Illuminating ecology and distribution of the rare fungus Phellinidium pouzarii in the Bavarian Forest National Park.

Due to their cryptic lifestyle, hidden diversity and a lack of ecological knowledge, conservation of wood-inhabiting fungi continues to be a niche interest. Molecular methods are able to provide deeper insights into the ecology of rare fungal species. We investigated the occurrence of the rare wood-inhabiting fungus Phellinidium pouzarii across the Bavarian Forest National Park in Germany using a fruit body survey, amplicon sequencing and qPCR.

The evaluation of a lean healthcare concept to improve the implementation of Digital Health innovations in secondary health care: a qualitative study within a Dutch hospital setting.

Background: Digital health innovations are considered a promising avenue in transforming the resourcing, organization and delivery of healthcare services and are often nurtured in organization-based innovation labs. One of their biggest challenges is developing effective processes for sifting through ideas. To improve the existing work process, innovation management is often rooted in lean thinking principles.

Functional diversity of the above-ground fungal community under long-term integrated, organic and biodynamic Vineyard Management.

Background: Sustainable agriculture increasingly emphasizes the importance of microbial communities in influencing plant health and productivity. In viticulture, understanding the impact of management practices on fungal communities is critical, given their role in disease dynamics, grape and wine quality. This study investigates the effects of integrated, organic, and biodynamic management practices on the diversity and function of fungal communities in a vineyard located in Geisenheim, Germany, focusing on above-ground parts such as bark, leaves, and grapes.

Hermansones A and B: Bioactive naphthazarin congeners from the European crust fungus Hermanssonia centrifuga.

Two previously undescribed naphthazarins named hermansones A (1) and B (2), were isolated from the wood-decaying basidiomycete Hermanssonia centrifuga. The study presents the first report of natural products from the species. The structures of the secondary metabolites were elucidated through NMR spectroscopy and mass spectrometry.

Structural Insights and Reaction Profile of a New Unspecific Peroxygenase from Produced in a Tandem-Yeast Expression System.

Fungal unspecific peroxygenases (UPOs) are gaining momentum in synthetic chemistry. Of special interest is the UPO from (UPO), which shows an exclusive repertoire of oxyfunctionalizations, including the terminal hydroxylation of alkanes, the α-oxidation of fatty acids and the C-C cleavage of corticosteroids. However, the lack of heterologous expression systems to perform directed evolution has impeded its engineering for practical applications.

p-Terphenyl and Orsellinic Acid Derivatives from the European Polyporales Terana coerulea and Sparassis brevipes.

Investigation of the secondary metabolites of the solid-state rice cultures from the European basidiomycetes Terana coerulea and Sparassis brevipes afforded three previously undescribed secondary metabolites identified as two p-terphenyl derivatives (1 and 2) and one orsellinic acid congener (3) in addition to another known, isoeverninic acid (4). Chemical structures of the isolated compounds were elucidated through comprehensive 1D and 2D NMR spectroscopic analyses, coupled with HR-MS and other spectral methods. The isolated compounds were assessed for their cytotoxic and antimicrobial activities.

Protoilludene and Alkenoic Acid Derivatives from the European Polypore .

Chemical investigation of the solid-state rice culture of the endangered European polypore (Hymenochaetaceae) afforded a previously undescribed protoilludene derivative () in addition to six known compounds (-). Chemical structures of the isolated compounds were established based on HR-ESI-MS, comprehensive 1D/2D NMR spectroscopic analyses, and comparisons with the literature. All isolated compounds were assessed for their cytotoxic and antimicrobial activities.

Dentifragilones A-B and Other Benzoic Acid Derivatives from the European Basidiomycete .

A chemical and biological exploration of the European polypore afforded two previously undescribed natural products ( and ), together with three known derivatives (-). Chemical structures of the isolated compounds were confirmed through 1D/2D NMR spectroscopic analyses, mass spectrometry, and by comparison with the reported literature. The relative and absolute configurations of were determined according to the ROESY spectrum and time-dependent density functional theory electronic circular dichroism (TDDFT-ECD), respectively.

Comparative Study of Toxic Terpenoidal Aldehydes and Lactone Derivatives from the European Polypore .

Two unprecedented isomeric secondary metabolites named vibralactones Z () and Z (), in addition to eleven known compounds (-), were isolated from solid-state rice culture medium of (Bondarzewiaceae). Chemical structures of the isolated compounds were established via spectral analyses. The new lactone derivatives were weakly active against without any significant cytotoxicity, while the molecules containing an aldehyde functionality showed significant antimicrobial and cytotoxic effects.

Enzymatic machinery of wood-inhabiting fungi that degrade temperate tree species.

Deadwood provides habitat for fungi and serves diverse ecological functions in forests. We already have profound knowledge of fungal assembly processes, physiological and enzymatic activities, and resulting physico-chemical changes during deadwood decay. However, in situ detection and identification methods, fungal origins, and a mechanistic understanding of the main lignocellulolytic enzymes are lacking.

Methotrexate plus ustekinumab versus ustekinumab monotherapy in patients with active psoriatic arthritis (MUST): a randomised, multicentre, placebo-controlled, phase 3b, non-inferiority trial.

Background: The role of methotrexate in combination with biological agents in patients with psoriatic arthritis remains unclear. The MUST phase 3b trial aimed to compare the efficacy of ustekinumab plus placebo with ustekinumab plus methotrexate in patients with active psoriatic arthritis.

Methods: In this investigator-initiated, randomised, multicentre, placebo-controlled, phase 3b non-inferiority trial done in 22 centres in Germany, patients with active psoriatic arthritis received open-label ustekinumab and were randomly assigned (1:1) to masked concomitant therapy with placebo or methotrexate (ongoing or new).

Differences in treatment response between female and male psoriatic arthritis patients during IL-12/23 therapy with or without methotrexate: post hoc analysis of results from the randomised MUST trial.

Background: The influence of sex on treatment outcomes during interleukin-12/23 therapy in patients with psoriatic arthritis (PsA) has not been explored.

Objective: To conduct exploratory post hoc analyses of sex-stratified data from the MUST trial, an investigator-initiated, multicentre, phase 3b study in which patients with active PsA initiating treatment with open-label ustekinumab were randomised to treatment with placebo or methotrexate (MTX).

Methods: We evaluated baseline characteristics, key treatment outcomes and adverse events stratified by sex, with a focus on outcomes that did not include erythrocyte sedimentation rate (ESR) as a component due to the known elevation of ESR in females.

Real-world effectiveness of golimumab in the treatment of patients with active rheumatoid arthritis, psoriatic arthritis, or axial spondyloarthritis who failed initial TNF-α inhibitor therapy: a pooled analysis of European prospective observational studie.

Objectives: Rheumatoid arthritis (RA), psoriatic arthritis (PsA), and axial spondyloarthritis (axSpA) patients often experience secondary non-response to a first-line tumour necrosis factor alpha inhibitor (TNFαi). This pooled analysis of six observational studies in Europe (GO-BEYOND program) provides an estimate of second-line golimumab (GLM) effectiveness for these rheumatic diseases.

Methods: The GO-BEYOND studies included common disease-specific endpoints allowing for a pooled analysis.

Real-World Effectiveness and Safety of SDZ ETN, an Etanercept Biosimilar, in Patients with Rheumatic Diseases: Final Results from Multi-Country COMPACT Study.

Introduction: COMPACT, a non-interventional study, evaluated the persistence, effectiveness, safety and patient-reported outcomes (PROs) in patients with rheumatoid arthritis (RA), axial-spondyloarthritis (axSpA) or psoriatic arthritis (PsA) treated with SDZ ETN (etanercept [ETN] biosimilar) in Europe and Canada.

Methods: Patients (aged ≥ 18 years) who have been treated with SDZ ETN were categorised on the basis of prior treatment status (groups A-D): patients in clinical remission or with low disease activity under treatment with reference ETN or biosimilar ETN and switched to SDZ ETN; patients who received non-ETN targeted therapies and switched to SDZ ETN; biologic-naïve patients who started SDZ ETN after conventional therapy failure; or disease-modifying anti-rheumatic drug (DMARD)-naïve patients with RA considered suitable for treatment initiation with a biologic and started on treatment with SDZ ETN. The primary endpoint was drug persistence, defined as time from study enrolment until discontinuation of SDZ ETN treatment.

Biologically active drimane derivatives isolated from submerged cultures of the wood-inhabiting basidiomycete .

Four previously undescribed drimane sesquiterpenoids were isolated from submerged cultures of the wood-inhabiting basidiomycete along with two compounds that were previously reported as synthetic or biotransformation compounds but not as natural products. The constitution and relative configuration of these compounds was determined based on high-resolution electrospray ionization mass spectrometry as well as by 1D and 2D nuclear magnetic resonance spectroscopy. The absolute configurations were established based on exemplary calculation of circular dichroism spectra and comparison with measured data as well as on biogenetic considerations.

Nitrogen addition increases mass loss of gymnosperm but not of angiosperm deadwood without changing microbial communities.

Enhanced nitrogen (N) deposition due to combustion of fossil fuels and agricultural fertilization is a global phenomenon which has severely altered carbon (C) and N cycling in temperate forest ecosystems in the northern hemisphere. Although deadwood holds a substantial amount of C in forest ecosystems and thus plays a crucial role in nutrient cycling, the effect of increased N deposition on microbial processes and communities, wood chemical traits and deadwood mass loss remains unclear. Here, we simulated high N deposition rates by adding reactive N in form of ammonium-nitrate (40 kg N ha yr) to deadwood of 13 temperate tree species over nine years in a field experiment in Germany.

Hericioic Acids and Hericiofuranoic Acid; Neurotrophic Agents from Cultures of the European Mushroom .

Neurodegenerative diseases are currently posing huge social, economic, and healthcare burdens among the aged populations worldwide with few and only palliative treatment alternatives available. Natural products continue to be a source of a vast array of potent neurotrophic molecules that could be considered as drug design starting points. The present study reports eight new isoindolinone and benzofuranone derivatives, for which we propose the trivial names, hericioic acids (-) and hericiofuranoic acid (), which were isolated from a solid culture (using rice as substrate) of the rare European edible mushroom .

Effectiveness of Different Rituximab Doses Combined with Leflunomide in the Treatment or Retreatment of Rheumatoid Arthritis: Part 2 of a Randomized, Placebo-Controlled, Investigator-Initiated Clinical Trial (AMARA).

Background: The optimal dose of rituximab in combination with leflunomide in patients with rheumatoid arthritis (RA) is not known.

Methods: In Part 1 (previously reported) of the investigator-initiated AMARA study (EudraCT 2009-015950-39; ClinicalTrials.gov NCT01244958), improvements at week (W)24 were observed in patients randomized to rituximab + leflunomide compared with placebo + leflunomide.

Antimicrobial and Cytotoxic Cyathane-Xylosides from Cultures of the Basidiomycete .

In our continued search for biologically active metabolites from cultures of rare Basidiomycota species, we found eight previously undescribed cyathane-xylosides from submerged cultures of , which were named dentifragilins A-H. In addition, the known cyathane derivatives striatal D and laxitextine A were isolated. All compounds were characterized by high-resolution electrospray ionization mass spectrometry (HR-ESIMS) as well as by 1D and 2D nuclear magnetic resonance (NMR) spectroscopy.

Cell-free production of the bifunctional glycoside hydrolase GH78 from Xylaria polymorpha.

The ability to catalyze diverse reactions with relevance for chemical and pharmaceutical research and industry has led to an increasing interest in fungal enzymes. There is still an enormous potential considering the sheer amount of new enzymes from the huge diversity of fungi. Most of these fungal enzymes have not been characterized yet due to the lack of high throughput synthesis and analysis methods.