Towards a research agenda for promoting responsible research practices

This opinion piece aims to inform future research funding programs on responsible research practices (RRP) based on three specific objectives: (1) to give a sketch of the current international discussion on responsible research practices (RRPs); (2) to give an overview of current initiatives and already obtained results regarding RRP; and (3) to give an overview of potential future needs for research on RRP. In this opinion piece, we have used seven iterative methodological steps (including literature review, ranking, and sorting exercises) to create the proposed research agenda. We identified six main themes that we believe need attention in future research: (1) responsible evaluation of research and researchers, (2) the influence of open science and transparency on RRP, (3) research on responsible mentoring, supervision, and role modeling, (4) the effect of education and training on RRP, (5) checking for reproducibility, and (6) responsible and fair peer review. These themes have in common that they address aspects of research that are mostly on the level of the scientific system, more than on the level of the individual researcher. Some current initiatives are already gathering substantial empirical evidence to start filling these gaps. We believe that with sufficient support from all relevant stakeholders, more progress can be made

Mechanically Derived Tissue Stromal Vascular Fraction Acts Anti-inflammatory on TNF Alpha-Stimulated Chondrocytes In Vitro

Enzymatically isolated stromal vascular fraction (SVF) has already shown to be effective as a treatment for osteoarthritis (OA). Yet, the use of enzymes for clinical purpose is highly regulated in many countries. Mechanical preparation of SVF results in a tissue-like SVF (tSVF) containing intact cell–cell connections including extracellular matrix (ECM) and is therefore less regulated. The purpose of this study was to investigate the immunomodulatory and pro-regenerative effect of tSVF on TNFα-stimulated chondrocytes in vitro. tSVF was mechanically derived using the Fractionation of Adipose Tissue (FAT) procedure. Characterization of tSVF was performed, e.g., cellular composition based on CD marker expression, colony forming unit and differentiation capacity after enzymatic dissociation (from heron referred to as tSVF-derived cells). Different co-cultures of tSVF-derived cells and TNFα-stimulated chondrocytes were analysed based on the production of sulphated glycosaminoglycans and the anti-inflammatory response of chondrocytes. Characterization of tSVF-derived cells mainly contained ASCs, endothelial cells, leukocytes and supra-adventitial cells. tSVF-derived cells were able to form colonies and differentiate into multiple cell lineages. Co-cultures with chondrocytes resulted in a shift of the ratio between tSVF cells: chondrocytes, in favor of chondrocytes alone (p < 0.05), and IL-1β and COX2 gene expression was upregulated in TNFα-treated chondrocytes. After treatment with (a conditioned medium of) tSVF-derived cells, IL-1β and COX2 gene expression was significantly reduced (p < 0.01). These results suggest mechanically derived tSVF stimulates chondrocyte proliferation while preserving the function of chondrocytes. Moreover, tSVF suppresses TNFα-stimulated chondrocyte inflammation in vitro. This pro-regenerative and anti-inflammatory effect shows the potential of tSVF as a treatment for osteoarthritis

Platelet Rich STROMA, the Combination of PRP and tSVF and Its Potential Effect on Osteoarthritis of the Knee

(1) Background: osteoarthritis (OA) of the knee is a degenerative disease accompanied by pain, reduced mobility and subsequent decrease in quality of life. Many studies on OA of the knee have reported that using an intercellular acting-derivate like platelet-rich plasma (PRP) results in a limited effect or none at all. Authors hypothesized that adding tissue-Stromal Vascular Fraction (tSVF) to PRP (Platelet Rich Stroma (PRS)) would reduce pain and improve functionality in osteoarthritis of the knee. (2) Methods: a consecutive case series of fifteen patients (aged 43-75 years) suffering from OA of the knee (Kellgren-Lawrence stage two to three) were treated with a single injection of autologous PRS. tSVF was mechanically isolated by means of the fractionation of adipose tissue (FAT) procedure. Clinical evaluation was done using a visual analogue score (VAS) score, an adapted Western Ontario and McMaster Universities Osteoarthritis index (WOMAC) and Lysholm score at fixed time points: pre-injection as well as three, six and twelve months post injection. (3) Results: VAS and WOMAC scores improved significantly after twelve months (p 0.05) in comparison to pre-injection measurements. No complications were seen in any of the patients. One patient was excluded due to a total knee arthroplasty. (4) Conclusions: a single injection with PRS for OA of the knee seems to lead to an improvement of function and simultaneous reduction of pain and joint stiffness for a period of twelve months. Further controlled trials are required to determine the optimal treatment regimen and evaluate long-term results

Understanding why civil servants are reluctant to carry out transition tasks

The transition literature attributes various transition tasks to government to support socio-technical transitions toward overcoming societal challenges. It is, however, difficult for civil servants to execute these transition tasks, because they partly conflict with Public Administration (PA) traditions that provide legitimacy to their work. This dilemma is discussed in neither the transition literature nor the PA literature. In this paper, we ask civil servants about the normative arguments that reflect their role perception within the institutional structures of their ministry, when it comes to executing transition tasks. We see these situated and enacted normative arguments and underlying assumptions as implicit rules determining legitimacy. The arguments civil servants used confirm that transition tasks are currently difficult to execute within the civil service. We found seven institutionalized rules that explain this difficulty and highlight the inadequacy of civil servants to adhere to the PA traditions while trying to execute transition tasks

Stress-induced formation of cell wall-deficient cells in filamentous actinomycetes

The cell wall is a shape-defining structure that envelopes almost all bacteria and protects them from environmental stresses. Bacteria can be forced to grow without a cell wall under certain conditions that interfere with cell wall synthesis, but the relevance of these wall-less cells (known as L-forms) is unclear. Here, we show that several species of filamentous actinomycetes have a natural ability to generate wall-deficient cells in response to hyperosmotic stress, which we call S-cells. This wall-deficient state is transient, as S-cells are able to switch to the normal mycelial mode of growth. However, prolonged exposure of S-cells to hyperosmotic stress yields variants that are able to proliferate indefinitely without their cell wall, similarly to L-forms. We propose that formation of wall-deficient cells in actinomycetes may serve as an adaptation to osmotic stress

Assessing mission-specific innovation systems: Towards an analytical framework

In the currently emerging paradigm of challenge-led and transformative innovation policies, there is increasing attention for addressing urgent societal problems by formulating clear, timebound and ambitious mission goals. Completing such transformative mission's places new demands on innovation systems, as actors and activities need to align around prioritised problem and solution directions. Consequently, new perspectives that support the appraisal of innovation systems’ performance are required for determining what hampers change processes, and which policy responses are appropriate. Following an abductive research approach, this paper aims to develop an analytical framework for assessing mission-specific innovation systems (MIS). We examine three sectoral cases in the mission for a Circular Economy in the Netherlands and propose three analytical steps: 1) a problem-solution analysis, 2) a structural analysis recognising the importance of mission arenas, and 3) a functional analysis addressing directionality provision, coordination, and regime transformation. We conclude with discussing operationalisation and application of the framework

The Addition of Tissue Stromal Vascular Fraction to Platelet-Rich Plasma Supplemented Lipofilling Does Not Improve Facial Skin Quality:A Prospective Randomized Clinical Trial

Background: Lipofilling has become popular as a treatment to improve aging-related skin characteristics (eg, wrinkles, pigmentation spots, pores, or rosacea). Different additives such as platelet-rich plasma (PRP) or stromal vascular fraction (SVF) have been combined with lipofilling to increase the therapeutic effect of adipose-derived stromal cells (ASCs). Objectives: The aim of this study was to examine the hypothesis that mechanically isolated SVF augments the therapeutic effect of PRP-supplemented lipofilling to improve facial skin quality. Methods: This prospective, double-blind, placebo-controlled, randomized trial was conducted between 2016 and 2019. In total, 28 female subjects were enrolled; 25 completed the follow-up. All patients received PRP-supplemented lipofilling with either mechanically isolated SVF or saline. SVF was isolated by fractionation of adipose tissue (tSVF). Results were evaluated by changes in skin elasticity and transepidermal water loss, changes in skin-aging-related features, ie, superficial spots, wrinkles, skin texture, pores, vascularity, and pigmentation, as well as patient satisfaction (FACE-Q), recovery, and number of complications up to 1 year postoperative. Results: The addition of tSVF to PRP-supplemented lipofilling did not improve skin elasticity, transepidermal water loss, or skin-aging-related features. No improvement in patient satisfaction with overall facial appearance or facial skin quality was seen when tSVF was added to PRP-supplemented lipofilling. Conclusions: In comparison to PRP-supplemented lipofilling, PRP-supplemented lipofilling combined with tSVF does not improve facial skin quality or patient satisfaction in a healthy population. PRP-supplemented lipofilling combined with tSVF can be considered a safe procedure

Chromosome-level reference genome of the soursop (Annona muricata): A new resource for Magnoliid research and tropical pomology

The flowering plant family Annonaceae includes important commercially grown tropical crops, but development of promising species is hindered by a lack of genomic resources to build breeding programs. Annonaceae are part of the magnoliids, an ancient lineage of angiosperms for which evolutionary relationships with other major clades remain unclear. To provide resources to breeders and evolutionary researchers, we report a chromosome‐level genome assembly of the soursop (Annona muricata). We assembled the genome using 444.32 Gb of DNA sequences (676× sequencing depth) from PacBio and Illumina short‐reads, in combination with 10× Genomics and Bionano data (v1). A total of 949 scaffolds were assembled to a final size of 656.77 Mb, with a scaffold N50 of 3.43 Mb (v1), and then further improved to seven pseudo‐chromosomes using Hi‐C sequencing data (v2; scaffold N50: 93.2 Mb, total size in chromosomes: 639.6 Mb). Heterozygosity was very low (0.06%), while repeat sequences accounted for 54.87% of the genome, and 23,375 protein‐coding genes with an average of 4.79 exons per gene were annotated using de novo, RNA‐seq and homology‐based approaches. Reconstruction of the historical population size showed a slow continuous contraction, probably related to Cenozoic climate changes. The soursop is the first genome assembled in Annonaceae, supporting further studies of floral evolution in magnoliids, providing an essential resource for delineating relationships of ancient angiosperm lineages. Both genome‐assisted improvement and conservation efforts will be strengthened by the availability of the soursop genome. As a community resource, this assembly will further strengthen the role of Annonaceae as model species for research on the ecology, evolution and domestication potential of tropical species in pomology and agroforestry