Dysbiosis of skin microbiota with increased fungal diversity is associated with severity of disease in atopic dermatitis

Background: Atopic dermatitis (AD) is a multifactorial inflammatory skin disease and an altered skin microbiota with an increase of Staphylococcus aureus has been reported. However, the role of fungi remains poorly investigated. Objectives: We aimed to improve the understanding of the fungal skin microbiota, the mycobiota, in AD in relation to the bacterial colonization. Methods: Skin swabs of 16 AD patients and 16 healthy controls (HC) from four different skin sites, that is antecubital crease, dorsal neck, glabella and vertex from multiple time points were analysed by DNA sequencing of the internal transcribed spacer region 1 (ITS1) and 16S rRNA gene for fungi and bacteria, respectively. Results: Malassezia spp. were the predominant fungi in all subjects but with a decreased dominance in severe AD patients in favour of non-Malassezia fungi, for example Candida spp. For bacteria, a decrease of Cutibacterium spp. in AD patients in favour of Staphylococcus spp., particularly S. aureus, was observed. Further, both bacterial and fungal community compositions of severe AD patients significantly differed from mild-to-moderate AD patients and HC with the latter two having overall similar microbiota showing some distinctions in bacterial communities. Conclusions: We conclude that severe AD is associated with a pronounced dysbiosis of the microbiota with increased fungal diversity. Potentially infectious agents, for example Staphylococcus and Candida, were increased in severe AD. Keywords: atopic dermatitis; bacteria; disease severity; fungi; skin microbiot

Surveillance and Outbreak Response Management System (SORMAS) to support the control of the Ebola virus disease outbreak in West Africa

In the context of controlling the current outbreak of Ebola virus disease (EVD), the World Health Organization claimed that ‘critical determinant of epidemic size appears to be the speed of implementation of rigorous control measures’, i.e. immediate follow-up of contact persons during 21 days after exposure, isolation and treatment of cases, decontamination, and safe burials. We developed the Surveillance and Outbreak Response Management System (SORMAS) to improve efficiency and timeliness of these measures. We used the Design Thinking methodology to systematically analyse experiences from field workers and the Ebola Emergency Operations Centre (EOC) after successful control of the EVD outbreak in Nigeria. We developed a process model with seven personas representing the procedures of EVD outbreak control. The SORMAS system architecture combines latest In-Memory Database (IMDB) technology via SAP HANA (in-memory, relational database management system), enabling interactive data analyses, and established SAP cloud tools, such as SAP Afaria (a mobile device management software). The user interface consists of specific front-ends for smartphones and tablet devices, which are independent from physical configurations. SORMAS allows real-time, bidirectional information exchange between field workers and the EOC, ensures supervision of contact follow-up, automated status reports, and GPS tracking. SORMAS may become a platform for outbreak management and improved routine surveillance of any infectious disease. Furthermore, the SORMAS process model may serve as framework for EVD outbreak modelling

User evaluation indicates high quality of the Surveillance Outbreak Response Management and Analysis System (SORMAS) after field deployment in Nigeria in 2015 and 2018

During the West African Ebola virus disease outbreak in 2014-15, health agencies had severe challenges with case notification and contact tracing. To overcome these, we developed the Surveillance, Outbreak Response Management and Analysis System (SORMAS). The objective of this study was to measure perceived quality of SORMAS and its change over time. We ran a 4-week-pilot and 8-week-implementation of SORMAS among hospital informants in Kano state, Nigeria in 2015 and 2018 respectively. We carried out surveys after the pilot and implementation asking about usefulness and acceptability. We calculated the proportions of users per answer together with their 95% confidence intervals (CI) and compared whether the 2015 response distributions differed from those from 2018. Total of 31 and 74 hospital informants participated in the survey in 2015 and 2018, respectively. In 2018, 94% (CI: 89-100%) of users indicated that the tool was useful, 92% (CI: 86-98%) would recommend SORMAS to colleagues and 18% (CI: 10-28%) had login difficulties. In 2015, the proportions were 74% (CI: 59-90%), 90% (CI: 80-100%), and 87% (CI: 75-99%) respectively. Results indicate high usefulness and acceptability of SORMAS. We recommend mHealth tools to be evaluated to allow repeated measurements and comparisons between different versions and users

PD-L1 Dependent Immunogenic Landscape in Hot Lung Adenocarcinomas Identified by Transcriptome Analysis

Background: Lung cancer is the most frequent cause of cancer-related deaths worldwide. The clinical development of immune checkpoint blockade has dramatically changed the treatment paradigm for patients with lung cancer. Yet, an improved understanding of PD-1/PD-L1 checkpoint blockade- responsive biology is warranted. Methods: We aimed to identify the landscape of immune cell infiltration in primary lung adenocarcinoma (LUAD) in the context of tumoral PD-L1 expression and the extent of immune infiltration ("hot" vs. "cold" phenotype). The study comprises LUAD cases (n = 138) with "hot" (≥150 lymphocytes/HPF) and "cold" (<150 lymphocytes/HPF) tumor immune phenotype and positive (>50%) and negative (<1%) tumor PD-L1 expression, respectively. Tumor samples were immunohistochemically analyzed for expression of PD-L1, CD4, and CD8, and further investigated by transcriptome analysis. Results: Gene set enrichment analysis defined complement, IL-JAK-STAT signaling, KRAS signaling, inflammatory response, TNF-alpha signaling, interferon-gamma response, interferon-alpha response, and allograft rejection as significantly upregulated pathways in the PD-L1-positive hot subgroup. Additionally, we demonstrated that STAT1 is upregulated in the PD-L1-positive hot subgroup and KIT in the PD-L1-negative hot subgroup. Conclusion: The presented study illustrates novel aspects of PD-L1 regulation, with potential biological relevance, as well as relevance for immunotherapy response stratification

BILDUNG VON CELLULASE UND PROTEIN BEIM WACHSTUM VON CHAETOMIUM CELLULOLYTICUM AUF CELLULOSEHALTIGEN SUBSTRATEN

Microbial protein (SCP) production from ligno-cellulosic materials and also the enzymatic hydrolysis of cellulose and hemicellulose have received increased interest in recent years. The thermotolerant fungus Chaetomium cellulolyticum /1/ was recently reported as an object for SCP production from cellulosic substrates /2,3/. In the present paper we examined growth of C. cellulolyticum on glucose, crystalline cellulose, and on chemically non-treated newspaper. Studies were also made on SCP production and on formation of extracellular cellulase. A mutant strain of C, cellulolyticum was isclated which produced higher levels | of extracellular cellulase compared to the parent type. In order to study the effect of chemical pretreatment of ligno-cellulosic substrate on SCP production, the mutant was grown on alkali-treated newspaper