Classification of Quantitative Light-Induced Fluorescence Images Using Convolutional Neural Network

Images are an important data source for diagnosis and treatment of oral diseases. The manual classification of images may lead to misdiagnosis or mistreatment due to subjective errors. In this paper an image classification model based on Convolutional Neural Network is applied to Quantitative Light-induced Fluorescence images. The deep neural network outperforms other state of the art shallow classification models in predicting labels derived from three different dental plaque assessment scores. The model directly benefits from multi-channel representation of the images resulting in improved performance when, besides the Red colour channel, additional Green and Blue colour channels are used.Comment: Full version of ICANN 2017 submissio

Maturation of the infant respiratory microbiota, environmental drivers and health consequences: a prospective cohort study

Rationale: Perinatal and postnatal influences are presumed important drivers of the early-life respiratory microbiota composition. We hypothesized that the respiratory microbiota composition and development in infancy is affecting microbiota stability and thereby resistance against respiratory tract infections (RTIs) over time. Objectives: To investigate common environmental drivers, including birth mode, feeding type, antibiotic exposure, and crowding conditions, in relation to respiratory tract microbiota maturation and stability, and consecutive risk of RTIs over the first year of life. Methods: In a prospectively followed cohort of 112 infants, we characterized the nasopharyngeal microbiota longitudinally from birth on (11 consecutive sample moments and the maximum three RTI samples per subject; in total, n = 1,121 samples) by 16S-rRNA gene amplicon sequencing. Measurements and Main Results: Using a microbiota-based machine-learning algorithm, we found that children experiencing a higher number of RTIs in the first year of life already demonstrate an aberrant microbial developmental trajectory from the first month of life on as compared with the reference group (0-2 RTIs/yr). The altered microbiota maturation process coincided with decreased microbial community stability, prolonged reduction of Corynebacterium and Dolosigranulum, enrichment of Moraxella very early in life, followed by later enrichment of Neisseria and Prevotella spp. Independent drivers of these aberrant developmental trajectories of respiratory microbiota members were mode of delivery, infant feeding, crowding, and recent antibiotic use. Conclusions: Our results suggest that environmental drivers impact microbiota development and, consequently, resistance against development of RTIs. This supports the idea that microbiota form the mediator between early-life environmental risk factors for and susceptibility to RTIs over the first year of life

Which patients with ES-SCLC are most likely to benefit from more aggressive radiotherapy: A secondary analysis of the Phase III CREST trial

Introduction: In ES-SCLC patients with residual intrathoracic disease after first-line chemotherapy, the addition of thoracic radiotherapy reduces the risk of intrathoracic recurrence, and improves 2-year survival. To identify patient subgroups for future trials investigating higher dose (extra)thoracic radiotherapy, we investigated the prognostic importance of number and sites of metastases in patients included in the CREST trial. Materials/methods: Additional data on sites and numbers of metastases were collected from individual records of 260 patients from the top 9 recruiting centers in the randomized CREST trial (53% of 495 study patients), which compared thoracic radiotherapy (TRT) to no TRT in ES-SCLC patients after any response to chemotherapy. All patients received prophylactic cranial irradiation. Results: The clinical characteristics and outcomes of the 260 patients analyzed here did not differ significantly from that of the other 235 patients included in the CREST trial, except that fewer patients had a WHO = 0 performance status (24% vs 45%), and a higher proportion had WHO = 2 (15% vs 5%; p <0.0001). No distant metastases were recorded in 5%, 39% had metastases confined to one organ, 34% to two, and 22% to three or more organ sites. Metastases were present in the liver (47%), bone (40%), lung (28%), extrathoracic (non-supraclavicular) lymph nodes (19%), supraclavicular nodes (18%), adrenals (17%) and other sites (12%). The OS (p = 0.02) and PFS (p = 0.04) were significantly better in patients with 2 or fewer metastases, with OS significantly worse if liver (p = 0.03) and/or bone metastases (p= 0.04) were present. Discussion: This analysis of patients recruited from the top 9 accruing centers in the CREST trial suggests that future studies evaluating more intensive thoracic and extra-thoracic radiotherapy in ES-SCLC should focus on patients with fewer than 3 distant metastases. (C) 2017 The Author(s). Published by Elsevier Ireland Ltd

Deep Sequencing Analyses of Low Density Microbial Communities: Working at the Boundary of Accurate Microbiota Detection

Introduction: Accurate analyses of microbiota composition of low-density communities (10 3 –10 4 bacteria/sample) can be challenging. Background DNA from chemicals and consumables, extraction biases as well as differences in PCR efficiency can significantly interfere with microbiota assessment. This study was aiming to establish protocols for accurate microbiota analysis at low microbial density. Methods: To examine possible effects of bacterial density on microbiota analyses we compared microbiota profiles of seria

Developmental Regulation of the Streptomyces lividans ram Genes: Involvement of RamR in Regulation of the ramCSAB Operon

Streptomycetes are filamentous soil bacteria that produce spores through a complex process of morphological differentiation. The ram cluster plays an important part during the development. The ram genes encode a membrane-bound kinase (RamC), a small protein (RamS), components of an ABC transporter (RamAB), and a response regulator (RamR). While the introduction of an extra copy of the ram cluster accelerates development in Streptomyces lividans, ramABR disruption mutants are unable to produce aerial hyphae and spores. The developmental regulation of ram gene transcription was analyzed. Transcription of the ram genes occurred only on solid rich media and not on minimal media. The ramR gene is transcribed from a single promoter during all growth stages, with the highest levels during aerial growth. The ramCSAB genes comprise one operon and are transcribed from one principal promoter, P1, directly upstream of ramC. Transcription of ramCSAB was already observed during vegetative growth, but was strongly upregulated upon initiation of formation of aerial hyphae and was decreased during late stages of development. A large inverted repeat located downstream of ramS terminated the majority of transcripts. The introduction of ramR on a multicopy vector in S. lividans strongly induced P1 activity, while disruption of this regulator eliminated all P1 promoter activity. This shows that ramR is a crucial activator of ramCSAB transcription. Importantly, in bldA, bldB, bldD, or bldH mutants, ramR and ramCSAB are not transcribed, while ram gene transcription was observed in the earliest whi mutant, whiG. This indicates that the transcription of the ram genes marks the transition from vegetative to aerial growth

The impact of maltitol-sweetened chewing gum on the dental plaque biofilm microbiota composition

Background: The oral cavity harbors a complex microbial ecosystem, intimately related to oral health and disease. The use of polyol-sweetened gum is believed to benefit oral health through stimulation of salivary flow and impacting oral pathogenic bacteria. Maltitol is often used as sweetener in food products. This study aimed to establish the in vivo effects of frequent consumption of maltitol-sweetened chewing gum on the dental plaque microbiota in healthy volunteers and to establish the cellular and molecular effects by in vitro cultivation and transcriptional analysis. Results: An intervention study was performed in 153 volunteers, randomly assigned to three groups (www.trialregister.nl; NTR4165). One group was requested to use maltitol gum five times daily, one group used gum-base, and the third group did not use chewing gum. At day 0 and day 28, 24 h-accumulated supragingival plaque was collected at the lingual sites of the lower jaw and the buccal sites of the upper jaw and analyzed by 16S ribosomal rRNA gene sequencing. At day 42, 2 weeks after completion of the study, lower-jaw samples were collected and analyzed. The upper buccal plaque microbiota composition had lower bacterial levels and higher relative abundances of (facultative) aerobic species compared to the lower lingual sites. There was no difference in bacterial community structure between any of the three study groups (PERMANOVA). Significant lower abundance of several bacterial phylotypes was found in maltitol gum group compared to the gum-base group, including Actinomyces massiliensis HOT 852 and Lautropia mirabilis HOT 022. Cultivation studies confirmed growth inhibition of A. massiliensis and A. johnsonii by maltitol at levels of 1% and higher. Transcriptome analysis of A. massiliensis revealed that exposure to maltitol resulted in changes in the expression of genes linked to osmoregulation, biofilm formation, and central carbon metabolism. Conclusion: The results showed that chewing itself only marginally impacted the plaque microbiota composition. Use of maltitol-sweetened gum lowered abundance of several bacterial species. Importantly, the species impacted play a key role in the early formation of dental biofilms. Further studies are required to establish if frequent use of maltitol gum impacts early dental-plaque biofilm development

Analysis of Temporal Gene Expression during Bacillus subtilis Spore Germination and Outgrowth

Bacillus subtilis forms dormant spores upon nutrient depletion. Under favorable environmental conditions, the spore breaks its dormancy and resumes growth in a process called spore germination and outgrowth. To elucidate the physiological processes that occur during the transition of the dormant spore to an actively growing vegetative cell, we studied this process in a time-dependent manner by a combination of microscopy, analysis of extracellular metabolites, and a genome-wide analysis of transcription. The results indicate the presence of abundant levels of late sporulation transcripts in dormant spores. In addition, the results suggest the existence of a complex and well-regulated spore outgrowth program, involving the temporal expression of at least 30% of the B. subtilis genome

Associations of the oral microbiota and Candida with taste, smell, appetite and undernutrition in older adults

Poor taste and smell function are widely thought to contribute to the development of poor appetite and undernutrition in older adults. It has been hypothesized that the oral microbiota play a role as well, but evidence is scarce. In a cross-sectional cohort of 356 older adults, we performed taste and smell tests, collected anthropometric measurements and tongue swabs for analysis of microbial composition (16S rRNA sequencing) and Candida albicans abundance (qPCR). Older age, edentation, poor smell and poor appetite were associated with lower alpha diversity and explained a significant amount of beta diversity. Moreover, a lower Streptococcus salivarius abundance was associated with poor smell identification score, whereas high C. albicans abundance seemed to be associated with poor smell discrimination score. In our population, neither the tongue microbiota, nor C. albicans were associated with poor taste or directly with undernutrition. Our findings do suggest a host-microbe interaction with regard to smell perception and appetite