557 research outputs found
Machine Learning approaches for the design of biomechanically compatible bone tissue engineering scaffolds
Triply-Periodic Minimal Surfaces (TPMS) analytical formulation does not provide a direct correlation between the input parameters (analytical) and the mechanical and morphological properties of the structure. In this work, we created a dataset with more than one thousand TPMS scaffolds for the training of Machine Learning (ML) models able to find such correlation. Finite Element Modeling and image analysis have been used to characterize the scaffolds. In particular, we trained three different ML models, exploring both a linear and non-linear approach, to select the features able to predict the input parameters. Furthermore, the features used for the prediction can be selected in three different modes: i) fully automatic, through a greedy algorithm, ii) arbitrarily, by the user and iii) in a combination of the two above methods: i.e. partially automatic and partially through a user-selection. The latter, coupled with the non-linear ML model, exhibits a median error less than 3% and a determination coefficient higher than 0.89 for each of the selected features, and all of them are accessible during the design phase. This approach has been applied to the design of a hydroxyapatite TPMS scaffolds with prescribed properties obtained from a real trabecular-like hydroxyapatite scaffold. The obtained results demonstrate that the ML model can effectively design a TPMS scaffold with prescribed features on the basis of biomechanical, mechanobiology and technological constraints
Simultaneous optical diagnostic velocity and scalar field by molecular tagging technique Stratified Flames View project
International audienc
Computational models for the simulation of the elastic and fracture properties of highly porous 3D-printed hydroxyapatite scaffolds
Bone scaffolding is a promising approach for the treatment of critical-size bone defects. Hydroxyapatite can be used to produce highly porous scaffolds as it mimics the mineralized part of bone tissue, but its intrinsic brittleness limits its usage. Among 3D printing techniques, vat photopolymerization allows for the best printing resolution for ceramic materials. In this study, we implemented a Computed micro-Tomography based Finite Element Model of a hydroxyapatite porous scaffold fabricated by vat photopolymerization. We used the model in order to predict the elastic and fracture properties of the scaffold. From the stress–strain diagram of a simulated compression test, we computed the stiffness and the strength of the scaffolds. We found that three morphometric features substantially affect the crack pattern. In particular, the crack propagation is not only dependent on the trabecular thickness but also depends on the slenderness and orientation of the trabeculae with respect to the load. The results found in this study can be used for the design of ceramic scaffolds with heterogeneous pore distribution in order to tailor and predict the compressive strength
Mechanical Properties of Robocast Glass Scaffolds Assessed through Micro-CT-Based Finite Element Models
In this study, the mechanical properties of two classes of robocast glass scaffolds are obtained through Computed micro-Tomography (micro-CT) based Finite Element Modeling (FEM) with the specific purpose to explicitly account for the geometrical defects introduced during manufacturing. Both classes demonstrate a fiber distribution along two perpendicular directions on parallel layers with a (Formula presented.) tilting between two adjacent layers. The crack pattern identified upon compression loading is consistent with that found in experimental studies available in literature. The finite element models have demonstrated that the effect of imperfections on elastic and strength properties may be substantial, depending on the specific type of defect identified in the scaffolds. In particular, micro-porosity, fiber length interruption and fiber detaching were found as key factors. The micro-pores act as stress concentrators promoting fracture initiation and propagation, while fiber detachment reduces the scaffold properties substantially along the direction perpendicular to the fiber plane
The consumption of seaweed as a protective factor in the etiology of breast cancer: proof of principle
Cyclosporine Regimens in Plaque Psoriasis: An Overview with Special Emphasis on Dose, Duration, and Old and New Treatment Approaches
Cyclosporine A (CsA) is one of the most effective systemic drugs available for the treatment of psoriasis, as evidenced by the results of several randomized studies and by a prolonged experience in dermatological setting. In clinical practice, CsA is usually used for the induction of psoriasis remission at a daily dose included in the range of 2.5–5 mg/kg and with intermittent short-term regimens, lasting on average 3–6 months. The magnitude and rapidity of response are dose dependent, as well as the risk of development of adverse events. Therefore, the dose should be tailored to patient’s needs and general characteristics and adjusted during the treatment course according to both the efficacy and tolerability. Some studies support the feasibility of pulse administration of CsA for a few days per week for both the induction and the maintenance of response in psoriasis patients. This paper will review the data on CsA regimens for plaque-type psoriasis and will focus the attention on dose, treatment duration, novel schedules, and role in combination therapies, including the association with biologicals
MEK inhibition leads to BRCA2 downregulation and sensitization to DNA damaging agents in pancreas and ovarian cancer models
Targeting the DNA damage response (DDR) in tumors with defective DNA repair
is a clinically successful strategy. The RAS/RAF/MEK/ERK signalling pathway is
frequently deregulated in human cancers. In this study, we explored the effects of
MEK inhibition on the homologous recombination pathway and explored the potential
for combination therapy of MEK inhibitors with DDR inhibitors and a hypoxia-activated
prodrug.
We studied effects of combining pimasertib, a selective allosteric inhibitor of
MEK1/2, with olaparib, a small molecule inhibitor of poly (adenosine diphosphate
[ADP]-ribose) polymerases (PARP), and with the hypoxia-activated prodrug
evofosfamide in ovarian and pancreatic cancer cell lines. Apoptosis was assessed
by Caspase 3/7 assay and protein expression was detected by immunoblotting.
DNA damage response was monitored with ÎłH2AX and RAD51 immunofluorescence
staining. In vivo antitumor activity of pimasertib with evofosfamide were assessed
in pancreatic cancer xenografts.
We found that BRCA2 protein expression was downregulated following pimasertib
treatment under hypoxic conditions. This translated into reduced homologous
recombination repair demonstrated by levels of RAD51 foci. MEK inhibition was
sufficient to induce formation of ÎłH2AX foci, suggesting that inhibition of this pathway
would impair DNA repair. When combined with olaparib or evofosfamide, pimasertib
treatment enhanced DNA damage and increased apoptosis. The combination of
pimasertib with evofosfamide demonstrated increased anti-tumor activity in BRCA
wild-type Mia-PaCa-2 xenograft model, but not in the BRCA mutated BxPC3 model.
Our data suggest that targeted MEK inhibition leads to impaired homologous
recombination DNA damage repair and increased PARP inhibition sensitivity in BRCA-
2 proficient cancers
Family history of cancer, body weight, and p53 nuclear overexpression in Duke's C colorectal cancer.
To examine the hypothesis that colorectal carcinomas with and without TP53 mutations may be characterised by aetiological heterogeneity, we analysed a group of 107 patients with primary Dukes' C colorectal cancer seen at the Memorial Sloan-Kettering Cancer Center (MSKCC) from 1986 to 1990. We assessed p53 overexpression using the monoclonal antibody PAb 1801, and identified 42 (39%) patients displaying p53-positive phenotype, defined as > or = 25% of positive cells. Patients with two or more first-degree relatives with cancer had an odds ratio (OR) of 2.9 (95% CI 1.0-8.3) for p53 overexpression in comparison with those without a family history of cancer (trend test, P = 0.11). A possible association between body weight and p53 overexpression was observed. The ORs were 1.9 for the second quartile, 1.9 for the third quartile and 3.4 for the highest quartile in comparison with the lowest quartile (trend test, P = 0.06). No association between occupational physical activity, smoking, drinking, parity and p53 overexpression was identified. The results suggest that p53 overexpression may be related to genetic predisposition to colorectal cancer, and p53-positive and p53-negative colorectal cancers may be controlled by different aetiological pathways
Assessment of DXA derived bone quality indexes and bone geometry parameters in early breast cancer patients: A single center cross-sectional study
Background: Bone mineral density (BMD) lacks sensitivity in individual fracture risk assessment in early breast cancer (EBC) patients treated with aromatase inhibitors (AIs). New dual-energy X-ray absorptiometry (DXA) based risk factors are needed. Methods: Trabecular bone score (TBS), bone strain index (BSI) and DXA parameters of bone geometry were evaluated in postmenopausal women diagnosed with EBC. The aim was to explore their association with morphometric vertebral fractures (VFs). Subjects were categorized in 3 groups in order to evaluate the impact of AIs and denosumab on bone geometry: AI-naive, AI-treated minus (AIDen-) or plus (AIDen+) denosumab. Results: A total of 610 EBC patients entered the study: 305 were AI-naive, 187 AIDen-, and 118 AIDen+. In the AI-naive group, the presence of VFs was associated with lower total hip BMD and T-score and higher femoral BSI. As regards as bone geometry parameters, AI-naive fractured patients reported a significant increase in femoral narrow neck (NN) endocortical width, femoral NN subperiosteal width, intertrochanteric buckling ratio (BR), intertrochanteric endocortical width, femoral shaft (FS) BR and endocortical width, as compared to non-fractured patients. Intertrochanteric BR and intertrochanteric cortical thickness significantly increased in the presence of VFs in AIDen- patients, not in AIDen+ ones. An increase in cross-sectional area and cross-sectional moment of inertia, both intertrochanteric and at FS, significantly correlated with VFs only in AIDen+. No association with VFs was found for either lumbar BSI or TBS in all groups. Conclusions: Bone geometry parameters are variably associated with VFs in EBC patients, either AI-naive or AI treated in combination with denosumab. These data suggest a tailored choice of fracture risk parameters in the 3 subgroups of EBC patients
- …