The Bare Necessities: Uncovering Essential and Condition‐Critical Genes with Transposon Sequencing

Summary

Querying gene function in bacteria has been greatly accelerated by the advent of transposon sequencing (Tn‐seq) technologies (related Tn‐seq strategies are known as TraDIS, INSeq, RB‐TnSeq and HITS). Pooled populations of transposon mutants are cultured in an environment and next‐generation sequencing tools are used to determine areas of the genome that are important for bacterial fitness. In this review we provide an overview of Tn‐seq methodologies and discuss how Tn‐seq has been applied, or could be applied, to the study of oral microbiology. These applications include studying the essential genome as a means to rationally design therapeutic agents. Tn‐seq has also contributed to our understanding of well‐studied biological processes in oral bacteria. Other important applications include in vivo pathogenesis studies and use of Tn‐seq to probe the molecular basis of microbial interactions. We also highlight recent advancements in techniques that act in synergy with Tn‐seq such as CRISPR interference and microfluidic chip platforms.

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The Bare Necessities: Uncovering Essential and Condition‐Critical Genes with Transposon Sequencing

Summary

Querying gene function in bacteria has been greatly accelerated by the advent of transposon sequencing (Tn‐seq) technologies (related Tn‐seq strategies are known as TraDIS, INSeq, RB‐TnSeq and HITS). Pooled populations of transposon mutants are cultured in an environment and next‐generation sequencing tools are used to determine areas of the genome that are important for bacterial fitness. In this review we provide an overview of Tn‐seq methodologies and discuss how Tn‐seq has been applied, or could be applied, to the study of oral microbiology. These applications include studying the essential genome as a means to rationally design therapeutic agents. Tn‐seq has also contributed to our understanding of well‐studied biological processes in oral bacteria. Other important applications include in vivo pathogenesis studies and use of Tn‐seq to probe the molecular basis of microbial interactions. We also highlight recent advancements in techniques that act in synergy with Tn‐seq such as CRISPR interference and microfluidic chip platforms.

This article is protected by copyright. All rights reserved.

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K-Means Clustering Optimizing Deep Stacked Sparse Autoencoder

Abstract

Because of the large structure and long training time, the development cycle of the common depth model is prolonged. How to speed up training is a problem deserving of study. In order to accelerate training, K-means clustering optimizing deep stacked sparse autoencoder (K-means sparse SAE) is presented in this paper. First, the input features are divided into K small subsets by K-means clustering, then each subset is input into corresponding autoencoder model for training, which only has fewer nodes in the hidden layer than traditional models. After training, each autoencoder's trained weights and biases is merged to obtain the next layer's input features by feedforward network. The above steps are repeated till the softmax layer, then fine-tuning is carried out. Using MNIST-Rotation datasets to train the network that has three hidden layers and each layer has 800 nodes, the improved model has higher classification accuracy and shorter training time when K = 10. With K increasing, the training time is reduced to almost the same as the fine-tuning time but the recognition ability is descended. Compared with the recently stacked denoising sparse autoencoder, the recognition accuracy is improved by 1%, not only the noise factor is not selected but also the training speed is significantly increased. The trained filters from the improved model is also used to train convolutional autoencoder, and it performs better than traditional models. We find that pre-training stage doesn't need large samples simultaneously, and small samples parallel training reduces the probability of falling into the local minimum.

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K-Means Clustering Optimizing Deep Stacked Sparse Autoencoder

Abstract

Because of the large structure and long training time, the development cycle of the common depth model is prolonged. How to speed up training is a problem deserving of study. In order to accelerate training, K-means clustering optimizing deep stacked sparse autoencoder (K-means sparse SAE) is presented in this paper. First, the input features are divided into K small subsets by K-means clustering, then each subset is input into corresponding autoencoder model for training, which only has fewer nodes in the hidden layer than traditional models. After training, each autoencoder's trained weights and biases is merged to obtain the next layer's input features by feedforward network. The above steps are repeated till the softmax layer, then fine-tuning is carried out. Using MNIST-Rotation datasets to train the network that has three hidden layers and each layer has 800 nodes, the improved model has higher classification accuracy and shorter training time when K = 10. With K increasing, the training time is reduced to almost the same as the fine-tuning time but the recognition ability is descended. Compared with the recently stacked denoising sparse autoencoder, the recognition accuracy is improved by 1%, not only the noise factor is not selected but also the training speed is significantly increased. The trained filters from the improved model is also used to train convolutional autoencoder, and it performs better than traditional models. We find that pre-training stage doesn't need large samples simultaneously, and small samples parallel training reduces the probability of falling into the local minimum.

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Impacts of a shared book-reading intervention for Italian-speaking children with developmental language disorder.

CONCLUSIONS & IMPLICATIONS: The present parent-based SBR intervention for Italian-speaking preschoolers with DLD showed effects, albeit modest, on both maternal and child communicative behaviours. The results suggest that extralinguistic strategies may be implemented successfully by parents and may be effective in enhancing children's engagement and language production in the short term. Further investigations are needed that provide a longer intervention period and examine the joint impact of therapist- and parent-based intervention for children with DLD. PMID: 30729644 [PubMed - as supplied by publisher] (Source: International Journal of Language and Communication Disorders)

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Impacts of a shared book-reading intervention for Italian-speaking children with developmental language disorder.

CONCLUSIONS & IMPLICATIONS: The present parent-based SBR intervention for Italian-speaking preschoolers with DLD showed effects, albeit modest, on both maternal and child communicative behaviours. The results suggest that extralinguistic strategies may be implemented successfully by parents and may be effective in enhancing children's engagement and language production in the short term. Further investigations are needed that provide a longer intervention period and examine the joint impact of therapist- and parent-based intervention for children with DLD. PMID: 30729644 [PubMed - as supplied by publisher] (Source: International Journal of Language and Communication Disorders)

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Three-dimensional skeletal changes after early proportional condylectomy for condylar hyperplasia

The purpose of this study was to evaluate volumetric and dentoskeletal changes in 21 patients with active unilateral condylar hyperplasia (AUCH) after proportional condylectomy. A split-mouth design was used: control group healthy joints (HS, healthy side) and test group affected joints (AS, affected side) (21 per group). Cone beam tomography scans were obtained at T0 (preoperative), T1 (10days after the intervention), and T2 (approximately 12 months post-surgery). The condylar unit volume (CUV), articular cavity volume (ACV), and dentoalveolar units (DAUs) were measured.

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Learning condyle repositioning during orthognathic surgery with a surgical navigation system

Condyle repositioning during bilateral sagittal splint osteotomy (BSSO) is a challenging step for the inexperienced surgeon. We aimed to demonstrate the benefit of navigation for learning the condyle repositioning. We treated 100 patients who underwent a BSSO. A trainee performed the condyle repositioning of one side in two phases. In the first one, the trainee positioned without watching the screen of the Orthopilot Navigation system (ONS). In the second one, the trainee could use the ONS to replace the condyle.

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Learning condyle repositioning during orthognathic surgery with a surgical navigation system

Condyle repositioning during bilateral sagittal splint osteotomy (BSSO) is a challenging step for the inexperienced surgeon. We aimed to demonstrate the benefit of navigation for learning the condyle repositioning. We treated 100 patients who underwent a BSSO. A trainee performed the condyle repositioning of one side in two phases. In the first one, the trainee positioned without watching the screen of the Orthopilot Navigation system (ONS). In the second one, the trainee could use the ONS to replace the condyle.

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Three-dimensional skeletal changes after early proportional condylectomy for condylar hyperplasia

The purpose of this study was to evaluate volumetric and dentoskeletal changes in 21 patients with active unilateral condylar hyperplasia (AUCH) after proportional condylectomy. A split-mouth design was used: control group healthy joints (HS, healthy side) and test group affected joints (AS, affected side) (21 per group). Cone beam tomography scans were obtained at T0 (preoperative), T1 (10days after the intervention), and T2 (approximately 12 months post-surgery). The condylar unit volume (CUV), articular cavity volume (ACV), and dentoalveolar units (DAUs) were measured.

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Management of velopharyngeal insufficiency by modified Furlow palatoplasty with pharyngeal flap: a retrospective outcome review

The surgical approach for the correction of residual velopharyngeal insufficiency requiring secondary surgery at Chang Gung Memorial Hospital is the modified Furlow palatoplasty with pharyngeal flap (mFP-PF). The aim of this study was to describe the mFP-PF technique and to determine the results obtained with regard to improvements in velopharyngeal function in patients undergoing this surgery. This retrospective analysis included 58 non-syndromic patients treated during the period 1992–2015 who complained of hypernasal speech after primary cleft palate repair and failed postoperative speech therapy.

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Management of velopharyngeal insufficiency by modified Furlow palatoplasty with pharyngeal flap: a retrospective outcome review

The surgical approach for the correction of residual velopharyngeal insufficiency requiring secondary surgery at Chang Gung Memorial Hospital is the modified Furlow palatoplasty with pharyngeal flap (mFP-PF). The aim of this study was to describe the mFP-PF technique and to determine the results obtained with regard to improvements in velopharyngeal function in patients undergoing this surgery. This retrospective analysis included 58 non-syndromic patients treated during the period 1992–2015 who complained of hypernasal speech after primary cleft palate repair and failed postoperative speech therapy.

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Role of mammary serine protease inhibitor on the inflammatory response in oral lichen planus

Abstract

Objectives

Oral lichen planus (OLP) is a chronic inflammatory condition with an unclear pathological mechanism. IκB kinase α (IKKα)‐regulated mammary serine protease inhibitor (MASPIN) has been shown to mediate inflammation, particularly in cancers. Here, we explored the expression of MASPIN in OLP and its role in the inflammatory response.

Materials and Methods

Immunohistochemistry staining and reverse transcription‐polymerase chain reaction assays were used to detect the subcellular localisation and expression of MASPIN and IKKα in OLP and healthy control tissues. Levels of the inflammatory factors were compared with enzyme‐linked immunosorbent assays. MASPIN and IKKα were overexpressed and silenced, respectively, in an inflammation model of human oral keratinocytes (HOKs) stimulated with lipopolysaccharide (LPS).

Results

MASPIN expression was down‐regulated, whereas IKKα expression was up‐regulated in OLP tissues (P < 0.01). The levels of tumour necrosis factor‐alpha and interleukin‐6 in OLP tissues were increased compared to those of healthy controls (P < 0.01). MASPIN overexpression in LPS‐stimulated HOK cells inhibited the levels of IKKα and the secretion of inflammatory cytokines. By contrast, IKKα silencing promoted the expression of MASPIN and inhibited the secretion of inflammatory cytokines.

Conclusion

Both MASPIN and IKKα are involved in the inflammatory process of OLP, suggesting potential therapeutic targets.

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Role of mammary serine protease inhibitor on the inflammatory response in oral lichen planus

Abstract

Objectives

Oral lichen planus (OLP) is a chronic inflammatory condition with an unclear pathological mechanism. IκB kinase α (IKKα)‐regulated mammary serine protease inhibitor (MASPIN) has been shown to mediate inflammation, particularly in cancers. Here, we explored the expression of MASPIN in OLP and its role in the inflammatory response.

Materials and Methods

Immunohistochemistry staining and reverse transcription‐polymerase chain reaction assays were used to detect the subcellular localisation and expression of MASPIN and IKKα in OLP and healthy control tissues. Levels of the inflammatory factors were compared with enzyme‐linked immunosorbent assays. MASPIN and IKKα were overexpressed and silenced, respectively, in an inflammation model of human oral keratinocytes (HOKs) stimulated with lipopolysaccharide (LPS).

Results

MASPIN expression was down‐regulated, whereas IKKα expression was up‐regulated in OLP tissues (P < 0.01). The levels of tumour necrosis factor‐alpha and interleukin‐6 in OLP tissues were increased compared to those of healthy controls (P < 0.01). MASPIN overexpression in LPS‐stimulated HOK cells inhibited the levels of IKKα and the secretion of inflammatory cytokines. By contrast, IKKα silencing promoted the expression of MASPIN and inhibited the secretion of inflammatory cytokines.

Conclusion

Both MASPIN and IKKα are involved in the inflammatory process of OLP, suggesting potential therapeutic targets.

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A strategy for high‐dimensional multivariable analysis classifies childhood asthma phenotypes from genetic, immunological and environmental factors

Abstract

Background

Associations between childhood asthma phenotypes and genetic, immunological and environmental factors have been previously established. Yet, strategies to integrate high‐dimensional risk factors from multiple distinct data sets, and thereby increase the statistical power of analyses, have been hampered by a preponderance of missing data and lack of methods to accommodate them.

Methods

We assembled questionnaire, diagnostic, genotype, microarray, RT‐qPCR, flow cytometry and cytokine data (referred to as data modalities) to use as input factors for a classifier that could distinguish healthy children, mild‐to‐moderate allergic asthmatics and non‐allergic asthmatics. Based on data from 260 German children aged 4‐14 from our university outpatient clinic, we built a novel multi‐level prediction approach for asthma outcome which could deal with a present complex missing data structure.

Results

The optimal learning method was boosting based on all data sets, achieving an area‐underneath‐the‐receiver‐operating‐characteristic curve (AUC) for three classes of phenotypes of 0.81 (95%‐confidence interval (CI): 0.65‐0.94) using leave‐one‐out cross‐validation. Besides improving the AUC, our integrative multi‐level learning approach led to tighter CIs than using smaller complete predictor data sets (AUC=0.82[0.66‐0.94] for boosting). The most important variables for classifying childhood asthma phenotypes comprised novel identified genes, namely PKN2 (protein kinase N2), PTK2 (protein tyrosine kinase 2), and ALPP (alkaline phosphatase, placental).

Conclusion

Our combination of several data modalities using a novel strategy improved classification of childhood asthma phenotypes but requires validation in external populations. The generic approach is applicable to other multi‐level data‐based risk prediction settings, which typically suffer from incomplete data.

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Follow‐up, 18 months off HDM immunotherapy, of a randomized controlled study on the primary prevention of atopy

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Delayed drug hypersensitivity to bortezomib: desensitization and tolerance to its analogue carfilzomib

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Septocutaneous perforator mapping and clinical applications of the medial arm flap

The medial arm flap has a long history but remains underused despite providing multiple advantages. We reviewed our experience with using the medial arm flap in order to clarify the distribution of septocutaneous perforators and its relationship with pedicled flap design.

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Digital Model Simulation Technology for Ear Reconstruction of Microtia with Craniofacial Asymmetry

Craniofacial asymmetry is often observed in microtia patients, duing to the accompanied craniofacial microsomia deformity, such as mandibular dysplasia and/or depression of the mastoid region, which makes it difficult to obtain symmetrical results in ear reconstruction [1]. In the process of reconstruction, both ear location and framework fabrication are interfered by the asymmetry. Mandibular hypoplasia and the heterotopic residual ear can not be regarded as an appropriate locating reference, which poses difficulties to the surgeon when determining the location for the reconstructed ear.

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Post mastectomy upper limb lymphedema: combined vascularized lymph node transfer and scar release with fat graft expedites surgical and patients’ related outcomes. a retrospective comparative study

Lymphedema resulting from breast cancer treatment is a chronic condition which can significantly compromise quality of life. Several works have documented the efficacy of vascularized lymph node flap transfer (VLNT) for the treatment of advanced stage lymphedema. Given that the axillary scar may contribute to the patient's existing lymphedema, authors assumed that combining VLNT and scar release with fat graft could be an effective strategy of treatment. The purpose of this study is to compare the efficacy in limb's circumference reduction and health-related quality of life between a combined strategy, namely VLN and axillary scar release with fat grafting, and just VLN transfer for patients' affected by post mastectomy upper limb lymphedema.

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