Comparing Outcomes with Bone Marrow or Peripheral Blood Stem Cells as Graft Source for Matched Sibling Transplants in Severe Aplastic Anemia across Different Economic Regions

Bone marrow (BM) is the preferred graft source for hematopoietic stem cell transplantation (HSCT) in severe aplastic anemia (SAA) compared to mobilized peripheral blood stem cells (PBSC). We hypothesized that this recommendation may not apply to those regions where patients present later in their disease course, with heavier transfusion load and with higher graft failure rates. Patients with SAA who received HSCT from an HLA-matched sibling donor from 1995 to 2009 and reported to the Center for International Blood and Marrow Transplant Research or the Japan Society for Hematopoietic Cell Transplantation were analyzed. The study population was categorized by gross national income per capita (GNI) and region/countries into four groups. Groups analyzed were high income countries (HIC), which were further divided into US-Canada (N=486) and other HIC (N=1264), upper middle-income (UMIC) (N=482), and combined lower middle, low income countries (LM-LIC) (N=142). In multivariate analysis, overall survival (OS) was highest with BM as graft source in HIC compared to PBSC in all countries or BM in UMIC or LM-LIC (p<0.001). There was no significant difference in OS between BM and PBSC in UMIC (p=0.32) or LM-LIC (p=0.23). In LM-LIC the 28-day neutrophil engraftment was higher with PBSC compared to BM (97% vs. 77%, p<0.001). Chronic GVHD was significantly higher with PBSC in all groups. Whereas BM should definitely be the preferred graft source for HLA-matched sibling HSCT in SAA, PBSC may be an acceptable alternative in countries with limited resources when treating patients at high risk of graft failure and infective complications

Chile's export diversification since 1960: A free market miracle or mirage?

Conventional wisdom has proclaimed Chile's recent economic development a 'free market miracle'. In an examination of Chile's export diversification experience, this article departs from that view. By analysing the dynamics underlying the emergence of the salmon, fruit, forestry and wine sectors in Chile's export basket since the 1960s, the study sheds light on the crucial role of industrial policy in the process of capability accumulation that shapes new industries. The article undertakes a qualitative historical analysis of the scope and nature of policy interventions in each of the four sectors and conducts a quantitative policy evaluation using the difference-in-difference method. It finds that public institutions are essential in overcoming market failures inhibiting the emergence of new industries. Specifically, it shows that the government has a key role to play as a catalyst of human capital accumulation, as a venture capitalist, in trade promotion, and in ensuring 'national' sector reputation through a strong regulatory and quality control role. By elaborating on the dynamic process of structural transformation and capability accumulation, this article contributes to theoretical debates on the role of vertical policies in the emergence of new competitive sectors, and debates relating to static versus dynamic approaches to comparative advantage

Effects of medroxyprogesterone acetate (MPA) in activating progesterone receptor signaling in benign and cancer-associated fibroblasts of the endometrium

MedroxyprOgesterone acetate (MPA) is used for conservative treatment for endometrial cancer (EC); however, patients often develop progesterone resistance. Most typical and atypical endometrial hyperplasia shows regression after MPA treatment Primary type 1 .EC responds moderately to MFA therapy (50-70%). Yet, MPA treatment only o ffe rs 10-20% response rates and survival of less than one year in advanced and recurrent Fe. It was shown that secretion from normal fibroblast cells inhibit while cancer 'fibroblasts cells promote the proliferation of EC cells. Interestingly, a recent study showed that progesterone receptor (PH.) expression in normal fibroblast is important for progesterone inhibitory effects on cancer cells. It has also been shown that estrogen is responsible for increasing PR expression. However, it is still largely unknown, if and how, fibroblasts from endometrial cancers modulate EC response to progesterone. BAF and CAF were isolated from human endometrial primary cultured cells using antibody-conjugated. magnetic beads. Fibroblast and epithelial markers expression, and progesterone receptor (PR) expression were determined using quantitative real-time peR (qRT-PCR) and western blotting, PR nuclear translocation was determines using immunofluorescence assay. Cell viability was determined using MTT assay. Fibroblasts expressed high levels of fibroblast markers but not epithelial cell markers indicating minimal epithelial cells contamination. Both BAP and CAl: expressed varied levels of PR expression. PR nuclear translocation occurs within 6 hours of 10 nM MPA treatment in RAPs and CAFs. Their response to MFA growth inhibition was similar (20% growth inhibition when compared to vehicle) after treated with 1-400 oM MPA for 72 hours. The cell viability was 22% and 9% lower in BAFs and CAPs, respectively following 100 nM MPA treatment in the presence of 10 nIV!E2 compared to MPA alone. Our data suggests that PR signaling in CAP can be activated, and but has lower response to combination of MPA and estrogen treatment

X-ray photoelectron spectroscopic studies of H2SO4 protonated polyaniline

Polymer33132857-2859POLM

Self-doped polyaniline and polypyrrole. A comparative study by X-ray photoelectron spectroscopy

Polymer communications Guildford3213412-414POCO

Exact Dirichlet boundary Physics-informed Neural Network EPINN for solid mechanics

Physics-informed neural networks (PINNs) have been rapidly developed for solving partial differential equations. The xact Dirichlet boundary condition hysics-nformed eural etwork (EPINN) is proposed to achieve efficient simulation of solid mechanics problems based on the principle of least work with notably reduced training time. There are five major building features in the EPINN framework. First, for the 1D solid mechanics problem, the neural networks are formulated to exactly replicate the shape function of linear or quadratic truss elements. Second, for 2D and 3D problems, the tensor decomposition was adopted to build the solution field without the need of generating the finite element mesh of complicated structures to reduce the number of trainable weights in the PINN framework. Third, the principle of least work was adopted to formulate the loss function. Fourth, the exact Dirichlet boundary condition (i.e., displacement boundary condition) was implemented. Finally, the meshless finite difference (MFD) was adopted to calculate gradient information efficiently. By minimizing the total energy of the system, the loss function is selected to be the same as the total work of the system, which is the total strain energy minus the external work done on the Neumann boundary conditions (i.e., force boundary conditions). The exact Dirichlet boundary condition was implemented as a hard constraint compared to the soft constraint (i.e., added as additional terms in the loss function), which exactly meets the requirement of the principle of least work. The EPINN framework is implemented in the Nvidia Modulus platform and GPU-based supercomputer and has achieved notably reduced training time compared to the conventional PINN framework for solid mechanics problems. Typical numerical examples are presented. The convergence of EPINN is reported and the training time of EPINN is compared to conventional PINN architecture and finite element solvers. Compared to conventional PINN architecture, EPINN achieved a speedup of more than 13 times for 1D problems and more than 126 times for 3D problems. The simulation results show that EPINN can even reach the convergence speed of finite element software. In addition, the prospective implementations of the proposed EPINN framework in solid mechanics are proposed, including nonlinear time-dependent simulation and super-resolution network

The immunohistochemistry signature of mismatch repair (MMR) proteins in a multiethnic Asian cohort with endometrial carcinoma

Endometrial cancer is the most common gynecologic cancer in developed countries and is rising in incidence globally. Although the 5-year survival rates are >80%, factors beyond conventional pathologic features that predict clinical outcomes are still being elucidated. The aims of this study were to define the prevalence and associations of deficient mismatch repair (dMMR) protein expression (MLH1, MSH2, MSH6, PMS2) by immunohistochemistry in a multiethnic Southeast Asian cohort with endometrioid endometrial cancer. A total of 77 patients with adequate formalin-fixed paraffin-embedded specimens were identified. The sections were stained in 2 centers for 4 MMR proteins and examined by 2 independent specialist histopathologists. The mean age for the cohort was 58.6 yr, with 19.4% (15/77) of patients’ cancers showing loss of 2 MMR proteins. All 13 cancers with absent MLH1 showed PMS2 loss (13/15), whereas absent MSH2 correlated with MHS6 loss (2/15). There were no significant differences for dMMR cases in age, body mass index, histopathologic characteristics, and clinical outcomes. In dMMR cases, an overrepresentation of patients of Indian ethnic origin was observed compared with Chinese and Malays. These findings suggest that dMMR protein expression in a Southeast Asian endometrial cancer cohort does not correlate with disease outcomes

Surface studies of chemically processed polyaniline films

Synthetic Metals533333-345SYME

Expression of neuronal markers in the endometrium of women with and those without endometriosis

STUDY QUESTION How do the expression patterns of neuronal markers differ in the endometrium of women with and without endometriosis?SUMMARY ANSWER The neuronal markers, PGP9.5, NGFp75 and VR1, are expressed in the endometrium at levels that do not differ between women with and without endometriosis.WHAT IS KNOWN ALREADY Aberrant neuronal growth within the uterus may contribute to abnormal fertility and uterine dysfunction. However, controversy still exists as to whether aberrant innervation in the endometrium is associated with gynaecological pathology such as endometriosis. This may reflect the use of subjective methods such as histology to assess the innervation of the endometrium. We, therefore, employed a quantitative method, western blotting, to study markers of endometrial innervation in the presence and absence of endometriosis.STUDY DESIGN, SIZE, DURATION This study included 45 women undergoing laparoscopic examination for the diagnosis of endometriosis. Endometrial samples were analysed by western blot for the expression of neuronal and neurotrophic markers, PGP9.5, VR1 and NGFp75.PARTICIPANTS/MATERIALS, SETTINGS, METHODS Endometrial pipelle biopsies were obtained from patients with (n = 20, study group) and without (n = 25, control group) endometriosis. Tissue was analysed by immunohistochemistry and western blot analysis for the expression of pan-neuronal marker, PGP9.5, sensory nociceptive marker, TPVR1, and low-affinity neurotrophic growth factor receptor, NGFRp75.MAIN RESULTS AND THE ROLE OF CHANCE PGP9.5, NGFp75 and VR1 were expressed in the endometrium of women, independent of the presence of endometriosis. Furthermore, the expression level of PGP9.5, VR1 and NGFp75 did not alter between the two cohorts of women.LIMITATIONS, REASONS FOR CAUTION Studies of this nature are subject to the heterogeneous nature of patient population and tissue samples despite attempts to standardize these parameters. Hence, further studies using similar methodology will be required to confirm our results.WIDER IMPLICATIONS OF THE FINDINGS Our results highlight that sensory neuronal markers are present in women with and without endometriosis. Future work will assess what the targets of the endometrial nerves are and investigate their function, their impact on endometrial biology and, in particular, whether aberrant neuronal function, rather than the mere presence of neuronal function, could be the root cause of subfertility and/or pain affecting many endometriosis sufferers. Our results do not, however, confirm the previous paradigm of increased innervation in the endometrium of women with endometriosis, nor the use of nerve cell detection from pipelle biopsies to diagnose endometriosis.STUDY FUNDING/COMPETING INTEREST(S) This work was funded by the Infertility Research Trust (IRT) and the University of Malaya. There are no competing interests

Cancer-Associated Fibroblasts Promote Proliferation of Endometrial Cancer Cells

Endometrial cancer is the most commonly diagnosed gynecologic malignancy worldwide; yet the tumor microenvironment, especially the fibroblast cells surrounding the cancer cells, is poorly understood. We established four primary cultures of fibroblasts from human endometrial cancer tissues (cancer-associated fibroblasts, CAFs) using antibody-conjugated magnetic bead isolation. These relatively homogenous fibroblast cultures expressed fibroblast markers (CD90, vimentin and alpha-smooth muscle actin) and hormonal (estrogen and progesterone) receptors. Conditioned media collected from CAFs induced a dose-dependent proliferation of both primary cultures and cell lines of endometrial cancer in vitro (175%) when compared to non-treated cells, in contrast to those from normal endometrial fibroblast cell line (51%) (P<0.0001). These effects were not observed in fibroblast culture derived from benign endometrial hyperplasia tissues, indicating the specificity of CAFs in affecting endometrial cancer cell proliferation. To determine the mechanism underlying the differential fibroblast effects, we compared the activation of PI3K/Akt and MAPK/Erk pathways in endometrial cancer cells following treatment with normal fibroblasts- and CAFs-conditioned media. Western blot analysis showed that the expression of both phosphorylated forms of Akt and Erk were significantly down-regulated in normal fibroblasts-treated cells, but were up-regulated/maintained in CAFs-treated cells. Treatment with specific inhibitors LY294002 and U0126 reversed the CAFs-mediated cell proliferation (P<0.0001), suggesting for a role of these pathways in modulating endometrial cancer cell proliferation. Rapamycin, which targets a downstream molecule in PI3K pathway (mTOR), also suppressed CAFs-induced cell proliferation by inducing apoptosis. Cytokine profiling analysis revealed that CAFs secrete higher levels of macrophage chemoattractant protein (MCP)-1, interleukin (IL)-6, IL-8, RANTES and vascular endothelial growth factor (VEGF) than normal fibroblasts. Our data suggests that in contrast to normal fibroblasts, CAFs may exhibit a pro-tumorigenic effect in the progression of endometrial cancer, and PI3K/Akt and MAPK/Erk signaling may represent critical regulators in how endometrial cancer cells respond to their microenvironment