Dissociable Neural Mechanisms for Human Inference Processing Predicted by Static and Contextual Language Models.

Language models (LMs) continue to reveal non-trivial relations to human language performance and the underlying neurophysiology. Recent research has characterized how word embeddings from an LM can be used to generate integrated discourse representations in order to perform inference on events. The current research investigates how such event knowledge may be coded in distinct manners in different classes of LMs and how this maps onto different forms of human inference processing. To do so, we investigate inference on events using two well-documented human experimental protocols from Metusalem et al. (2012) and McKoon and Ratcliff (1986), compared with two protocols for simpler semantic processing. Interestingly, this reveals a dissociation in the relation between local semantics versus event-inference depending on the LM. In a series of experiments, we observed that for the static LMs (word2vec/GloVe), there was a clear dissociation in the relation between semantics and inference for the two inference tasks. In contrast, for the contextual LMs (BERT/RoBERTa), we observed a correlation between semantic and inference processing for both inference tasks. The experimental results suggest that inference as measured by Metusalem and McKoon rely on dissociable processes. While the static models are able to perform Metusalem inference, only the contextual models succeed in McKoon inference. Interestingly, these dissociable processes may be linked to well-characterized automatic versus strategic inference processes in the psychological literature. This allows us to make predictions about dissociable neurophysiological markers that should be found during human inference processing with these tasks.

Subclinical myocardial damage after anthracycline chemotherapy in Japanese patients with breast cancer.

BACKGROUND: Data on the incidence, timing, and severity of myocardial damage after anthracycline-based chemotherapy (AC) in Japanese patients with breast cancer are limited. METHOD: We evaluated cancer therapy-related cardiac dysfunction (CTRCD) in Japanese women with breast cancer (n = 51) after the first AC according to the definitions of the 2022 European Society of Cardiology onco-cardiology guideline, including assessment of high-sensitivity troponin I (TnI) and B-type natriuretic peptide (BNP) levels. RESULTS: CTRCD was detected in 67 % of the patients (3.9 %, 7.8 %, 9.8 %, 43 %, 37 %, 22 %, 20 %, and 9.8 % of patients at 1 week and 1, 2, 3, 6, 9, 12, and 15 months post-AC, respectively) without significant left ventricular ejection fraction reduction (<50 %) and heart failure. Elevated TnI levels (>26 pg/mL) were found in 43 % of patients, and elevated BNP levels (≥35 pg/mL) were observed in 22 % of patients during the follow-up period. CONCLUSIONS: Approximately two-thirds of the Japanese patients in this study experienced CTRCD, which was frequently observed at 3 or 6 months post-AC. However, all patients with CTRCD were diagnosed with mild asymptomatic CTRCD. Although, these patients were diagnosed with mild asymptomatic CTRCD, careful long-term follow-up will be required.

Opinion attribution improves motivation to exchange subjective opinions with humanoid robots.

In recent years, the development of robots that can engage in non-task-oriented dialogue with people, such as chat, has received increasing attention. This study aims to clarify the factors that improve the user's willingness to talk with robots in non-task oriented dialogues (e.g., chat). A previous study reported that exchanging subjective opinions makes such dialogue enjoyable and enthusiastic. In some cases, however, the robot's subjective opinions are not realistic, i.e., the user believes the robot does not have opinions, thus we cannot attribute the opinion to the robot. For example, if a robot says that alcohol tastes good, it may be difficult to imagine the robot having such an opinion. In this case, the user's motivation to exchange opinions may decrease. In this study, we hypothesize that regardless of the type of robot, opinion attribution affects the user's motivation to exchange opinions with humanoid robots. We examined the effect by preparing various opinions of two kinds of humanoid robots. The experimental result suggests that not only the users' interest in the topic but also the attribution of the subjective opinions to them influence their motivation to exchange opinions. Another analysis revealed that the android significantly increased the motivation when they are interested in the topic and do not attribute opinions, while the small robot significantly increased it when not interested and attributed opinions. In situations where there are opinions that cannot be attributed to humanoid robots, the result that androids are more motivating when users have the interests even if opinions are not attributed can indicate the usefulness of androids.

Exploring the eating experience of a pneumatically-driven edible robot: Perception, taste, and texture.

This study investigated the effects of animated food consumption on human psychology. We developed a movable, edible robot and evaluated the participants' impressions induced by the visualization of its movements and eating of the robot. Although several types of edible robots have been developed, to the best of our knowledge, the psychological effects associated with the eating of a robot have not been investigated. We developed a pneumatically driven edible robot using gelatin and sugar. We examined its perceived appearance and the participants' impressions when it was eaten. In the robot-eating experiment, we evaluated two conditions: one in which the robot was moved and one in which it was stationary. Our results showed that participants perceived the moving robot differently from the stationary robot, leading to varied perceptions, when consuming it. Additionally, we observed a difference in perceived texture when the robot was bitten and chewed under the two conditions. These findings provide valuable insights into the practical applications of edible robots in various contexts, such as the medical field and culinary entertainment.

Self-administered questionnaires enhance emotion estimation of individuals with autism spectrum disorders in a robotic interview setting.

Background: Robots offer many unique opportunities for helping individuals with autism spectrum disorders (ASD). Determining the optimal motion of robots when interacting with individuals with ASD is important for achieving more natural human-robot interactions and for exploiting the full potential of robotic interventions. Most prior studies have used supervised machine learning (ML) of user behavioral data to enable robot perception of affective states (i.e., arousal and valence) and engagement. It has previously been suggested that including personal demographic information in the identification of individuals with ASD is important for developing an automated system to perceive individual affective states and engagement. In this study, we hypothesized that assessing self-administered questionnaire data would contribute to the development of an automated estimation of the affective state and engagement when individuals with ASD are interviewed by an Android robot, which will be linked to implementing long-term interventions and maintaining the motivation of participants. Methods: Participants sat across a table from an android robot that played the role of the interviewer. Each participant underwent a mock job interview. Twenty-five participants with ASD (males 22, females 3, average chronological age = 22.8, average IQ = 94.04) completed the experiment. We collected multimodal data (i.e., audio, motion, gaze, and self-administered questionnaire data) to train a model to correctly classify the state of individuals with ASD when interviewed by an android robot. We demonstrated the technical feasibility of using ML to enable robot perception of affect and engagement of individuals with ASD based on multimodal data. Results: For arousal and engagement, the area under the curve (AUC) values of the model estimates and expert coding were relatively high. Overall, the AUC values of arousal, valence, and engagement were improved by including self-administered questionnaire data in the classification. Discussion: These findings support the hypothesis that assessing self-administered questionnaire data contributes to the development of an automated estimation of an individual's affective state and engagement. Given the efficacy of including self-administered questionnaire data, future studies should confirm the effectiveness of such long-term intervention with a robot to maintain participants' motivation based on the proposed method of emotion estimation.

Therapeutic potential of robots for people who stutter: a preliminary study.

Introduction: Growing anecdotal evidence suggests the feasibility of robotic intervention for people who suffer from disorders related to state anxiety. Few studies have been conducted on utilizing robots for persons who stutter (PWS). The present study examines the feasibility of using a robot for speech therapy for PWS. Methods: We prepared four settings (i.e., interviews with unfamiliar persons, interviews with unfamiliar communication robots, reading sentences aloud with a tandem robot that can utter the same words as a user by repeating the user's voice after a short delay, and reading sentences aloud while being alone). We assessed the potential of the robots as both interlocutors and practice partners in training with delayed auditory feedback (DAF) for PWS. Moreover, we assessed the relationship between the trait of stuttering and the participants' affinity to the robots. Results: Eleven PWS participated in the study. Eight (72.7%) participants had fewer stuttering-related psychological symptoms when they communicated with robots than when they communicated with humans. Spearman's rank correlation analysis revealed that there was a significant negative correlation between the Modified Erickson Communication Attitude scale (S-24) and the difference between the scores for stuttering-related psychological symptoms pertaining to the communication robot and humans (p < 0.01). Six participants (54.5%) had fewer stuttering-related psychological symptoms when they read aloud with the tandem robot than when they read aloud alone. There were significant positive correlations between S-24 and the differences between the scores for stuttering-related psychological symptoms when reading aloud with the tandem robot and those when reading aloud alone (p < 0.01). Discussion: The communication robot and tandem utterance robot can sometimes be burdensome, although both robots were always easier to talk to for PWS in this preliminary study. The participants with positive speech-related attitudes were more inclined to decrease stuttering-related psychological symptoms when communicating with CommU than when communicating with humans. The participants whose speech-related attitudes were negative were more inclined to show a decrease in stuttering-related psychological symptoms when reading aloud with the tandem robot. Further studies are needed to provide more detailed information.

Comprehensive prognostic prediction of metastatic breast cancer treated with eribulin using blood­based parameters and ratio.

Eribulin is widely used to treat metastatic breast cancer (BC). Higher neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) are associated with higher mortality in several cancer types. However, the association between BC prognosis and peripheral immune status remains controversial. In the present study, the relative effects of NLR and PLR on survival in patients with metastatic BC were quantified and their clinical prognostic value was evaluated. This retrospective study included 156 patients with metastatic BC who received eribulin monotherapy at Saitama Medical University International Medical Center. Clinicopathological features were examined (peripheral blood findings and biochemical liver and kidney function test results) and univariate and multivariate analyses were conducted of the overall survival (OS). The 156 patients treated with eribulin had a median follow-up duration of 18.3 months. Before eribulin treatment, patients with absolute lymphocyte counts (ALC) >1,500/µl, NLR <3.0, and PLR <150 had significantly longer OS than those with lower ALC, and higher NLR and PLR (median OS, 25.5 vs. 15.5 months; P<0.01; 20.3 vs. 13.6 months, P<0.01; and 29.2 vs. 14.8 months; P<0.001, respectively). Patients with anemia [hemoglobin (Hb) <10 g/dl] or liver dysfunction [albumin-bilirubin (ALBI) grade 2/3] had significantly shorter OS than those without (P<0.001, respectively). Multivariate analysis revealed low ALBI grade (P<0.001), high Hb (P<0.01) and low PLR (P<0.05) as independent factors of longer OS after eribulin administration. Low PLR, anemia and liver dysfunction might be factors associated with prolonged OS in patients with metastatic BC on eribulin therapy, which could be clinically useful, as their evaluation requires neither new equipment nor invasive testing.

Changes in cell-free DNA after short-term palbociclib and fulvestrant treatment for advanced or metastatic hormone receptor-positive and human epidermal growth factor 2-negative breast cancer.

PURPOSE: Here, we investigated the potential predictive and elucidating efficacy of cell-free DNA (cfDNA) changes on clinical outcomes and biological effects, respectively, after short-term palbociclib and fulvestrant treatment for patients with hormone receptor (HR)-positive and human epidermal growth factor 2 (HER2)-negative advanced or metastatic breast cancer (ABC). METHODS: In this secondary analysis of the Japan Breast Cancer Research Group-M07 (FUTURE) trial, blood cfDNA was obtained before palbociclib treatment and on day 15 of cycle one (28-day cycle). Target enrichment was performed using next-generation sequencing; progression-free survival (PFS) was compared based on cfDNA changes between baseline and day 15 of cycle one after combination therapy. RESULTS: Fifty-six patients (112 paired blood samples) were examined. The median follow-up time was 8.9 months. PIK3CA (30.4%, 17/56), FOXA1 (30.4%, 17/56), and ESR1 (28.6%, 16/56) were most frequently mutated at baseline. The number of mutated genes was significantly decreased on day 15 compared with that at baseline (paired t test: P value = 0.025). No significant difference was observed in PFS (decrease group, 7.9 m vs the others, 9.3 m; log-rank P value = 0.75; hazard ratio, 1.13; 95% confidence interval, 0.53-2.41). Among patients without previous aromatase inhibitor treatment (n = 15), three (20%) had ESR1 mutations after progression to fulvestrant. CONCLUSION: No significant association was observed between changes in mutated genes after short-term palbociclib and fulvestrant treatment and disease progression; a significant reduction in cfDNA mutation level was observed on day 15 of cycle one. Clinical meanings of cfDNA should be investigated in the future trials.

Comparison of cisplatin-based versus standard preoperative chemotherapy in patients with operable triple-negative breast cancer: propensity score matching and inverse probability of treatment weighting analysis.

PURPOSE: The efficacy of carboplatin is non-equivalent to that of cisplatin (CDDP) for various tumor types in curative settings. However, the role of CDDP in operable triple-negative breast cancer (TNBC) patients remains unknown. We conducted a multicenter observational study to examine the effects of CDDP added to preoperative chemotherapy in patients with TNBC. METHODS: This retrospective study consecutively included previously untreated patients with stage I-III TNBC treated with preoperative chemotherapy with or without CDDP. The primary endpoint was distant disease-free survival (DDFS). Propensity score matching (PSM) and inverse probability of treatment weighting (IPTW) were used to minimize confounding biases in comparisons between the two groups. RESULTS: A total of 138 patients were enrolled in the study. Of these, 52 were in the CDDP group and 86 in the non-CDDP group. DDFS was significantly better in the CDDP group than in the non-CDDP group (unadjusted hazard ratio (HR) 0.127 and p < 0.001, PSM HR 0.141 and p < 0.003, IPTW HR 0.123 and p = < 0.001). Furthermore, among the patients with residual cancer burden (RCB) class II/III, DDFS was better in the CDDP group than in the non-CDDP group (unadjusted HR 0.192 and p = 0.013, PSM HR 0.237 and p = 0.051, IPTW HR 0.124 and p = 0.059). CONCLUSION: Our study showed that CDDP-containing regimens achieved favorable prognoses in patients with operable TNBC, especially for the RCB class II/III population. Confirmative studies are warranted to elucidate the role of CDDP in TNBC treatment.

Development of depression assessment tools using humanoid robots -Can tele-operated robots talk with depressive persons like humans?

BACKGROUND: Depression is a common mental disorder and causes significant social loss. Early intervention for depression is important. Nonetheless, depressed patients tend to conceal their symptoms from others based on shame and stigma, thus hesitate to visit psychiatrists especially during early phase. We hypothesize that application of humanoid robots would be a novel solution. Depressed patients may feel more comfortable talking with such robots than humans. METHODS: We recruited 13 patients with major depressive disorder (MDD) and 27 healthy volunteers as controls. Participants took both tele-operated humanoid robot and human interviews to evaluate severity of depression using the Hamilton Depression Rating Scale (HDRS). In addition, participants completed a self-administered questionnaire asking about their impressions of the robot interview. RESULTS: Confidence interval and t-test analysis have revealed that the HDRS scores are equally reliable between robot and human interviews. No significant differences were observed between the two interviews regarding "nervousness about the interview" and "hesitancy to talk about depressed moods and suicidal ideation." Compared to human interviews, robot interviews yielded significantly lower scores on shame-related factors especially among patients with MDD. LIMITATION: Small sample size, and the evaluator is male only. CONCLUSIONS: This is the first report to show the reliability of tele-operated humanoid robot interviews for assessment of depression. Robot interviews are potentially equally reliable as human interviews. Robot interviews are suggested to be more appropriate in assessing shame-related suppressed emotions and hidden thoughts of depressed patients in clinical practice, which may reduce the stigma associated with depression.

Social robot for older adults with cognitive decline: a preliminary trial.

The number of older adults living alone is rapidly increasing. Loneliness in older adults not only degrade their quality of life but also causes troubles such as heavy burden on the medical staff, especially when cognitive decline is present. Social robots could be used in several ways to reduce such problems. As a first step towards this goal, we introduced conversation robots into the homes of older adults with cognitive decline to evaluate the robot's availability and acceptance during several months. The study involved two steps, one for evaluating the robustness of the proposed robotic system, and the second one to examine the long-term acceptance of social robots by older adults with cognitive decline living alone. Our data shows that after several weeks of human-robot interaction, the participants continued to use the robot and successfully integrated them into their lives. These results open the possibility of further research involving how sustained interaction can be achieved, as well as which factors contributed to the acceptance of the robot.

Effect of having and switching multiple avatars on the operator's right to talk and receive social support.

People with communication difficulties encounter several challenges in their daily online interactions, such as a limited right to talk (RoT), insufficient social support (SS), and a low sense of being attended to (SoBA). Computer-mediated technologies are limited in addressing such problems owing to their limited capacity in transferring verbal and nonverbal cues between users. In this study, to address the limited RoT, low SS, and low SoBA challenges, we proposed a robotic video conference system with two teleoperated robot avatars. The proposed system was compared with another robotic video conference system that adopts only one teleoperated robot avatar. In the field experiment, 37 participants took part in two discussion sessions using each system type, where RoT, SS, and SoBA were adopted as the measured indices. The proposed system significantly increased the users' RoT and SS compared with other robotic video conference systems. This study contributes to the literature by demonstrating the effect exerted by the type of robotic video conference adopted on users' feelings about RoT, SS, and SoBA.

Clinicopathological prognostic characteristics and long­term outcomes of patients with breast cancer and collagen disorder in comparison to those without collagen disorder.

Collagen disorders are chronic autoimmune diseases with a complex clinical course; however, the risk of breast cancer in patients with collagen disorders remains unclear. The present study aimed to investigate long-term outcomes in women with breast cancer and collagen disorders. A total of 25 patients with breast cancer and collagen disorders who were treated between January 2004 and December 2011 were included. The clinicopathological factors, treatment, recurrence-free survival (RFS) and overall survival (OS) were reviewed. The mean age was 56.4±12.6 years, and 14, eight and three patients had cancer of clinical stages I, II and III, respectively. Regarding comorbid collagen disorders, 11 patients had rheumatoid arthritis, four had systemic lupus erythematosus, four had polymyositis/dermatomyositis, two had mixed connective tissue disease, two had Sjogren's syndrome, one had scleroderma and one had adult-onset Still's disease. The expression statuses of hormone receptors (HR) and human epidermal growth factor receptor 2 (HER2) were HR(+), HER2(+) and HR(-)HER2(-) in 20 (80.0%), four (16.0%) and four (16.0%) patients, respectively. A total of 22 (84.0%) patients received steroids or immunosuppressive drugs for collagen disorders. The collagen disorder group had a higher mean Ki-67 labeling index than the control group (41.1 vs. 20.8%; P=0.007). After median observation periods of 103 and 114 months, the RFS and OS rates were lower in the collagen group than in the control group (64.5 and 80.7% vs. 85.3 and 94.3%, respectively; P<0.01). Patients with breast cancer and collagen disorders had relatively high Ki-67 expression, and relatively low RFS and OS rates. Thorough follow-up is necessary for patients with breast cancer who also have collagen disorders and high Ki-67 values.

Human-like interactions prompt people to take a robot's perspective.

The increasing need for human-robot interaction requires not only robots to understand how humans think, but also humans to understand robots. Interestingly, little attention has been given to how humans interpret robots' behaviors. In this study, we adopted a social mental rotation task and investigated whether socially engaging behaviors could influence how people take a robot's perspectives. In a real lab, two android robots with neutral appearance sat opposite each other by a table with conflicting perspectives. Before the participant started the experiment, one of the robots behaved more interactively than the other by showing more socially engaging behaviors. Then the participant was required to identify rotated normal or mirrored digits presented inbetween the two robots. Results revealed a significant interactive effect between the digits type (normal; mirrored) and robot type (interactive; noninteractive). When digits were oriented to the interactive robot, we found a larger RT difference between normal and mirrored digits. In general, these findings suggested that robots' interactive behaviors could influence how people spontaneously consider the robot's perspective. Future studies may further consider how interactive behaviors can shape human-robot relationships and facilitate human-robot interaction.

A risk-based subgroup analysis of the effect of adjuvant S-1 in estrogen receptor-positive, HER2-negative early breast cancer.

PURPOSE: The Phase III POTENT trial demonstrated the efficacy of adding S-1 to adjuvant endocrine therapy for estrogen receptor-positive, HER2-negative early breast cancer. We investigated the efficacy of S-1 across different recurrence risk subgroups. METHODS: This was a post-hoc exploratory analysis of the POTENT trial. Patients in the endocrine-therapy-only arm were divided into three groups based on composite risk values calculated from multiple prognostic factors. The effects of S-1 were estimated using the Cox model in each risk group. The treatment effects of S-1 in patients meeting the eligibility criteria of the monarchE trial were also estimated. RESULTS: A total of 1,897 patients were divided into three groups: group 1 (≤ lower quartile of the composite values) (N = 677), group 2 (interquartile range) (N = 767), and group 3 (> upper quartile) (N = 453). The addition of S-1 to endocrine therapy resulted in 49% (HR: 0.51, 95% CI: 0.33-0.78) and 29% (HR: 0.71, 95% CI 0.49-1.02) reductions in invasive disease-free survival (iDFS) events in groups 2 and 3, respectively. We could not identify any benefit from the addition of S-1 in group 1. The addition of S-1 showed an improvement in iDFS in patients with one to three positive nodes meeting the monarchE cohort 1 criteria (N = 290) (HR: 0.47, 95% CI: 0.29-0.74). CONCLUSIONS: The benefit of adding adjuvant S-1 was particularly marked in group 2. Further investigations are warranted to explore the optimal usage of adjuvant S-1.

Social skills training using multiple humanoid robots for individuals with autism spectrum conditions.

Introduction: Social skills training (SST) is used to help individuals with autism spectrum conditions (ASC) better understand the perspectives of others and social interactions, develop empathy skills, and learn how to engage with others socially. However, many individuals with ASC cannot easily sustain high motivation and concentration during such an intervention when it is administered by humans. We developed a social skills training program using multiple humanoid robots (STUH), including an android robot, that aimed to enable individuals with ASC to become familiar with the perspectives of others and improve their sociability and empathy skills. The objective of the present study was to investigate the effectiveness of STUH for these individuals. Methods: In STUH, we prepared 50 social exercises that consisted of conversations and behavioral interactions between an android robot and a simple humanoid robot. We prepared another humanoid robot that featured a cartoon-like and mechanical design, which played the role of host. In the first half-session of STUH, participants worked on the exercise from the perspective of an outsider. In the second half-session of STUH, they simulated experience by using robots as their avatars. The intervention associated with STUH was conducted for five days in total. We conducted an analysis of variance (ANOVA) featuring the intervention time point as the independent variable to examine changes in each score on the sociability index items. Results: In total, 14 individuals with ASC participated in the study. The results of multiple comparison tests using the Bonferroni method indicated that all sociability index items improved between preintervention and follow-up. Our program enabled the participants to become familiar with the perspectives of others and improve their sociability. Discussion: Given the promising results of this study, future studies featuring long-term follow-up should be conducted to draw definitive conclusions about the efficacy of our training system.

A new group-based online job interview training program using computer graphics robots for individuals with autism spectrum disorders.

Introduction: Job interviews are a major barrier to employment for individuals with autism spectrum disorders (ASD). During the coronavirus pandemic, establishing online job interview training at home was indispensable. However, many hurdles prevent individuals with ASD from concentrating on online job interview training. To facilitate the acquisition of interview skills from home for individuals with ASD, we developed a group interview training program with a virtual conferencing system (GIT-VICS Program) that uses computer graphics (CG) robots. Methods: This study investigated the feasibility of the GIT-VICS Program in facilitating skill acquisition for face-to-face job interviews in pre-post measures. In the GIT-VICS Program, five participants were grouped and played the roles of interviewees (1), interviewers (2), and human resources (2). They alternately practiced each role in GIT-VICS Program sessions conducted over 8 or 9 days over three consecutive weeks. Before and after the GIT-VICS Program, the participants underwent a mock face-to-face job interview with two experienced human interviewers (MFH) to evaluate its effect. Results: Fourteen participants completed the trial procedures without experiencing any technological challenges or distress that would have led to the termination of the session. The GIT-VICS Program improved their job interview skills (verbal competence, nonverbal competence, and interview performance). Discussion: Given the promising results of this study and to draw clear conclusions about the efficacy of CG robots for mock online job interview training, future studies adding appropriate guidance for manner of job interview by experts are needed.

Influence of collaborative customer service by service robots and clerks in bakery stores.

In recent years, various service robots have been deployed in stores as recommendation systems. Previous studies have sought to increase the influence of these robots by enhancing their social acceptance and trust. However, when such service robots recommend a product to customers in real environments, the effect on the customers is influenced not only by the robot itself, but also by the social influence of the surrounding people such as store clerks. Therefore, leveraging the social influence of the clerks may increase the influence of the robots on the customers. Hence, we compared the influence of robots with and without collaborative customer service between the robots and clerks in two bakery stores. The experimental results showed that collaborative customer service increased the purchase rate of the recommended bread and improved the impressions of the robot and store experience of the customers. Because the results also showed that the workload required for the clerks to collaborate with the robot was not high, this study suggests that all stores with service robots may demonstrate high effectiveness in introducing collaborative customer service.

Vimentin-positive invasive breast carcinoma of no special type: A breast carcinoma with lethal biological characteristics.

Vimentin is a stable mesenchymal immunohistochemical marker and is widely recognized as a major marker of mesenchymal tumors. The purpose of the present study was to investigate if the vimentin expression status might serve as a significant predictor of outcomes in patients with invasive breast carcinoma of no special type (IBC-NST) and to investigate, by comprehensive RNA sequencing analyses, the mechanisms involved in the heightened malignant potential of vimentin-positive IBC-NSTs. This study, conducted using the data of 855 patients with IBC-NST, clearly identified vimentin expression status as a very important independent biological parameter for accurately predicting the outcomes in patients with IBC-NST. RNA sequence analyses clearly demonstrated significant upregulation of coding RNAs known to be closely associated with cell proliferation or cellular senescence, and significant downregulation of coding RNAs known to be closely associated with transmembrane transport in vimentin-positive IBC-NSTs. We conclude that vimentin-positive IBC-NSTs show heightened malignant biological characteristics, possibly attributable to the upregulation of RNAs closely associated with proliferative activity and cellular senescence, and downregulation of RNAs closely associated with transmembrane transport in IBC-NSTs.

Clinical and genetic features of cystic fibrosis in Japan.

Cystic fibrosis (CF) is an autosomal recessive disease caused by pathogenic variants in CF transmembrane conductance regulator (CFTR). While CF is the most common hereditary disease in Caucasians, it is rare in East Asia. In the present study, we have examined clinical features and the spectrum of CFTR variants of CF patients in Japan. Clinical data of 132 CF patients were obtained from the national epidemiological survey since 1994 and CF registry. From 2007 to 2022, 46 patients with definite CF were analyzed for CFTR variants. All exons, their boundaries, and part of promoter region of CFTR were sequenced and the presence of large deletion and duplications were examined by multiplex ligation-dependent probe amplification. CF patients in Japan were found to have chronic sinopulmonary disease (85.6%), exocrine pancreatic insufficiency (66.7%), meconium ileus (35.6%), electrolyte imbalance (21.2%), CF-associated liver disease (14.4%), and CF-related diabetes (6.1%). The median survival age was 25.0 years. The mean BMI percentile was 30.3%ile in definite CF patients aged < 18 years whose CFTR genotypes were known. In 70 CF alleles of East Asia/Japan origin, CFTR-dele16-17a-17b was detected in 24 alleles, the other variants were novel or very rare, and no pathogenic variants were detected in 8 alleles. In 22 CF alleles of Europe origin, F508del was detected in 11 alleles. In summary, clinical phenotype of Japanese CF patients is similar to European patients, but the prognosis is worse. The spectrum of CFTR variants in Japanese CF alleles is entirely different from that in European CF alleles.