Funding multinational investigator-initiated clinical studies in Europe: why and how?

Investigator-initiated clinical studies (IICSs), also referred to as non-commercial, academic or independent clinical studies, address important research questions that are usually neglected by industry despite their high societal value. Indeed, industry may direct their focus and resources on studies that will yield results and products that can ultimately generate revenue for the company. Conversely, IICS research questions include (a) refining or getting new indications of available treatments (drug repurposing); (b) optimisation, by comparing various health products or treatment regimens; and (c) innovation, especially for advanced therapies.

Fungal communities are passengers in community development of dune ecosystems, while bacteria are not.

An increasing number of studies of above-belowground interactions provide a fundamental basis for our understanding of the coexistence between plant and soil communities. However, we lack empirical evidence to understand the directionality of drivers of plant and soil communities under natural conditions: 'Are soil microorganisms driving plant community functioning or do they adapt to the plant community?' In a field experiment in an early successional dune ecosystem, we manipulated soil communities by adding living (i.e.

Clickable polyethyleneimine incorporated into triblock copolymeric micelles as an efficient platform in the delivery of siRNA to NSCLC cells.

The efficacy of transfection vectors to cross the endosomal membrane into the cytosol is a central aspect in the development of nucleic acid-based therapeutics. The challenge remains the same: Delivery, Delivery, Delivery. Despite a rational and appropriate construct of triblock polymeric micelles, which could serve as an ideal platform for the co-delivery of siRNAs and hydrophobic anticancer drugs, we show here its inability to properly convey oligonucleotides to their final destination.

Mapping regional funding for COVID-19 research in the Asia-Pacific region.

Introduction: The Global Research Collaboration for Infectious Disease Preparedness (GloPID-R) is a network of funders supporting research on infectious diseases of epidemic/pandemic potential. GloPID-R is establishing regional hubs to strengthen stakeholder engagement particularly among low-income and middle-income countries. The first pilot hub, led from Republic of Korea (South Korea), has been launched in the Asia-Pacific region, a region highly prone to outbreaks of emerging infectious diseases.

Combining antidepressants and attention bias modification in primary health care (DEPTREAT): Protocol for a pragmatic randomized controlled trial.

Background: Major depressive disorder (MDD) is a highly prevalent psychiatric condition associated with significant disability, mortality and economic burden. A large proportion of MDD patients are treated in primary health care in the local community. Attentional Bias Modification (ABM) training in combination with antidepressants could be an effective treatment.

Parallel Computation of Piecewise Linear Morse-Smale Segmentations.

This article presents a well-scaling parallel algorithm for the computation of Morse-Smale (MS) segmentations, including the region separators and region boundaries. The segmentation of the domain into ascending and descending manifolds, solely defined on the vertices, improves the computational time using path compression and fully segments the border region. Region boundaries and region separators are generated using a multi-label marching tetrahedra algorithm.

Procedural Defect Modeling for Virtual Surface Inspection Environments.

Development of automated visual surface inspection systems heavily depends on the availability of defected product samples. Both inspection hardware configuration and training of defect detection models require diversified, representative and precisely annotated data. Reliable training data of sufficient size is frequently challenging to obtain.

MITF deficiency and oncogenic GNAQ each promote proliferation programs in zebrafish melanocyte lineage cells.

Uveal melanoma (UM) is the most common primary malignancy of the adult eye but lacks any FDA-approved therapy for the deadly metastatic disease. Thus, there is a great need to dissect the driving mechanisms for UM and develop strategies to evaluate potential therapeutics. Using an autochthonous zebrafish model, we previously identified MITF, the master melanocyte transcription factor, as a tumor suppressor in GNAQ -driven UM.

Impact considerations of post-production processes on cell and gene drug products.

Cell and gene therapies are demonstrating clinical efficacy, but prohibitive product costs and operational complexity bottlenecks may limit expanded patient access to these innovative and transformative products. An initial survey and subsequent article published through the International Society for Cell & Gene Therapy in 2017 presented a roadmap on how specific steps, from tissue procurement and material acquisition to facility operation and production, contribute to the high cost of cell and gene therapies. Herein the authors expanded the investigation to provide considerations to better understand how post-production procedures can impact a product's accessibility to patients.

MITF deficiency accelerates GNAQ-driven uveal melanoma.

Cutaneous melanoma (CM) and uveal melanoma (UM) both originate from the melanocytic lineage but are primarily driven by distinct oncogenic drivers, BRAF/NRAS or GNAQ/GNA11, respectively. The melanocytic master transcriptional regulator, MITF, is essential for both CM development and maintenance, but its role in UM is largely unexplored. Here, we use zebrafish models to dissect the key UM oncogenic signaling events and establish the role of MITF in UM tumors.

Cell size is a determinant of stem cell potential during aging.

Stem cells are remarkably small. Whether small size is important for stem cell function is unknown. We find that hematopoietic stem cells (HSCs) enlarge under conditions known to decrease stem cell function.

The Role of Anti-angiogenesis in the Treatment Landscape of Non-small Cell Lung Cancer - New Combinational Approaches and Strategies of Neovessel Inhibition.

Tumor progression depends primarily on vascular supply, which is facilitated by angiogenic activity within the malignant tissue. Non-small cell lung cancer (NSCLC) is a highly vascularized tumor, and inhibition of angiogenesis was projected to be a promising therapeutic approach. Over a decade ago, the first anti-angiogenic agents were approved for advanced stage NSCLC patients, however, they only produced a marginal clinical benefit.

Music therapy as an adjunct in cardiac device lead extraction procedures: A randomized controlled trial.

Background: Evidence of music therapy as an effective supportive therapy in invasive cardiac procedures is increasing, but more research is needed.

Aims: To evaluate the impact of music therapy on stress responses during cardiac device lead extraction procedures performed in local anaesthesia.

Methods: Sixty-four patients undergoing cardiac implantable electronic device lead extraction at Oslo University Hospital Ulleval from March 2018 to September 2019 were randomized to music therapy (n = 32) or control (n = 32).

Insight Beyond Numbers: The Impact of Qualitative Factors on Visual Data Analysis.

As of today, data analysis focuses primarily on the findings to be made inside the data and concentrates less on how those findings relate to the domain of investigation. Contemporary visualization as a field of research shows a strong tendency to adopt this data-centrism. Despite their decisive influence on the analysis result, qualitative aspects of the analysis process such as the structure, soundness, and complexity of the applied reasoning strategy are rarely discussed explicitly.

A giant exoplanet orbiting a very-low-mass star challenges planet formation models.

Surveys have shown that super-Earth and Neptune-mass exoplanets are more frequent than gas giants around low-mass stars, as predicted by the core accretion theory of planet formation. We report the discovery of a giant planet around the very-low-mass star GJ 3512, as determined by optical and near-infrared radial-velocity observations. The planet has a minimum mass of 0.

Single-cell RNA-seq analysis of Mesp1-induced skeletal myogenic development.

The Mesp1 lineage contributes to cardiac, hematopoietic and skeletal myogenic development. Interestingly, muscle stem cells residing in craniofacial skeletal muscles primarily arise from Mesp1+ progenitors, but those in trunk and limb skeletal muscles do not. To gain insights into the difference between the head and trunk/limb muscle developmental processes, we studied Mesp1+ skeletal myogenic derivatives via single-cell RNA-seq and other strategies.

Molecular weight distribution characterization of reactive higher ethyleneamines using size-exclusion chromatography with conventional calibration.

Ethyleneamines have been produced and commercialized for decades in the chemical industry for a diverse range of applications. The presence of amine functional groups provides them opportunity to adsorb onto surfaces which can make them a very challenging sample matrix to analyze using separation techniques. In the present report, a new aqueous SEC-RI method, which enables MWD characterization of higher ethyleneamines, is described.

Hierarchical Image Semantics Using Probabilistic Path Propagations for Biomedical Research.

Image segmentation is an important subtask in biomedical research applications, such as estimating the position and shape of a tumor. Unfortunately, advanced image segmentation methods are not widely applied in research applications as they often miss features, such as uncertainty communication, and may lack an intuitive approach for the use of the underlying algorithm. To solve this problem, this paper fuses a fuzzy and a hierarchical segmentation approach together, thus providing a flexible multiclass segmentation method based on probabilistic path propagations.

Uveal melanoma driver mutations in GNAQ/11 yield numerous changes in melanocyte biology.

Uveal melanoma (UM) is the most common primary intraocular cancer and has a high incidence of metastasis, which lacks any effective treatment. Here, we present zebrafish models of UM, which are driven by melanocyte-specific expression of activating GNAQ or GNA11 alleles, GNAQ/11 , the predominant initiating mutations for human UM. When combined with mutant tp53, GNAQ/11 transgenics develop various melanocytic tumors, including UM, with near complete penetrance.

Apply or Die: On the Role and Assessment of Application Papers in Visualization.

Application-oriented papers provide an important way to invigorate and cross-pollinate the visualization field, but the exact criteria for judging an application paper's merit remain an open question. This article builds on a panel at the 2016 IEEE Visualization Conference entitled "Application Papers: What Are They, and How Should They Be Evaluated?" that sought to gain a better understanding of prevalent views in the visualization community. This article surveys current trends that favor application papers, reviews the benefits and contributions of this paper type, and discusses their assessment in the review process.

STRAD Wheel: Web-Based Library for Visualizing Temporal Data.

Recent advances in web development, including the introduction of HTML5, have opened a door for visualization researchers and developers to quickly access larger audiences worldwide. Open source libraries for the creation of interactive visualizations are becoming more specialized but also modular, which makes them easy to incorporate in domain-specific applications. In this context, the authors developed STRAD (Spatio-Temporal-Radar) Wheel, a web-based library that focuses on the visualization and interactive query of temporal data in a compact view with multiple temporal granularities.