Publish or patent?: Knowledge dissemination in agricultural biotechnology

"Plant transformation research has achieved outstanding progress in the development of transgenic crops over the past decades, and the research results have been spread through journal publications and patents. With the recent emergence of stronger intellectual property rights, investments in crop research and the landscape of plant transformation research have changed, along with the patterns of knowledge dissemination. In this paper, we discuss the recent trends in plant transformation research by examining patent and journal publication data during the last decade. The data analysis shows that there have been significant shifts toward applied research by developing countries and toward patenting as a means of knowledge dissemination during the past few decades, reflecting the increasing role of the private sector in developing countries in crop improvement research." from authors' abstractBiotechnology research, patents, Crop improvement, Science and technology, Genetic resources, Biodiversity, Journal publication, Developing countries,

A novel estimand to adjust for rescue treatment in clinical trials

The interpretation of randomised clinical trial results is often complicated by intercurrent events. For instance, rescue medication is sometimes given to patients in response to worsening of their disease, either in addition to the randomised treatment or in its place. The use of such medication complicates the interpretation of the intention-to-treat analysis. In view of this, we propose a novel estimand defined as the intention-to-treat effect that would have been observed, had patients on the active arm been switched to rescue medication if and only if they would have been switched when randomised to control. This enables us to disentangle the treatment effect from the effect of rescue medication on a patient's outcome, while avoiding the strong extrapolations that are typically needed when inferring what the intention-to-treat effect would have been in the absence of rescue medication. We develop an inverse probability weighting method to estimate this estimand under specific untestable assumptions, in view of which we propose a sensitivity analysis. We use the method for the analysis of a clinical trial conducted by Janssen Pharmaceuticals, in which chronically ill patients can switch to rescue medication for ethical reasons. Monte Carlo simulations confirm that the proposed estimator is unbiased in moderate sample sizes

Gold nanoparticles meet medical radionuclides

Thanks to their unique optical and physicochemical properties, gold nanoparticles have gained increased interest as radiosensitizing, photothermal therapy and optical imaging agents to enhance the effectiveness of cancer detection and therapy. Furthermore, their ability to carry multiple medically relevant radionuclides broadens their use to nuclear medicine SPECT and PET imaging as well as targeted radionuclide therapy. In this review, we discuss the radiolabeling process of gold nanoparticles and their use in (multimodal) nuclear medicine imaging to better understand their specific distribution, uptake and retention in different in vivo cancer models. In addition, radiolabeled gold nanoparticles enable image-guided therapy is reviewed aswell as the enhancement of targeted radionuclide therapy and nanobrachytherapy through an increased dose deposition and radiosensitization, as demonstrated by multiple Monte Carlo studies and experimental in vitro and in vivo studies. (C) 2021 The Authors. Published by Elsevier Inc

Effects of dose and formulation of carvacrol and thymol on bacteria and some functional traits of the gut in piglets after weaning

Two trials were conducted to study the effects of dose and formulation of carvacrol and thymol on bacterial counts, metabolites and functional traits of the gut in weaned piglets. In the first experiment (Exp. I), 25 piglets (28 d, 6.59 +/- 0.48 kg BW) were allocated to five dietary treatments: a control diet, or the same diet supplemented with either carvacrol or thymol at doses of 500 and 2000 mg kg(-1). In the second experiment (Exp. II), 35 piglets (28 d, 7.99 +/- 0.73 kg BW) were assigned to seven dietary treatments: the same control diet as in Exp. I, or this diet supplemented with thymol in one of three formulations (on celite, on alphacel or microencapsulated) at doses of 500 and 2000 mg kg(-1). At 11/12 days post-weaning piglets were euthanised, and digesta from stomach, proximal and distal small intestine were sampled for bacteriological and biochemical analysis. Small intestinal tissue was sampled for histomorphological determinations. In none of the experiments or sections of the gut was the number of bacteria lowered by the carvacrol or thymol supplementation. In Exp. I, the villus/crypt ratio at the distal small intestine for the experimental diets (1.30-1.32) was higher than for the control diet (1.24) (p < 0.05). Thymol fed animals in Exp. II had a lower number of intra-epithelial lymphocytes at the proximal (p < 0.05) and at the distal (p < 0.1) small intestine as compared to control animals. Mean concentration of the active ingredient in the stomach and proximal small intestine for the 2000 mg kg(-1) carvacrol diet was 521 and 5 mg kg(-1) fresh digesta, respectively, and for the 2000 mg kg(-1) thymol diets it ranged between 475 and 647 and between 13 and 24 mg kg(-1) fresh digesta, respectively. Cumulative absorption in the proximal small intestine was higher than 90% for all treatments and was not affected by formulation type. These data suggest that carvacrol and thymol can improve gut health, but evidence for clear antimicrobial effects towards the major culturable bacteria of the pig foregut is limited

Gene selection with multiple ordering criteria

BACKGROUND: A microarray study may select different differentially expressed gene sets because of different selection criteria. For example, the fold-change and p-value are two commonly known criteria to select differentially expressed genes under two experimental conditions. These two selection criteria often result in incompatible selected gene sets. Also, in a two-factor, say, treatment by time experiment, the investigator may be interested in one gene list that responds to both treatment and time effects. RESULTS: We propose three layer ranking algorithms, point-admissible, line-admissible (convex), and Pareto, to provide a preference gene list from multiple gene lists generated by different ranking criteria. Using the public colon data as an example, the layer ranking algorithms are applied to the three univariate ranking criteria, fold-change, p-value, and frequency of selections by the SVM-RFE classifier. A simulation experiment shows that for experiments with small or moderate sample sizes (less than 20 per group) and detecting a 4-fold change or less, the two-dimensional (p-value and fold-change) convex layer ranking selects differentially expressed genes with generally lower FDR and higher power than the standard p-value ranking. Three applications are presented. The first application illustrates a use of the layer rankings to potentially improve predictive accuracy. The second application illustrates an application to a two-factor experiment involving two dose levels and two time points. The layer rankings are applied to selecting differentially expressed genes relating to the dose and time effects. In the third application, the layer rankings are applied to a benchmark data set consisting of three dilution concentrations to provide a ranking system from a long list of differentially expressed genes generated from the three dilution concentrations. CONCLUSION: The layer ranking algorithms are useful to help investigators in selecting the most promising genes from multiple gene lists generated by different filter, normalization, or analysis methods for various objectives

Aberrant Mucin Assembly in Mice Causes Endoplasmic Reticulum Stress and Spontaneous Inflammation Resembling Ulcerative Colitis

Michael McGuckin and colleagues identify two mutations that cause aberrant mucin oligomerization in mice. The resulting phenotype, including endoplasmic reticulum stress, resembles clinical and pathologic features of human ulcerative colitis

The Cumulative Effects of Polymorphisms in the DNA Mismatch Repair Genes and Tobacco Smoking in Oesophageal Cancer Risk

The DNA mismatch repair (MMR) enzymes repair errors in DNA that occur during normal DNA metabolism or are induced by certain cancer-contributing exposures. We assessed the association between 10 single-nucleotide polymorphisms (SNPs) in 5 MMR genes and oesophageal cancer risk in South Africans. Prior to genotyping, SNPs were selected from the HapMap database, based on their significantly different genotypic distributions between European ancestry populations and four HapMap populations of African origin. In the Mixed Ancestry group, the MSH3 rs26279 G/G versus A/A or A/G genotype was positively associated with cancer (OR = 2.71; 95% CI: 1.34–5.50). Similar associations were observed for PMS1 rs5742938 (GG versus AA or AG: OR = 1.73; 95% CI: 1.07–2.79) and MLH3 rs28756991 (AA or GA versus GG: OR = 2.07; 95% IC: 1.04–4.12). In Black individuals, however, no association between MMR polymorhisms and cancer risk was observed in individual SNP analysis. The interactions between MMR genes were evaluated using the model-based multifactor-dimensionality reduction approach, which showed a significant genetic interaction between SNPs in MSH2, MSH3 and PMS1 genes in Black and Mixed Ancestry subjects, respectively. The data also implies that pathogenesis of common polymorphisms in MMR genes is influenced by exposure to tobacco smoke. In conclusion, our findings suggest that common polymorphisms in MMR genes and/or their combined effects might be involved in the aetiology of oesophageal cancer