Malignancy rates in Crohn's disease patients with perianal fistula: A German retrospective cohort study

BACKGROUND Patients with inflammatory bowel disease are at increased risk of colorectal and extra-intestinal cancer. However, the overall cancer risk in patients with Crohn's disease (CD) with perianal fistulas (PF) (CPF) and those with CD without PF (non-PF CD) is unclear. OBJECTIVE To describe the prevalence and incidence of cancer in patients with CPF and non-PF CD, and to estimate incidence rate ratio (IRR) of cancer between CPF and non-PF CD groups. METHODS A retrospective cohort study was conducted using the German InGef (Institute for Applied Health Research Berlin) research database. Patients with a CD record and PF from 1 January 2013 to 31 December 2014 were identified and followed up from 1 January 2015 until the first occurrence of cancer, end of health insurance contributing data, death, or end of study period (31 December 2020). Prevalence of any type of cancer including patients with CD diagnosed with cancer in the selection period and incidence of cancer excluding patients with CD diagnosed with cancer in the selection period were calculated. RESULTS In total, 10,208 patients with CD were identified. Of 824 patients with CPF (8.1%), 67 had had a malignancy (6-year period crude malignancy prevalence 8.13% [95% confidence interval (CI) 6.36%-10.21%]), which was lower than patients with non-PF CD (19.8% [95% CI 19%-20.6%]). Incidence (per 100,000 person-years) in patients with CPF was 1184 (95% CI 879-1561) and in non-PF CD was 2365 (95% CI 2219-2519). There was no significant difference in the adjusted IRR of cancer for the CPF group compared with the non-PF CD group (0.83 [95% CI 0.62-1.10]; p = 0.219). CONCLUSION There was no significant difference in the incidence of any cancer in patients with CPF compared with non-PF CD. However, patients with CPF had a higher numerical risk of cancer than the general German population

Financial or environmental-impact information promote ESG investments: Evidence from a large incentivized online-experiment

Effective stimulation of investments in Environmental, Social, and Governance (ESG) requires reliable knowledge of motives that drive investors’ decisions. We investigate how information on financial return and environmental impact as well as the combination of both affect the decision to invest sustainably. Moreover, we test whether offering a general or granular choice on sustainability preferences affects investment decisions. An incentivized online experiment with experienced retail investors and a representative sample of the Austrian population (N = 2254) shows that information on financial impact as well as on environmental impact stimulates sustainable investments. However, the combination of both types of information yields no additional positive effect. Information has no strong effect on investor satisfaction. Also, the difference in choice options on sustainability preferences has no large impact on investment decisions or satisfaction. An explorative analysis suggests that women and investors holding high biospheric values as well as investors with high financial literacy, and trust in ESG products are more likely to invest sustainably. Additional results on the revision and stability of investment decisions are discussed

Financial Return and Environmental Impact Information Promotes ESG Investments: Evidence from a Large, Incentivized Online Experiment

Sustainable investments are characterized by considerations about financial returns as well as environmental impact. We investigate how information on both aspects alone and in combination impacts the decision to invest sustainably. Moreover, we test whether letting investors express their sustainability preferences in a more detailed way affects their investment decisions. We run an incentivized online experiment with experienced retail investors and a representative sample of the Austrian population (N = 2,254 in total). We find that information on financial returns and information on environmental impact both stimulate sustainable investments. However, presenting the two types of information in combination yields no greater effect than presenting one of them alone. Furthermore, we find no evidence that investment decisions are affected by whether sustainability preferences are elicited generally or in a more detailed format. Results also show that sustainable investments are positively correlated with investors’ biospheric values and their financial literacy

Synthetic Studies Toward the Skyllamycins: Total Synthesis and Generation of Simplified Analogues

Herein, we report our synthetic studies toward the skyllamycins, a highly modified class of nonribosomal peptide natural products which contain a number of interesting structural features, including the extremely rare α-OH-glycine residue. Before embarking on the synthesis of the natural products, we prepared four structurally simpler analogues. Access to both the analogues and the natural products first required the synthesis of a number of nonproteinogenic amino acids, including three β-OH amino acids that were accessed from the convenient chiral precursor Garner’s aldehyde. Following the preparation of the suitably protected nonproteinogenic amino acids, the skyllamycin analogues were assembled using a solid-phase synthetic route followed by a final stage solution-phase cyclization reaction. To access the natural products (skyllamycins A–C) the synthetic route used for the analogues was modified. Specifically, linear peptide precursors containing a C-terminal amide were synthesized via solid-phase peptide synthesis. After cleavage from the resin the N-terminal serine residue was oxidatively cleaved to a glyoxyamide moiety. The target natural products, skyllamycins A–C, were successfully prepared via a final step cyclization with concomitant formation of the unusual α-OH-glycine residue. Purification and spectroscopic comparison to the authentic isolated material confirmed the identity of the synthetic natural products.AR

The Natural Products Atlas : an open access knowledge base for microbial natural products discovery

Despite rapid evolution in the area of microbial natural products chemistry, there is currently no open access database containing all microbially produced natural product structures. Lack of availability of these data is preventing the implementation of new technologies in natural products science. Specifically, development of new computational strategies for compound characterization and identification are being hampered by the lack of a comprehensive database of known compounds against which to compare experimental data. The creation of an open access, community-maintained database of microbial natural product structures would enable the development of new technologies in natural products discovery and improve the interoperability of existing natural products data resources. However, these data are spread unevenly throughout the historical scientific literature, including both journal articles and international patents. These documents have no standard format, are often not digitized as machine readable text, and are not publicly available. Further, none of these documents have associated structure files (e.g., MOL, InChI, or SMILES), instead containing images of structures. This makes extraction and formatting of relevant natural products data a formidable challenge. Using a combination of manual curation and automated data mining approaches we have created a database of microbial natural products (The Natural Products Atlas, www.npatlas.org) that includes 24 594 compounds and contains referenced data for structure, compound names, source organisms, isolation references, total syntheses, and instances of structural reassignment. This database is accompanied by an interactive web portal that permits searching by structure, substructure, and physical properties. The Web site also provides mechanisms for visualizing natural products chemical space and dashboards for displaying author and discovery timeline data. These interactive tools offer a powerful knowledge base for natural products discovery with a central interface for structure and property-based searching and presents new viewpoints on structural diversity in natural products. The Natural Products Atlas has been developed under FAIR principles (Findable, Accessible, Interoperable, and Reusable) and is integrated with other emerging natural product databases, including the Minimum Information About a Biosynthetic Gene Cluster (MIBiG) repository, and the Global Natural Products Social Molecular Networking (GNPS) platform. It is designed as a community-supported resource to provide a central repository for known natural product structures from microorganisms and is the first comprehensive, open access resource of this type. It is expected that the Natural Products Atlas will enable the development of new natural products discovery modalities and accelerate the process of structural characterization for complex natural products libraries

Selective isolation of Burkholderia, untargeted metabolomics, and biofilm inhibition screening for the discovery of bacterial natural products

The study of natural products is dedicated to the discovery, evaluation, and use of specialized metabolites from natural sources for crop, animal, and human health. The methods required to isolate, characterize, and find utility for these important compounds are continually developing and finding new methods for exploring the diversity of chemistry available in the natural world. This work explores methods in selecting source organisms, comparison of the resulting natural products extracts with an established source of bioactive compounds, and biological screening of a vast library for the discovery of compounds for potential medical use. In the course of this work, a new and robust selection method is described for the one-step isolation of Burkholderia from complex environmental samples. This method introduces a systematic methodology for isolation of other priority organisms. The comparative untargeted metabolomics of the extracts from the Burkholderia library with an existing library of marine actinobacteria highlights the value of continued exploration of both new taxa and additional strains of known organisms for the discovery of important natural products. Finally, the high-throughput image-based screening of extracts and pure compounds for the inhibition and dispersion of V. cholerae biofilms highlights the difficulty and utility of natural products drug discovery for potential medical applications. This work demonstrates the various and important facets of natural products research from the beginning acquisition of organisms and their resulting compounds to the evaluation of these molecules prior to clinical use