Autogene cevumeran with or without atezolizumab in advanced solid tumors: a phase 1 trial.

Effective targeting of somatic cancer mutations to enhance the efficacy of cancer immunotherapy requires an individualized approach. Autogene cevumeran is a uridine messenger RNA lipoplex-based individualized neoantigen-specific immunotherapy designed from tumor-specific somatic mutation data obtained from tumor tissue of each individual patient to stimulate T cell responses against up to 20 neoantigens. This ongoing phase 1 study evaluated autogene cevumeran as monotherapy (n = 30) and in combination with atezolizumab (n = 183) in pretreated patients with advanced solid tumors.

Video-tracked entry and exit behaviour at washed and damaged pyrethroid-treated bednets.

Insecticide-treated nets (ITNs) are the most effective method for malaria prevention in Africa. Using near-infrared video tracking in a laboratory environment, we recorded and assessed bednet entry and exit by a northern Tanzanian population of at a human-occupied untreated net and a PermaNet® 2.0 ITN.

Single-centre prospective evaluation of the first 5 years of cystic fibrosis newborn screening in Germany.

Background: In 2016, nationwide cystic fibrosis newborn screening (CFNS) was newly implemented in Germany, using an immunoreactive trypsin/pancreatitis-associated protein/DNA screening algorithm that differs from most other nationwide screening programmes.

Methods: We analysed real-life feasibility of the confirmation process with respect to our pre-specified procedural objectives. These included overall accuracy through false-negative and false-positive results, effectiveness of the Bavarian tracking system, and accuracy of Macroduct and Nanoduct sweat conductivity compared with quantitative chloride determination.

BNT162b vaccines protect rhesus macaques from SARS-CoV-2.

A safe and effective vaccine against COVID-19 is urgently needed in quantities that are sufficient to immunize large populations. Here we report the preclinical development of two vaccine candidates (BNT162b1 and BNT162b2) that contain nucleoside-modified messenger RNA that encodes immunogens derived from the spike glycoprotein (S) of SARS-CoV-2, formulated in lipid nanoparticles. BNT162b1 encodes a soluble, secreted trimerized receptor-binding domain (known as the RBD-foldon).

Retained primary teeth in STAT3 hyper-IgE syndrome: early intervention in childhood is essential.

Background: STAT3 hyper-IgE syndrome (STAT3-HIES) is a rare primary immunodeficiency that clinically overlaps with atopic dermatitis. In addition to eczema, elevated serum-IgE, and recurrent infections, STAT3-HIES patients suffer from characteristic facies, midline defects, and retained primary teeth. To optimize dental management we assessed the development of dentition and the long-term outcomes of dental treatment in 13 molecularly defined STAT3-HIES patients using questionnaires, radiographs, and dental investigations.

Coupled Electrochemical and Microbial Catalysis for the Production of Polymer Bricks.

Power-to-X technologies have the potential to pave the way towards a future resource-secure bioeconomy as they enable the exploitation of renewable resources and CO . Herein, the coupled electrocatalytic and microbial catalysis of the C -polymer precursors mesaconate and 2S-methylsuccinate from CO and electric energy by in situ coupling electrochemical and microbial catalysis at 1 L-scale was developed. In the first phase, 6.

Diffuse retro-reflective imaging for improved video tracking of mosquitoes at human baited bednets.

Robust imaging techniques for tracking insects have been essential tools in numerous laboratory and field studies on pests, beneficial insects and model systems. Recent innovations in optical imaging systems and associated signal processing have enabled detailed characterization of nocturnal mosquito behaviour around bednets and improvements in bednet design, a global essential for protecting populations against malaria. Nonetheless, there remain challenges around ease of use for large-scale recordings and extracting data reliably in the critical areas of the bednet where the optical signal is attenuated.

Impaired memory B-cell development and antibody maturation with a skewing toward IgE in patients with STAT3 hyper-IgE syndrome.

Background: Signal transducer and activator of transcription 3 hyper-IgE syndrome (STAT3-HIES) is caused by heterozygous mutations in the STAT3 gene and is associated with eczema, elevated serum IgE, and recurrent infections resembling severe atopic dermatitis, while clinically relevant specific IgE is almost absent.

Methods: To investigate the impact of STAT3 signaling on B-cell responses, we assessed lymph node and bone marrow, blood B and plasma cell subsets, somatic hypermutations in Ig genes, and in vitro proliferation and antibody production in STAT3-HIES patients and healthy controls.

Results: Lymph nodes of STAT3-HIES patients showed normal germinal center architecture and CD138 plasma cells residing in the paracortex, which expressed IgE, IgG, and IgM but not IgA.

Lung disease in STAT3 hyper-IgE syndrome requires intense therapy.

Background: Pulmonary complications are responsible for high morbidity and mortality rates in patients with the rare immunodeficiency disorder STAT3 hyper-IgE syndrome (STAT3-HIES). The aim of this study was to expand knowledge about lung disease in STAT3-HIES.

Methods: The course of pulmonary disease, radiological and histopathological interrelations, therapeutic management, and the outcome of 14 STAT3-HIES patients were assessed.

Towards electroenzymatic processes involving old yellow enzymes and mediated cofactor regeneration.

Old yellow enzymes are able to catalyze asymmetric C=C reductions. A mediated electroenzymatic process to regenerate the NADPH in combination with an old yellow enzyme was investigated. Due to the fact that the overall process was affected by a broad set of parameters, a design of experiments (DoE) approach was chosen to identify suitable process conditions.

Lung disease caused by mutations.

Background: Knowledge about the clinical spectrum of lung disease caused by variations in the ATP binding cassette subfamily A member 3 (ABCA3) gene is limited. Here we describe genotype-phenotype correlations in a European cohort.

Methods: We retrospectively analysed baseline and outcome characteristics of 40 patients with two disease-causing ABCA3 mutations collected between 2001 and 2015.

Eradication of methicillin resistant Staphylococcus aureus detected for the first time in cystic fibrosis: A single center observational study.

Objective: To retrospectively identify CF patients with methicillin resistant Staphylococcus aureus (MRSA) and to assess the long-term success of an eradication scheme introduced in 2002 for all newly colonized patients.

Patients: All microbiological results from all 505 CF patients followed between 2002 and 2012 were analyzed focusing on the detection of MRSA.

Methods: Retrospective patient record analysis of MRSA positive CF patients regarding eradication and clinical outcome.

Tools to explore ABCA3 mutations causing interstitial lung disease.

Background: Interstitial lung diseases (ILD) comprise disorders of mostly unknown cause. Among the few molecularly defined entities, mutations in the gene encoding the ATP-binding cassette (ABC), subfamily A, member 3 (ABCA3) lipid transporter represent the main cause of inherited surfactant dysfunction disorders, a subgroup of ILD. Whereas many cases are reported, specific methods to functionally define such mutations are rarely presented.

Categorizing diffuse parenchymal lung disease in children.

Background: Aim of this study was to verify a systematic and practical categorization system that allows dynamic classification of pediatric DPLD irrespective of completeness of patient data.

Methods: The study was based on 2322 children submitted to the kids-lung-register between 1997 and 2012. Of these children 791 were assigned to 12 DPLD categories, more than 2/3 belonged to categories manifesting primarily in infancy.

Engineering Methylobacterium extorquens for de novo synthesis of the sesquiterpenoid α-humulene from methanol.

Over the last 10 to 15 years, metabolic engineering of microbes has become a versatile tool for high-level de novo synthesis of terpenoids, with the sesquiterpenoids armopha-1,4-diene, farnesene and artemisinic acid as prime examples. However, almost all cell factory approaches towards terpenoids to date have been based on sugar as the raw material, which is mainly used as a food resource and subject to high price volatilities. In this study we present de novo synthesis of the sesquiterpenoid α-humulene from the abundantly available non-food carbon source methanol by metabolically engineered Methylobacterium extorquens AM1.

GATA2 deficiency in children and adults with severe pulmonary alveolar proteinosis and hematologic disorders.

Background: The majority of cases with severe pulmonary alveolar proteinosis (PAP) are caused by auto-antibodies against GM-CSF. A multitude of genetic and exogenous causes are responsible for few other cases. Goal of this study was to determine the prevalence of GATA2 deficiency in children and adults with PAP and hematologic disorders.

Genotype alone does not predict the clinical course of SFTPC deficiency in paediatric patients.

Patients with interstitial lung disease due to surfactant protein C (SFTPC) mutations are rare and not well characterised. We report on all subjects collected over a 15-year period in the kids-lung register with interstitial lung disease and a proven SFTPC mutation. We analysed clinical courses, interventions and outcomes, as well as histopathological and radiological interrelations.

Endobronchial lesions caused by nontuberculous mycobacteria in apparently healthy pediatric patients.

Pulmonary disease caused by nontuberculous mycobacteria in healthy children is rare, and its pathogenesis is unknown in most cases and standardized treatment is lacking. Here, we report various endobronchial manifestations in 5 patients including hitherto undescribed diffuse tracheobronchial granulomas in 2 patients. Bronchoscopic debulking was performed in all patients and tuberculostatic treatment in 4.

The chemokine CCL18 characterises Pseudomonas infections in cystic fibrosis lung disease.

Cystic fibrosis (CF) lung disease is characterised by chronic Pseudomonas aeruginosa infection and leukocyte infiltration. Chemokines recruit leukocytes to sites of infection. Gene expression analysis identified the chemokine CCL18 as upregulated in CF leukocytes.

Endless: a purine-binding RNA motif that can be expressed in cells.

It is becoming increasingly clear that nature uses RNAs extensively for regulating vital functions of the cell, and short sequences are frequently used to suppress gene expression. However, controlling the concentration of small molecules intracellularly through designed RNA sequences that fold into ligand-binding structures is difficult. The development of "endless", a triplex-based folding motif that can be expressed in mammalian cells and binds the second messenger 3',5'-cyclic guanosine monophosphate (cGMP), is described.

Binding cofactors with triplex-based DNA motifs.

Cofactors are pivotal compounds for the cell and many biotechnological processes. It is therefore interesting to ask how well cofactors can be bound by oligonucleotides designed not to convert but to store and release these biomolecules. Here we show that triplex-based DNA binding motifs can be used to bind nucleotides and cofactors, including NADH, FAD, SAM, acetyl CoA, and tetrahydrofolate (THF).

The basidiomycetous yeast Trichosporon may cause severe lung exacerbation in cystic fibrosis patients - clinical analysis of Trichosporon positive patients in a Munich cohort.

Background: The relevance of Trichosporon species for cystic fibrosis (CF) patients has not yet been extensively investigated.

Methods: The clinical course of CF patients with Trichosporon spp. in their respiratory secretions was analysed between 2003 and 2010 in the Munich CF center.

Sequential targeting of CFTR by BAC vectors generates a novel pig model of cystic fibrosis.

Cystic fibrosis (CF) is the most common lethal inherited disease in Caucasians and is caused by mutations in the CFTR gene. The disease is incurable and medical treatment is limited to the amelioration of symptoms or secondary complications. A comprehensive understanding of the disease mechanisms and the development of novel treatment options require appropriate animal models.

Designed nucleotide binding motifs.

Gaps in the central strand of oligonucleotide triplexes bind nucleoside phosphates tightly. Watson-Crick and Hoogsteen base pairing as design principle yield motifs with high affinity for nucleoside phosphates with A or G as nucleobase, including ATP. The second messenger 3',5'-cAMP is bound with nanomolar affinity.