Sequence analysis of rabies virus in humans exhibiting encephalitic or paralytic rabies

Two distinct clinical patterns, encephalitic (furious) and paralytic (dumb), have been recognized in human rabies. It has been postulated that different rabies virus variants associated with particular vectors may be responsible for these different clinical manifestations. Analysis of the glycoprotein (G), nucleoprotein (N), and phosphoprotein (P) genes of rabies viruses from 2 human cases of encephalitic rabies and from 2 human cases of paralytic rabies demonstrated only minor nucleotide differences. Deduced amino-acid patterns of the N protein were identical in both human and canine samples that came from the same geographic location, regardless of the clinical form. All differences in amino-acid patterns of the G protein were found outside the ectodomain, in either the signal peptide or the transmembrane and endodomains. None of the amino-acid differences of the P protein was within the interactive site with dynein. These findings support the concept that clinical manifestations of rabies are not explained solely by the associated rabies virus variant.     

Transmission dynamics of rabies virus in Thailand: Implications for disease control

Background  

In Thailand, rabies remains a neglected disease with authorities continuing to rely on human death statistics while ignoring the financial burden resulting from an enormous increase in post-exposure prophylaxis. Past attempts to conduct a mass dog vaccination and sterilization program have been limited to Bangkok city and have not been successful. We have used molecular epidemiology to define geographic localization of rabies virus phylogroups and their pattern of spread in Thailand.     

Infections and treatment of wounds in survivors of the 2004 Tsunami in Thailand

On 26 December 2004, a tsunami devastated the west coast of Thailand and caused 8457 injuries and 5395 deaths. Data were collected from 26 December 2004 to 31 January 2005 at four public hospitals to describe the character and treatment of wounds of 523 persons who were injured during tsunami and sought medical treatment. Wounds were contaminated with mud, sand, debris and sea water and had an infection rate of 66·5% (674/1013). Most wounds (45%) had poly‐microbial infection with gram‐negative rods such as Escherichia coli, Klebsiella pneumoniae, Proteus and Pseudomonas species. The risk of wound infection increased with size of the wound and presence of an open fracture. Infections occurred more frequently on the lower than upper trunk of the body. Early treatment with antibiotics was protective against wound infection. Many patients asked to have their wounds sutured so that they could return to their village to look for their families and to repair damage. This report suggests that wounds should be aggressively debrided and suturing postponed if possible. Patients should be given broad spectrum antibiotics to assist with wound healing.     

Complex genetic structure of the rabies virus in Bangkok and its surrounding provinces, Thailand: implications for canine rabies control

Dog vaccination and population management have been suggested as priorities in attempts at disease control in canine rabies-endemic countries. Budget limitations and the complexity of social, cultural and religious variables have complicated progress in the developing world. In Bangkok, Thailand, an intensive canine vaccination and sterilization programme has been in place since November 2002. Our objective was to determine if the rabies virus could be mapped according to its genetic variations and geographical location on the small localized scale of Bangkok and its surrounding provinces. Phylogenetic characterization of 69 samples from Bangkok and five neighbouring and two remote provinces, by limited sequence analysis of the rabies virus nucleoprotein gene, distinguished six different clades. Rabies viruses of four clades were intermixed in Bangkok and in the surrounding highly populated regions whereas the other two clades were confined to rural and less populated provinces. Such a complex pattern of gene flow, particularly in Bangkok, may affect the outcome of canine control programmes.     

Correlation of camptothecin-producing ability and phylogenetic relationship in the genus Ophiorrhiza

Camptothecin (CPT) is an essential precursor of semisynthetic chemotherapeutic agents for cancers throughout the world. In spite of the rapid growth of market demand, CPT raw material is still harvested by extraction from Camptotheca acuminata and Nothapodytes foetida because its total synthesis is not cost-effective. In this study, we examined eight species of the genus Ophiorrhiza (Rubiaceae) from Thailand as novel alternative sources of CPT. CPT and/or 9-methoxy camptothecin (9-MCPT) were detected at different amounts in the leaf and root extracts of five species. We found that the CPT production ability of Ophiorrhiza spp. in Thailand was related mainly to species, not habitat. Chloroplast MATK and nuclear TOPI genes of eight species were investigated and compared with those of other Ophiorrhiza sequences from GenBank in order to classify and study the evolution in this genus. The molecular phylogenetic trees of both separated and combined MATK and TOPI nucleotide sequences revealed a major clade of Ophiorrhiza taxa correlated with production of CPT and its derivatives. Several amino acid markers of CPT- or 9-MCPT-producing Ophiorrhiza plants were also suggested from the alignment of TopI amino acid sequences. Our findings suggest that genetic factors play an important role in determining the CPT- and 9-MCPT-producing properties of Ophiorrhiza plants. Consequently, MATK and TOPI gene sequences could be utilized for the prediction of CPT and 9-MCPT production ability of members of Ophiorrhiza.     

Whole-genome sequencing of synchronous thyroid carcinomas identifies aberrant DNA repair in thyroid cancer dedifferentiation

The genetics underlying thyroid cancer dedifferentiation is only partly understood and has not yet been characterised using comprehensive pan-genomic analyses. We investigated a unique case with synchronous follicular thyroid carcinoma (FTC), poorly differentiated thyroid carcinoma (PDTC), and anaplastic thyroid carcinoma (ATC), as well as regional lymph node metastases from the PDTC and ATC from a single patient using whole-genome sequencing (WGS). The FTC displayed mutations in CALR, RB1, and MSH2, and the PDTC exhibited mutations in TP53, DROSHA, APC, TERT, and additional DNA repair genes – associated with an immense increase in sub-clonal somatic mutations. All components displayed an overrepresentation of C>T transitions with associated microsatellite instability (MSI) in the PDTC and ATC, with borderline MSI in the FTC. Clonality analyses pinpointed a shared ancestral clone enriched for mutations in TP53-associated regulation of DNA repair and identified important sub-clones for each tumour component already present in the corresponding preceding lesion. This genomic characterisation of the natural progression of thyroid cancer reveals several novel genes of interest for future studies. Moreover, the findings support the theory of a stepwise dedifferentiation process and suggest that defects in DNA repair could play an important role in the clonal evolution of thyroid cancer. © 2019 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.     

Growth of the Pulmonary Valve Annulus after the Modified Blalock-Taussig Shunt in Patients with Tetralogy of Fallot

Background: The surgical outcomes of tetralogy of Fallot (TOF) have evolved dramatically and have resulted in lower mortality rate. Currently, the many cardiac centers have a trend to early single-stage complete repair more than a staged repair. However, the patients who have an early primary repair were required transannular patch augmentation of a pulmonary valve frequently. This effect has been developed a chronic pulmonary insufficiency may lead to right ventricular dilation, dysfunction. In this era, the aim of treatment of TOF is attempted to preserve pulmonary valve annulus for prevent right ventricular dysfunction in the future. The systemic to pulmonary artery shunt is a palliative procedure or known as staged repair for symptomatic patients with TOF. The modified Blalock-Taussig shunt (mBTS) is the most useful systemic to pulmonary shunt and perform as an initial procedure before complete repair. The mBTS can provide increase pulmonary blood flow as well as improve oxygenation and also promote pulmonary artery (PA) growth. However, the effect of this procedure to promote growth of a pulmonary valve annulus is still debate. Objectives: To compare a growth of pulmonary valve annulus between after staged repair and primary repair in patients with TOF (without pulmonary atresia). Methods: A retrospective case-control study, review of patients with TOF underwent total repair at our hospitals from January 2005 and December 2017 was performed, a total number of 112 patients underwent TOF repair. Twenty-nine patients (26%) underwent a staged repair (mBTS group) and 83 (74%) underwent total repair only or primary repair (PR group). We evaluated diameter of pulmonary valve annulus by using echocardiography at the time of first diagnosis and before complete repair on both groups. Results: The age of diagnosis of mBTS group were younger than PR group (p = 0.011). Therefore, pulmonary valve annuls were smaller in mBTS group. (Z-score, −2.93 ± 1.42 vs. −1.89 ± 0.97; p = 0.001). However, the growth potential of pulmonary valve annulus was increase more than PR group significantly (Z-score, −1.46 ± 1.02 vs. −2.11 ± 1.19; p = 0.009) Even though a patent ductus arteriosus was found commonly in PR group (p = 0.018). Conclusions: Our results suggest the systemic to pulmonary shunt or mBTS can promote growth of pulmonary valve annulus in patients with TOF.     

Prediction of Healing Performance of Autogenous Healing Concrete Using Machine Learning

Cracks typically develop in concrete due to shrinkage, loading actions, and weather conditions; and may occur anytime in its life span. Autogenous healing concrete is a type of self-healing concrete that can automatically heal cracks based on physical or chemical reactions in concrete matrix. It is imperative to investigate the healing performance that autogenous healing concrete possesses, to assess the extent of the cracking and to predict the extent of healing. In the research of self-healing concrete, testing the healing performance of concrete in a laboratory is costly, and a mass of instances may be needed to explore reliable concrete design. This study is thus the world’s first to establish six types of machine learning algorithms, which are capable of predicting the healing performance (HP) of self-healing concrete. These algorithms involve an artificial neural network (ANN), a k-nearest neighbours (kNN), a gradient boosting regression (GBR), a decision tree regression (DTR), a support vector regression (SVR) and a random forest (RF). Parameters of these algorithms are tuned utilising grid search algorithm (GSA) and genetic algorithm (GA). The prediction performance indicated by coefficient of determination (R²) and root mean square error (RMSE) measures of these algorithms are evaluated on the basis of 1417 data sets from the open literature. The results show that GSA-GBR performs higher prediction performance (R²_GSA-GBR = 0.958) and stronger robustness (RMSE_GSA-GBR = 0.202) than the other five types of algorithms employed to predict the healing performance of autogenous healing concrete. Therefore, reliable prediction accuracy of the healing performance and efficient assistance on the design of autogenous healing concrete can be achieved.     

Self-Healing Performance Assessment of Bacterial-Based Concrete Using Machine Learning Approaches

Bacterial-based self-healing concrete (BSHC) is a well-known healing technology which has been investigated for a few decades for its excellent crack healing capacity. Nevertheless, considered as costly and time-consuming, the healing performance (HP) of concrete with various types of bacteria can be designed and evaluated only in laboratory environments. Employing machine learning (ML) models for predicting the HP of BSHC is inspired by practical applications using concrete mechanical properties. The HP of BSHC can be predicted to save the time and cost of laboratory tests, bacteria selection and healing mechanisms adoption. In this paper, three types of BSHC, including ureolytic bacterial healing concrete (UBHC), aerobic bacterial healing concrete (ABHC) and nitrifying bacterial healing concrete (NBHC), and ML models with five kinds of algorithms consisting of the support vector regression (SVR), decision tree regression (DTR), deep neural network (DNN), gradient boosting regression (GBR) and random forest (RF) are established. Most importantly, 22 influencing factors are first employed as variables in the ML models to predict the HP of BSHC. A total of 797 sets of BSHC tests available in the open literature between 2000 and 2021 are collected to verify the ML models. The grid search algorithm (GSA) is also utilised for tuning parameters of the algorithms. Moreover, the coefficient of determination (R²) and root mean square error (RMSE) are applied to evaluate the prediction ability, including the prediction performance and accuracy of the ML models. The results exhibit that the GBR model has better prediction ability (R²_GBR = 0.956, RMSE_GBR = 6.756%) than other ML models. Finally, the influence of the variables on the HP is investigated by employing the sensitivity analysis in the GBR model.