Correlation of Immunological and Histopathological Features with Gene Expression-Based Classifiers in Colon Cancer Patients

The purpose of this study was to evaluate the association between four distinct histopathological features: (1) tumor infiltrating lymphocytes, (2) mucinous differentiation, (3) tumor-stroma ratio, plus (4) tumor budding and two gene expression-based classifiers—(1) consensus molecular subtypes (CMS) plus (2) colorectal cancer intrinsic subtypes (CRIS). All four histopathological features were retrospectively scored on hematoxylin and eosin sections of the most invasive part of the primary tumor in 218 stage II and III colon cancer patients from two independent cohorts (AMC-AJCC-90 and AC-ICAM). RNA-based CMS and CRIS assignments were independently obtained for all patients. Contingency tables were constructed and a χ2 test was used to test for statistical significance. Odds ratios with 95% confidence intervals were calculated. The presence of tumor infiltrating lymphocytes and a mucinous phenotype (>50% mucinous surface area) were strongly correlated with CMS1 (p < 0.001 and p = 0.008) and CRIS-A (p = 0.006 and p < 0.001). The presence of mucus (≥ 10%) was associated with CMS3: mucus was present in 64.1% of all CMS3 tumors (p < 0.001). Although a clear association between tumor-stroma ratio and CMS4 was established in this study (p = 0.006), still 32 out of 61 (52.5%) CMS4 tumors were scored as stroma-low, indicating that CMS4 tumors cannot be identified solely based on stromal content. Higher budding counts were seen in CMS4 and CRIS-B tumors (p = 0.045 and p = 0.046). No other associations of the measured parameters were seen for any of the other CRIS subtypes. Our analysis revealed clear associations between histopathologic features and CMS or CRIS subtypes. However, identification of distinct molecular subtypes solely based on histopathology proved to be infeasible. Combining both molecular and morphologic features could potentially improve patient stratification.     

Zero Risk Does Not Exist: Lessons Learned from Microbial Risk Assessment Related to Use of Water and Safety of Fresh Produce

Risk assessments related to use of water and safety of fresh produce originate from both water and food microbiology studies. Although the set‐up and methodology of risk assessment in these 2 disciplines may differ, analysis of the current literature reveals some common outcomes. Most of these studies from the water perspective focus on enteric virus risks, largely because of their anticipated high concentrations in untreated wastewater and their resistance to common wastewater treatments. Risk assessment studies from the food perspective, instead, focus mainly on bacterial pathogens such as Salmonella and pathogenic Escherichia coli. Few site‐specific data points were available for most of these microbial risk assessments, meaning that many assumptions were necessary, which are repeated in many studies. Specific parameters lacking hard data included rates of pathogen transfer from irrigation water to crops, pathogen penetration, and survival in or on food crops. Data on these factors have been investigated over the last decade and this should improve the reliability of future microbial risk estimates. However, the sheer number of different foodstuffs and pathogens, combined with water sources and irrigation practices, means that developing risk models that can span the breadth of fresh produce safety will be a considerable challenge. The new approach using microbial risk assessment is objective and evidence‐based and leads to more flexibility and enables more tailored risk management practices and guidelines. Drawbacks are, however, capacity and knowledge to perform the microbial risk assessment and the need for data and preferably data of the specific region.     

Long‐Range Domain Structure and Symmetry Engineering by Interfacial Oxygen Octahedral Coupling at Heterostructure Interface

In epitaxial thin film systems, the crystal structure and its symmetry deviate from the bulk counterpart due to various mechanisms such as epitaxial strain and interfacial structural coupling, which is accompanyed by a change in their properties. In perovskite materials, the crystal symmetry can be described by rotations of sixfold coordinated transition metal oxygen octahedra, which are found to be altered at interfaces. Here, it is unraveled how the local oxygen octahedral coupling at perovskite heterostructural interfaces strongly influences the domain structure and symmetry of the epitaxial films resulting in design rules to induce various structures in thin films using carefully selected combinations of substrate/buffer/film. Very interestingly it is discovered that these combinations lead to structure changes throughout the full thickness of the film. The results provide a deep insight into understanding the origin of induced structures in a perovskite heterostructure and an intelligent route to achieve unique functional properties.     

Structure–Property Relation of SrTiO3/LaAlO3 Interfaces

A large variety of transport properties have been observed at the interface between the insulating oxides SrTiO₃ and LaAlO₃ such as insulation, 2D interface metallicity, 3D bulk metallicity, magnetic scattering, and superconductivity. The relation between the structure and the properties of the SrTiO₃/LaAlO₃ interface can be explained in a meaningful way by taking into account the relative contribution of three structural aspects: oxygen vacancies, structural deformations (including cation disorder), and electronic interface reconstruction. The emerging phase diagram is much richer than for related bulk oxides due to the occurrence of interface electronic reconstruction. The observation of this interface phenomenon is a display of recent advances in thin film deposition and characterization techniques, and provides an extension to the range of exceptional electronic properties of complex oxides.     

Modelling the effect of sublethal injury on the distribution of the lag times of individual cells of Lactobacillus plantarum

The effect of heat stress on subsequent duration of the lag time of individual cells of Lactobacillus plantarum was analysed by flow cytometry. The results show clearly that both the mean and the standard deviation of the distribution of the lag time increased after sublethal heat treatment. The distributions of the lag times or the log lag times of untreated and treated cells, respectively, could be described as extreme value distributions. From these distributions, the distribution of the minimum lag times could be calculated and thus the effect of inoculum size on the apparent lag could be deduced. The results show clearly that the apparent lag time is dependent on the size of the inoculum, especially when the inoculum is sublethally injured.     

Influence of DOC on the Inactivation Efficiency of Ozonation Assessed with Clostridium perfringens and a Lab-Scale Continuous Flow System

Routine quality monitoring for fecal indicators after ozonation at the river-lake waterworks Weesperkarspel of Amsterdam Water Supply (AWS) show large variation in inactivation. The influence of the high DOC in the water on the inactivation efficiency was investigated. Results showed a higher inactivation of Clostridium perfringens in the AWS water than in a water with low DOC at the same CT conditions. The contribution of the gas feed chamber to the overall inactivation of C. perfringens was high in the AWS water and was reduced after DOC reduction with GAC. This result may alter the current CT concept of the process. Further research will be focused on the ozone dosage strategy and control related to the required CT for inactivation and the production of by-products.     

Patterning of Epitaxial Perovskites from Micro and Nano Molded Stencil Masks

A process is developed that combines soft lithographic molding with pulsed laser deposition (PLD) to make heteroepitaxial patterns of functional perovskite oxide materials. Micro‐ and nanostructures of sacrificial ZnO are made by micro molding in capillaries (MiMiC) and nano transfer molding, respectively, and used to screen the single crystalline substrates during subsequent PLD. ZnO is used because of its compatibility with the high temperatures reached during PLD and because of the ease of its removal after use by benefiting from its amphoteric nature. Sub‐micrometer sized lines of La_0.67Sr_0.33MnO₃ are made by the transfer molding approach, preserving the anisotropic features expected for a fully oriented thin film and taking account for the magnetostatic contribution from the line shapes. Different patterns of SrRuO₃ are made with lateral dimensions of a few micrometers having individual features for which electrical isolation is illustrated. The bottom‐up soft lithographic methods can be compliantly utilized for making epitaxial structures of various shapes and sizes in the μm down to the nm range, and offer unique opportunities for fundamental studies as well as for realizing technological applications.