Evaluation of PET/CT imaging with [89Zr]Zr-DFO-girentuximab: a phase 1 clinical study in Japanese patients with renal cell carcinoma (Zirdac-JP).

BACKGROUND: PET/CT imaging with Zirconium-89 labeled [89Zr]Zr-DFO-girentuximab, which targets tumor antigen CAIX, may aid in the differentiation and characterization of clear cell renal cell carcinomas (RCC) and other renal and extrarenal lesions, and has been studied in European and American cohorts. We report results from a phase I study that evaluated the safety profile, biodistribution, and dosimetry of [89Zr]Zr-DFO-girentuximab in Japanese patients with suspected RCC. METHODS: Eligible adult patients received 37 MBq (± 10%; 10 mg mass dose) of intravenous [89Zr]Zr-DFO-girentuximab. Safety and tolerability profile was assessed based on adverse events, concomitant medications, physical examination, vital signs, hematology, serum chemistry, urinalysis, human anti-chimeric antibody measurement, and 12-lead electrocardiograms at predefined intervals. Biodistribution and normal organ and tumor dosimetry were evaluated with PET/CT images acquired at 0.5, 4, 24, 72 h and Day 5 ± 2 d after administration. RESULTS: [89Zr]Zr-DFO-girentuximab was administered in six patients as per protocol. No treatment-emergent adverse events were reported. Dosimetry analysis showed that radioactivity was widely distributed in the body, and that the absorbed dose in healthy organs was highest in the liver (mean ± standard deviation) (1.365 ± 0.245 mGy/MBq), kidney (1.126 ± 0.190 mGy/MBq), heart wall (1.096 ± 0.232 mGy/MBq), and spleen (1.072 ± 0.466 mGy/MBq). The mean effective dose, adjusted by the radioactive dose administered, was 0.470 mSv/MBq. The radiation dose was highly accumulated in the targeted tumor, while any abnormal accumulation in other organs was not reported. CONCLUSIONS: This study demonstrates that [89Zr]Zr-DFO-girentuximab administered to Japanese patients with suspected RCC has a favorable safety profile and is well tolerated and has a similar dosimetry profile to previously studied populations.

Anomalous Hall Transport by Optically Injected Isospin Degree of Freedom in Dirac Semimetal Thin Film.

Chirality of massless fermions emerging in condensed matter is a key to understand their characteristic behavior as well as to exploit their functionality. However, the chiral nature of massless fermions in Dirac semimetals has remained elusive, due to equivalent occupation of carriers with the opposite chirality in thermal equilibrium. Here, we show that the isospin degree of freedom, which labels the chirality of massless carriers from a crystallographic point of view, can be injected by circularly polarized light. Terahertz Faraday rotation spectroscopy successfully detects the anomalous Hall conductivity by a light-induced isospin polarization in a three-dimensional Dirac semimetal, Cd3As2. Spectral analysis of the Hall conductivity reveals a long scattering time and a long decay time, which are characteristic of the isospin. The long-lived, robust, and reversible character of the isospin promises a potential application of Dirac semimetals in future information technology.

Disentangling the Competing Mechanisms of Light-Induced Anomalous Hall Conductivity in Three-Dimensional Dirac Semimetal.

We experimentally elucidate the origin of the anomalous Hall conductivity in a three-dimensional Dirac semimetal, Cd_{3}As_{2}, driven by circularly polarized light. Using time-resolved terahertz Faraday rotation spectroscopy, we determine the transient Hall conductivity spectrum with special attention to its sign. Our results clearly show the dominance of direct photocurrent generation assisted by the terahertz electric field. The contribution from the Floquet-Weyl nodes is found to be minor when the driving light is in resonance with interband transitions. We develop a generally applicable classification of microscopic mechanisms of light-induced anomalous Hall conductivity.

The role of perspective-taking in suppressing stereotypes about mathematics.

OBJECTIVE: When people attempt to suppress stereotypes, they often end up making stereotypical judgments. The adverse effects of this form of suppression are called "paradoxical effects." This study examined the effect of perspective-taking as a strategy to reduce the paradoxical effects related to stereotype suppression. Specifically, this study addressed stereotypes within the context of women's mathematical abilities, with Japanese university students as participants. It was predicted that when participants suppressed the stereotype of a woman, those who engaged in perspective-taking toward that woman would make less stereotypical judgments of other women, compared with those who did not. Moreover, as this study focuses on gender stereotypes, an exploratory analysis was conducted to investigate whether the effects of engaging in perspective-taking about women vary depending on the participants' gender. RESULTS: Although no significant effect was observed and the hypothesis was not supported, and while the results of this study were statistically inadequate, they suggest that among the female participants, those who did not engage in perspective-taking showed the paradoxical effects of stereotype suppression. However, those paradoxical effects were not observed among those who performed perspective-taking.

Free from your experiences to grow: belief in free will moderates the relationship between attachment avoidance and personal growth initiative.

BACKGROUND: Attachment theory proposes that attachment security facilitates personal growth. However, attachment security origins in relationship history, and thus, how people treat their experiences may influence the outcomes of attachment security. People differ in the degree in believing that human beings have free will, and belief in free will may influence the relationship between experiences and outcomes. The present cross-sectional study investigated the relationships between attachment security, belief in free will, and personal growth initiative. METHODS: We used the cross-sectional data of 346 Chinese college students for data analysis, including correlational analyses, regression, and moderation analyses. The nine-item Chinese version of the Experiences in Close Relationships-Relationship Structures Scale, the sixteen-item Chinese version of the Personal Growth Initiative Scale-II, and the seven-item Free Will subscale of the Chinese version of the Free Will and Determinism Plus Scale were utilized. RESULTS: Results showed attachment avoidance and belief in free will, not attachment anxiety, was associated with personal growth initiative. Belief in free will moderated the association between attachment avoidance and personal growth initiative. When the centered score of belief in free will was higher than 0.64, attachment avoidance was no longer associated with personal growth initiative. 85.84% of our data were below this Johnson-Neyman significance region, and 14.16% were above. In other words, only those who scored higher than 0.64 on free will beliefs were able to pursue personal growth despite their high attachment avoidance. CONCLUSIONS: These findings suggest that when believing in free will, avoidantly attached people may believe in their ability to pursue personal growth and think their future has more possibilities, not influenced by other factors like social support, which they think they lack.

Biocompatible topical delivery system of high-molecular-weight hyaluronan into human stratum corneum using magnesium chloride.

Non-invasive delivery of hyaluronan into the stratum corneum (SC) is extremely difficult because of its high molecular weight and the strong barrier of the SC. We developed a safe method of administering hyaluronan into the human SC and determined its penetration route. The amount of hyaluronan that penetrated into the SC was 1.5-3 times higher in the presence of magnesium chloride hexahydrate (MgCl2) than other metal chlorides. The root-mean-square radius of hyaluronan in water decreased with the addition of MgCl2. Moreover, MgCl2 solutions maintained their dissolved state on a plastic plate for a long time, suggesting that size compaction and inhibition of hyaluronan precipitation on the skin enhanced hyaluronan into the SC. Our results also strongly suggest that an intercellular route contributes to the penetration of hyaluronan from the upper to the middle layer of the SC. No disruption to the SC barrier was observed after continuous use once a day for 1 month, demonstrating the potential of our method for the safe, topical application of hyaluronan.

Microwave Dynamical Conductivity in the Quantum Hall Regime.

Dynamical conductivity contains information of dissipative and nondissipative processes induced by ac-electric fields. In the integer quantum Hall (QH) effect where the nondissipative Hall current is the most prominent feature, its robustness is assured by localized states within the Landau levels. We establish a noncontact method with a circular cavity resonator and detect the real and imaginary parts of the longitudinal and Hall conductivities at a microwave frequency in magnetic fields. The conventional Shubnikov-de Haas oscillations and QH plateaus are observed in the real parts of longitudinal and Hall conductivities, respectively, while periodic structures can be seen in the imaginary parts which are scaled by the QH filling factor. The latter originates from intra-Landau level transitions between different orbital angular momenta. The results demonstrate that the dynamical conductivity measurement provides microscopic information which is not accessible by conventional static methods. The present noncontact method would pave the way to reveal the electron dynamics in other two-dimensional systems such as twisted bilayer graphene.

Early initiation of tolvaptan is associated with early discharge in patients with heart failure regardless of age.

BACKGROUND: Elderly patients with heart failure (HF) have been observed to decrease activities of daily living (ADL) during hospitalization. Prevention of ADL decline from shortening of hospital stays is especially important in the elderly, because decreasing ADL is associated with poor prognosis. We investigated the relationship between the early initiation of tolvaptan (TLV) after hospitalization and the length of hospital stay in patients with HF aged younger than 80 years and aged 80 years and older. METHODS: We analyzed 146 patients younger than 80 years (< 80) and 101 patients aged 80 years and older (≥ 80) who were hospitalized with HF from February 2011 to June 2016 and had initiated TLV. The relationship between the time until commencement of TLV and the length of hospital stay was assessed. Additionally, a comparison made between the TLV early start group (within the median) and the delayed start group (over the median) for both groups. Multivariate analysis was also performed on factors that required hospital stays below the median. RESULTS: A significant correlation was observed between time to TLV initiation and the length of hospital stay (< 80: r = 0.382, P < 0.001; ≥ 80: r = 0.395, P < 0.001). The length of hospital stay in the early group was significantly longer than that in the delayed group for both groups (< 80: early 21.0 ± 13.0 days and 33.0 ± 22.7 days, respectively, P < 0.001; ≥ 80: early 21.3 ± 12.5 days and 32.9 ± 17.9 days, respectively, P < 0.001). Conversely, no statistically significant difference found in the length of hospital stay after initiation of TLV. Moreover, no increase in adverse events in the elderly observed. A multivariate analysis revealed that a predictive factor for short-term hospitalization was early administration of TLV regardless of age. CONCLUSIONS: The early initiation of TLV after hospitalization was associated with a shorter length of hospital stay in patients with HF regardless of age.

Evaluation of balloon pulmonary angioplasty using lung perfusion SPECT in patients with chronic thromboembolic pulmonary hypertension.

BACKGROUND: The aim of this study was to evaluate the effect of balloon pulmonary angioplasty (BPA) using lung perfusion single-photon emission computed tomography (SPECT) in patients with chronic thromboembolic pulmonary hypertension (CTEPH). METHODS AND RESULTS: 20 consecutive patients (64 ± 15 years) who were diagnosed with CTEPH and underwent BPA were included in this study. All patients underwent lung perfusion SPECT before and after BPA. The relationship between functional %volume of the lung calculated from the lung perfusion SPECT (FVL-LPSPECT), and other clinical parameters before and after BPA was assessed using the Wilcoxon signed-rank test. The correlation between each parameter and mean pulmonary artery pressure (mPAP) using the Spearman's correlation was performed. To determine predictors of mPAP for evaluating treatment effectiveness, significant parameters were included in multiple regression analysis. After BPA, world health organization functional classification, six-minute walk distance (6MWD), mPAP, and FVL-LPSPECT significantly improved. FVL-LPSPECT (r = - 0.728, P < 0.001) and 6MWD (r = - 0.571, P = 0.009) were significant correlation of mPAP. In the multiple regression analysis, FVL-LPSPECT was the most significant predictor of improvement in mPAP after BPA (P < 0.001). CONCLUSIONS: This study demonstrated that the lung perfusion SPECT could be a potential measurement of the effectiveness of BPA in patients with CTEPH.

The role of mindfulness and attachment security in facilitating resilience.

BACKGROUND: In recent years, there has been growing interest in exploring ways to facilitate positive psychological dispositions, including resilience. The goal of the present study was to explore the possibility that trait mindfulness facilitates attachment security and thus enhances resilience. METHODS: We conducted two studies based on cross-sectional surveys. In Study 1, data of 207 students studying in Japan was collected. In Study 2, we used a different sample of 203 participants and different measurements to replicate the findings of Study 1. RESULTS: The results of Study 1 revealed that mindfulness positively predicted resilience, while attachment anxiety and avoidance were mediators between mindfulness and resilience. The results of Study 2 showed that mindfulness positively predicted resilience, and the mediating effect of attachment avoidance was significant, but the mediating effect of attachment anxiety was not significant. CONCLUSIONS: It is possible to facilitate attachment security through cultivating trait mindfulness, and in this way, resilience could be enhanced. The effect of different components of mindfulness on attachment and resilience requires further studies.

Appropriate Balloon Pulmonary Angioplasty for Chronic Thromboembolic Pulmonary Hypertension Improves Right Ventricular Ejection Fraction via Lung Perfusion Scan.

Balloon pulmonary angioplasty (BPA) is a robust treatment and has been performed among patients with inoperable chronic thromboembolic pulmonary hypertension (CTEPH). A lung perfusion scan (LPS) is required for inspection in deciding the curative effect judgment and treatment lesion of BPA. Nevertheless, the impact of BPA in the improvement of right heart system function is not well known. We investigated whether BPA improves right heart function alongside other parameters.We studied 20 patients with CTEPH (mean age 63.6 ± 15.9 years, male 30.0%) who underwent BPA. All study sets including right heart catheter, pulmonary angiography, 6-minute walk test (6MWT), blood gas analysis, and LPS were performed before BPA treatment. All parameters using right heart catheter and oxygenation level were measured at room air temperature. Regarding LPS, right ventricular ejection fraction (RVEF) was calculated using the first-pass method. These parameters before BPA were compared with those after BPA.In total, 120 BPAs were performed (mean number of procedures/patient; 6.0 ± 2.4 sessions). Per BPA session, 6.0 ± 2.4 areas and 10.0 ± 4.3 lesions were treated with a volume of 181.3 ± 53.5 mL of contrast media. No complication required an invasive procedure. World Health Organization functional class, 6MWT, pulmonary artery pressure, pulmonary vascular resistance, and oxygenation level were significantly improved after BPA. RVEF via LPS was also significantly improved after BPA (45.0 ± 6.2% to 50.6 ± 2.9%, P < 0.001).In the present study, we found that RVEF via LPS was improved through appropriate BPA alongside the other parameters. It would be useful to be able to evaluate right heart function.

Systematic analysis of exonic germline and postzygotic de novo mutations in bipolar disorder.

Bipolar disorder is a severe mental illness characterized by recurrent manic and depressive episodes. To better understand its genetic architecture, we analyze ultra-rare de novo mutations in 354 trios with bipolar disorder. For germline de novo mutations, we find significant enrichment of loss-of-function mutations in constrained genes (corrected-P = 0.0410) and deleterious mutations in presynaptic active zone genes (FDR = 0.0415). An analysis integrating single-cell RNA-sequencing data identifies a subset of excitatory neurons preferentially expressing the genes hit by deleterious mutations, which are also characterized by high expression of developmental disorder genes. In the analysis of postzygotic mutations, we observe significant enrichment of deleterious ones in developmental disorder genes (P = 0.00135), including the SRCAP gene mutated in two unrelated probands. These data collectively indicate the contributions of both germline and postzygotic mutations to the risk of bipolar disorder, supporting the hypothesis that postzygotic mutations of developmental disorder genes may contribute to bipolar disorder.

Scanning Tunneling Microscopy as a Single Majorana Detector of Kitaev's Chiral Spin Liquid.

We propose a local detection scheme for the Majorana zero mode (MZM) carried by a vison in Kitaev's chiral spin liquid (CSL) using scanning tunneling microscopy (STM). The STM introduces a single Majorana into the system through hole-charge injection and the Majorana interacts with the MZM to form a stable composite object. We derive the exact analytical expression of single-hole Green's function in the Mott insulating limit of Kitaev's model, and show that the differential conductance has split peaks, as a consequence of resonant tunneling through the vison-hole composite. The peak splitting turns out comparable to the Majorana gap in CSL, well within the reach of experimental observation.

5-aminolevulinic acid-mediated photodynamic therapy can target aggressive adult T cell leukemia/lymphoma resistant to conventional chemotherapy.

Photodynamic therapy (PDT) is an emerging treatment for various solid cancers. We recently reported that tumor cell lines and patient specimens from adult T cell leukemia/lymphoma (ATL) are susceptible to specific cell death by visible light exposure after a short-term culture with 5-aminolevulinic acid, indicating that extracorporeal photopheresis could eradicate hematological tumor cells circulating in peripheral blood. As a bridge from basic research to clinical trial of PDT for hematological malignancies, we here examined the efficacy of ALA-PDT on various lymphoid malignancies with circulating tumor cells in peripheral blood. We also examined the effects of ALA-PDT on tumor cells before and after conventional chemotherapy. With 16 primary blood samples from 13 patients, we demonstrated that PDT efficiently killed tumor cells without influencing normal lymphocytes in aggressive diseases such as acute ATL. Importantly, PDT could eradicate acute ATL cells remaining after standard chemotherapy or anti-CCR4 antibody, suggesting that PDT could work together with other conventional therapies in a complementary manner. The responses of PDT on indolent tumor cells were various but were clearly depending on accumulation of protoporphyrin IX, which indicates the possibility of biomarker-guided application of PDT. These findings provide important information for developing novel therapeutic strategy for hematological malignancies.

Paddy fields located in water storage zones could take over the wetland plant community.

Land use change could affect not only local species richness but also community assemblies. Essentially, the possible patterns of plant community assemblies are nonrandom species loss (nestedness) and species turnover. Plant community assemblies in human-mediated land use have a combination of both nestedness and turnover. This is because of historical effects that cause nonrandom species loss due to previous and/or original habitat quality and because of direct effects of human activities that cause species turnover. We investigated the complexity of the process of plant community assemblage in a paddy field, which is a typical agricultural land use in the monsoon season in central Japan. Using multi-temporal plant monitoring records, we tested the relationship between the ratio of species nestedness/turnover through multi-temporal and both the original habitat conditions and the extent of human modification. The findings revealed that paddy fields that originated from wetland habitat had a high nestedness ratio, whereas paddy fields that were largely consolidated had a high turnover ratio. Thus, we could divide the community assembly processes in human-mediated land use based on original habitat conditions and human activities. This concept could help land managers establish conservation and/or restoration plans that take into account community assembly.

h/e oscillations in interlayer transport of delafossites.

Microstructures can be carefully designed to reveal the quantum phase of the wave-like nature of electrons in a metal. Here, we report phase-coherent oscillations of out-of-plane magnetoresistance in the layered delafossites PdCoO2 and PtCoO2 The oscillation period is equivalent to that determined by the magnetic flux quantum, h/e, threading an area defined by the atomic interlayer separation and the sample width, where h is Planck's constant and e is the charge of an electron. The phase of the electron wave function appears robust over length scales exceeding 10 micrometers and persisting up to temperatures of T > 50 kelvin. We show that the experimental signal stems from a periodic field modulation of the out-of-plane hopping. These results demonstrate extraordinary single-particle quantum coherence lengths in delafossites.

Cardio-ankle vascular index predicts the 1-year prognosis of heart failure patients categorized in clinical scenario 1.

The sudden increase in blood pressure by vascular dysfunction is associated with the development of acute decompensated heart failure (ADHF) categorized in clinical scenario (CS) 1. However, the relationship between vascular function and prognosis in ADHF patients with CS1 is unclear. 3239 consecutive ADHF patients between January 2012 and June 2018 were enrolled. ADHF patients with CS1 undergoing ankle brachial index/cardio-ankle vascular index (CAVI) were included and patients with peripheral artery disease were excluded. Finally, 113 patients were analyzed. The primary endpoint of the present study was composite endpoint at 1 year (the cardiac death or re-hospitalization by ADHF). Cox proportional hazard analysis was conducted to identify independent predictors of composite endpoint. 25 patients (22.1%) were developed composite endpoint. CAVI in patients who have composite endpoint were significantly higher than without non-composite endpoint (composite endpoint group: 9.9 ± 1.3 non-composite endpoint group 8.7 ± 1.7, P = 0.001). The composite endpoint group was elderly and had higher ejection fraction, lower hemoglobin, and less used beta blockers, and renin angiotensin aldosterone system inhibitors. After adjustment by these confounding factors, CAVI was independently associated with the occurrence of composite endpoint (hazard ratio 1.69, 95% CI 1.05-2.73, P = 0.032). A cut-off value of CAVI for predicting composite endpoint was 8.65 (sensitivity 0.444, specificity 0.920, area under the curve 0.724, 95% CI 0.614-0.834). High CAVI was associated with the occurrence of composite endpoint after CS1 ADHF.