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ABSTRACT Aim: In this study, we aimed to analyze the effect of prognostic nutritional index and neutrophile lymphocyte ratio on the overall survival (OS) in patients treated with regorafenib. Materials and Methods: Metastatic colorectal cancer (CRC) patients who treated with regorafenib between 2016 and 2020 in a single center were evaluated retrospectively. ROC analysis was used for neutrophile lymphocyte ratio (NLR's) and prognostic nutritional index (PNI's) optimum cut-off value. The relationship between OS with PNI and NLR was investigated. Results: Fifty-two patient's data were analyzed. The median age was 57 years, 22 (41.5) of the patients were female. The optimal cut-off value of PNI for OS was 45.7 according to ROC curve analysis. The median NLR value was accepted as 2.7. Median OS was 8.3 months. Patients who have high PNI value than 45.7 had longer OS (12.09 months vs. 6.31 months hazard ratio [HR]: 0.37 95 confidence interval [CI]: 0.19-0.73 P = 0.003) and there was a tendency for longer OS with low NLR value then median (12.05 months vs. 6.14 months HR: 0.54 95 CI: 0.29-1.23 P = 0.057). Primary tumor resected patients had longer OS than nonresected patients (12.05 months vs. 6.30 months HR: 0.34 95 CI: 0.17-0.66 P = 0.001). In multivariate analysis, high PNI value more than 45.7 (HR: 0.40 95 CI: 0.18-0.88 P = 0.02) and resection of the primary tumor (HR: 0.40 95 CI: 0.21-0.80 P = 0.01) were the only independent factors for longer OS. Conclusion: Metastatic CRC patients with high pretreatment PNI and primary tumor resected are more likely to have longer OS with regorafenib. PNI is more reliable index than NLR to predict OS in metastatic CRC patients treated with regorafenib. Keywords: Disease control, neutrophil-lymphocyte ratio, prognostic nutritional index, Author(s): Bulent Erdogan (corresponding author) [1]; Erkan Ozcan [1]; Ivo Gokmen [1]; Ali Gokyer [1]; Ahmet Kucukarda [1]; Osman Kostek [1]; Muhammet Bekir Hacıoglu [1]; Sernaz Uzunoglu [1]; Irfan Cicin [...]

Mg-based biodegradable metallic implants are gaining increased attraction for applications in orthopedics and dentistry. However, their current applications are hampered by their high rate of corrosion, degradation, and rapid release of ions and gas bubbles into the physiological medium. The aim of the present study is to investigate the osteogenic and angiogenic potential of coated Mg-based implants in a sheep cranial defect model. Although their osteogenic potential was studied to some extent, their potential to regenerate vascularized bone formation was not studied in detail. We have studied the potential of magnesium–calcium (MgCa)-based alloys modified with zinc (Zn)- or gallium (Ga)-doped calcium phosphate (CaP) coatings as a strategy to control their degradation rate while enhancing bone regeneration capacity. MgCa and its implants with CaP coatings (MgCa/CaP) as undoped or as doped with Zn or Ga (MgCa/CaP + Zn and MgCa/CaP + Ga, respectively) were implanted in bone defects created in the sheep cranium. MgCa implants degraded faster than the others at 4 weeks postop and the weight loss was ca. 50%, while it was ca. 15% for MgCa/CaP and <10% in the presence of Zn and Ga with CaP coating. Scanning electron microscopy (SEM) analysis of the implant surfaces also revealed that the MgCa implants had the largest degree of structural breakdown of all the groups. Radiological evaluation revealed that surface modification with CaP to the MgCa implants induced better bone regeneration within the defects as well as the enhancement of bone–implant surface integration. Bone volume (%) within the defect was ca. 25% in the case of MgCa/CaP + Ga, while it was around 15% for undoped MgCa group upon micro-CT evaluation. This >1.5-fold increase in bone regeneration for MgCa/CaP + Ga implant was also observed in the histopathological examination of the H&E- and Masson’s trichrome-stained sections. Immunohistochemical analysis of the bone regeneration (antiosteopontin) and neovascularization (anti-CD31) at the defect sites revealed >2-fold increase in the expression of the markers in both Ga- and Zn-doped, CaP-coated implants. Zn-doped implants further presented low inflammatory reaction, notable bone regeneration, and neovascularization among all the implant groups. These findings indicated that Ga- and Zn-doped CaP coating is an important strategy to control the degradation rate as well as to achieve enhanced bone regeneration capacity of the implants made of Mg-based alloys.

Encapsulating multiple growth factors within a scaffold enhances the regenerative capacity of engineered bone grafts through their localization and controls the spatiotemporal release profile. In this study, we bioprinted hybrid bone grafts with an inherent built-in controlled growth factor delivery system, which would contribute to vascularized bone formation using a single stem cell source, human adipose-derived stem/stromal cells (ASCs) in vitro. The strategy was to provide precise control over the ASC-derived osteogenesis and angiogenesis at certain regions of the graft through the activity of spatially positioned microencapsulated BMP-2 and VEGF within the osteogenic and angiogenic bioink during bioprinting. The 3D-bioprinted vascularized bone grafts were cultured in a perfusion bioreactor. Results proved localized expression of osteopontin and CD31 by the ASCs, which was made possible through the localized delivery activity of the built-in delivery system. In conclusion, this approach provided a methodology for generating off-the-shelf constructs for vascularized bone regeneration and has the potential to enable single-step, in situ bioprinting procedures for creating vascularized bone implants when applied to bone defects.

Effective skeletal muscle tissue engineering relies on control over the scaffold architecture for providing muscle cells with the required directionality, together with a mechanical property match with the surrounding tissue. Although recent advances in 3D printing fulfill the first requirement, the available synthetic polymers either are too rigid or show unfavorable surface and degradation profiles for the latter. In addition, natural polymers that are generally used as hydrogels lack the required mechanical stability to withstand the forces exerted during muscle contraction. Therefore, one of the most important challenges in the 3D printing of soft and elastic tissues such as skeletal muscle is the limitation of the availability of elastic, durable, and biodegradable biomaterials. Herein, we have synthesized novel, biocompatible and biodegradable, elastomeric, segmented polyurethane and polyurethaneurea (TPU) copolymers which are amenable for 3D printing and show high elasticity, low modulus, controlled biodegradability, and improved wettability, compared to conventional polycaprolactone (PCL) and PCL-based TPUs. The degradation profile of the 3D printed TPU scaffold was in line with the potential tissue integration and scaffold replacement process. Even though TPU attracts macrophages in 2D configuration, its 3D printed form showed limited activated macrophage adhesion and induced muscle-like structure formation by C2C12 mouse myoblasts in vitro, while resulting in a significant increase in muscle regeneration in vivoin a tibialis anterior defect in a rat model. Effective muscle regeneration was confirmed with immunohistochemical assessment as well as evaluation of electrical activity produced by regenerated muscle by EMG analysis and its force generation via a custom-made force transducer. Micro-CT evaluation also revealed production of more muscle-like structures in the case of implantation of cell-laden 3D printed scaffolds. These results demonstrate that matching the tissue properties for a given application via use of tailor-made polymers can substantially contribute to the regenerative outcomes of 3D printed tissue engineering scaffolds.

To investigate follicular fluid (FF) phthalate levels in adolescents undergoing fertility preservation compared to oocyte donors and explore its association with ovarian reserve and cumulus cell gene expression.

In the presence of cutouts, the buckling strength of shell structures under compression significantly decreases. In order to compensate this, these structures are reinforced with stiffeners. In this study, the objective is to optimize the stiffener geometry and pattern on a cylindrical shell with two square holes to maximize the buckling load capacity without increase in its weight. A finite element model is developed to evaluate the buckling load of the structure. A good correlation is observed between the nonlinear analysis results of the model and the numerical and experimental results reported in the literature. Optimization is achieved in two levels. In the first level, topology optimization is performed to obtain the optimal stiffener pattern over the shell surface based on linear eigenvalue buckling analysis. In the second level, the stiffener heights and the shell thickness are optimized using a local search algorithm, Nelder–Mead; the buckling load levels are obtained by carrying out nonlinear buckling analyses in ANSYS. A Python code is developed to implement the optimization method and conduct analyses in ANSYS. The results show that stiffeners need to be introduced around the cutouts and the regions near the top and bottom edges for maximum buckling load capacity. The results also reveal that stiffeners on the mid lateral surfaces of the cylinder do not make significant contribution to the buckling strength. The bucking load of the optimized stiffened geometry is 22% higher than that of the unreinforced geometry having the same weight.

A cyclic simple shear liquefaction box (CSSLB) was designed and manufactured to allow laboratory testing of saturated sands under cyclic or transient strain-controlled conditions. The box accommodates pore water pressure transducers, linear variable displacement transducers, and bender elements and bending disks. To induce shear strains, the box has two rotating walls connected to two translating rigid walls with a flexible sealant. When the tops of the rotating walls are fixed against translation and the base of the CSSLB, which rests on a shaking table, is excited with a displacement time history, shear strains are induced in a soil specimen. Two-dimensional numerical analyses of plan and elevation sections of the CSSLB were performed, demonstrating that the design of the box and the mechanism for shearing can induce controlled shear strains in sand specimens with minimal boundary effects. Example test results from sand specimens subjected to cyclic and earthquake shear strain time histories are presented and illustrate how well the CSSLB with its instrumentation is suited for conducting tests on relatively large soil specimens.

Bender element and bending disk setups were designed and implemented in a liquefaction box that accommodated a large sand specimen (190 mm × 300 mm × 490 mm). The box was manufactured for testing fully and partially saturated sand specimens under cyclic and earthquake excitation. Special housings for bender elements (31.8 mm × 12.7 mm × 0.51 mm) were manufactured to allow insertion of the elements through the side walls of the box. The bender elements were used to measure shear wave velocities in multiple directions to ascertain the uniformity of a sand specimen prepared in the liquefaction box. Large bending disks (31.8 mm × 0.41 mm) in special housings were utilized to measure compression wave velocities with the aim of investigating the presence and effect of the degree of partial saturation in specimens. The housings for bender elements and bending disks were designed to minimize the boundary effects of the Plexiglas walls of the liquefaction box. This paper provides details of the experimental setup and the designs of the bender element and bending disk housings. Sample test results of shear and compression wave measurements are also included to demonstrate successful application of the test setup. The experimental setup described is well suited for utilizing bender elements and bending disks for shear and compression wave velocity measurements in fully and partially saturated large sand specimens.

Do live birth rates (LBR), obstetric and perinatal outcomes vary between women who underwent frozen embryo transfer (ET) in the immediately subsequent menstrual cycle, and with those who underwent delayed frozen ET.

In orthopedic surgery, metals are preferred to support or treat damaged bones due to their high mechanical strength. However, the necessity for a second surgery for implant removal after healing creates problems. Therefore, biodegradable metals, especially magnesium (Mg), gained importance, although their extreme susceptibility to galvanic corrosion limits their applications. The focus of this study was to control the corrosion of Mg and enhance its biocompatibility. For this purpose, surfaces of magnesium–calcium (MgCa1) alloys were modified with calcium phosphate (CaP) or CaP doped with zinc (Zn) or gallium (Ga) via microarc oxidation. The effects of surface modifications on physical, chemical, and mechanical properties and corrosion resistance of the alloys were studied using surface profilometry, goniometry, scanning electron microscopy (SEM), energy-dispersive X-ray spectroscopy (EDS), nanoindentation, and electrochemical impedance spectroscopy (EIS). The coating thickness was about 5–8 μm, with grain sizes of 43.1 nm for CaP coating and 28.2 and 58.1 nm for Zn- and Ga-doped coatings, respectively. According to EIS measurements, the capacitive response (Yc) decreased from 11.29 to 8.72 and 0.15 Ω–1cm–2snupon doping with Zn and Ga, respectively. The Ecorrvalue, which was −1933 mV for CaP-coated samples, was found significantly electropositive at −275 mV for Ga-doped ones. All samples were cytocompatible according to indirect tests. In vitroculture with Saos-2 cells led to changes in the surface compositions of the alloys. The numbers of cells attached to the Zn-doped (2.6 × 104cells/cm2) and Ga-doped (6.3 × 104cells/cm2) coatings were higher than that on the surface of the undoped coating (1.0 × 103cells/cm2). Decreased corrosivity and enhanced cell affinity of the modified MgCa alloys (CaP coated and Zn and Ga doped, with Ga-doped ones having the greatest positive effect) make them novel and promising candidates as biodegradable metallic implant materials for the treatment of bone damages and other orthopedic applications.