Stakeholder-in-the-Loop Fair Decisions: A Framework to Design Decision Support Systems in Public and Private Organizations

Due to the opacity of machine learning technology, there is a need for explainability and fairness in the decision support systems used in public or private organizations. Although the criteria for appropriate explanations and fair decisions change depending on the values of those who are affected by the decisions, there is a lack of discussion framework to consider the appropriate outputs for each stakeholder. In this paper, we propose a discussion framework that we call "stakeholder-in-the-loop fair decisions." This is proposed to consider the requirements for appropriate explanations and fair decisions. We identified four stakeholders that need to be considered to design accountable decision support systems and discussed how to consider the appropriate outputs for each stakeholder by referring to our works. By clarifying the characteristics of specific stakeholders in each application domain and integrating the stakeholders' values into outputs that all stakeholders agree upon, decision support systems can be designed as systems that ensure accountable decision makings

Mammalian MicroRNAs: Post-Transcriptional Gene Regulation in RNA Virus Infection and Therapeutic Applications

RNA silencing mediated by microRNAs (miRNAs) is a recently discovered gene regulatory mechanism involved in various aspects of biology, such as development, cell differentiation and proliferation, and innate immunity against viral infections. miRNAs, which are a class of small (21–25 nucleotides) RNAs, target messenger RNA (mRNA) through incomplete base-pairing with their target sequences resulting in mRNA degradation or translational repression. Although studies of miRNAs have led to numerous sensational discoveries in biology, many fundamental questions about their expression and function still remain. In this review, we discuss the dynamics of the mammalian miRNA machinery and the biological function of miRNAs, focusing on RNA viruses and the various therapeutic applications of miRNAs against viral infections

Computational Analysis of Dancing Cells

Collective cell migration is observed during morphogenesis, angiogenesis, and wound healing, and this type of cell migration also contributes to efficient metastasis in some kinds of cancers. Because collectively migrating cells are much better organized than a random assemblage of individual cells, there seems to be a kind of order in migrating clusters. Extensive research has identified a large number of molecules involved in collective cell migration, and these factors have been analyzed using dramatic advances in imaging technology. To date, however, it remains unclear how myriad cells are integrated as a single unit. Recently, we observed unbalanced collective cell migrations that can be likened to either precision dancing or awa-odori, Japanese traditional dancing similar to the style at Rio Carnival, caused by the impairment of the conformational change of JRAB/MICAL-L2. This review begins with a brief history of image-based computational analyses on cell migration, explains why quantitative analysis of the stylization of collective cell behavior is difficult, and finally introduces our recent work on JRAB/MICAL-L2 as a successful example of the multidisciplinary approach combining cell biology, live imaging, and computational biology. In combination, these methods have enabled quantitative evaluations of the “dancing style” of collective cell migration

Numerical Simulation on Sand Accumulation behind Artificial Reefs and Enhancement of Windblown Sand to Hinterland

Salients were formed in the lee of two artificial reefs (submerged breakwaters) constructed on Kimigahama Beach in Chiba Prefecture, Japan, owing to the wave-sheltering effect of the reefs, and then, a significant amount of fine sand was transported inland from the salients by wind action. In this study, not only shoreline changes after the installation of the two artificial reefs but also beach changes caused by windblown sand were predicted using a model, in which the BG model (a model for predicting three-dimensional beach changes due to waves based on Bagnold’s concept) is combined with a cellular automaton method. Reproduction calculation was carried out on the basis of field data. Beach changes after the artificial reefs were removed were also predicted and the effect of beach nourishment was investigated. It was concluded that landward sand transport by wind is accelerated when wave-sheltering structures such as an artificial reef are constructed on a coast composed of fine sand, and such an effect can be successfully predicted by using the present model

Exploring the Impact of Lay User Feedback for Improving AI Fairness

Fairness in AI is a growing concern for high-stakes decision making. Engaging stakeholders, especially lay users, in fair AI development is promising yet overlooked. Recent efforts explore enabling lay users to provide AI fairness-related feedback, but there is still a lack of understanding of how to integrate users' feedback into an AI model and the impacts of doing so. To bridge this gap, we collected feedback from 58 lay users on the fairness of a XGBoost model trained on the Home Credit dataset, and conducted offline experiments to investigate the effects of retraining models on accuracy, and individual and group fairness. Our work contributes baseline results of integrating user fairness feedback in XGBoost, and a dataset and code framework to bootstrap research in engaging stakeholders in AI fairness. Our discussion highlights the challenges of employing user feedback in AI fairness and points the way to a future application area of interactive machine learning

Methotrexate for the treatment of juvenile idiopathic arthritis: process to approval for JIA indication in Japan

Methotrexate (MTX), the primary treatment for the articular-type juvenile idiopathic arthritis (JIA), is effective and brings about radiological improvement. Patient compliance is good, and it is recognized that its known side effects, namely, disruption of liver function and induction of pulmonary lesions, are unlikely to be severe at the low MTX doses that are administered. In Japan, MTX was granted approval in 1999 by the then Ministry of Health and Welfare specifically for treating rheumatoid arthritis in adult patients, allowing it be generally used in medical institutions for patients having National Health Insurance. However, in the pediatric field, its use outside the indications has so far been unavoidable, and has been left to the discretion of the physician. Finally, at the present conference, expansion of the indications of MTX for JIA was approved in Japan. It is noteworthy that this expansion of indications was achieved without requiring clinical trials on children sponsored by the pharmaceutical company: it was achieved rather by collecting necessary information through ongoing efforts (including collection and analysis of information about approval status in foreign countries, adequate evidence from the literature, implementation of a clinical use survey in Japan, etc.). It also merits attention that the maximum dose (10 mg/m2) was set on the basis of pharmacokinetic data from children, rather than relying on the dosing method and dose for adults

Tim23–Tim50 pair coordinates functions of translocators and motor proteins in mitochondrial protein import

Mitochondrial protein traffic requires coordinated operation of protein translocator complexes in the mitochondrial membrane. The TIM23 complex translocates and inserts proteins into the mitochondrial inner membrane. Here we analyze the intermembrane space (IMS) domains of Tim23 and Tim50, which are essential subunits of the TIM23 complex, in these functions. We find that interactions of Tim23 and Tim50 in the IMS facilitate transfer of precursor proteins from the TOM40 complex, a general protein translocator in the outer membrane, to the TIM23 complex. Tim23–Tim50 interactions also facilitate a late step of protein translocation across the inner membrane by promoting motor functions of mitochondrial Hsp70 in the matrix. Therefore, the Tim23–Tim50 pair coordinates the actions of the TOM40 and TIM23 complexes together with motor proteins for mitochondrial protein import

The first Japanese MDPL case

Mandibular hypoplasia, deafness, progeroid features and lipodystrophy (MDPL) syndrome is a rare autosomal dominant disorder caused by heterozygous POLD1 mutations. To date, 13 patients affected by POLD1 mutation-caused MDPL have been described. We report a clinically undiagnosed 11-year-old male who noted joint contractures at 6 years of age. Targeted exome sequencing identified a known POLD1 mutation [NM_002691.3:c.1812_1814del, p.(Ser605del)] that diagnosed him as the first Japanese/East Asian MDPL case

SOX2 suppresses CDKN1A to sustain growth of lung squamous cell carcinoma.

Since the SOX2 amplification was identified in lung squamous cell carcinoma (lung SCC), SOX2 transcriptional downstream targets have been actively investigated; however, such targets are often cell line specific. Here, in order to identify highly consensus SOX2 downstream genes in lung SCC cells, we used RNA-seq data from 178 lung SCC specimens (containing tumor and tumor-associated cells) and analyzed the correlation between SOX2 and previously-reported SOX2-controlled genes in lung SCC. In addition, we used another RNA-seq dataset from 105 non-small cell lung cancer cell lines (NSCLC; including 4 lung SCC cell lines) and again analyzed the correlation between SOX2 and the reported SOX2-controlled genes in the NSCLC cell lines (no tumor-associated cells). We combined the two analyses and identified genes commonly correlated with SOX2 in both datasets. Among the 99 genes reported as SOX2 downstream and/or correlated genes, we found 4 negatively-correlated (e.g., CDKN1A) and 11 positively-correlated genes with SOX2. We used biological studies to demonstrate that CDKN1A was suppressed by SOX2 in lung SCC cells. G1 cell cycle arrest induced by SOX2 siRNA was rescued by CDKN1A siRNA. These results indicate that the tumorigenic effect of SOX2 in lung SCC cells is mediated in part by suppression of CDKN1A

Fluorescent Reporter Signals, EGFP, and DsRed, Encoded in HIV-1 Facilitate the Detection of Productively Infected Cells and Cell-Associated Viral Replication Levels

Flow cytometric analysis is a reliable and convenient method for investigating molecules at the single cell level. Previously, recombinant human immunodeficiency virus type 1 (HIV-1) strains were constructed that express a fluorescent reporter, either enhanced green fluorescent protein, or DsRed, which allow the monitoring of HIV-1-infected cells by flow cytometry. The present study further investigated the potential of these recombinant viruses in terms of whether the HIV-1 fluorescent reporters would be helpful in evaluating viral replication based on fluorescence intensity. When primary CD4+ T cells were infected with recombinant viruses, the fluorescent reporter intensity measured by flow cytometry was associated with the level of CD4 downmodulation and Gag p24 expression in infected cells. Interestingly, some HIV-1-infected cells, in which CD4 was only moderately downmodulated, were reporter-positive but Gag p24-negative. Furthermore, when the activation status of primary CD4+ T cells was modulated by T cell receptor-mediated stimulation, we confirmed the preferential viral production upon strong stimulation and showed that the intensity of the fluorescent reporter within a proportion of HIV-1-infected cells was correlated with the viral replication level. These findings indicate that a fluorescent reporter encoded within HIV-1 is useful for the sensitive detection of productively infected cells at different stages of infection and for evaluating cell-associated viral replication at the single cell level