A patient network-based machine learning model for disease prediction: The case of type 2 diabetes mellitus

Applied Intelligence - In recent years, the prevalence of chronic diseases such as type 2 diabetes mellitus (T2DM) has increased, bringing a heavy burden to healthcare systems. While regular...     

Immunomodulatory Drugs for the Treatment of B Cell Malignancies

Accumulating evidence suggests that the tumor microenvironment (TME) is involved in disease progression and drug resistance in B cell malignancies, by supporting tumor growth and facilitating the ability of malignant cells to avoid immune recognition. Immunomodulatory drugs (IMiDs) such as lenalidomide have some direct anti-tumor activity, but critically also target various cellular compartments of the TME including T cells, NK cells, and stromal cells, which interfere with pro-tumor signaling while activating anti-tumor immune responses. Lenalidomide has delivered favorable clinical outcomes as a single-agent, and in combination therapy leads to durable responses in chronic lymphocytic leukemia (CLL) and several non-Hodgkin lymphomas (NHLs) including follicular lymphoma (FL), diffuse large B cell lymphoma (DLBCL), and mantle cell lymphoma (MCL). Recently, avadomide, a next generation cereblon E3 ligase modulator (CELMoD), has shown potent anti-tumor and TME immunomodulatory effects, as well as promising clinical efficacy in DLBCL. This review describes how the pleiotropic effects of IMiDs and CELMoDs could make them excellent candidates for combination therapy in the immuno-oncology era—a concept supported by preclinical data, as well as the recent approval of lenalidomide in combination with rituximab for the treatment of relapsed/refractory (R/R) FL.     

Room-temperature dislocation plasticity in SrTiO3 tuned by defect chemistry

Dislocations have been identified to modify both the functional and mechanical properties of some ceramic materials. Succinct control of dislocation-based plasticity in ceramics will also demand knowledge about dislocation interaction with point defects. Here, we propose an experimental approach to modulate the dislocation-based plasticity in single-crystal SrTiO₃ based on the concept of defect chemistry engineering, for example, by increasing the oxygen vacancy concentration via reduction treatment. With nanoindentation and bulk compression tests, we find that the dislocation-governed plasticity is significantly modified at the nano-/microscale, compared to the bulk scale. The increase in oxygen vacancy concentration after reduction treatment was assessed by impedance spectroscopy and is found to favor dislocation nucleation but impede dislocation motion as rationalized by the nanoindentation pop-in and nanoindentation creep tests.     

Comparative analysis of different properties of polyhydroxyalkanoates isolated from two different bacterial strains: Alkaliphilus oremlandii OhILAs and recombinant Escherichia coli XL1B

We synthesized poly(3‐hydroxybutyrate‐co‐3‐hydroxyvalerate) [P(3‐HB‐co‐3‐HV)] copolymer having different contents of 3‐hydroxyvalerate (3‐HV) units (16.04, 16.3, 24.95, 25.62, and 16.52 mol % 3‐HV) with different yields of polyhydroxyalkanoates (PHAs) by feeding with different cooking oils and with Alkaliphilus oremlandii OhILAs strain. The PHA production efficiency of the Alkaiphilus strain was compared with that of the control strain, Bacillus cereus. The synthesis of each PHA biopolymer was performed with different toxic spent oils as the sole carbon source in an oil‐in‐water‐based microemulsion medium. We observed that the productivity of the poly(3‐hydroxybutyrate) [P(3‐HB)] copolymer from the Alkaliphilus strain was higher than those of the PHAs isolated from B. cereus and the Escherichia coli XL1B strain. The synthesized PHA copolymers were characterized by ¹H‐NMR and Fourier transform infrared (FTIR) spectroscopy. In the ¹H‐NMR spectra, a doublet resonance peak at 1.253 ppm of the/ methyl protons of the 3‐hydroxybutyrate (3‐HB) side group and one at 0.894 ppm due to the methyl protons of the 3‐HV side group indicated the presence of 3‐HB and 3‐HV units in the copolymer. The chemical shift values at 1.25 and 2.2 ppm, due to the resonance absorption peaks of the methyl protons and methylene protons, confirmed the synthesis of the P(3‐HB) homopolymer. From the FTIR spectra, a strong C?O stretching frequency in the range of 1745–1727 cm^?1, together with strong C? O stretching bands near 1200 cm^?1 and a strong band near 3400 cm^?1, confirmed the synthesis of P(3‐HB‐co‐3‐HV) and P(3‐HB). Thus, waste cooking oil as a substrate provided an alternate route for the formation of P(3‐HB‐co‐3‐HV) and P(3‐HB) by Alkaliphilus and E. coli strains, respectively. © 2014 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2014 , 131, 41080.     

Structural and high temperature conduction studies of (Na<Subscript>0.46</Subscript>Bi<Subscript>0.46</Subscript>Ba<Subscript>0.08</Subscript>) (Mn<Subscript>x</Subscript>Ti<Subscript>1−x</Subscript>O<Subscript>3</Subscript>)–CuO lead-free piezoelectric ceramics

Polycrystalline lead-free (Na_0.46Bi_0.46Ba_0.08)(Mn_xTi_1?xO₃)?+?0.2CuO ceramics (x?=?0.0, 0.5, 2.0, 3.0 wt%) were prepared via solid-state reaction method. X-ray diffraction (XRD) analysis confirmed the formation of single-phase perovskite structure and indicated the presence of morphotropic phase boundary, where the tetragonal and rhombohedral phases co-existed for all the synthesized compositions. Scanning electron microscopy (SEM) analysis revealed that the average grain size decreased with the increase in Mn content. Impedance spectroscopy (IS) indicated that Mn doping was found to decrease the grain boundary resistance. Two semi-circles were observed for higher Mn content which indicates the contribution of both bulk grains and grain boundaries. Non-Debye type and temperature dependent relaxation phenomenon was also revealed by IS studies. The activation energies at different frequencies were found to be 0.05–0.9 eV, indicating hopping charge conduction mechanism. These results have comprehensive implications for the expanded use of BNT based lead free piezoelectric ceramics for practical applications.     

Dislocation-tuned electrical conductivity in solid electrolytes (9YSZ): A micro-mechanical approach

Tailoring the electrical conductivity of functional ceramics by introducing dislocations is a comparatively recent research focus, and its merits were demonstrated through mechanical means. Especially bulk deformation at high temperatures is suggested to be a promising method to introduce a high dislocation density. So far, however, controlling dislocation generation and their annihilation remains difficult. Although deforming ceramics generate dislocations on multiple length scales, dislocation annihilation at the same time appears to be the bottleneck to use the full potential of dislocations-tailoring the electrical conductivity. Here, we demonstrate the control over these aspects using a micromechanical approach on yttria-stabilized zirconia - YSZ. Targeted indentation well below the dislocation annihilation temperature resulted in extremely dense dislocation networks, visualized by chemical etching and electron channeling contrast imaging. Microcontact-impedance measurements helped evaluate the electrical response of operating individual slip systems. A significant conductivity enhancement is revealed in dislocation-rich regions compared to pristine ones in fully stabilized YSZ. This enhancement is mainly attributed to oxygen ionic conductivity. Thus, the possibility of increasing the conductivity is illustrated and provides a prospect to transfer the merits of dislocation-tuned electrical conductivity to solid oxygen electrolytes.