Cystoid Macular Edema following Treatment with Nanoparticle Albumin-Bound Paclitaxel and Atezolizumab for Metastatic Breast Cancer

Cystoid macular edema (CME) is a rare side effect associated with chemotherapy. Although the development of CME has been reported to occur following treatment with taxane drugs, such as nanoparticle albumin-bound paclitaxel (Nab-PTX), the occurrence of CME with treatment with atezolizumab has not yet been reported. Here, we report the case of a 49-year-old woman who developed CME 19 months into chemotherapy with Nab-PTX and atezolizumab. Improvement was not achieved with steroid injections into the Tenon’s sac, and Nab-PTX and atezolizumab treatments were ceased. One month later, there was subjective improvement in her symptoms. Although many reports have indicated that cessation of chemotherapy has successfully improved CME, a specific treatment for CME has not yet been established. Clinicians should be aware of the ophthalmologic side effects and offer immediate treatment if symptoms develop

A framework for leveraging multi-rater data in brain decoding analysis: Prediction of evaluation drawn from population data using sparse probit regression

Introduction: Using stimuli (e.g., images, videos, products) labeled by a number of raters has recently become common in brain decoding analysis, where subjective emotion/impression for stimuli felt by the population is predicted from brain responses. However, there remains no established method for constructing a decoder using such multi-rater labels. In previous studies, the variability across multiple raters was assumed to reflect noise, and the answers for a binary judgment were averaged across raters. Then, the average scores (i.e., empirical probabilities) for individual stimuli were predicted using standard regression methods. While this procedure is a simple and popular approach, it is not appropriate because most of these regression methods ignore the fact that probability is the variable to be predicted. To address this in an appropriate manner, we present a new framework in this study.Methods: Here, we assume that individual answers for a binary judgment about a stimulus follow a Bernoulli distribution. We then predicted the probability of positive answers from the human functional magnetic resonance imaging (fMRI) response to the stimulus using probit regression. We also introduced sparse regularization into probit regression (sparse probit regression) to prevent overfitting.Results: In both simulation and real fMRI data analysis, sparse probit regression more accurately predicted the probabilities of positive answers for individual stimuli than probit regression without sparse regularization, indicating that sparseness results in better decoding performance. Sparse probit regression also outperformed linear regression using the same type of sparse regularization, reflecting the advantage of our appropriate treatment of probability.Discussion & Conclusion: Our results suggest that our framework using sparse probit regression provides an effective method for the population prediction of emotion/impression assessment based on brain activity.第5回ヒト脳イメージング研究

eSPRESSO: topological clustering of single-cell transcriptomics data to reveal informative genes for spatio–temporal architectures of cells

[Background] Bioinformatics capability to analyze spatio–temporal dynamics of gene expression is essential in understanding animal development. Animal cells are spatially organized as functional tissues where cellular gene expression data contain information that governs morphogenesis during the developmental process. Although several computational tissue reconstruction methods using transcriptomics data have been proposed, those methods have been ineffective in arranging cells in their correct positions in tissues or organs unless spatial information is explicitly provided. [Results] This study demonstrates stochastic self-organizing map clustering with Markov chain Monte Carlo calculations for optimizing informative genes effectively reconstruct any spatio–temporal topology of cells from their transcriptome profiles with only a coarse topological guideline. The method, eSPRESSO (enhanced SPatial REconstruction by Stochastic Self-Organizing Map), provides a powerful in silico spatio–temporal tissue reconstruction capability, as confirmed by using human embryonic heart and mouse embryo, brain, embryonic heart, and liver lobule with generally high reproducibility (average max. accuracy = 92.0%), while revealing topologically informative genes, or spatial discriminator genes. Furthermore, eSPRESSO was used for temporal analysis of human pancreatic organoids to infer rational developmental trajectories with several candidate ‘temporal’ discriminator genes responsible for various cell type differentiations. [Conclusions] eSPRESSO provides a novel strategy for analyzing mechanisms underlying the spatio–temporal formation of cellular organizations

Clinical Significance of Measuring Urinary Sulfated Bile Acids in Adult Patients with Hepatobiliary Diseases.

Background/Aims: Measurement of urinary sulfated bile acid (USBA) level is a simple urine test that reflects the degree of cholestasis in newborns. The aim of this study was to clarify the clinical significances of this test for liver diseases in adults. Methodology: We examined the relationship between USBA level in a urine sample by enzymatic assay and clinical parameters and postoperative complications in 27 patients with hepatobiliary diseases who underwent surgical procedures between 2002 and 2007. Results: Mean USBA in all patients before surgery was 39.8 ± 64.0 μmol/L (median value was 6.6). USBA level was increased in patients with cholestasis. USBA level was significantly correlated with serum total bile acid, total bilirubin level and serum hyaluronic acid level (r=0.850, 0.602 and 0.504, respectively) (p<0.05) and, furthermore, tended to be correlated with liver-uptake ratio (LHL15) by technetium-99m galactosyl human serum albumin (99mTc-GSA) scintigraphy and alanine aminotransferase level (r=-0.469 and 0.436, respectively but not significant). USBA level tended to be associated with postoperative uncontrolled ascites (p=0.050, not significant). Postoperative USBA level by day 7 was not changed; however, USBA level in patients with cholestatic diseases was decreased Conclusions: USBA is a simple and sensitive noninvasive test for cholestasis and also useful to predict postoperative uncontrolled ascites after hepatic resections

Prognostic impact of cancer stem cell-related markers in non-small cell lung cancer patients treated with induction chemoradiotherapy

The expression of several cancer stem cell (CSC)-related markers has been confirmed in non-small cell lung cancer (NSCLC). The aim of this study was to clarify the clinical role of CSC-related markers in patients with NSCLC undergoing induction chemoradiotherapy (CRT). Fifty patients with clinically diagnosed N2 or N3 NSCLC who underwent induction CRT with docetaxel and cisplatin concurrently with thoracic radiation followed by surgery were examined in this study. The expressions of CSC related markers (CD133, ALDH1, ABCG2, and Bmi-1) were examined using immunohistochemical staining in surgically resected specimens. Among the 50 patients, 20 patients had no residual tumor cells in the resected specimen when examined pathologically; CSC-related marker expressions and their correlation to survival were evaluated in the other 30 patients. After a median follow-up period of 72 months, the 5-year overall survival rate of the patients with CD133-positive or ALDH1-positive specimens was significantly worse than that of the patients with both CD133-negative and ALDH1-negative expressions (449% vs. 90.0%, respectively; P=0.042). In a multivariate analysis. CD133 and ALDH1 negativity (P=0.047) and cN2-3 single station metastasis (P=0.03) were significant independent prognostic factors for prolonged survival. The expressions of CSC-related markers after CRT were significantly correlated with a poor prognosis in patients with NSCLC. The development of therapeutic strategies including adjuvant therapy that take CSC-related marker positivity into consideration is likely to be a key factor in further improvements of the prognosis of patients undergoing trimodality therapy

A new technique for seeding chondrocytes onto solvent-preserved human meniscus using the chemokinetic effect of recombinant human bone morphogenetic protein-2

Many investigators are currently studying the use of decellularized tissue allografts from human cadavers as scaffolds onto which patients’ cells could be seeded, or as carriers for genetically engineered cells to aid cell transplantation. However, it is difficult to seed cells onto very dense regular connective tissue which has few interstitial spaces. Here, we discuss the development of a chemotactic cell seeding technique using solvent-preserved human meniscus. A chemokinetic response to recombinant human bone morphogenetic protein-2 (rhBMP-2) was observed in a monolayer culture of primary chondrocytes derived from femoral epiphyseal cartilage of 2-day-old rats. The rhBMP-2 significantly increased their migration upto 10 ng/ml in a dose-dependent manner. When tested with solvent-preserved human meniscus as a scaffold, which has few interstitial spaces, rhBMP-2 was able to induce chondrocytes to migrate into the meniscus. After a 3-week incubation, newly-formed cartilaginous extracellular matrix was synthesized by migrated chondrocytes throughout the meniscus, down to a depth of 3 mm. These findings demonstrate that rhBMP-2 may be a natural chemokinetic factor in vivo, which induces migration of proliferative chondrocytes into the narrow interfibrous spaces. Our results suggest a potential application of rhBMP-2 for the designed distribution of chondrocytes into a scaffold to be used for tissue engineering