Robustness of magnetic resonance radiomic features to pixel size resampling and interpolation in patients with cervical cancer.

BACKGROUND: Radiomics is a promising field in oncology imaging. However, the implementation of radiomics clinically has been limited because its robustness remains unclear. Previous CT and PET studies suggested that radiomic features were sensitive to variations in pixel size and slice thickness of the images. The purpose of this study was to assess robustness of magnetic resonance (MR) radiomic features to pixel size resampling and interpolation in patients with cervical cancer. METHODS: This retrospective study included 254 patients with a pathological diagnosis of cervical cancer stages IB to IVA who received definitive chemoradiation at our institution between January 2006 and June 2020. Pretreatment MR scans were analyzed. Each region of cervical cancer was segmented on the axial gadolinium-enhanced T1- and T2-weighted images; 107 radiomic features were extracted. MR scans were interpolated and resampled using various slice thicknesses and pixel spaces. Intraclass correlation coefficients (ICCs) were calculated between the original images and images that underwent pixel size resampling (OP), interpolation (OI), or pixel size resampling and interpolation (OP+I) as well as among processed image sets with various pixel spaces (P), various slice thicknesses (I), and both (P + I). RESULTS: After feature standardization, ≥86.0% of features showed good robustness when compared between the original and processed images (OP, OI, and OP+I) and ≥ 88.8% of features showed good robustness when processed images were compared (P, I, and P + I). Although most first-order, shape, and texture features showed good robustness, GLSZM small-area emphasis-related features and NGTDM strength were sensitive to variations in pixel size and slice thickness. CONCLUSION: Most MR radiomic features in patients with cervical cancer were robust after pixel size resampling and interpolation following the feature standardization process. The understanding regarding the robustness of individual features after pixel size resampling and interpolation could help future radiomics research.

An autophagy enhancer ameliorates diabetes of human IAPP-transgenic mice through clearance of amyloidogenic oligomer.

We have reported that autophagy is crucial for clearance of amyloidogenic human IAPP (hIAPP) oligomer, suggesting that an autophagy enhancer could be a therapeutic modality against human diabetes with amyloid accumulation. Here, we show that a recently identified autophagy enhancer (MSL-7) reduces hIAPP oligomer accumulation in human induced pluripotent stem cell-derived ß-cells (hiPSC-ß-cells) and diminishes oligomer-mediated apoptosis of ß-cells. Protective effects of MSL-7 against hIAPP oligomer accumulation and hIAPP oligomer-mediated ß-cell death are significantly reduced in cells with knockout of MiTF/TFE family members such as Tfeb or Tfe3. MSL-7 improves glucose tolerance and ß-cell function of hIAPP+ mice on high-fat diet, accompanied by reduced hIAPP oligomer/amyloid accumulation and ß-cell apoptosis. Protective effects of MSL-7 against hIAPP oligomer-mediated ß-cell death and the development of diabetes are also significantly reduced by ß-cell-specific knockout of Tfeb. These results suggest that an autophagy enhancer could have therapeutic potential against human diabetes characterized by islet amyloid accumulation.

The relationship between employment status and self-rated health among wage workers in South Korea: the moderating role of household income.

The purpose of the study reported in this article was to investigate the relationship between employment status and self-rated health (SRH) and the moderating effect of household income among wage workers in South Korea. This research analyzed the Korean Labor and Income Panel Study, 2005 to 2008. Of the 10,494 respondents participating in the survey during the period, a total of 1,548 people whose employment status had remained either precarious or nonprecarious were selected. A moderated multiple regression model was used to examine the main effect of employment status on SRH and the moderating effect of total household income on the relationship between employment status and SRH. Among 343 precarious workers and 1,205 nonprecarious workers, after controlling for gender, age, education, smoking, and drinking, employment status was associated with SRH of wage workers, and household income was found to have a moderating effect on SRH in that higher income buffers the link between unstable employment status and low SRH. Unstable employment, combined with low income, was significantly related to precarious wage workers' perceived health. To promote public health, efforts may be needed to secure not only people's employment, but also their income.

Bax inhibitor-1 enhances survival and neuronal differentiation of embryonic stem cells via differential regulation of mitogen-activated protein kinases activities.

Bax inhibitor-1 (BI-1), a member of the BI-1 family of integral membrane proteins, was originally identified as an inhibitor of stress-induced cell death in mammalian cells. Previous studies have shown that the withdrawal of leukemia inhibitory factor (LIF) results in differentiation of the majority of mouse embryonic stem (mES) cells into various cell lineages, while some ES cells die within 3days. Thus, to investigate the function of BI-1 in ES cell survival and neuronal differentiation, we generated mES cell lines that overexpress BI-1 or a carboxy-terminal BI-1ΔC mutant. Overexpression of BI-1 in mES cells significantly increased cell viability and resistance to apoptosis induced by LIF withdrawal, while the control vector or BI-1ΔC-overexpressing mES cells had no effect. Moreover, overexpression of BI-1 produced significant inhibition of the p38 mitogen-activated protein kinases (MAPK) pathway in response to LIF withdrawal, while activity of the extracellular signal-regulated kinase (ERK)/c-Jun N-terminal kinase (JNK) MAPK pathway was increased. Interestingly, we found that BI-1-overexpressing cells showed higher expression levels of neuroectodermal markers (Otx1, Lmx1b, En1, Pax2, Wnt1, Sox1, and Nestin) and greater neuronal differentiation efficiency than control or BI-1ΔC-overexpressing mES cells did. Considering these findings, our results indicated that BI-1-modulated MAPK activity plays a key role in protecting mES cells from LIF-withdrawal-induced apoptosis and in promoting their differentiation toward neuronal lineages.

Self-renewal of embryonic stem cells through culture on nanopattern polydimethylsiloxane substrate.

Embryonic stem (ES) cells can undergo continual proliferation and differentiation into cells of all somatic cell lineages in vitro; they are an unlimited cell source for regenerative medicine. However, techniques for maintaining undifferentiated ES cells are often inefficient and result in heterogeneous cell populations. Here, we determined effects of nanopattern polydimethylsiloxane (PDMS) as a culture substrate in promoting the self-renewal of mouse ES (mES) cells, compared to commercial plastic culture dishes. After many passages, mES cells efficiently maintained their undifferentiated state on nanopattern PDMS, but randomly differentiated on commercial plastic culture dishes, as indicated by partially altered morphologies and decreases in alkaline phosphatase activity and stage-specific expression of embryonic antigen-1. Under nanopattern PDMS conditions, we found increased activities of STAT3 and Akt, important proteins involved in maintaining the self-renewal of mES cells. The substrate-cell interactions also enhanced leukemia inhibitory factor (LIF)-downstream signaling and inhibited spontaneous differentiation, concomitant with reduced focal adhesion kinase (FAK) signaling. This reduction in FAK signaling was shown to be important for promoting mES cell self-renewal. Thus, our data demonstrates that nanopattern PDMS contributes to maintaining the self-renewal of mES cells and may be applicable in the large-scale production of homogeneously undifferentiated mES cells.

Differentiation and transplantation of functional pancreatic beta cells generated from induced pluripotent stem cells derived from a type 1 diabetes mouse model.

The nonobese diabetic (NOD) mouse is a classical animal model for autoimmune type 1 diabetes (T1D), closely mimicking features of human T1D. Thus, the NOD mouse presents an opportunity to test the effectiveness of induced pluripotent stem cells (iPSCs) as a therapeutic modality for T1D. Here, we demonstrate a proof of concept for cellular therapy using NOD mouse-derived iPSCs (NOD-iPSCs). We generated iPSCs from NOD mouse embryonic fibroblasts or NOD mouse pancreas-derived epithelial cells (NPEs), and applied directed differentiation protocols to differentiate the NOD-iPSCs toward functional pancreatic beta cells. Finally, we investigated whether the NPE-iPSC-derived insulin-producing cells could normalize hyperglycemia in transplanted diabetic mice. The NOD-iPSCs showed typical embryonic stem cell-like characteristics such as expression of markers for pluripotency, in vitro differentiation, teratoma formation, and generation of chimeric mice. We developed a method for stepwise differentiation of NOD-iPSCs into insulin-producing cells, and found that NPE-iPSCs differentiate more readily into insulin-producing cells. The differentiated NPE-iPSCs expressed diverse pancreatic beta cell markers and released insulin in response to glucose and KCl stimulation. Transplantation of the differentiated NPE-iPSCs into diabetic mice resulted in kidney engraftment. The engrafted cells responded to glucose by secreting insulin, thereby normalizing blood glucose levels. We propose that NOD-iPSCs will provide a useful tool for investigating genetic susceptibility to autoimmune diseases and generating a cellular interaction model of T1D, paving the way for the potential application of patient-derived iPSCs in autologous beta cell transplantation for treating diabetes.

Induced pluripotent stem cell research: a revolutionary approach to face the challenges in drug screening.

Discovery of induced pluripotent stem (iPS) cells in 2006 provided a new path for cell transplantation and drug screening. The iPS cells are stem cells derived from somatic cells that have been genetically reprogrammed into a pluripotent state. Similar to embryonic stem (ES) cells, iPS cells are capable of differentiating into three germ layers, eliminating some of the hurdles in ES cell technology. Further progress and advances in iPS cell technology, from viral to non-viral systems and from integrating to non-integrating approaches of foreign genes into the host genome, have enhanced the existing technology, making it more feasible for clinical applications. In particular, advances in iPS cell technology should enable autologous transplantation and more efficient drug discovery. Cell transplantation may lead to improved treatments for various diseases, including neurological, endocrine, and hepatic diseases. In studies on drug discovery, iPS cells generated from patient-derived somatic cells could be differentiated into specific cells expressing specific phenotypes, which could then be used as disease models. Thus, iPS cells can be helpful in understanding the mechanisms of disease progression and in cell-based efficient drug screening. Here, we summarize the history and progress of iPS cell technology, provide support for the growing interest in iPS cell applications with emphasis on practical uses in cell-based drug screening, and discuss some challenges faced in the use of this technology.

The generation of iPS cells using non-viral magnetic nanoparticle based transfection.

Induced pluripotent stem (iPS) cells have been generated from various somatic cells; however, a major restriction of the technology is the use of potentially harmful genome-integrating viral DNAs. Here, without a viral vector, we generated iPS cells from fibroblasts using a non-viral magnetic nanoparticle-based transfection method that employs biodegradable cationic polymer PEI-coated super paramagnetic nanoparticles (NP). Our findings support the possible use of transient expression of iPS genes in somatic cells by magnet-based nanofection for efficient generation of iPS cells. Results of dynamic light scattering (DLS) analysis and TEM analyses demonstrated efficient conjugation of NP with iPS genes. After transfection, nanofection-mediated iPS cells showed ES cell-like characteristics, including expression of endogenous pluripotency genes, differentiation of three germ layer lineages, and formation of teratomas. Our results demonstrate that magnet-based nanofection may provide a safe method for use in generation of virus-free and exogenous DNA-free iPS cells, which will be crucial for future clinical applications in the field of regenerative medicine.