Machine-Learning Guided Quantum Chemical and Molecular Dynamics Calculations to Design Novel Hole-Conducting Organic Materials.

Materials exhibiting higher mobilities than conventional organic semiconducting materials such as fullerenes and fused thiophenes are in high demand for applications such as printed electronics, organic solar cells, and image sensors. In order to discover new molecules that might show improved charge mobility, combined density functional theory (DFT) and molecular dynamics (MD) calculations were performed, guided by predictions from machine learning (ML). A ML model was constructed based on 32 values of theoretically calculated hole mobilities for thiophene derivatives, benzodifuran derivatives, a carbazole derivative and a perylene diimide derivative with the maximum value of 10-1.96 cm2/(V s). Sequential learning, also known as active learning, was applied to select compounds on which to perform DFT/MD calculation of hole mobility to simultaneously improve the mobility surrogate model and identify high mobility compounds. By performing 60 cycles of sequential learning with 165 DFT/MD calculations, a molecule having a fused thioacene structure with its calculated hole mobility of 10-1.86 cm2/(V s) was identified. This values is higher than the maximum value of mobility in the initial training data set, showing that an extrapolative discovery could be made with the sequential learning.

Assessing the frontier: Active learning, model accuracy, and multi-objective candidate discovery and optimization.

Discovering novel chemicals and materials can be greatly accelerated by iterative machine learning-informed proposal of candidates-active learning. However, standard global error metrics for model quality are not predictive of discovery performance and can be misleading. We introduce the notion of Pareto shell error to help judge the suitability of a model for proposing candidates. Furthermore, through synthetic cases, an experimental thermoelectric dataset and a computational organic molecule dataset, we probe the relation between acquisition function fidelity and active learning performance. Results suggest novel diagnostic tools, as well as new insights for the acquisition function design.

Malrotation in Congenital Diaphragmatic Hernia: Is It Really a Problem?

INTRODUCTION: Congenital diaphragmatic hernia (CDH) has been associated with other congenital malformations, such as intestinal rotation abnormalities. However, there is no standard evaluation and treatment of intestinal rotation during initial CDH repair. This study evaluates intestinal malrotation in CDH patients. MATERIALS AND METHODS: All patients with a CDH treated in a high-volume center between 2000 and 2015 were retrospectively evaluated. Demographics, gastrointestinal characteristics, surgical treatment, and abdominal outcomes (acute surgery, small bowel obstruction, and volvulus) were described. RESULTS: A total of 197 CDH patients were surgically repaired. In 76 (39%) patients, a malrotation was described at initial CDH repair, in 39 (20%) patients, a normal rotation, but 82 patients (42%) had no report on intestinal rotation. During follow-up (range: 2-16 years), 12 additional malrotations were diagnosed, leading to a prevalence of at least 45% (n = 88). These were mostly diagnosed due to acute small bowel obstruction, of which three had a volvulus. Of the 12 later diagnosed malrotations, 58% required acute surgery, compared to 3% of the 76 initially diagnosed patients (p < 0.001). CONCLUSION: Malrotation is associated with CDH, with a prevalence of at least 45% and in 21% a normal intestinal rotation. "Missed" malrotations have a higher risk on need for acute surgery later in life.

Single-Crystal Automated Refinement (SCAR): A Data-Driven Method for Determining Inorganic Structures.

Single-crystal diffraction is one of the most common experimental techniques in chemistry for determining a crystal structure. However, the process of crystal structure determination and refinement is not always straightforward. Methods for simplifying and rationalizing the path to the most optimal crystal structure model have been incorporated into various data processing and crystal structure solution software, with the focus generally on aiding macromolecular or protein structure determination. In this work, we propose a new method that uses single-crystal data to determine the crystal structures of inorganic, extended solids called "single-crystal automated refinement" (SCAR). The approach was developed using data mining and machine learning methods and considers several structural features common in inorganic solids, like atom assignment based on physically reasonable distances, atomic statistical mixing, and crystallographic site deficiency. The output is a tree of possible solutions for the data set with a corresponding fit score indicating the most reasonable crystal structure. Here, the foundation for SCAR is presented followed by the implementation of SCAR to determine two newly synthesized and previously unreported phases, ZrAu0.5Os0.5 and Nd4Mn2AuGe4. The structure solutions are found to be comparable with those produced by manually solving the data set, including the same refined mixed occupancies and atomic deficiency, supporting the validity of this automatic structure solution method. The proposed SCAR program is thus verified as being a fast and reliable assistant in determining even complex single-crystal diffraction data for extended inorganic solids.

Next generation genome sequencing reveals phylogenetic clades with different level of virulence among Salmonella Typhimurium clinical human isolates in Hong Kong.

BACKGROUND: Salmonella Typhimurium is frequently isolated from foodborne infection cases in Hong Kong, but the lack of genome sequences has hindered in-depth epidemiological and phylogenetic studies. In this study, we sought to reconstruct the phylogenetic relationship and investigate the distribution and mutation patterns of virulence determinants among local S. Typhimurium clinical isolates using their genome sequences. RESULTS: We obtained genome sequences of 20 S. Typhimurium clinical isolates from a local hospital cluster using a 454 GS FLX Titanium sequencing platform. Phylogenetic analysis was performed based on single nucleotide polymorphism positions of the core genome against the reference strain LT2. Antimicrobial susceptibility was determined using minimal inhibitory concentration for five antimicrobial agents and analyses of virulence determinants were performed through referencing to various databases. Through phylogenetic analysis, we revealed two distinct clades of S. Typhimurium isolates and three outliers in Hong Kong, which differ remarkably in antimicrobial susceptibility and presentation and mutations of virulence determinants. The local isolates were not closely related to many of the previously sequenced S. Typhimurium isolates, except LT2. As the isolates in the two clades spanned over 10 years of isolation, they probably represent endemic strains. The outliers are possibly introduced from outside of Hong Kong. The close relatedness of members in one of the clades to LT2 and the Japanese stool isolate T000240 suggests the potential reemergence of LT2 progeny in regions nearby. CONCLUSIONS: Our study demonstrated the utility of next-generation sequencing coupled to traditional microbiological testing method in a retrospective epidemiological study involving multiple clinical isolates. The evolution of multidrug- and ciprofloxacin-resistant strains among the more virulent clade is also an increasing concern.

Genome Sequences of Salmonella enterica Serotype Typhimurium Blood Clinical Isolate ST4848/06 and Stool Isolate ST1489/06.

Salmonella enterica serotype Typhimurium human blood strains isolated from outside Africa are rarely sequenced. Here, we report the draft genome sequences of two S. Typhimurium clinical strains isolated in the same year, one from blood and another from stool, in order to gain insights into the genetic basis leading to invasive diseases.

Draft genome sequence of Salmonella enterica serovar Typhimurium ST1660/06, a multidrug-resistant clinical strain isolated from a diarrheic patient.

Salmonella enterica serovar Typhimurium is one of the most prevalent serovars of Salmonella that causes human gastroenteritis. Here, we report the draft genome sequence of the S. Typhimurium multidrug-resistant strain ST1660/06. Comparative genomic analysis unveiled three strain-specific genomic islands that potentially confer the multidrug resistance and virulence of the strain.

A cost-effective and universal strategy for complete prokaryotic genomic sequencing proposed by computer simulation.

BACKGROUND: Pyrosequencing techniques allow scientists to perform prokaryotic genome sequencing to achieve the draft genomic sequences within a few days. However, the assemblies with shotgun sequencing are usually composed of hundreds of contigs. A further multiplex PCR procedure is needed to fill all the gaps and link contigs into complete chromosomal sequence, which is the basis for prokaryotic comparative genomic studies. In this article, we study various pyrosequencing strategies by simulated assembling from 100 prokaryotic genomes. FINDINGS: Simulation study shows that a single end 454 Jr. run combined with a paired end 454 Jr. run (8 kb library) can produce: 1) ~90% of 100 assemblies with < 10 scaffolds and ~95% of 100 assemblies with < 150 contigs; 2) average contig N50 size is over 331 kb; 3) average single base accuracy is > 99.99%; 4) average false gene duplication rate is < 0.7%; 5) average false gene loss rate is < 0.4%. CONCLUSIONS: A single end 454 Jr. run combined with a paired end 454 Jr. run (8 kb library) is a cost-effective way for prokaryotic whole genome sequencing. This strategy provides solution to produce high quality draft assemblies for most of prokaryotic organisms within days. Due to the small number of assembled scaffolds, the following multiplex PCR procedure (for gap filling) would be easy. As a result, large scale prokaryotic whole genome sequencing projects may be finished within weeks.

Staphylococcus aureus carriage in the anterior nares of close contacts of patients with atopic dermatitis.

OBJECTIVE: To study the prevalence of Staphylococcus aureus colonization in close contacts of patients with atopic dermatitis (AD) and the influence on AD severity. DESIGN: Prospective case-control study. SETTING: Pediatric dermatology clinic in a Hong Kong university hospital. Patients We recruited 211 subjects prospectively, including 50 AD patients, 50 non-AD control subjects, 60 close contacts of AD patients, and 51 close contacts of controls. Intervention Nasal swabs and skin swabs were taken. Severity of AD was assessed using the SCORAD (Scoring Atopic Dermatitis) index. MAIN OUTCOME MEASURES: The prevalence of S aureus colonization in the close contacts of AD patients was compared with that of the close contacts of non-AD controls. Between-group differences were assessed, where appropriate, by unpaired t test or Pearson chi(2) test. Multivariate logistic regression using the forward stepwise method was performed to identify independent predictors of severe AD. A probability value of P < .05 was considered statistically significant. RESULTS: Significantly more nasal carriers of S aureus were found among the close contacts of AD patients (14 of 60 [23%]) than among the close contacts of non-AD controls (4 of 51 [8%] [P = .03]). The difference was still significant after the exclusion of the AD patients' close contacts who also had AD (24% vs 8% [P = .03]). By multivariate analysis, only skin colonization of S aureus was independently associated with severe AD (odds ratio, 17.0; 95% confidence interval, 1.60-181.1 [P = .02]). CONCLUSIONS: Anterior nares of close contacts of AD patients are reservoirs of S aureus. The presence of S aureus carriers among close contacts does not predict AD severity. Skin colonization is associated with severe AD.

Persistent Staphylococcus capitis septicemia in a preterm infant.

A preterm infant had persistent Staphylococcus capitis septicemia with 11 consecutive positive blood cultures over a period of 33 days. The clinical evidence suggested that the source of infection probably originated from the gastrointestinal tract. The combination of rifampin and linezolid treatment, together with prolonged stoppage of enteral feeding, successfully terminated the infection. Rifampin and linezolid should be considered as alternative antimicrobial agents when glycopeptides fail to eradicate Gram-positive pathogens from the host.

Psychrobacter bacteraemia in a cirrhotic patient after the consumption of raw geoduck clam.

Psychrobacter species rarely cause infections in human. We reported herein a 62-year-old cirrhotic patient who presented with fever and diarrhoea after the consumption of raw geoduck clam. Blood culture grew Psychrobacter phenylpyruvicus which was sensitive to most anti-microbial agents. The patient responded promptly to intravenous antibiotics. This is the first report of human infection with this unusual organism which illustrates the potential health hazards of eating raw geoduck clam in patients with advanced liver disease.