Macrophages are activated toward phagocytic lymphoma cell clearance by pentose phosphate pathway inhibition.

Macrophages in the B cell lymphoma microenvironment represent a functional node in progression and therapeutic response. We assessed metabolic regulation of macrophages in the context of therapeutic antibody-mediated phagocytosis. Pentose phosphate pathway (PPP) inhibition induces increased phagocytic lymphoma cell clearance by macrophages in vitro, in primary human chronic lymphocytic leukemia (CLL) patient co-cultures, and in mouse models.

Efficacy in patients with -positive non-small-cell lung cancer treated with dacomitinib who had skin adverse events: analyses from ARCHER 1050.

We investigated association between skin adverse events (AEs) and efficacy with dacomitinib in patients with -positive non-small-cell lung cancer (NSCLC). analyses from ARCHER 1050 evaluated efficacy in patients who did and did not experience grade ≥2 skin AEs with dacomitinib. Landmark analyses were performed at 3 and 6 months.

Protocol for an intervention for new parents experiencing moderate psychosocial adversity: pilot feasibility randomised trial.

Background: Parents exposed to psychosocial adversities often experience challenges which, combined with the needs of a new-born infant, can be difficult to manage and increase the risk of poor outcomes for both parents and infants. Psychosocial adversity can disrupt the development of parental-foetal attachment to the baby during pregnancy, which can have a negative effect on parental care and quality of interaction during the postnatal period. This intervention is based on the proposition that enhanced parental capacity to mentalise and emotionally connect to unborn children during pregnancy, and better understanding about how to manage distressing infant behaviour (i.

Assessing the impact of inland navigation on the faecal pollution status of large rivers: A novel integrated field approach.

The contribution of ships to the microbial faecal pollution status of water bodies is largely unknown but frequently of human health concern. No methodology for a comprehensive and target-orientated system analysis was available so far. We developed a novel approach for integrated and multistage impact evaluation.

Linking antibiotic resistance gene patterns with advanced faecal pollution assessment and environmental key parameters along 2300 km of the Danube River.

The global spread of antimicrobial resistance (AMR) in the environment is a growing health threat. Large rivers are of particular concern as they are highly impacted by wastewater discharge while being vital lifelines serving various human needs. A comprehensive understanding of occurrence, spread and key drivers of AMR along whole river courses is largely lacking.

TMPRSS2 isoform 1 downregulation by G-quadruplex stabilization induces SARS-CoV-2 replication arrest.

Background: SARS-CoV-2 infection depends on the host cell factors angiotensin-converting enzyme 2, ACE2, and the transmembrane serinprotease 2, TMPRSS2. Potential inhibitors of these proteins would be ideal targets against severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) infection. Our data opens the possibility that changes within TMPRSS2 can modulate the outcome during a SARS-CoV-2 infection.

Diagnostic Ultrasound for Acute Appendicitis: The Gold Standard.

Background: Acute appendicitis may present a diagnostic dilemma. The aim of this study was to review the accuracy of ultrasound in the diagnosis of paediatric acute appendicitis.

Method: Ultrasound studies performed for investigation of appendicitis during 2015-2021 were retrieved from a tertiary paediatric hospital database and reviewed.

A probabilistic-deterministic approach for assessing climate change effects on infection risks downstream of sewage emissions from CSOs.

The discharge of pathogens into urban recreational water bodies during combined sewer overflows (CSOs) pose a potential threat for public health which may increase in the future due to climate change. Improved methods are needed for predicting the impact of these effects on the microbiological urban river water quality and infection risks during recreational use. The aim of this study was to develop a novel probabilistic-deterministic modelling approach for this purpose building on physically plausible generated future rainfall time series.

Performance of bacterial and mitochondrial qPCR source tracking methods: A European multi-center study.

With the advent of molecular biology diagnostics, different quantitative PCR assays have been developed for use in Source Tracking (ST), with none of them showing 100% specificity and sensitivity. Most studies have been conducted at a regional level and mainly in fecal slurry rather than in animal wastewater. The use of a single molecular assay has most often proven to fall short in discriminating with precision the sources of fecal contamination.

Low antimicrobial resistance in Escherichia coli isolates from two large Austrian alpine karstic spring catchments.

The increasing occurrence of antibiotic resistant bacteria poses a threat to global public health. Clinically relevant resistances also spread through the environment. Aquatic ecosystems in particular represent important dispersal pathways.

Have genetic targets for faecal pollution diagnostics and source tracking revolutionized water quality analysis yet?

The impacts of nucleic acid-based methods - such as PCR and sequencing - to detect and analyze indicators, genetic markers or molecular signatures of microbial faecal pollution in health-related water quality research were assessed by rigorous literature analysis. A wide range of application areas and study designs has been identified since the first application more than 30 years ago (>1100 publications). Given the consistency of methods and assessment types, we suggest defining this emerging part of science as a new discipline: genetic faecal pollution diagnostics (GFPD) in health-related microbial water quality analysis.

The Global Characterisation of a Drug-Dendrimer Conjugate - PEGylated poly-lysine Dendrimer.

The recent emergence of drug-dendrimer conjugates within pharmaceutical industry research and development introduces a range of challenges for analytical and measurement science. These molecules are very high molecular weight (100-200kDa) with a significant degree of structural complexity. The characteristics and quality attributes that require understanding and definition, and impact efficacy and safety, are diverse.

Probabilistic fecal pollution source profiling and microbial source tracking for an urban river catchment.

We developed an innovative approach to estimate the occurrence and extent of fecal pollution sources for urban river catchments. The methodology consists of 1) catchment surveys complemented by literature data where needed for probabilistic estimates of daily produced fecal indicator (FIBs, E. coli, enterococci) and zoonotic reference pathogen numbers (Campylobacter, Cryptosporidium and Giardia) excreted by human and animal sources in a river catchment, 2) generating a hypothesis about the dominant sources of fecal pollution and selecting a source targeted monitoring design, and 3) verifying the results by comparing measured concentrations of the informed choice of parameters (i.

Incidence and risk factors for anastomotic bile leakage in hepatic resection with bilioenteric reconstruction - A international multicenter study.

Background: Anastomotic leak (AL) after bilioenteric reconstruction (BR) is a feared complication after bile duct resection, especially in combination with liver resection. Literature on surgical outcome is sparse. This study aimed to determine the incidence and risk factors for AL after combined liver and bile duct resection with a focus on operative or endoscopic reinterventions.

Corrigendum: Genetic microbial source tracking support QMRA modeling for a riverine wetland drinking water resource.

[This corrects the article DOI: 10.3389/fmicb.2021.

Amyloidogenicity assessment of transthyretin gene variants.

Objective: Hereditary transthyretin-mediated amyloidosis is a treatable condition caused by amyloidogenic variants in the transthyretin-gene resulting in severe peripheral neuropathy or cardiomyopathy. Only about a third of over 130 known variants are clearly pathogenic, most are classified as variants of uncertain significance. A clear delineation of these into pathogenic or non-pathogenic is highly desirable but hampered by low frequency and penetrance.

Wastewater-based epidemiology in countries with poor wastewater treatment - Epidemiological indicator function of SARS-CoV-2 RNA in surface waters.

Wastewater-based epidemiology (WBE) surveillance of COVID-19 and other future outbreaks is a challenge for developing countries as most households are not connected to a sewerage system. In December 2019, SARS-CoV-2 RNA was detected in the Danube River at a site severely affected by wastewaters from Belgrade. Rivers are much more complex systems than wastewater systems, and efforts are needed to address all the factors influencing the adoption of WBE as an alternative to targeting raw wastewater.

Circulating Cell-Free DNA Assessment in Biofluids from Children with Neuroblastoma Demonstrates Feasibility and Potential for Minimally Invasive Molecular Diagnostics.

Liquid biopsy strategies in pediatric patients are challenging due to low body weight. This study investigated cfDNA size distribution and concentration in blood, bone marrow, cerebrospinal fluid, and urine from 84 patients with neuroblastoma classified as low ( = 28), intermediate ( = 6), or high risk ( = 50) to provide key data for liquid biopsy biobanking strategies. The average volume of blood and bone marrow plasma provided ranged between 1 and 2 mL.

Radiation doses from low-dose CT scans in SPECT/CT and PET/CT examinations: A survey in Germany.

Aim: Recently, dose reference levels (DRLs) have been defined in Germany for auxiliary low-dose CT scans in hybrid SPECT/CT and PET/CT examinations, based on data from 2016/17. Here, another survey from 2020 was evaluated and compared with the new DRLs as well as with similar surveys from foreign countries.

Methods: The survey, which had already been conducted in the Nordic countries, queried for various examinations including the following values: patient weight and height, volume CT dose index (CTDI), dose length product (DLP).

Targeted Analysis of Cell-free Circulating Tumor DNA is Suitable for Early Relapse and Actionable Target Detection in Patients with Neuroblastoma.

Purpose: Treating refractory or relapsed neuroblastoma remains challenging. Monitoring body fluids for tumor-derived molecular information indicating minimal residual disease supports more frequent diagnostic surveillance and may have the power to detect resistant subclones before they give rise to relapses. If actionable targets are identified from liquid biopsies, targeted treatment options can be considered earlier.

AA-amyloidosis in captive northern tree shrews ().

A high prevalence of AA-amyloidosis was identified in a breeding colony of northern tree shrews () in a retrospective analysis, with amyloid deposits in different organs being found in 26/36 individuals (72%). Amyloid deposits, confirmed by Congo red staining, were detected in kidneys, intestines, skin, and lymph nodes, characteristic of systemic amyloidosis. Immunohistochemically, the deposited amyloid was intensely positive with anti-AA-antibody (clone mc4), suggesting AA-amyloidosis.

The Relevance of G-Quadruplexes for DNA Repair.

DNA molecules can adopt a variety of alternative structures. Among these structures are G-quadruplex DNA structures (G4s), which support cellular function by affecting transcription, translation, and telomere maintenance. These structures can also induce genome instability by stalling replication, increasing DNA damage, and recombination events.

Identifying Inorganic Turbidity in Water Samples as Potential Loss Factor During Nucleic Acid Extraction: Implications for Molecular Fecal Pollution Diagnostics and Source Tracking.

Molecular diagnostic methods are increasingly applied for food and environmental analysis. Since several steps are involved in sample processing which can affect the outcome (e.g.