Rationale and design of the BECA project: Smartwatch-based activation of the chain of survival for out-of-hospital cardiac arrest.

Aim: Out-of-hospital cardiac arrest is a major health problem, and the overall survival rate is low (4.6%-16.4%).

Recording ten-fold larger I conductances with automated patch clamping using equimolar Cs solutions.

The rapid delayed rectifier potassium current (I) is important for cardiac repolarization and is most often involved in drug-induced arrhythmias. However, accurately measuring this current can be challenging in human-induced pluripotent stem cell (hiPSC)-derived cardiomyocytes because of its small current density. Interestingly, the ion channel conducting I, hERG channel, is not only permeable to K ions but also to Cs ions when present in equimolar concentrations inside and outside of the cell.

Resistance to white spot syndrome virus in the European shore crab is associated with suppressed virion trafficking and heightened immune responses.

Introduction: All decapod crustaceans are considered potentially susceptible to White Spot Syndrome Virus (WSSV) infection, but the degree of White Spot Disease (WSD) susceptibility varies widely between species. The European shore crab can be infected with the virus for long periods of time without signs of disease. Given the high mortality rate of susceptible species, the differential susceptibility of these resistant hosts offers an opportunity to investigate mechanisms of disease resistance.

Molecular detection of SARS-COV-2 in exhaled breath at the point-of-need.

The SARS-CoV-2 pandemic has highlighted the need for improved technologies to help control the spread of contagious pathogens. While rapid point-of-need testing plays a key role in strategies to rapidly identify and isolate infectious patients, current test approaches have significant shortcomings related to assay limitations and sample type. Direct quantification of viral shedding in exhaled particles may offer a better rapid testing approach, since SARS-CoV-2 is believed to spread mainly by aerosols.

Exhaled breath SARS-CoV-2 shedding patterns across variants of concern.

Objectives: We performed exhaled breath (EB) and nasopharyngeal (NP) quantitative polymerase chain reaction (qPCR) and NP rapid antigen testing (NP RAT) of SARS-CoV-2 infections with different variants.

Methods: We included immuno-naïve alpha-infected (n = 11) and partly boosted omicron-infected patients (n = 8) as high-risk contacts. We compared peak NP and EB qPCR cycle time (ct) values between cohorts (Wilcoxon-Mann-Whitney test).

Molecular mechanisms of embryonic tail development in the self-fertilizing mangrove killifish Kryptolebias marmoratus.

Using the self-fertilizing mangrove killifish, we characterized two mutants, shorttail (stl) and balltail (btl). These mutants showed abnormalities in the posterior notochord and muscle development. Taking advantage of a highly inbred isogenic strain of the species, we rapidly identified the mutated genes, noto and msgn1 in the stl and btl mutants, respectively, using a single lane of RNA sequencing without the need of a reference genome or genetic mapping techniques.

Transformed Canine and Murine Mesenchymal Stem Cells as a Model for Sarcoma with Complex Genomics.

Sarcomas are rare mesenchymal tumors with a broad histological spectrum, but they can be divided into two groups based on molecular pathology: sarcomas with simple or complex genomics. Tumors with complex genomics can have aneuploidy and copy number gains and losses, which hampers the detection of early, initiating events in tumorigenesis. Often, no benign precursors are known, which is why good models are essential.

A laboratory investigation into features of morphology and physiology for their potential to predict reproductive success in male frogs.

Amphibian populations are declining globally, however, the contribution of reduced reproduction to declines is unknown. We investigated associations between morphological (weight/snout-vent length, nuptial pad colour/size, forelimb width/size) and physiological (nuptial pad/testis histomorphology, plasma hormones, gene expression) features with reproductive success in males as measured by amplexus success and fertility rate (% eggs fertilised) in laboratory maintained Silurana/Xenopus tropicalis. We explored the robustness of these features to predict amplexus success/fertility rate by investigating these associations within a sub-set of frogs exposed to anti-androgens (flutamide (50 μg/L)/linuron (9 or 45 μg/L)).

Pharmacology beyond the patient - The environmental risks of human drugs.

Background: The presence of pharmaceuticals in the environment is a growing global concern and although environmental risk assessment is required for approval of new drugs in Europe and the USA, the adequacy of the current triggers and the effects-based assessments has been questioned.

Objective: To provide a comprehensive analysis of all regulatory compliant aquatic ecotoxicity data and evaluate the current triggers and effects-based environmental assessments to facilitate the development of more efficient approaches for pharmaceuticals toxicity testing.

Methods: Publicly-available regulatory compliant ecotoxicity data for drugs targeting human proteins was compiled together with pharmacological information including drug targets, Cmax and lipophilicity.

Exposure to an anti-androgenic herbicide negatively impacts reproductive physiology and fertility in Xenopus tropicalis.

Amphibians are threatened on a global scale and pollutants may be contributing to population declines, but how chemicals impact on their reproduction is poorly understood. We conducted a life cycle analysis to investigate the impacts of early life exposure to two anti-androgens (exposure until completion of metamorphosis;stage 66): flutamide, (50 µg/L)/linuron (9 and 45 µg/L)) on sexual development and breeding competence in Xenopus tropicalis. Our analyses included: mRNA levels of dmrt1, cyp17, amh, cyp19, foxl2 and ar (tadpoles/metamorphs), gonadal histomorphology (metamorphs/adults), mRNA levels of ar/gr (adult male brain/gonad/forelimb), testosterone/corticosterone levels (adult males), secondary sexual characteristics (forelimb width/nuptial pad: adult males) and breeding competence (amplexus/fertility: adult males).

ECOdrug: a database connecting drugs and conservation of their targets across species.

Pharmaceuticals are designed to interact with specific molecular targets in humans and these targets generally have orthologs in other species. This provides opportunities for the drug discovery community to use alternative model species for drug development. It also means, however, there is potential for mode of action related effects in non-target wildlife species as many pharmaceuticals reach the environment through patient use and manufacturing wastes.

Molecular Mechanisms of White Spot Syndrome Virus Infection and Perspectives on Treatments.

Since its emergence in the 1990s, White Spot Disease (WSD) has had major economic and societal impact in the crustacean aquaculture sector. Over the years shrimp farming alone has experienced billion dollar losses through WSD. The disease is caused by the White Spot Syndrome Virus (WSSV), a large dsDNA virus and the only member of the Nimaviridae family.

De novo assembly of the Carcinus maenas transcriptome and characterization of innate immune system pathways.

Background: The European shore crab, Carcinus maenas, is used widely in biomonitoring, ecotoxicology and for studies into host-pathogen interactions. It is also an important invasive species in numerous global locations. However, the genomic resources for this organism are still sparse, limiting research progress in these fields.

Laboratory testing for factor inhibitors.

Inhibitor assays are performed when patients present with unexplained prolonged routine coagulation test times and unexpected and/or unusual bleeding (potential for acquired haemophilia) as well as being a part of normal congenital haemophilia management and monitoring, particularly when bleeding occurs on therapy, or when increments in factor levels post-factor replacement remain lower than expected. In this article, we will describe the assays used, as well as their development, pitfalls in testing such as inter-laboratory variability and false negative/positive results, as well as some strategies for overcoming these pitfalls and potential alternative test approaches. The inter-laboratory coefficient of variation often approaches (and sometimes exceeds) 50%, as evidenced by various external quality assessment groups, and this variability has not improved over recent years.

HIV surveillance systems in the Asia Pacific region.

In 2011, the United Nations Joint Programme on HIV/AIDS (UNAIDS) Regional Support Team for Asia-Pacific conducted a stock-taking process of available strategic information in the Asia Pacific region. This paper summarizes the progress of HIV surveillance for 20 countries in the region, covering population size estimates of key populations at higher risk, HIV case reporting, HIV sentinel surveillance and probability surveys of behavioural and biological markers. Information on surveillance activities was obtained from publically available surveillance reports and protocols, supplemented by personal communication with the UNAIDS monitoring and evaluation advisers and surveillance experts in country.

Acquired functional coagulation inhibitors: review on epidemiology, results of a wet-workshop on laboratory detection, and implications for quality of inhibitor diagnosis.

The accurate detection and quantification of coagulation inhibitors remains a challenging problem for most diagnostic laboratories. Prolonged screening assays and abnormal results of mixing tests with normal plasma may indicate the presence of such inhibitors. Yet, the presence of lupus anticoagulant, heparin, and potential contamination of plasma with therapeutically active antithrombotic drugs has to also be ruled out.

Real-time monitoring of DNA hybridization and melting processes using a fiber optic sensor.

In this paper a fiber optic surface plasmon resonance (FO-SPR) sensor was used to analyze the melting process of DNA linked to silica nanoparticles. Real-time monitoring of a DNA melting process has rarely been studied using surface plasmon resonance (SPR), since most commercial SPR setups do not allow for dynamic and accurate temperature control above 50 °C. The FO-SPR sensor platform, with silica nanobead signal amplification, allows sensing inside a standard PCR thermocycler, which makes high resolution DNA melting curve analysis possible.

A novel hemostasis assay for the simultaneous measurement of coagulation and fibrinolysis.

Thrombin and plasmin are the key enzymes involved in coagulation and fibrinolysis. A novel hemostasis assay (NHA) was developed to measure thrombin and plasmin generation in a single well by a fluorimeter. The NHA uses two fluorescent substrates with non-interfering fluorescent excitation and emission spectra.

Integrating protein-protein interaction networks with gene-gene co-expression networks improves gene signatures for classifying breast cancer metastasis.

Multiple studies have illustrated that gene expression profiling of primary breast cancers throughout the final stages of tumor development can provide valuable markers for risk prediction of metastasis and disease sub typing. However, the identification of a biologically interpretable and universally shared set of markers proved to be difficult. Here, we propose a method for de novo grouping of genes by dissecting the protein-protein interaction network into disjoint sub networks using pair wise gene expression correlation measures.

The factor VIII inhibitor assays can be standardized: results of a workshop.

Background: The Bethesda and the Nijmegen assays are commonly used for the measurement of inhibitor levels in hemophilia A patients. Despite test innovations, the between-laboratory coefficient of variation (CVb) of factor VIII inhibitor test data in external quality surveys remains very high (40-60%) with a high degree of false-negative and false-positive results resulting in undesired effects on treatment.

Objectives: Organization of a workshop in order to address the causes of this phenomenon and to suggest ways to improve the assays.

Thrombocytopenia in early malaria is associated with GP1b shedding in absence of systemic platelet activation and consumptive coagulopathy.

Thrombocytopenia develops early in malaria, but the underlying mechanisms remain incompletely understood. We studied the aetiology of malaria-associated thrombocytopenia in volunteers experimentally infected with Plasmodium falciparum malaria, in Indonesian malaria patients and in ex vivo studies. In experimental human malaria, the decrease in platelet counts was associated with a concurrent rise in young platelets (immature platelet fraction) and thrombopoietin.