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In this study, we investigated how the temporal properties of the preparation phase for upper limb movements are affected by the reaching direction and distance. Twelve right-handed participants performed three motor tasks: two types of reaching movements and one finger-lifting movement. The reaching movements were performed from the home position to 15 target locations (five directions and three distances) as quickly and precisely as possible under two conditions: pre-cueing the target to allocate the sufficient time for the motor-planning process before movement initiation, and no-cuing. The finger lifting movement was performed by lifting the index finger (from the home position) upward in the air as quickly as possible. The reaction time (RT), movement time (MT), and kinematics of the index finger were obtained for each condition. In addition, differential RTs (DRT) were calculated by subtracting the RT for no-cue lifting from that for no-cue reaching, thereby implicitly representing the time required for the motor-planning process for reaching movements. The results indicated the anisotropy of the DRTs being larger in the forward and left-forward directions than that in the right-forward direction, and larger in the forward direction than that in the right direction for the middle distance. It is suggested that the temporal costs of the motor-planning process depend on the movement direction and distance. In the kinematic analysis, the MTs showed the anisotropy being the largest in the left-forward among all directions. Meanwhile, the time from peak velocity to terminate the movement (TFPV) was significantly longer in the left-forward direction when no-cueing the target than when pre-cueing. These results suggest that reaching movement is refined during the online-control process to accomplish the intended performance if a reaching movement under the no-cue condition is initiated before building sufficient motor planning, especially in the direction requiring large temporal costs. It is likely that humans achieve their intended movements by allocating the temporal costs required before and after movement initiation according to the difficulty of motor control which varies with the direction and distance., Competing Interests: Declaration of competing interest None., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Objective: To investigate the impact of different tracer modifications on the imaging of cancer metabolism, focusing on the comparison of fluorescent glucose-analog tracers (2-NBDG and 2-DG-750) and the radiolabeled tracer 18F-FDG in both in-vitro and in-vivo settings., Methods: We conducted an in-vitro comparative study using four cancer cell lines, each with unique glucose uptake characteristics. The study involved direct comparison of three tracers: 2-NBDG, 2-DG-750 and 18F-FDG, examining their internalization behaviors, metabolic functionality and localization effects in cancer metabolism imaging., Results: The study revealed that each tracer exhibits distinct internalization behaviors correlated with imaging label size and type. 18F-FDG showed the highest uptake efficiency. Fluorescent molecules were found to accumulate in tumors primarily due to hydrophobic interactions and possible aggregation, indicating inefficiency in metabolism and suitability for imaging metabolic phenomena when compared to radiolabeled biomolecules., Conclusion: Our findings demonstrate that despite certain impracticalities, nuclear imaging, particularly using radiolabeled biomolecules like 18F-FDG, offers significant potential for accurately capturing biological phenomena. This is crucial for future advancements in both clinical and research settings. The study emphasizes the limitations of fluorescent molecules in imaging metabolic activities due to their inefficient metabolism and aggregation tendencies., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Importance: Immune checkpoint inhibitor (ICI) plus chemotherapy combination treatment (ICI-chemotherapy) is now a standard treatment for non-small cell lung cancer (NSCLC) without targetable oncogene alterations, but there are few data on ICI-chemotherapy for patients 75 years and older., Objective: To inform the choice of first-line drugs in clinical practice and assess the safety and efficacy of ICI-chemotherapy combination treatment in older adult patients with previously untreated advanced NSCLC., Design, Setting, and Participants: This retrospective cohort study included 58 centers in Japan. The cohort consisted of patients 75 years and older with clinical stage IIIB, IIIC, IV, postoperative or radiotherapy recurrent NSCLC. Patients started first-line systemic therapy between December 2018 and March 2021. Those receiving first-line molecular targeted drugs were excluded. The data were analyzed from February 2022 to October 2022., Exposures: Systemic therapy., Main Outcomes and Measures: The main outcomes were overall survival (OS), progression-free survival (PFS), and safety., Results: A total of 1245 patients (median [range] age, 78 [75-95] years; 967 [78%] male) with NSCLC were included in the cohort. Programmed death ligand-1 (PD-L1) expression of less than 1% occurred in 268 tumors (22%); 1% to 49% in 387 tumors (31%); 50% and higher in 410 tumors (33%), and unknown expression in 180 tumors (14%). Median OS was 20.0 (95% CI, 17.1-23.6) months for the 354 patients receiving ICI-chemotherapy (28%); 19.8 (95% CI, 16.5-23.8) months for the 425 patients receiving ICI alone (34%); 12.8 (95% CI, 10.7-15.6) months for the 311 patients receiving platinum-doublet chemotherapy (25%); and 9.5 (95% CI, 7.4-13.4) months for the 155 patients receiving single-agent chemotherapy (12%). After propensity score matching, no differences in OS and PFS were found between the patients receiving ICI-chemotherapy vs ICI alone. Each group consisted of 118 patients. For PD-L1 expression of 1% and higher the OS hazard ratio (HR) was 0.98 (95% CI, 0.67-1.42; P = .90), and the PFS HR was 0.92 (95% CI, 0.67-1.25; P = .59). Significance was also not reached when separately analyzed for lower or higher PD-L1 expression (1%-49% or ≥50%). However, grade 3 or higher immune-related adverse events occurred in 86 patients (24.3%) treated with ICI-chemotherapy and 76 (17.9%) with ICI alone (P = .03)., Conclusions and Relevance: In this study, ICI-chemotherapy combination treatment did not improve survival and increased the incidence of grade 3 and higher immune-related adverse events compared with ICI alone in patients 75 years and older. Based on these results, ICI alone may be recommended for older adult patients with PD-L1-positive NSCLC.

Human body movements are based on the intrinsic trade-off between speed and accuracy. Fitts's law (1954) shows that the time required for movement is represented by a simple logarithmic equation and is applicable to a variety of movements. However, few studies have determined the role of the direction in modulating the performance of upper limb movements and the effects of the interactions between direction and distance and between direction and target size. This study examined the variations in temporal properties of the speed-accuracy trade-off in arm-pointing movements that directly manipulate objects according to the direction, distance, and target size. Participants performed pointing movements to the targets with 3 different sizes presented at 15 locations (5 directions and 3 distances) on a horizontal plane. Movement time (MT) for each trial in each condition was obtained. Subsequently, Mackenzie's model (1992), MT = a + b log2(D/W +1), where D and W represent the distance and width of the target, respectively, was fitted. The slope factor b, a fitted parameter in the equation, was calculated and evaluated according to the changes in the direction, distance, and target size. The results showed that MTs exhibited anisotropy in the hemifield, being the smallest in the right-forward direction. Additionally, the slope factor b, as a function of distance, was smaller in the rightward direction than in the forward and left-forward directions. These results suggest that the degree of difficulty of upper limb movements expands heterogeneously in various directions around the body., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Okuuchi et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

3D structured cells have great drug screening potential because they mimic in vivo tissues better than 2D cultured cells. In this study, multi-block copolymers composed of poly(2-methoxyethyl acrylate) (PMEA) and polyethylene glycol (PEG) are developed as a new kind of biocompatible polymers. PEG imparts non-cell adhesion while PMEA acts as an anchoring segment to prepare the polymer coating surface. The multi-block copolymers show higher stability in water than PMEA. A specific micro-sized swelling structure composed of a PEG chain is observed in the multi-block copolymer film in water. A single NIH3T3-3-4 spheroid is formed in 3 h on the surface of the multi-block copolymers with 8.4 wt% PEG. However, at a PEG content of 0.7 wt%, spheroid formed after 4 days. The adenosine triphosphate (ATP) activity of cells and the internal necrotic state of the spheroid change depending on PEG loading in the multi-block copolymers. As the formation rate of cell spheroid on low-PEG-ratio multi-block copolymers is slow, internal necrosis of cell spheroid is less likely to occur. Consequently, the cell spheroid formation rate by changing the PEG chain content in multi-block copolymers is successfully controlled. These unique surfaces are suggested to be useful for 3D cell culture., (© 2023 The Authors. Macromolecular Bioscience published by Wiley-VCH GmbH.)

Anaplastic lymphoma kinase ( ALK )-positive lung cancer is a rare cancer that occurs in approximately 5% of non-small-cell lung cancer (NSCLCs) patients. Despite the excellent efficacy of ALK-tyrosine kinase inhibitor in ALK -positive NSCLCs, most patients experience resistance. We conducted a phase II study to investigate the combination of alectinib with bevacizumab in ALK -positive NSCLC patients after failure of alectinib. In this study, ALK -positive nonsquamous NSCLC patients previously treated with alectinib received bevacizumab 15 mg/kg on day 1 every 3 weeks and alectinib 600 mg/day until disease progression. The primary endpoints were progression-free survival (PFS) and the safety of alectinib and bevacizumab. The secondary endpoints included overall survival (OS) and correlation of circulating tumor DNA and plasma proteins with PFS. Of the 12 patients treated, the median PFS was 3.1 months (95% CI 1.2-16.1), and the median OS was 24.1 months (95% CI 8.3-not estimable). The EML4-ALK fusion gene in circulating tumor DNA was significantly correlated with shorter PFS (1.2 months vs. 11.4 months, HR 5.2, p = 0.0153). Two patients experienced grade 3 adverse events; however, none of the patients required dose reduction. Although the primary endpoint was not met, alectinib combined with bevacizumab showed clinical efficacy in ALK -positive patients.

Background: Although the addition of immune checkpoint inhibitors (ICIs) to platinum-doublet chemotherapy has improved the efficacy of first-line therapy in extensive-disease small cell lung cancer (SCLC) patients, the best treatment option for patients with recurrent SCLC has not yet been determined. We conducted a retrospective study to evaluate the efficacy and safety of amrubicin (AMR) therapy after treatment with ICIs., Methods: We retrospectively assessed patients with recurrent SCLC who received AMR after chemoimmunotherapy at the Niigata Lung Cancer Treatment Group from August 2019 to February 2021., Results: This analysis included 30 patients. The median progression-free survival (PFS) and overall survival (OS) were 3.8 (95% CI: 2.7-4.2) and 10 (95% CI: 7.4-14.8) months, respectively. The median PFS and OS did not significantly differ between the sensitive and refractory groups [PFS; 3.1 (95% CI: 1.1-4.0) vs. 4.2 (95% CI: 2.3-4.8) months, P=0.1142, OS; 10.0 (95% CI: 5.2-14.8) vs. 10.4 (95% CI: 3.8-NE) months, P=0.5525]. The most common adverse event was grade ≥3 neutropenia, which occurred in 22 of 30 patients (73%), and 2 patients (7%) discontinued AMR due to adverse events., Conclusions: AMR after chemoimmunotherapy shows good clinical efficacy and safety in patients with recurrent SCLC., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://tlcr.amegroups.com/article/view/10.21037/tlcr-22-225/coif). Kohei Kushiro has received personal fees from Kyowa Kirin. SW has received personal fees from Eli Lilly, Novartis Pharma, Chugai Pharma, Boehringer Ingelheim, Ono Pharmaceutical, Taiho Pharmaceutical, Pfizer, AstraZeneca, Bristol-Myers, MSD and Daiichi Sankyo. AO has received personal fees from DAIICHI SANKYO COMPANY, Nipro Corporation and Chugai Pharma. SS has received personal fees from Chugai Pharma, Taiho Pharma, AstraZeneca and MSD. KN has received personal fees from AstraZeneca, Boehringer Ingelheim, MSD and Taiho Pharmaceutical. Yu Saida has received personal fees from Chugai Pharmaceutical, Nippon Kayaku and Ono Pharmaceutical. TO has received personal fees from Chugai Pharmaceutical, AstraZeneca, Taiho Pharmaceutical, Bristol-Myers and Kyowa Kirin. KI has received personal fees from AstraZeneca, Bristol-Myers, Ono Pharmaceutical, Novartis International AG, Kyowa Kirin, Chugai Pharma, Boehringer Ingelheim, Taiho Pharmaceutical and Daiichi Sankyo Company. Kenichi Koyama has received personal fees from Ono Pharma, Chugai Pharma and AstraZeneca. Toshiaki Kikuchi has received grants and personal fees from Chugai Pharma, Eli Lilly, Taiho Pharmaceutical, Ono Pharmaceutical, Shionogi, KYORIN Pharmaceutical, Boehringer Ingelheim, MSD, Daiichi Sankyo, AstraZeneca, TEIJIN PHARMA and Nobelpharma; personal fees from Janssen Pharmaceutical, Insmed, AN2 Therapeutics, Bristol-Myers, Taisho Toyama Pharmaceutical, Japan BCG Laboratory, Mylan N.V., Astellas Pharma, Pfizer, Novartis and Roche Diagnostics; and participates in Janssen Pharmaceutical’s data safety oversight or advisory committee. The other authors have no conflicts of interest to declare., (2022 Translational Lung Cancer Research. All rights reserved.)

With the development of measurement technology, data on the movements of actual games in various sports can be obtained and used for planning and evaluating the tactics and strategy. Defense in team sports is generally difficult to be evaluated because of the lack of statistical data. Conventional evaluation methods based on predictions of scores are considered unreliable because they predict rare events throughout the game. Besides, it is difficult to evaluate various plays leading up to a score. In this study, we propose a method to evaluate team defense from a comprehensive perspective related to team performance by predicting ball recovery and being attacked, which occur more frequently than goals, using player actions and positional data of all players and the ball. Using data from 45 soccer matches, we examined the relationship between the proposed index and team performance in actual matches and throughout a season. Results show that the proposed classifiers predicted the true events (mean F1 score > 0.483) better than the existing classifiers which were based on rare events or goals (mean F1 score < 0.201). Also, the proposed index had a moderate correlation with the long-term outcomes of the season (r = 0.397). These results suggest that the proposed index might be a more reliable indicator rather than winning or losing with the inclusion of accidental factors., Competing Interests: The authors have declared that no competing interests exist.

In the field of tissue engineering and biomaterials, controlling the surface properties and mechanical properties of scaffold materials is crucial and has attracted much attention. Here, two types of bilayer polymer brushes composed of a hydrophilic underlying layer and a cationic surface layer [made of poly(2-aminoethyl methacrylate)] with a thickness gradient were prepared by surface-initiated atom-transfer radical polymerization. To investigate the influence of the stiffness as a mechanical property of the polymer brush on cell behavior, the underlayer was prepared from either 2-methacryloyloxyethyl phosphorylcholine or oligo(ethylene glycol) methyl ether methacrylate, with the bilayers designated as gradient poly(2-methacryloyloxyethyl phosphorylcholine)- block -poly(2-aminoethyl methacrylate) [grad-p M bA] and gradient poly(oligo[ethylene glycol] methyl ether methacrylate)- block -poly(2-aminoethyl methacrylate) [grad-p EG bA], respectively. Characterization of these surfaces was performed by spectroscopic ellipsometry, X-ray reflectivity, and determination of the zeta potential, static contact angle, and force curve. These diblock copolymer brushes with a thickness gradient helped to distinguish the effects of the mechanical and surface properties of the brushes on cell behavior. The attachment and motility of L929 fibroblasts and epithelial MCF 10A cells on the fabricated brushes were then assessed. L929 cells had a round shape on the thin surface layer of grad-p M bA and spread well on thicker areas. In contrast, MCF 10A cells spread well in areas of any thickness of either grad-p M bA or grad-p EG bA. Single MCF 10A cells migrated randomly on grad-p M bA, whereas grouped cells started to climb up along the thickness gradient of grad-p M bA. In contrast, both single and grouped MCF 10A cells migrated randomly on grad-p EG bA. These thickness gradient diblock copolymer brushes are simple, reproducible, and reasonable platforms that can facilitate practical applications of biomaterials, for example, in tissue engineering and biomaterials.

Temperature is a key indicator of infection and disease, however, it is difficult to measure at a cellular level. Nanoparticles are applied to measure the cellular temperature, and enhancement of the stability and reliability of the signal and higher biocompatibility are demanded. We have developed fluorescent polymeric nanoparticles loaded with temperature-sensitive units (as rhodamine B) and internal reference units (as coumarin) for imaging and ratiometric sensing of the cellular temperature in the physiological range. The fluorescence signal of the nanoparticles was stable in the bio-environment and the ratiometric sensing strategy could overcome the concentration effect of nanoparticles. The nanoparticles were endocytosed by cells and partially presented in mitochondria. The fluorescence intensity ratio of rhodamine B and coumarin using nanoparticles showed good linear correlations in buffer solutions, cell suspensions, and imaging of living cells. Using the fluorescent polymeric nanoparticles, the change of temperature of cells during influenza virus infection could be individually monitored., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Objectives: Although immune checkpoint inhibitors (ICIs) have been shown to improve overall survival (OS) in advanced non-small-cell lung cancer (NSCLC) patients, ICIs sometimes cause various types of immune-related adverse events (irAEs), which lead to the interruption of ICI treatment. This study aims to evaluate the clinical significance of the continuation of ICIs in NSCLC patients with irAEs and to assess the safety and efficacy of the readministration of ICIs after their discontinuation due to irAEs., Methods: We retrospectively identified patients with advanced NSCLC who were treated with first- to third-line anti-programmed cell death-1 (PD-1) therapy from January 2016 through October 2017 at multiple institutions belonging to the Niigata Lung Cancer Treatment Group. Progression-free survival (PFS) and OS from the initiation of ICI treatment were analyzed in patients with and without irAEs, with and without ICI interruption, and with and without ICI readministration. A 6-week landmark analysis of PFS and OS was performed to minimize the lead-time bias associated with time-dependent factors., Results: Of 231 patients who received anti-PD-1 antibodies, 93 patients (40%) developed irAEs. Of 84 eligible patients with irAEs, 32 patients (14%) continued ICIs, and OS was significantly longer in patients who continued ICIs than that in patients who discontinued ICIs [not reached (95% CI: NE-NE) vs . not reached (95% CI: 22.4-NE); p = 0.025]. Of 52 patients who discontinued ICIs, 14 patients (6.1%) readministered ICIs, and OS in patients with ICI readministration was significantly longer than that in patients without ICI readministration [not reached (95% CI: NE-NE) vs . not reached (95% CI: 8.4-NE); p = 0.031]., Conclusion: The current study demonstrated that both the continuation and readministration of ICIs after irAE occurrence improved OS compared to the permanent interruption of ICIs in NSCLC patients with ICI-related irAEs., Competing Interests: SW reports grants and personal fees from AstraZeneca, personal fees from Chugai Pharma, personal fees from Ono Pharmaceutical, personal fees from Bristol-Myers, grants and personal fees from Boehringer Ingelheim, personal fees from Eli Lilly, personal fees from MSD, personal fees from Taiho Pharmaceutical, personal fees from Pfizer, personal fees from Novartis, and personal fees from Daiichi Sankyo outside the submitted work. TO reports personal fees from Boehringer Ingelheim, personal fees from MSD, personal fees from Eli Lilly, personal fees from AstraZeneca, personal fees from Chugai-pharm, and personal fees from Bristol-Myers Squibb outside the submitted work. SS reports personal fees from AstraZeneca, personal fees from Chugai Pharma, personal fees from Taiho Pharmaceutical, and personal fees from MSD outside the submitted work. KN reports personal fees from AstraZeneca, personal fees from Boehringer Ingelheim, personal fees from Taiho Pharmaceutical, and personal fees from MSD outside the submitted work. AI reports personal fees from AstraZeneca, personal fees from Chugai Pharma, personal fees from Bristol-Myers, personal fees from Boehringer Ingelheim, personal fees from Ono Pharmaceutical, personal fees from Taiho Pharmaceutical, personal fees from Novartis International AG, and personal fees from Daiichi Sankyo Company outside the submitted work. SH reports personal fees from GlaxoSmithKline Inc. outside the submitted work. TA reports personal fees from Eli Lilly Japan, personal fees from Chugai Pharmaceutical, personal fees from Taiho Pharmaceutical, personal fees from Ono Pharmaceutical, personal fees from Bristol-Myers Squibb, personal fees from AstraZeneca, and personal fees from Mylan outside the submitted work. SM reports personal fees from Chugai Pharmaceutical, personal fees from ONO Pharmaceutical, personal fees from AstraZeneca, personal fees from Eli Lilly, personal fees from MSD, personal fees from Boehringer Ingelheim, personal fees from Taiho Pharmaceutical, personal fees from Novartis, personal fees from Bristol-Myers Squibb, and personal fees from Kyowa Hakko Kirin outside the submitted work. HT reports grants and personal fees from Bristol-Myers Squibb, grants and personal fees from Eli Lilly, grants and personal fees from MSD, grants and personal fees from Taiho pharmaceutical, grants and personal fees from Pfizer, grants and personal fees from Novartis, grants and personal fees from Chugai pharmaceutical, grants and personal fees from Astra Zeneca, grants and personal fees from Boehringer Ingelheim, grants and personal fees from Ono pharmaceutical, and grants and personal fees from Merck outside the submitted work. MO reports personal fees from AstraZeneca, personal fees from Ono Pharmaceutical, personal fees from Bristol-Myers, personal fees from Boehringer Ingelheim, personal fees from MSD, and personal fees from Taiho Pharmaceutical outside the submitted work. NA reports personal fees from Meiji Seika Pharma, grants from MSD, and personal fees from MSD outside the submitted work. MH reports personal fees from Boehringer-Ingelheim Japan, personal fees from AstraZeneca, personal fees from Taiho Pharmaceutical, and personal fees from Daiichi Sankyo outside the submitted work. YO reports personal fees from Boehringer-Ingelheim Japan and personal fees from Meiji Seika Pharma outside the submitted work. TKo reports personal fees from AstraZeneca, Boehringer-Ingelheim, Sanofi Genzyme, Novartis, Daiichi Sankyo, Kyorin Pharmaceutical, and GlaxoSmithKline outside the submitted work. TKi reports grants and personal fees from Chugai Pharma, grants and personal fees from Boehringer Ingelheim, grants and personal fees from Eli Lilly, grants and personal fees from MSD K.K., personal fees from Astellas Pharma Inc., grants and personal fees from Taiho Pharmaceutical Co., Ltd., personal fees from Bristol-Myers Squibb Company, personal fees from Pfizer Japan Inc., grants and personal fees from Daiichi Sankyo Co., Ltd., personal fees from Taisho Toyama Pharmaceutical Co., Ltd., personal fees from Janssen Pharmaceutical K.K., personal fees from Japan BCG Laboratory, grants and personal fees from Ono Pharmaceutical Co., Ltd., personal fees from Novartis Pharma K.K., personal fees from Mylan N.V., grants and personal fees from AstraZeneca, personal fees from Roche Diagnostics K.K., grants and personal fees from Shionogi & Co., Ltd., grants from TEIJIN PHARMA Ltd., and grants from KYORIN Pharmaceutical Co., Ltd., outside the submitted work. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Fujisaki, Watanabe, Ota, Kushiro, Sato, Takahashi, Ohtsubo, Shoji, Nozaki, Ichikawa, Hokari, Kondo, Miyabayashi, Abe, Miura, Tanaka, Okajima, Terada, Matsumoto, Ishida, Iwashima, Sato, Yoshizawa, Aoki, Hayashi, Ohshima, Koya and Kikuchi.)

Background: Although immune checkpoint inhibitors (ICIs) are effective for advanced non-small cell lung cancer (NSCLC), ICIs may cause interstitial lung disease (ILD), which results in treatment discontinuation and is sometimes fatal. Despite the high incidence of ICI-related ILD, there are few cancer treatment options for patients. This study aimed to evaluate the safety and efficacy of subsequent systemic cancer therapy in NSCLC patients with ICI-related ILD., Methods: We retrospectively assessed NSCLC patients who received programmed cell death-1 (PD-1) inhibitors as first- to third-line therapy at participating institutions of the Niigata Lung Cancer Treatment Group from January 2016 to October 2017., Results: This analysis included 231 patients, 32 (14%) of whom developed ICI-related ILD. Of these patients, 16 (7%) received subsequent systemic cancer treatments. The median overall survival (OS) tended to be longer in the systemic cancer therapy group than in the no systemic cancer therapy group [22.2 months (95% CI: 1-NE) vs. 4.5 months (95% CI: 1-NE); P=0.067]. ICI-related ILD recurred in half of the patients who received systemic cancer therapy, and the median OS tended to be shorter in patients with recurrent ICI-related ILD [22.0 months (95% CI: 1-NE) vs. 7.0 months (95% CI: 1-NE); P=0.3154]., Conclusions: According to the current study, systemic cancer treatment is effective in patients with ICI-related ILD; however, its safety is uncertain because of the high risk of ICI-related ILD recurrence and poor survival outcome following ILD recurrence., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://dx.doi.org/10.21037/tlcr-21-198). Satoshi Watanabe has received grants and personal fees from AstraZeneca, personal fees from Chugai Pharma, personal fees from Ono Pharmaceutical, personal fees from Bristol-Myers, grants and personal fees from Boehringer Ingelheim, personal fees from Eli Lilly, personal fees from MSD, personal fees from Taiho Pharmaceutical, personal fees from Pfizer, personal fees from Novartis, personal fees from Daiichi Sankyo. Takeshi Ota has received personal fees from Boehringer Ingelheim, personal fees from MSD, personal fees from Eli Lilly, personal fees from AstraZeneca, personal fees from Chugai-pharm, personal fees from Bristol-Myers Squibb. Satoshi Shoji has received personal fees from AstraZeneca, personal fees from Chugai Pharma, personal fees from Taiho Pharmaceutical, personal fees from MSD. Koichiro Nozaki has received personal fees from AstraZeneca, personal fees from Boehringer Ingelheim, personal fees from Taiho Pharmaceutical, personal fees from MSD. Kosuke Ichikawa has received personal fees from AstraZeneca, personal fees from Chugai Pharma, personal fees from Bristol-Myers, personal fees from Boehringer Ingelheim, personal fees from Ono Pharmaceutical, personal fees from Taiho Pharmaceutical, personal fees from Novartis International AG, personal fees from Daiichi Sankyo Company. Satoshi Hokari has received personal fees from GlaxoSmithKline Inc. Masachika Hayashi has received personal fees from Boehringer-Ingelheim Japan, personal fees from AstraZeneca, personal fees from Taiho Pharmaceutical, personal fees from Daiichi Sankyo. Hiroyuki Ishikawa has received personal fees from AstraZeneca, personal fees from Bayer, personal fees from Daiichi Sankyo, grants from Eisai, personal fees from Fujifilm Toyama Chemical, grants from Guerbet Japan, grants and personal fees from Nihon Medi-Physics. Tetsuya Abe has received personal fees from Eli Lilly Japan, personal fees from Chugai Pharmaceutical, personal fees from Taiho Pharmaceutical, personal fees from Ono Pharmaceutical, personal fees from Bristol-Myers Squibb, personal fees from AstraZeneca, personal fees from Mylan. Satoru Miura has received personal fees from Chugai Pharmaceutical, personal fees from ONO Pharmaceutical, personal fees from AstraZeneca, personal fees from Eli Lilly, personal fees from MSD, personal fees from Boehringer Ingelheim, personal fees from Taiho Pharmaceutical, personal fees from Novartis, personal fees from Bristol-Myers Squibb, from Kyowa Hakko Kirin. Hiroshi Tanaka has received grants and personal fees from Bristol-Myers Squibb, grants and personal fees from Eli Lilly, grants and personal fees from MSD, grants and personal fees from Taiho pharmaceutical, grants and personal fees from Pfizer, grants and personal fees from Novartis, grants and personal fees from Chugai pharmaceutical, grants and personal fees from Astra Zeneca, grants and personal fees from Boehringer Ingelheim, grants and personal fees from Ono pharmaceutical, grants and personal fees from Merck. Masaaki Okajima has received personal fees from AstraZeneca, personal fees from Ono Pharmaceutical, personal fees from Bristol-Myers, personal fees from Boehringer Ingelheim, personal fees from MSD, personal fees from Taiho Pharmaceutical. Nobumasa Aoki has received personal fees from Meiji Seika Pharma, grants and personal fees from MSD. Yasuyoshi Ohshima has received personal fees from Boehringer-Ingelheim Japan, personal fees from Meiji seika pharma. Toshiyuki Koya has received personal fees from AstraZeneca, Boehringer-Ingelheim, Sanofi Genzyme, Novartis, Daiichi Sankyo, Kyorin Pharmaceutical and GlaxoSmithKline. Toshiaki Kikuchi has received grants and personal fees from Chugai Pharma, grants and personal fees from Boehringer Ingelheim, grants and personal fees from Eli Lilly, grants and personal fees from MSD K.K., personal fees from Astellas Pharma Inc., grants and personal fees from Taiho Pharmaceutical CO., Ltd., personal fees from Bristol-Myers Squibb Company, personal fees from Pfizer Japan Inc., grants and personal fees from Daiichi Sankyo CO., Ltd., personal fees from Taisho Toyama Pharmaceutical Co., Ltd., personal fees from Janssen Pharmaceutical K.K., personal fees from Japan BCG Laboratory, grants and personal fees from Ono Pharmaceutical Co., Ltd., personal fees from Novartis Pharma K.K., personal fees from Mylan N.V., grants and personal fees from AstraZeneca, personal fees from Roche Diagnostics K.K., grants and personal fees from Shionogi & Co., Ltd., grants from TEIJIN PHARMA Ltd., grants from KYORIN Pharmaceutical Co., Ltd. The other authors have no conflicts of interest to declare., (2021 Translational Lung Cancer Research. All rights reserved.)

Concurrent body movements have been shown to enhance the accuracy of spatial judgment, but it remains unclear whether they also contribute to perceptual estimates of gravitational space not involving body movements. To address this, we evaluated the effects of static or dynamic arm movements during prolonged whole-body tilt on the subsequent perceptual estimates of visual or postural vertical. In Experiment 1, participants were asked to continuously perform static or dynamic arm movements during prolonged tilt, and we assessed their effects on the prolonged tilt-induced shifts of subjective visual vertical (SVV) at a tilted position (during-tilt session) or near upright (post-tilt session). In Experiment 2, we evaluated how static or dynamic arm movements during prolonged tilt subsequently affected the subjective postural vertical (SPV). In Experiment 1, we observed that the SVV was significantly shifted toward the direction of prolonged tilt in both sessions. The SVV shifts decreased when performing dynamic arm movements in the during-tilt session, but not in the post-tilt session. In Experiment 2, as well as SVV, the SPV was shifted toward the direction of prolonged tilt, but it was not significantly attenuated by the performance of static or dynamic arm movements. The results of the during-tilt session suggest that the central nervous system utilizes additional information generated by dynamic body movements for perceptual estimates of visual vertical., Competing Interests: The authors have declared that no competing interests exist.

In recent years, many types of micro-engineered platform have been fabricated to investigate the influences of surrounding microenvironments on cell migration. Previous researches demonstrated that microgroove-based topographies can influence cell motilities of normal and cancerous cells differently. In this study, the microgroove wall angle was altered from obtuse to acute angles and the resulting differences in the responses of normal and cancer cells were investigated to explore the geometrical characteristics that can efficiently distinguish normal and cancer cells. Interestingly, different trends in cell motilities of normal and cancer cells were observed as the wall angles were varied between 60-120°, and in particular, invasive cancer cells exhibited a unique, oscillatory migratory behavior. Results from the immunostaining of cell mechanotransduction components suggested that this difference stemmed from directional extensions and adhesion behaviors of each cell type. In addition, the specific behaviors of invasive cancer cells were found to be dependent on the myosin II activity, and modulating the activity could revert cancerous behaviors to normal ones. These novel findings on the interactions of acute angle walls and cancer cell migration provide a new perspective on cancer metastasis and additional strategies via microstructure geometries for the manipulations of cell behaviors in microscale biodevices.

To internally estimate gravitational direction and body orientation, the central nervous system considers several sensory inputs from the periphery and prior knowledge of gravity. It is hypothesized that the modulation of visual inputs, supplying indirect information of gravity, affects the prior knowledge established internally by other sensory inputs from vestibular and somatosensory systems, leading to the alteration of perceived body orientation relative to gravity. In order to test the hypothesis, we examined the effect of presenting a visual motion stimulus during a whole-body static tilt on the subsequent evaluation of the perceived postural vertical. Fifteen subjects watched a target moving along the body longitudinal axis directing from head to feet with constant downward acceleration (CA condition) or constant velocity (CV condition), or they did not receive any visual stimulation (NV condition) during the whole-body static tilt. Subsequently, the direction of the subjective postural vertical (SPV) was evaluated. The result showed that the SPV in the CA condition was significantly tilted toward the direction of the preceding tilt compared to that in the NV condition while those in the CV and NV conditions were not significantly different. The present result suggests that dynamic visual motion along body longitudinal axis with downward acceleration can modulate prior knowledge of gravity, and in turn this affects the perception of body verticality., (Copyright © 2019 Elsevier B.V. All rights reserved.)

On-site multiplex biosensors for innate immunity antibodies are ideal tools for monitoring health status of individuals against various diseases. This study introduces a novel antibody immunoassay testing platform incorporating microfiber-based arrays of antigens to capture specific antibodies. The fabrication and setup of the device revolved around electrospun polystyrene (ESPS) microfibers that act as three-dimensional membrane filters, capable of rapid and multifold analyte capture. In particular, the ESPS microfibers were patterned through localized oxygen plasma to create hydrophilic zones that facilitate fluid flows and immobilizations of antigens. The bulk of this robust antibody immunoassay platform could be installed into a compact syringe-driven cassette device, which could perform multiplex antibody immunoassay for antibodies specifically against Middle East respiratory syndrome coronavirus (MERS-CoV) with rapid preparation amounting to a total of 5 min, as well as high sensitivity and specificity for the MERS-CoV down to 200 μg/mL., (© 2019 The Authors.)

The present study utilized induced acceleration analysis to clarify the contributions of muscular and gravitational torques to the kinematics of vertical pointing movements performed by the upper limb. The study included eight healthy men with a mean age of 25 years. The experiment was divided into three blocks with ten trials in each, comprising five upward and five downward, randomly executed movements. The movements were recorded by a motion capture system and were subsequently analyzed. During the deceleration phase of the upward movement and the acceleration phase of the downward movement, the angular acceleration induced by gravitational torque contributed more to the generation of net induced angular acceleration than the angular acceleration induced by muscular torque. In addition, the difference between the net induced angular acceleration profiles during the upward and downward movements was mainly attributable to the difference between the respective angular acceleration profiles induced by muscular torque. These findings suggest that the central nervous system considers the gravitational effect on the upper limb in a phase-specific manner and accordingly generates a torque-derived kinematic difference with respect to the movement direction.

The involvement of intercellular interactions in various biological events indicates the importance of studying cell-cell interactions using fluid model surfaces. Here, we propose a fluid surface composed of a self-assembled monolayer (SAM) and poly(ethylene glycol)-conjugated phospholipid (PEG-lipid) derivatives, which can be an alternative to supported lipid membranes. The modification of SAM surfaces with PEG-lipids carrying functional peptides resulted in the formation of the fluid surfaces with different mobility, which was quantitatively determined by quartz crystal microbalance with dissipation (QCM-D) and fluorescence recovery after photobleaching (FRAP). Different types of fluid surfaces with calculated diffusion coefficients between 0.9 ± 0.25 and 0.16 ± 0.03 μm 2 /sec for PEG-lipids derivatives were fabricated, onto which arginylglycylaspartate (RGD) peptides were immobilized for cell adhesion, and compared to solid surfaces with the same surface density of RGD peptides. The fluid surfaces revealed that cell adhesions of epithelial cells (MCF-10 A) and human umbilical vein endothelial cells (HUVEC) could not be established on the surfaces with higher fluidity, while cells could adhere onto surfaces with lower fluidity, where the lateral diffusion of PEG-lipids was approximately 20 times lower, and solid surfaces. Interestingly, cells that adhered onto the surface with lower fluidity proliferated at a normal rate while maintaining their round morphology, which was a different shape from that observed on solid surfaces. Thus, the scaffold fluidity greatly influenced cell adhesion behaviors, demonstrating that it is an important parameter for designing novel biomimetic scaffolds for biomedical applications., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Gastric proton pump (H + ,K + -ATPase) which is responsible for H + secretion of gastric acid (HCl) in gastric parietal cells is the major therapeutic target for treatment of acid-related diseases. H + ,K + -ATPase consists of two subunits, a catalytic α-subunit (αHK) and a glycosylated β-subunit (βHK). N-glycosylation of βHK is essential for trafficking and stability of αHK in apical membrane of gastric parietal cells. Terminal sialic acid residues on sugar chains have an important role in various cellular functions. Recently, we succeeded in visualizing the sialylation and desialylation dynamics of βHK using a fluorescence bioimaging nanoprobe consisting of biocompatible polymers conjugated with lectins for detecting sialic acid. In H + ,K + -ATPase-expressing cell lines, rat gastric mucosa, and primary culture of rat gastric parietal cells, fluorescence imaging of sialic acid with the nanoprobe showed that sialylation of βHK is regulated by intragastric pH and that inhibition of gastric acid secretion induces desialylation of βHK. In biochemical and pharmacological studies, we revealed that enzyme activity of αHK is negatively regulated by desialylation of βHK. Our studies uncovered a novel negative-feedback mechanism of H + ,K + -ATPase in which sialic acids of βHK positively regulates H + ,K + -ATPase activity, and acidic pH decreases the pump activity by cleaving sialic acids of βHK. In this topic, we introduce the overview of our research using the bioimaging nanoprobe.

In our day-to-day life, we can accurately reach for an object in our gravitational environment without any effort. This can be achieved even when the body is tilted relative to gravity. This is accomplished by the central nervous system (CNS) compensation for gravitational forces and torque acting on the upper limbs, based on the magnitude of body tilt. The present study investigated how performance of upper limb movements was influenced by the alteration of body orientation relative to gravity. We observed the spatial trajectory of the index finger while the upper limb reached for a memorized target with the body tilted in roll plane. Results showed that the terminal location of the fingertip shifted toward the direction of body tilt away from the actual target location. The subsequent experiment examined if the perceived direction of the body longitudinal axis shifted relative to the true direction in roll plane. The results showed that the perceived direction of the body longitudinal axis shifted toward the direction of the body tilt, which correlated with the shift of the terminal location in the first experiment. These results suggest that the dissociation between the egocentric and gravitational coordinates induced by whole-body tilt leads to systematic shifts of the egocentric reference frame for action, which in turn influences the motor performance of goal-directed upper limb movements.

During metastasis, cancer cells are exposed to various three-dimensional microstructures within the body, but the relationship between cancer migration and three-dimensional geometry remain largely unclear. Here, such geometric effects on cancerous cells were investigated by characterizing the motility of various cancer cell types on microgroove-based topographies made of polydimethylsiloxane (PDMS), with particular emphasis on distinguishing cancerous and non-cancerous epithelial cells, as well as understanding the underlying mechanism behind such differences. The 90-degree walls enhanced motility for all cell lines, but the degrees of enhancements were less pronounced for the cancerous cells. Interestingly, while the non-cancerous epithelial cell types conformed to the three-dimensional geometrical cues and migrated along the walls, the cancerous cell types exhibited a unique behavior of climbing upright walls, and this was associated with the inability to form stable, polarized actin cytoskeleton along the walls of the microgrooves. Furthermore, when non-cancerous epithelial cell lines were altered to different levels of polarization capabilities and cancer malignancy or treated with inhibitory drugs, their three-dimensional geometry-dependent motility approached those of cancerous cell lines. Overall, the results suggest that cancerous cells may gradually lose geometrical recognition with increasing cancer malignancy, allowing them to roam freely ignoring three-dimensional geometrical cues during metastasis.

The conformation and dynamics of the unfolded state of ubiquitin doubly labeled regiospecifically with Alexa488 and Alexa647 were investigated using single-molecule fluorescence spectroscopy. The line confocal fluorescence detection system combined with the rapid sample flow enabled the characterization of unfolded proteins at the improved structural and temporal resolutions compared to the conventional single-molecule methods. In the initial stage of the current investigation, however, the single-molecule Förster resonance energy transfer (sm-FRET) data of the labeled ubiquitin were flawed by artifacts caused by the adsorption of samples to the surfaces of the fused-silica flow chip and the sample delivery system. The covalent coating of 2-methacryloyloxyethyl phosphorylcholine polymer to the flow chip surface was found to suppress the artifacts. The sm-FRET measurements based on the coated flow chip demonstrated that the histogram of the sm-FRET efficiencies of ubiquitin at the native condition were narrowly distributed, which is comparable to the probability density function (PDF) expected from the shot noise, demonstrating the structural homogeneity of the native state. In contrast, the histogram of the sm-FRET efficiencies of the unfolded ubiquitin obtained at a time resolution of 100 μs was distributed significantly more broadly than the PDF expected from the shot noise, demonstrating the heterogeneity of the unfolded state conformation. The variety of the sm-FRET efficiencies of the unfolded state remained even after evaluating the moving average of traces with a window size of 1 ms, suggesting that conformational averaging of the heterogeneous conformations mostly occurs in the time domain slower than 1 ms. Local structural heterogeneity around the labeled fluorophores was inferred as the cause of the structural heterogeneity. The heterogeneity and slow dynamics revealed by the line confocal tracking of sm-FRET might be common properties of the unfolded proteins.

Hydrogels are promising materials for biomedical applications, where timely degradation is often preferred. In the conventional design, however, the cleavage of polymer networks essentially causes considerable morphological changes (i.e., degradation-induced swelling), triggering various medical complications. Herein, we report a rational strategy to suppress the degradation-induced swelling based on the synthetic control of the polymer-solvent interaction parameter (χ) of constituent polymer networks. The resultant hydrogels with an optimal χ parameter (χ37 °C ≈0.53; non-osmostic hydrogels) displayed the capability to retain their original shape and degrade without generating significant swelling pressure under physiological conditions (Π37 °C <1 kPa). This concept of the safely degradable non-osmotic hydrogel is theoretically universal, and can be exploited for other types of synthetic hydrogels in various settings., (© 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Viral infections affect millions around the world, sometimes leading to severe consequences or even epidemics. Understanding the molecular dynamics during viral infections would provide crucial information for preventing or stopping the progress of infections. However, the current methods often involve the disruption of the infected cells or expensive and time-consuming procedures. In this study, fluorescent polymeric nanoparticles were fabricated and used as bioimaging nanoprobes that can monitor the progression of influenza viral infection through the changes in the expression levels of sialic acids expressed on the cell membrane. The nanoparticles were composed of a biocompatible monomer to prevent non-specific interactions, a hydrophobic monomer to form the core, a fluorescent monomer, and a protein-binding monomer to conjugate lectin, which binds sialic acids. It was shown that these lectin-tagged nanoparticles that specifically target sialic acids could track the changes in the expression levels of sialic acids caused by influenza viral infections in human lung epithelial cells. There was a sudden drop in the levels of sialic acid at the initial onset of virus infection (t = 0~1 h) and at approximately 4~5 h post-infection. The latter drop correlated with the production of viral proteins that was confirmed using traditional techniques. Thus, the accuracy, the rapidity and the efficacy of the nanoprobes were demonstrated. Such molecular bioimaging tools, which allow easy-handling and in situ monitoring, would be useful to directly observe and decipher the viral infection mechanisms.

In the present study, we investigated the kinematics of object-transport movement in a downward direction using a precision grip, to elucidate how the central nervous system (CNS) takes into account object weight when making the movement, even when participants are unable to recognize the weight until they grasp the object. We found that the kinematics during transport movement were significantly changed by the object weight, even when the weight was unrecognized visually, suggesting that the CNS controls object-transport movement in a downward direction according to object weight, regardless of the visual recognizability of the weight.

The gastric proton pump (H(+),K(+)-ATPase) consists of a catalytic α-subunit (αHK) and a glycosylated β-subunit (βHK). βHK glycosylation is essential for the apical trafficking and stability of αHK in gastric parietal cells. Here, we report the properties of sialic acids at the termini of the oligosaccharide chains of βHK. Sialylation of βHK was found in LLC-PK1 cells stably expressing αHK and βHK by staining of the cells with lectin-tagged fluorescent polymeric nanoparticles. This sialylation was also confirmed by biochemical studies using sialic acid-binding lectin beads and an anti-βHK antibody. The sialic acids of βHK are cleaved enzymatically by neuraminidase (sialidase) and nonenzymatically by an acidic solution (pH5). Interestingly, the enzymatic activity of H(+),K(+)-ATPase was significantly decreased by cleavage of the sialic acids of βHK. In contrast, βHK was not sialylated in the gastric tubulovesicles prepared from the stomach of fed hogs. The H(+),K(+)-ATPase activity in these tubulovesicles was not significantly altered by neuraminidase. Importantly, the sialylation of βHK was observed in the gastric samples prepared from the stomach of famotidine (a histamine H2 receptor antagonist)-treated rats, but not histamine (an acid secretagogue)-treated rats. The enzymatic activity of H(+),K(+)-ATPase in the samples of the famotidine-treated rats was significantly higher than in the histamine-treated rats. The effects of famotidine were weakened by neuraminidase. These results indicate that βHK is sialylated at neutral or weakly acidic pH, but not at acidic pH, suggesting that the sialic acids of βHK positively regulate the enzymatic activity of αHK., (Copyright © 2016 Elsevier B.V. All rights reserved.)

Understanding the interactions among materials, proteins and cells is critical for the development of novel biomaterials, and establishing a highly sensitive and quantitative method to standardize these interactions is desired. In this study, quartz crystal microbalance with dissipation (QCM-D) combined with microscopy was utilized to quantitatively monitor the entirety of the cell adhesion processes, starting from the protein adsorption, on various self-assembled monolayer (SAM) surfaces. Although the resulting cell adhesion morphologies were similar on most of the surfaces, the dynamic QCM-D signal patterns were unique on each surface, suggesting different forms of material-protein-cell interactions. The viscoelasticity and the density of the surface-adsorbed fibronectin (FN), as well as the relative exposure of the cell adhesive arginine-glycine-aspartic acid (RGD) motifs, were correlated to the different cell adhesion dynamics and mechanics. Some surfaces exhibited complicated behaviors alluding to the detachment/rearrangement of surface proteins or highly sparse but bioactive proteins that promote a slow adhesion process. This study underscores the potential use of the QCM-D signal pattern as a rule of thumb for delineating different protein-material and cell-protein interactions, and offers a rapid in vitro platform for the dynamic evaluation of protein and cell behaviors on novel biomaterials.

Systemic administration of a gamma-amino butyric acid type B (GABAB) receptor agonist, baclofen, affects various physiological and psychological processes. To date, the effects on oculomotor system have been well characterized in primates, however those in mice have not been explored. In this study, we investigated the effects of baclofen focusing on vestibular-related eye movements. Two rotational paradigms, i.e. sinusoidal rotation and counter rotation were employed to stimulate semicircular canals and otolith organs in the inner ear. Experimental conditions (dosage, routes and onset of recording) were determined based on the prior studies exploring the behavioral effects of baclofen in mice. With an increase in dosage, both canal and otolith induced ocular responses were gradually affected. There was a clear distinction in the drug sensitivity showing that eye movements derived from direct vestibulo-ocular reflex pathways were relatively unaltered, while the responses through higher-order neural networks in the vestibular system were substantially decreased. These findings were consistent with those observed in primates suggesting a well-conserved role of GABAB receptors in the oculomotor system across frontal-eyed and lateral-eyed animals. We showed here a previously unrecognized effect of baclofen on the vestibular oculomotor function in mice. When interpreting general animal performance under the drug, the potential contribution of altered balance system should be taken into consideration., (Copyright © 2016 Elsevier B.V. All rights reserved.)

In humans, observation of others' behaviors increases corticospinal excitability (CSE), which is interpreted in the contexts of motor resonance and the "mirror neuron system" (MNS). It has been suggested that observation of another individual's behavior manifests an embodied simulation of his/her mental state through the MNS. Thus, the MNS may involve understanding others' intentions of behaviors, thoughts, and emotions (i.e., social cognition), and may therefore exhibit a greater response when observing human-interactive behaviors that require a more varied and complex understanding of others. In the present study, transcranial magnetic stimulation was applied to the primary motor cortex of participants observing human-interactive behaviors between two individuals (c.f. one person reaching toward an object in another person's hand) and non-interactive individual behavior (c.f. one person reaching toward an object on a dish). We carefully controlled the kinematics of behaviors in these two conditions to exclude potential effects of MNS activity changes associated with kinematic differences between visual stimuli. Notably, motor evoked potentials, that reflect CSE, from the first dorsal interosseous muscle exhibited greater amplitude when the participants observed interactive behaviors than when they observed non-interactive behavior. These results provide neurophysiological evidence that the MNS is activated to a greater degree during observation of human-interactive behaviors that contain additional information about the individuals' mental states, supporting the view that the MNS plays a critical role in social cognition in humans., (Copyright © 2015 Elsevier Inc. All rights reserved.)