Large expert-curated database for benchmarking document similarity detection in biomedical literature search

Document recommendation systems for locating relevant literature have mostly relied on methods developed a decade ago. This is largely due to the lack of a large offline gold-standard benchmark of relevant documents that cover a variety of research fields such that newly developed literature search techniques can be compared, improved and translated into practice. To overcome this bottleneck, we have established the RElevant LIterature SearcH consortium consisting of more than 1500 scientists from 84 countries, who have collectively annotated the relevance of over 180 000 PubMed-listed articles with regard to their respective seed (input) article/s. The majority of annotations were contributed by highly experienced, original authors of the seed articles. The collected data cover 76% of all unique PubMed Medical Subject Headings descriptors. No systematic biases were observed across different experience levels, research fields or time spent on annotations. More importantly, annotations of the same document pairs contributed by different scientists were highly concordant. We further show that the three representative baseline methods used to generate recommended articles for evaluation (Okapi Best Matching 25, Term Frequency-Inverse Document Frequency and PubMed Related Articles) had similar overall performances. Additionally, we found that these methods each tend to produce distinct collections of recommended articles, suggesting that a hybrid method may be required to completely capture all relevant articles. The established database server located at https://relishdb.ict.griffith.edu.au is freely available for the downloading of annotation data and the blind testing of new methods. We expect that this benchmark will be useful for stimulating the development of new powerful techniques for title and title/abstract-based search engines for relevant articles in biomedical research.Peer reviewe

Isolation and structure elucidation of new natural products from bacteria and endophytic fungi by chemical screening

Die vorliegende Arbeit beschäftigt sich mit der Isolierung und Struktur­aufklärung neuer Sekundär­metaboliten aus Bakterien und endo­phytischen Pilzen durch chemisches Screening. Die antimikrobielle und cytotoxische Aktivität der Naturstoffe wird untersucht und ökologische, chemische und biosynthetische Zusammen­hänge herausgestellt.Fünf neue Actinomycine zeigen interessante Variationen im β-Peptidl­actonring, der u. a. die Aminosäure 4-Chlor- bzw. 4-Hydroxythreonin enthält. Bei Actinomycin G5 liegt erstmals ein zusätzlicher Ringschluss zum Chromophor vor. Die Zugabe von Anthranilsäure zur Kultur des Bakteriums Halomonas sp. Rk377a induzierte die Melaninbildung sowie die Biosynthese von drei Aminophenoxazon-Derivaten mit einem zuvor nicht beschriebenen Substitutions­muster. Der Actinomycet Gö M1 produziert aromatische und nicht-aromatische α -L-Glykoside, die den ungewöhnlichen Desoxyzucker 6-Desoxytalose enthalten. Durch Vorläufer-dirigierte Biosynthese konnte die Ausbeute erhöht und das Metabolitenspektrum erweitert werden.Im Rahmen eines BMBF-Forschungsverbunds wurden endophytische Pilze einem chemischen und biologischen Screening unterzogen. Als wichtigste Ergebnisse werden die Strukturen und biologischen Aktivitäten von vier neuen Naturstoffen beschrieben. Das Polyketid Chaetospiron aus Chaetomium sp. besitzt ein neuartiges Kohlenstoff­gerüst, das einen Tropolonring mit einem Spiroketal kombiniert. Ebenfalls ein Spiroketal ist Beauveriaspirolid aus Beauveria sp., das zusätzlich eine Epoxidfunktion hat. Phomopsofuran A aus Phomopsis sp. ist aus einem Pentaketid aufgebaut, das mit einer bei Mikroorganismen seltenen Tigloylgruppe verknüpft ist. Mit Bis(prehelminthosporol) aus Drechslera sp. wird ein neues dimeres Sesquiterpen vom seco-Sativentyp beschrieben, das in zwei diastereomeren Formen vorliegt

Acoustic user interfaces for ambient-assisted living technologies

This contribution discusses technologies for acoustic user interaction in ambient-assisted living (AAL) scenarios. Acoustic user interfaces allow for a natural and convenient way to interact with technical systems e.g. via sound or speech presentation or via speech input by means of automatic speech recognition (ASR) as well as by detection and classification of acoustic events. Older persons targeted by AAL technologies especially need more easy-to-use methods to interact with inherently complex supporting technology. As an example we designed and evaluated an application for acoustic user interaction with a multi-media reminder and calendar system. For this purpose, mainly older participants were involved in user studies to continuously evaluate and support the development strictly following a user-centred design process. The results suggest a wide acceptance of acoustic user interfaces by older users either for controlling inherently complex AAL systems by using robust ASR technologies or as a natural and ambient way of presenting information to the user. However, further research is needed to increase the robustness of ASR systems when using hands-free equipment, i.e. to provide a real ambient way of interaction, and to introduce personalised speech and sound presentation schemes accounting for the individual hearing capabilities and sound preferences

Accelerated Dereplication of Natural Products, Supported by Reference Libraries

Natural products are an indispensable source for drug discovery. The major challenge for exploiting this evolutionary optimized pool of potential lead structures is the fast and reliable recognition of known compounds, i. e. dereplication. This task is essential for the discovery process in high-throughput screening scenarios, since it allows the focus to be placed on novel chemical structures at an early stage. Furthermore, information on identified compounds will help to rationalize observed bioactivities. This article describes an effective, library-supported strategy for the dereplication of crude extracts and pre-fractionated samples, using an HPLC-based multidetector platform and NMR techniques, respectively

Affinities of Phylacia and the daldinoid Xylariaceae, inferred from chemotypes of cultures and ribosomal DNA sequences

A chemotaxonomic evaluation using hplc profiling was undertaken to resolve the infrageneric and intergeneric affinities of over 150 strains of Xylariaceae. Daldinia placentiformis, Hypoxylon nicaraguense, H. polyporus, and Phylacia sagrana were found to contain 8-methoxy-1-naphthol, which is apparently absent in Annulohypoxylon, Hypoxylon, and related genera with bipartite stromata. D. placentiformis and other species of Daldinia and Entonaema produced this naphthol, 5-hydroxy-2-methylchromone, isosclerone derivatives, and 'AB-5046' phytotoxins. Phylacia sagrana differed from most Daldinia spp., except for D. caldariorum, by producing eutypine derivatives in addition to the above compounds. indolylquinones were observed in H. nicaraguense and H. polyporus. Isosclerones were also identified in the A. multiforme complex, but Hypoxylon and other Annulohypoxylon and most Hypoxylon spp. studied Annulohypoxylon spp. contained S-methylmellein as the major metabolite of their cultures. Based on the occurrence of the above metabolites, further mellein-type dihydroisocoumarins, teleomorphic and anamorphic Xylariaceae with Nodulisporium-like anamorphs ('Hypoxyloideae') were divided into various chemotypes. A comparison of their 5.8S/ ITS nuc-rDNA sequences agreed in some important aspects with the above results: H. nicaraguense and H. polyporus appeared basal to a clade comprising Daldinia, Entonaema, and Ph. sagrana. The latter species appeared allied to D. caldariorum, but was distantly related to Pyrenomyxa morganii and Hypoxylon s. str. (C) 2007 The British Mycological Society. Published by Elsevier Ltd. All rights reserved

Increased soluble HLA in COVID-19 present a disease-related, diverse immunopeptidome associated with T cell immunity

Summary: HLA-presented antigenic peptides are central components of T cell-based immunity in infectious disease. Beside HLA molecules on cell surfaces, soluble HLA molecules (sHLA) are released in the blood suggested to impact cellular immune responses. We demonstrated that sHLA levels were significantly increased in COVID-19 patients and convalescent individuals compared to a control cohort and positively correlated with SARS-CoV-2-directed cellular immunity. Of note, patients with severe courses of COVID-19 showed reduced sHLA levels. Mass spectrometry-based characterization of sHLA-bound antigenic peptides, the so-called soluble immunopeptidome, revealed a COVID-19-associated increased diversity of HLA-presented peptides and identified a naturally presented SARS-CoV-2-derived peptide from the viral nucleoprotein in the plasma of COVID-19 patients. Of interest, sHLA serum levels directly correlated with the diversity of the soluble immunopeptidome. Together, these findings suggest an inflammation-driven release of sHLA in COVID-19, directly influencing the diversity of the soluble immunopeptidome with implications for SARS-CoV-2-directed T cell-based immunity and disease outcome