Functional and Biological Characterization of the LGR5Δ5 Splice Variant in HEK293T Cells.

The regulator of the canonical Wnt pathway, leucine-rich repeat-containing G protein-coupled receptor 5 (LGR5), is expressed in the stem cell compartment of several tissues and overexpressed in different human carcinomas. The isoform of the stem cell marker LGR5, named LGR5Δ5 and first described by our group, is associated with prognosis and metastasis in oral squamous cell carcinoma (OSCC) and soft tissue sarcoma (STS). In a proof-of-principle analysis, the function of LGR5Δ5 was investigated in HEK293T cells, a model cell line of the Wnt pathway, compared to full-length LGR5 (FL) expression.

Efficacy and safety of asunercept, a CD95L-selective inhibitor, in hospitalised patients with moderate-to-severe COVID-19: ASUNCTIS, a multicentre, randomised, open-label, controlled, phase 2 trial.

Background: The phase 2 ASUNCTIS study assessed the efficacy and safety of asunercept, a fully human CD95 (Fas) ligand-binding protein, in hospitalised patients with moderate-to-severe coronavirus disease (COVID-19) to assess the clinical benefit of CD95 ligand inhibition in this viral disease.

Methods: In this open-label, multicentre, randomised, controlled, phase 2 trial, patients with COVID-19-induced pneumonia and respiratory deterioration were randomly assigned (1:1:1:1) in 12 Russian and Spanish hospitals using an interactive web-response system to receive standard of care (SOC) or SOC plus weekly asunercept 25 mg, 100 mg, or 400 mg, administered intravenously for up to 4 weeks, or until hospital discharge or death. The randomisation was stratified according to the respiratory support methods at the time of enrolment, corresponding to categories 4-6 of a clinical severity assessment scale comprising 9 levels that was recommended by the World Health Organization (WHO) at the time of the study.

Integrated In-Plane Nanofluidic Devices for Resistive-Pulse Sensing.

Single-particle (or digital) measurements enhance sensitivity (10- to 100-fold improvement) and uncover heterogeneity within a population (one event in 100 to 10,000). Many biological systems are significantly influenced by rare or infrequent events, and determining what species is present, in what quantity, and the role of that species is critically important to unraveling many questions. To develop these measurement systems, resistive-pulse sensing is used as a label-free, single-particle detection technique and can be combined with a range of functional elements, e.

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.

NANOS1 restricts oral cancer cell motility and TGF-ß signaling.

Oral squamous cell carcinoma (OSCC) is the most frequent type of cancer of the head and neck area accounting for approx. 377,000 new cancer cases every year. The epithelial-to-mesenchymal transition (EMT) program plays an important role in OSCC progression and metastasis therefore contributing to a poor prognosis in patients with advanced disease.

[Kids Lung Registry and Child-EU Project - Progress in Rare and Interstitial Lung Diseases in Childhood Through Collaboration].

Background: Progress in rare and interstitial lung disease in childhood can most usefully be achieved through systematic, registry-based collection.

Question And Methods: What are the practicalities and benefits of participating in the pediatric lung registry/chILD-EU project? We report our clinical experiences.

Results: Pediatricians and pediatric pulmonologists identify children with rare lung diseases.

Characterization of Extracellular Vesicles by Resistive-Pulse Sensing on In-Plane Multipore Nanofluidic Devices.

Extracellular vesicles (EVs) are cell-derived, naturally produced, membrane-bound nanoscale particles that are linked to cell-cell communication and the propagation of diseases. Here, we report the design and testing of in-plane nanofluidic devices for resistive-pulse measurements of EVs derived from bovine milk and human breast cancer cells. The devices were fabricated in plane with three nanopores in series to determine the particle volume and diameter, two pore-to-pore regions to measure the electrophoretic mobility and zeta potential, and an in-line filter to prevent cellular debris and aggregates from entering the nanopore region.

Correlation between Circulating miR-16, miR-29a, miR-144 and miR-150, and the Radiotherapy Response and Survival of Non-Small-Cell Lung Cancer Patients.

Despite the success of current therapy concepts, patients with advanced non-small-cell lung cancer (NSCLC) still have a very poor prognosis. Therefore, biological markers are urgently needed, which allow the assessment of prognosis, or prediction of the success of therapy or resistance in this disease. Circulating microRNAs (miRs) have potential as biomarkers for the prognosis and prediction of response to therapy in cancer patients.

Impact of elexacaftor/tezacaftor/ivacaftor on lung function, nutritional status, pulmonary exacerbation frequency and sweat chloride in people with cystic fibrosis: real-world evidence from the German CF Registry.

Background: Treatment with elexacaftor/tezacaftor/ivacaftor (ETI) improves multiple clinical outcomes in people with cystic fibrosis (pwCF) with at least one F508del allele. This study evaluated the real-world impact of ETI on lung function, nutritional status, pulmonary exacerbation frequency, and sweat chloride concentrations in a large group of pwCF.

Methods: This observational cohort study used data from the German CF Registry for pwCF who received ETI therapy and were followed up for a period of 12 months.

Optimizing human-robot handovers: the impact of adaptive transport methods.

Humans are increasingly coming into direct physical contact with robots in the context of object handovers. The technical development of robots is progressing so that handovers can be better adapted to humans. An important criterion for successful handovers between robots and humans is the predictability of the robot for the human.

Dental Pulp Stem Cells for Salivary Gland Regeneration-Where Are We Today?

Xerostomia is the phenomenon of dry mouth and is mostly caused by hypofunction of the salivary glands. This hypofunction can be caused by tumors, head and neck irradiation, hormonal changes, inflammation or autoimmune disease such as Sjögren's syndrome. It is associated with a tremendous decrease in health-related quality of life due to impairment of articulation, ingestion and oral immune defenses.

ABCA3-related interstitial lung disease beyond infancy.

Background: The majority of patients with childhood interstitial lung disease (chILD) caused by pathogenic variants in ATP binding cassette subfamily A member 3 (ABCA3) develop severe respiratory insufficiency within their first year of life and succumb to disease if not lung transplanted. This register-based cohort study reviews patients with ABCA3 lung disease who survived beyond the age of 1 year.

Method: Over a 21-year period, patients diagnosed as chILD due to ABCA3 deficiency were identified from the Kids Lung Register database.

Antimicrobial Activity of Ceftazidime-Avibactam, Ceftolozane-Tazobactam, Cefiderocol, and Novel Darobactin Analogs against Multidrug-Resistant Pseudomonas aeruginosa Isolates from Pediatric and Adolescent Cystic Fibrosis Patients.

The emergence and spread of antimicrobial resistance (AMR) in Gram-negative pathogens, such as carbapenem-resistant Pseudomonas aeruginosa, pose an increasing threat to health care. Patients with immunodeficiencies or chronic pulmonary disease, like cystic fibrosis (CF), are particularly vulnerable to Pseudomonas infections and depend heavily on antibiotic therapy. To broaden limited treatment options, this study evaluated the potency of the recently licensed drugs ceftazidime-avibactam (CZA), ceftolozane-tazobactam (C/T), and cefiderocol (FDC) as well as two novel preclinical antibiotics, darobactins B (DAR B) and B9 (DAR B9), against clinical P.

SESN2 Knockdown Increases Betulinic Acid-Induced Radiosensitivity of Hypoxic Breast Cancer Cells.

Betulinic acid (BA) is a natural compound well known for its anti-inflammatory, anti-viral, anti-bacterial, anti-malarial effects and anti-tumor properties. Its enhanced cytotoxicity in tumor cells and induction of cell death in various cancer entities qualifies BA as an interesting candidate for novel treatment concepts. Our analyses showed enhanced cytotoxicity and radiosensitization under hypoxic conditions in human breast cancer cells.

Diffuse alveolar hemorrhage in children with interstitial lung disease: Determine etiologies!

Objective: Diffuse alveolar hemorrhage (DAH) in children is a rare condition resulting from different underlying diseases. This study aimed at describing characteristics and diagnostic measures in children with ILD (children's interstitial lung disease, chILD) and DAH to improve the diagnostic approach by increasing clinician's awareness of diagnostic shortcomings.

Patients And Methods: A retrospective data analysis of patients with ILD and DAH treated in our own or collaborating centers between 01/07/1997 and 31/12/2020 was performed.

Randomized controlled phase 2 trial of hydroxychloroquine in childhood interstitial lung disease.

Background: No results of controlled trials are available for any of the few treatments offered to children with interstitial lung diseases (chILD). We evaluated hydroxychloroquine (HCQ) in a phase 2, prospective, multicentre, 1:1-randomized, double-blind, placebo-controlled, parallel-group/crossover trial. HCQ (START arm) or placebo were given for 4 weeks.

Acute exacerbations in children's interstitial lung disease.

Introduction: Acute exacerbations (AEs) increase morbidity and mortality of patients with chronic pulmonary diseases. Little is known about the characteristics and impact of AEs on children's interstitial lung disease (chILD).

Methods: The Kids Lung Register collected data on AEs, the clinical course and quality of life (patient-reported outcomes - PRO) of rare paediatric lung diseases.

Nitric oxide stimulates type IV MSHA pilus retraction in via activation of the phosphodiesterase CdpA.

Bacteria use surface appendages called type IV pili to perform diverse activities including DNA uptake, twitching motility, and attachment to surfaces. The dynamic extension and retraction of pili are often required for these activities, but the stimuli that regulate these dynamics remain poorly characterized. To address this question, we study the bacterial pathogen , which uses mannose-sensitive hemagglutinin (MSHA) pili to attach to surfaces in aquatic environments as the first step in biofilm formation.

Case Report: Unilateral Sixth Cranial Nerve Palsy Associated With COVID-19 in a 2-year-old Child.

Children have been described to show neurological symptoms in acute coronavirus disease 2019 (COVID-19) and multisystemic inflammatory syndrome in children (MIS-C). We present a 2-year-old boy's clinical course of unilateral acute sixth nerve palsy in the context of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Onset of the palsy in the otherwise healthy boy occurred seven days after symptoms attributed to acute infection had subsided respectively 3 weeks after onset of respiratory symptoms.

Pulmonary alveolar proteinosis due to heterozygous mutation in OAS1: Whole lung lavages for long-term bridging to hematopoietic stem cell transplantation.

Introduction: Pulmonary alveolar proteinosis (PAP) is defined by increased accumulation of surfactant in the alveolar space. PAP has been reported to be associated with a large number of clinical conditions and diseases. Whole lung lavages (WLLs) can be helpful to stabilize the clinical course of PAP until the underlying condition is identified, which may enable more specific treatment.

Insights Into Patient Variability During Ivacaftor-Lumacaftor Therapy in Cystic Fibrosis.

The advent of cystic fibrosis transmembrane conductance regulator protein (CFTR) modulators like ivacaftor have revolutionised the treatment of cystic fibrosis (CF). However, due to the plethora of variances in disease manifestations in CF, there are inherent challenges in unified responses under CFTR modulator treatment arising from variability in patient outcomes. The pharmacokinetic (PK) data available for ivacaftor-lumacaftor cystic fibrosis (CF) transmembrane conductance regulator (CFTR) modulator drug combination is limited.

Identification of lymphocyte cell-specific protein-tyrosine kinase (LCK) as a driver for invasion and migration of oral cancer by tumor heterogeneity exploitation.

Background: Cancer metastases are the main cause of lethality. The five-year survival rate for patients diagnosed with advanced stage oral cancer is 30%. Hence, the identification of novel therapeutic targets is an urgent need.

GP88/PGRN Serum Levels Are Associated with Prognosis for Oral Squamous Cell Carcinoma Patients.

Progranulin (PGRN)/GP88 is a growth factor that is expressed in a wide range of tumor tissues. The secreted form is involved in various biological processes including proliferation and inflammation. In several tumor types, the serum GP88 level is associated with a patient's prognosis; however, data for oral squamous cell carcinomas (OSCCs) have not yet been reported.