Approach - feasibility of a national low-dose CT lung cancer screening program

BACKGROUND Lung cancer is the leading cause of cancer-related deaths in Switzerland. Despite this, there is no lung cancer screening program in the country. In the United States, low-dose computed tomography (LDCT) lung cancer screening is partially established and endorsed by guidelines. Moreover, evidence is growing that screening reduces lung cancer-related mortality and this was recently shown in a large European randomized controlled trial. Implementation of a lung cancer screening program, however, is challenging and depends on many country-specific factors. The goal of this article is to outline a potential Swiss lung cancer screening program. FRAMEWORK An exhaustive literature review on international screening models as well as interviews and site visits with international experts were initiated. Furthermore, workshops and interviews with national experts and stakeholders were conducted to share experiences and to establish the basis for a national Swiss lung cancer screening program. SCREENING APPROACH General practitioners, pulmonologists and the media should be part of the recruitment process. Decentralisation of the screening might lead to a higher adherence rate. To reduce stigmatisation, the screening should be integrated in a "lung health check". Standardisation and a common quality level are mandatory. The PLCOm2012 risk calculation model with a threshold of 1.5% risk for developing cancer in the next six years should be used in addition to established inclusion criteria. Biennial screening is preferred. LUNG RADS and NELSON+ are applied as classification models for lung nodules. CONCLUSION Based on data from recent studies, literature research, a health technology assessment, the information gained from this project and a pilot study the Swiss Interest Group for lung cancer screening (CH-LSIG) recommends the timely introduction of a systematic lung cancer screening program in Switzerland. The final decision is for the Swiss Cancer Screening Committee to make

Surgery in the Context of Multimodal Treatment of Non-Small Cell Lung Cancer.

Surgery in the Context of Multimodal Treatment of Non-Small Cell Lung Cancer

Geographic Distribution of Urban Retail and its Spatial Relationship with Subway Network: A Case Study of Retail POI Data in Shanghai

After over two decades of development, Subway has become one of the main transit modes for people's everyday commute, and is considered to attract and form retail clusters around subway stations. Based on a point of interest (POI) dataset of retail stores in Shanghai, this study looks into the geographic distribution of retail stores in Shanghai and examines its spatial relationship with subway network. The retails stores are classified into six types: department stores, specialty stores, convenience stores, restaurants and groceries, recreational facilities and personal service facilities. A series of spatial statistical analysis for measuring geographic distribution, analyzing geographic patterns and mapping clusters are conducted. The spatial pattern shows consistence to the polycentric urban structure of Shanghai and subway stations. In addition, six retail types reveal different extent of spatial clustering at different analysis scales. Last but not least, to qualify the spatial relationship between retail density and other influence factors, including density of population and local bus service, as well as the accessibility to subway station, Ordinary Least Squares (OLS) linear regression is conducted. It turns out that the Kernel Density estimation of retail stores is positively related to population density, bus stop density and existence of subway service, while negatively affected by distance from subway stations. Bus stop density tend to be the most significant influential factors, while department stores enjoy a relatively stronger correlation with distance from subway stations compared to other retail types