Quality by design approach for fabrication of extended-release buccal films for xerostomia employing hot-melt extrusion technology.

The study endeavors the fabrication of extended-release adipic acid (APA) buccal films employing a quality by design (QbD) approach. The films intended for the treatment of xerostomia were developed utilizing hot-melt extrusion technology. The patient-centered quality target product profile was created, and the critical quality attributes were identified accordingly. Three early-stage formulation development trials, complemented by risk assessment aligned the formulation and process parameters with the product quality standards. Employing a D-optimal mixture design, the formulations were systematically optimized by evaluating three formulation variables: amount of the release-controlling polymer Eudragit® (E RSPO), bioadhesive agent Carbopol® (CBP 971P), and pore forming agent polyethylene glycol (PEG 1500) as independent variables, and % APA release in 1, 4 and 8 h as responses. Using design of experiment software (Design-Expert®), a total of 16 experimental runs were computed and extruded using a Thermofisher ScientificTM twin screw extruder. All films exhibited acceptable content uniformity and extended-release profiles with the potential for releasing APA for at least 8 h. Films containing 30% E RSPO, 10% CBP 971P, and 20% PEG 1500 released 88.6% APA in 8 h. Increasing the CBP concentration enhanced adhesiveness and swelling capacities while decreasing E RSPO concentration yielded films with higher mechanical strength. The release kinetics fitted well into Higuchi and Krosmeyer-Peppas models indicating a Fickian diffusion release mechanism.

Joining of Aluminum and CFRP via Laser Powder Bed Fusion: Influence of Experimental Set-Up and Laser Processing on Microstructure and Mechanical Properties.

Additive-manufacturing-based joining methods enable tailored or even functionalized joints and allow for hybridization at small scales. The current study explored an innovative joining method for aluminum cast alloys (AlSi12) with thermoset carbon-fiber-reinforced polymers (CFRPs) via laser powder bed fusion (LPBF). The direct build-up of AlSi12 on a CFRP substrate proved to be challenging due to the dissimilar thermal properties of the considered materials, which led to substrate damage and low joint adhesion. These effects could be overcome by introducing an AlSi12 foil as an interlayer between the two joining partners, acting as a thermal barrier and further improving the AlSi12 melt wettability of the substrate. Within LPBF, the energy input in the form of volumetric laser energy density influenced both the porosity of the fused layers and the formation of thermally induced stresses due to the high cooling rates and different thermal expansion properties of the materials. While the AlSi12 volume density increased with a higher laser energy input, simultaneously increasing thermal stresses caused the debonding and deformation of the AlSi12 foil. However, within a narrow processing window of laser parameters, the samples achieved remarkably high shear strengths of τ > 20 MPa, comparable to those of conventional joining methods.

Influence of the Resin System and Sand Type on the Infiltration of 3D-Printed Sand Tools.

Binder jetting is a highly productive additive manufacturing (AM) method for porous parts. Due to its cost-effectiveness, it is used for large components and quantities ranging from prototyping to series production. Post-processing steps like sintering or infiltration are common in several applications to achieve high density and strength. This work investigates how 3D-printed sand molds can be infiltrated with epoxy resins without vacuum assistance to produce high-strength molds for thermoforming applications. Specimens 3D-printed from different sand types are infiltrated with resins of different viscosity and analyzed for infiltration velocity and depth. The infiltration velocities corresponded well with the correlation described in Washburn's equation: The resins' viscosities and the saturation level were decisive. Amongst the investigated sand types commonly used in foundries, sand type GS19 was found most suitable for infiltration. However, the sand type proved to be a less relevant influencing factor than the resins' viscosities and quantities applied. Infiltration of topology-optimized 3D-printed sand tools up to a wall thickness of 20 mm for thermoforming applications was found to be feasible.

Gene expression analysis of invasive breast carcinoma yields differential patterns in luminal subtypes of breast cancer.

Breast cancer is a heterogeneous disease, and new biomarkers are needed for more accurate classification and prediction of prognosis. The goal of this study is to assess the expression of breast cancer classification genes, to identify new molecular signatures in different intrinsic subtypes of breast cancer and to correlate their expression with different clinical variables. The study included 84 female patients newly diagnosed with non-metastatic breast cancer at the outpatient clinic at the National Cancer Institute, Cairo University, Egypt. Detection of 17 breast cancer classification genes was done using RT-PCR in tumor and normal tissues. Estrogen receptor (ER), progesterone receptor (PR), HER2, and Ki67 expression were assessed using IHC assay for intrinsic subtyping. Combined expression of FOXA1 and GATA3 was statistically higher in luminal subtypes in comparison to non-luminal subtypes. In Luminal A subtype; GRB7, EGFR, PTGS2, ID1, and KRT5 were significantly downregulated. FOXA1 and GATA3 were significantly upregulated in luminal B subtype, where EGFR and PTGS2 were significantly downregulated. While ESR1, EGFR, KRT5 and PTGS2 showed significantly low expression in tumor tissue in Her2 enriched subtype, TFF3 was significantly downregulated in triple negative subtype. GATA3 and FOXA1 expression exhibited significant correlation with tumor grade. Furthermore, GATA3, FOXA1, ESR1, and ID1 were also correlated significantly with staging of the tumor. Combined expression of ESR1, FOXA1 and GATA3 represents a molecular signature of luminal subtypes. Long term follow-up is needed to investigate the prognostic effect of breast cancer classification genes found in this study.

3D Printed Sand Tools for Thermoforming Applications of Carbon Fiber Reinforced Composites-A Perspective.

Tooling, especially for prototyping or small series, may prove to be very costly. Further, prototyping of fiber reinforced thermoplastic shell structures may rely on time-consuming manual efforts. This perspective paper discusses the idea of fabricating tools at reduced time and cost compared to conventional machining-based methods. The targeted tools are manufactured out of sand using the Binder Jetting process. These molds should fulfill the demands regarding flexural and compressive behavior while allowing for vacuum thermoforming of fiber reinforced thermoplastic sheets. The paper discusses the requirements and the challenges and presents a perspective study addressing this innovative idea. The authors present the idea for discussion in the additive manufacturing and FRP producing communities.

Effect of seasonal variation in ambient temperature on RNA quality of breast cancer tissue in a remote biobank setting.

Studies involving oncology especially diagnosis, prognosis and therapeutic monitoring are increasingly relying on molecular analyses. These analyses require high quality biomolecules to get accurate and precise results and this requires among others, monitoring for pre-analytical variables. The purpose of our study was to validate the SOPs of the newly established Egyptian National Cancer Institute (ENCI) biobank. We used a panel of 91 fresh frozen breast cancer tissue samples and their matched normal tissues and have investigated the overall quality (integrity and yield) of RNA extracted from fresh frozen breast tumor tissues and matched normal breast tissues. We investigated the effect of several factors including seasonal temperature variation, cold ischemia time, transportation method, and RNA extraction method. The RNA yield and quality were significantly increased with tumor samples collected in winter, transported on wet ice and using an automated RNA extraction platform. No significant effect was observed due to increased cold ischemia time >30 min. The effect of delay in time to cryopreservation on RNA degradation in fresh tissue samples may vary according to the type of tissue, temperature during tissue collection and transportation, and the use of stabilizing agents as RNA later.

Illumination of dense urban areas by light redirecting panels.

With the high population growth rate, especially in developing countries, and the scarcity of land resources, buildings are becoming so close to each other, depriving the lower floors and the alleys from sunlight and consequently causing health problems. Therefore, there is an urgent need for cost-effective efficient light redirecting panels that guide sun rays into those dim places. In this paper, we address this problem. A novel sine wave based panel is presented to redirect/diverge light downward and enhance the illumination level in those dark places. Simulation results show that the proposed panel improves the illuminance values by more than 200% and 400% in autumn and winter respectively, operates over wide solar altitude ranges, and redirects light efficiently. Experimental and simulation results are in good agreement.