Supporting shared hypothesis testing in the biomedical domain

Background: Pathogenesis of inflammatory diseases can be tracked by studying the causality relationships among the factors contributing to its development. We could, for instance, hypothesize on the connections of the pathogenesis outcomes to the observed conditions. And to prove such causal hypotheses we would need to have the full understanding of the causal relationships, and we would have to provide all the necessary evidences to support our claims. In practice, however, we might not possess all the background knowledge on the causality relationships, and we might be unable to collect all the evidence to prove our hypotheses. Results: In this work we propose a methodology for the translation of biological knowledge on causality relationships of biological processes and their effects on conditions to a computational framework for hypothesis testing. The methodology consists of two main points: hypothesis graph construction from the formalization of the background knowledge on causality relationships, and confidence measurement in a causality hypothesis as a normalized weighted path computation in the hypothesis graph. In this framework, we can simulate collection of evidences and assess confidence in a causality hypothesis by measuring it proportionally to the amount of available knowledge and collected evidences. Conclusions: We evaluate our methodology on a hypothesis graph that represents both contributing factors which may cause cartilage degradation and the factors which might be caused by the cartilage degradation during osteoarthritis. Hypothesis graph construction has proven to be robust to the addition of potentially contradictory information on the simultaneously positive and negative effects. The obtained confidence measures for the specific causality hypotheses have been validated by our domain experts, and, correspond closely to their subjective assessments of confidences in investigated hypotheses. Overall, our methodology for a shared hypothesis testing framework exhibits important properties that researchers will find useful in literature review for their experimental studies, planning and prioritizing evidence collection acquisition procedures, and testing their hypotheses with different depths of knowledge on causal dependencies of biological processes and their effects on the observed conditions

Biological performance of a promising Kefiran-biopolymer with potential in regenerative medicine applications: a comparative study with hyaluronic acid

Kefiran from kefir grains, an exopolysaccharide (EPS) produced by lactic acid bacteria (LAB), has received an increasing interest because of its safe status. This natural biopolymer is a water-soluble glucogalactan with probed health-promoting properties. However, its biological performance has yet to be completely recognized and properly exploited. This research was carried out to evaluate the in vitro antioxidant and the in vitro anti-inflammatory properties of Kefiran biopolymer. Regarding antioxidant activity, the results demonstrated that the Kefiran extract possessed the strongest reducing power and superoxide radical scavenging, over hyaluronic acid (HA, gold standard viscosupplementation treatment). This exopolysaccharide showed a distinct antioxidant performance in the majority of in vitro working mechanisms of antioxidant activity comparing to HA. Moreover, Kefiran presented an interesting capacity to scavenge nitric oxide radical comparing to the gold standard that did not present any potency. Finally, the cytotoxic effects of Kefiran extracts on hASCs were also performed and demonstrated no cytotoxic response, ability to improve cellular function of hASCs. This study demonstrated that Kefiran represented a great scavenger for reactive oxygen and nitrogen species and showed also that it could be an excellent candidate to promote tissue repair and regeneration.Hajer Radhouani, Cristiana Gonçalves and F. Raquel Maia were supported by grants with reference SFRH/BPD/100957/2014, SFRH/BPD/94277/2013 and SFRH/BPD/117492/2016, respectively of Fundação para a Ciência e a Tecnologia (FCT) from Portugal. JM Oliveira also would like to thank FCT for the fund provided under the program Investigador FCT 2015 (IF/01285/2015).info:eu-repo/semantics/publishedVersio

Functionally graded additive manufacturing to achieve functionality specifications of osteochondral scaffolds

Osteoarthritis (OA) is a degenerative joint disease, characterized by cartilage loss and changes in bone at the interface of a joint resulting in pain, stiffness and reduced mobility. OA is one of the most prevalent chronic conditions as identified in Bone and Joint Decade. According to the World Health Organization, 40% of people over the age of 70 have OA. This joint disease affects around 0.4 billion people with patients in Europe accounting for up to 30%. The figure is set to increase with the ageing problem. Current non-surgical treatments for OA involve non-steroidal anti-inflammatory drug administration. Surgical treatments include osteotomy, abrasion arthroplasty, micro-fracture and autologous chondrocyte implantation (ACI). This is a two-stage surgical procedure with the associate costs and infection being the main concern. For small osteochondral defects, micro-fracture (MF) marrow stimulation and for large cartilaginous defects the autologous chondrocyte implantation are considered as necessary treatments. However, MF produces fibrocartilage not native hyaline cartilage. For defects that have progressed to a stage that affects the subchondral bone, other treatments are no longer effective and joint replacement operation is the only alternative. The demand for innovative therapeutic alternatives for complete healing of OA is significant. The treatment of cartilage and osteochondral (OC) defects remains a challenge since treatments so far have failed to achieve complete restoration of the properties of joint cartilage. Many new technologies, such as osteochondral tissue engineering, have been studied and applied to repair osteochondral defects. Commercially available osteochondral scaffolds have been used in patients with OC defects. However, no products have so far demonstrated to provide biomechanical properties suitable to promote the durable regeneration of large OC defects [1]. The main issue with these commercially available OC scaffolds is poor cartilage fill associated with fibrocartilage formation. The aim of this paper is to define the functionality and performance which would be required for intended clinical applications in the treatment of osteoarthritis and also to show that the capabilities of 3D bioprinting and functionally graded additive manufacturing scaffolds are suitable to meet most of these requirements.The authors would like to thank H2020-MSCARISE programme, as this work is part of developments carried out in BAMOS project, funded from the European Union’s Horizon 2020 research and innovation programme under Grant Agreement No. 734156.info:eu-repo/semantics/publishedVersio