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Proton pump inhibitors (PPIs) are potent inhibitors of gastric acid secretion, used as first-line agents in treating peptic ulcers. However, we have previously reported that PPIs may diminish the therapeutic effect of anti-vascular endothelial growth factor (VEGF) drugs in patients with cancer. In this study, we explored the effects of vonoprazan, a novel gastric acid secretion inhibitor used for the treatment of peptic ulcers, on the secretion of VEGF in cancer cells and attempted to propose it as an alternative PPI for cancer chemotherapy. The effects of PPI and vonoprazan on VEGF expression in cancer cells were compared by real-time reverse transcription-polymerase chain reaction and ELISA. The interaction of vonoprazan and PPIs with transcriptional regulators by docking simulation analysis. In various cancer cell lines, including the human colorectal cancer cell line (LS174T), PPI increased VEGF messenger RNA expression and VEGF protein secretion, while this effect was not observed with vonoprazan. Molecular docking simulation analysis showed that vonoprazan had a lower binding affinity for estrogen receptor alpha (ER-α), one of the transcriptional regulators of VEGF, compared to PPI. Although the PPI-induced increase in VEGF expression was counteracted by pharmacological ER-α inhibition, the effect of vonoprazan on VEGF expression was unchanged. Vonoprazan does not affect VEGF expression in cancer cells, which suggests that vonoprazan might be an alternative to PPIs, with no interference with the therapeutic effects of anti-VEGF cancer chemotherapy.

A 67-year-old man was admitted to our hospital for massive pleural effusion. He had a history of mandibular gingival carcinoma treated with radiation therapy (RT). Based on the cytology findings of pleural effusion and a thoracoscopic pleural biopsy, we finally diagnosed him with radiation-associated angiosarcoma. Retrospective cell-block immunocytochemistry with pleural effusion also showed potential utility for the diagnosis. This case highlights the importance of considering the possibility of radiation-associated secondary cancer in patients with pleural effusion who have a history of RT.

Owing to the coronavirus disease 2019 (COVID-19) pandemic, understanding how to hold future online academic conferences effectively is imperative. We assessed the impact of COVID-19 on academic conferences, including facilities and settings for attendance, participation status, cost burden, and preferences for future styles of holding conferences, through a web-based questionnaire survey of 2,739 Japanese medical professionals, from December 2020 to February 2021. Of the participants, 28% preferred web conferences, 60% preferred a mix of web and on-site conferences, and 12% preferred on-site conferences. Additionally, 27% of the presenters stopped presenting new findings at web conferences. The proportion of participants who audio-recorded or filmed the sessions, despite prohibition, was six times higher at web than face-to-face conferences. Since the COVID-19 outbreak, the percentage of participants attending general presentations decreased from 91 to 51%. While web conferencing offers advantages, these are offset by a decrease in presentations pertaining to novel findings and data.The online version contains supplementary material available at 10.1007/s10639-022-11032-5.

In April 2018, the Clinical Trials Act pertaining to investigator-initiated clinical trials was passed in Japan. The purpose of this study was to investigate activity in investigator-initiated clinical studies before and after enforcement of the new Clinical Trials Act. This was done by analysing the records of the Ethics Committee of Tokushima University Hospital, which reviews studies based on the Japanese government's Ethical Guidelines for Medical and Health Research Involving Human Subjects prior to the Clinical Trials Act, and records of the Certified Review Board established at Tokushima University under the Clinical Trials Act in 2018. The number of new applications to these two review boards during fiscal years 2015-2017 (pre-Act) and fiscal years 2018 and 2019 (post-Act) were used as an indicator of activity in investigator-initiated clinical studies. The number of new applications to the Ethics Committee was 303, 261, 316, 303, and 249 in 2015, 2016, 2017, 2018, and 2019, respectively. The data show that the total number of new interventional studies decreased from 50.3 in average in 2015-2017 (pre-Act) to 42 in 2018 and 40 in 2019 (post-Act), respectively. These results suggest that fewer interventional studies were started following enforcement of the new Clinical Trials Act. To confirm this trend and identify contributing factors, further studies are required. In addition, possible way, such as broader contribution of clinical research coordinators, to promote clinical studies in the new Clinical Trials Act era should be examined.

Purpose Accumulation of data on patient response to immune checkpoint inhibitors (ICIs) has enabled the analysis of adverse events (AEs) that have been difficult to analyze to date. The development of multiple AEs is often fatal; therefore, their characterization is important. Hence, we retrospectively investigated anti-programmed cell death protein 1 (PD1)/ programmed death-ligand 1 (PDL1) therapy by conducting a case-control study to determine the clinical characteristics of AEs associated with multiple ICIs. Methods We utilized the Japan Medical Data Center claims database, a prescription-diagnostics database, to obtain records of patients treated with PD1/PDL1 inhibitors, which were then analyzed. A total of 116,091 ICI-associated prescription-diagnostics data reports were retrieved. ICI-associated safety reports of individual cases till November 2020 were also analyzed. Furthermore, a narrowed search for immune-related AEs (irAEs) yielded 3,173 cases from the prescription-diagnostics data. Results There was a high incidence of concomitant AEs, and endocrine dysfunctions (hypophysitis, thyroiditis, and adrenal complications) had a high co-occurrence rate. Diabetes mellitus, hepatitis, and colitis overlapped in patients who developed thyroid dysfunction. In addition, there was a high incidence of myositis, myasthenia gravis, and myocarditis co-occurrence. Further analysis revealed a high mortality rate for interstitial pneumonia and diabetes mellitus (38%). In concomitant cases of myocarditis and other irAEs, severe cardiac diseases were developed. Conclusion Anti-PD1/PDL1 therapy may cause fatal clinical manifestations when accompanied by multiple irAEs. This study may provide adequate awareness among healthcare providers toward these characteristics.

The role of research ethics consultants in biomedical research has increased to the point that they have an advisory capacity at all research institutes. For such professionals, we have established an educational system, which includes teaching materials, training methods, and nationwide educational workshops. These workshops have served to examine the developed system’s usefulness and to provide realistic training for consultant candidates. In addition, we have used the current workshop to encourage clinical research investigators (and related personnel) to participate. Subsequently, we examined its usefulness as an opportunity to provide exposure to research ethics. In October 2019, we held a 1-day pilot workshop in Tokushima, Japan, which included a basic lecture in research ethics. During the lecture, two sets of materials were used for case discussion: case 1, covering issues related to a clinical trial, and case 2, covering issues related to human biological specimens. At the end of the workshop, a 30-item self-reporting anonymous questionnaire was provided. Of the 13 total participants, 9 (70%) were clinical research investigators and related personnel, while 6 (46%) had no direct intention to act as consultants. Respondents indicated that case 2 was more difficult than case 1. However, both cases were generally accepted as educational materials; thus, satisfaction was expressed in relation to both. As the evaluations of the cases were generally positive, we will further examine the usefulness of participation in the workshop in the cultivation of research ethics in the investigator community.

Background Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disorder, with its currently approved drugs, including riluzole and edaravone, showing limited therapeutic effects. Therefore, safe and effective drugs are urgently necessary. EPI-589 is an orally available, small-molecule, novel redox-active agent characterized by highly potent protective effects against oxidative stress with high blood-brain barrier permeability. Given the apparent oxidative stress and mitochondrial dysfunction involvement in the pathogenesis of ALS, EPI-589 may hold promise as a therapeutic agent. Objective This protocol aims to describe the design and rationale for the EPI-589 Early Phase 2 Investigator-Initiated Clinical Trial for ALS (EPIC-ALS). Methods EPIC-ALS is an explorative, open-labeled, single-arm trial that evaluates the safety and tolerability of EPI-589 in patients with ALS. This trial consists of 12-week run-in, 24-week treatment, and 4-week follow-up periods. Patients will receive 500 mg of EPI-589 3 times daily over the 24-week treatment period. Clinical assessments include the mean monthly change of Amyotrophic Lateral Sclerosis Functional Rating Scale–Revised total score. The biomarkers are selected to analyze the effect on oxidative stress and neuronal damage. The plasma biomarkers are 8-hydroxy-2′-deoxyguanosine (8-OHdG), 3-nitrotyrosine (3-NT), neurofilament light chain (NfL), phosphorylated neurofilament heavy chain (pNfH), homocysteine, and creatinine. The cerebrospinal fluid biomarkers are 8-OHdG, 3-NT, NfL, pNfH, and ornithine. The magnetic resonance biomarkers are fractional anisotropy in the corticospinal tract and N-acetylaspartate in the primary motor area. Results This trial began data collection in September 2021 and is expected to be completed in October 2023. Conclusions This study can provide useful data to understand the characteristics of EPI-589. Trial Registration Japan Primary Registries Network jRCT2061210031; tinyurl.com/2p84emu6 International Registered Report Identifier (IRRID) DERR1-10.2196/42032

Despite the importance and acceptance of research ethics consultation as an entity in many medical research areas, little is known about its status in nursing research. Focusing on inquiries from nurse researchers, we retrospectively analyzed records of integrated clinical research consultation, provided by members of the Clinical Research Center independently of the research ethics committee, at a Japanese university hospital during 2018–2019. Among various consultations in nursing studies ( n = 101), 43 were related to research ethics. The main issues in research ethics consultation were compatibility with guidelines ( n = 28; 65%) and application of ethics review ( n = 12; 28%). Future studies should investigate international settings and address the relevance of research ethics consultation to promote proper nursing studies.

We searched for the $\alpha$ condensed state in $^{13}$C by measuring the $\alpha$ inelastic scattering at $E_{\alpha} = 388$ MeV at forward angles including 0 degrees. We performed the distorted-wave Born-approximation calculation with the single-folding potential and the multipole decomposition analysis to determine the isoscalar transition strengths in $^{13}$C. We found a bump structure around $E_x = 12.5$ MeV due to the isoscalar monopole ($IS0$) transition. A peak-fit analysis suggested that this bump consisted of several $1/2^-$ states. We propose that this bump is due to the mirror state of the 13.5 MeV-state in $^{13}$N, which dominantly decays to the $\alpha$ condensed state in $^{12}$C. It was speculated that the $1/2^-$ states around $E_x = 12.5$ MeV were candidates for the $\alpha$ condensed state, but the $3\alpha + n$ orthogonality condition model suggests that the $\alpha$ condensed state is unlikely to emerge as the negative parity states. We also found two $1/2^+$ or $3/2^+$ states at $E_x = 14.5$ and 16.1 MeV excited with the isoscalar dipole ($IS1$) strengths. We suggest that the 16.1-MeV state is a possible candidate for the $\alpha$ condensed state predicted by the cluster-model calculations on the basis of the good correspondence between the experimental and calculated level structures. However, the theoretical $IS1$ transition strength for this state is significantly smaller than the measured value. Further experimental information is strongly desired to establish the $\alpha$ condensed state in $^{13}$C., Comment: 24 pages, 12 figures, published in PTEP

The inside of the electrical double layer at perovskite oxide heterointerfaces is examined. Here, we report the local polarization and valence distribution in ${\mathrm{LaNiO}}_{3}$/${\mathrm{LaMnO}}_{3}$ and ${\mathrm{LaMnO}}_{3}$/${\mathrm{LaNiO}}_{3}$ bilayers on a ${\mathrm{SrTiO}}_{3}$ (001) substrate. Simultaneous measurements of two aspects of the structure are realized by using Bayesian inference based on resonant- and nonresonant-surface x-ray diffraction data. The results show that the average Mn valences are ${\mathrm{Mn}}^{3.12+}$ and ${\mathrm{Mn}}^{3.19+}$ for the two samples. The intensity of their local electric field is $\ensuremath{\sim}1$ GV/m and the direction of the field points from ${\mathrm{LaMnO}}_{3}$ to ${\mathrm{LaNiO}}_{3}$.

Background : Enforcement of the 2018 Clinical Trials Act (CTA) in Japan resulted in strict and complicated regulations surrounding intervention studies. Few Japan-specific measures have been developed to promote intervention studies in Japan despite concerns about CTA's negative influence on such studies. Therefore, this study examined the changes in academic investigators' interest in conducting clinical studies before and after enforcement of the CTA to determine measures to promote specified clinical trials. Methods : We conducted a questionnaire survey with investigators belonging to the Institute of Biomedical Sciences, Tokushima University Graduate School, before and after enforcement of the CTA. Results : Investigators had lesser interest in intervention studies in the post-questionnaire survey (post) group than in the pre-questionnaire survey (pre) group. Their desire for "project management" was significantly higher in the post-group than in the pre-group. Their desire for "support for preparing documents when conducting specified clinical trials" was significantly higher in the group interested in conducting specified clinical trials than that in the not-interested group. Conclusion : We revealed that investigators were highly interested in "project management" and "support for preparing documents when conducting specified clinical trials" after enforcement of the CTA. Measures for these desires may promote specified clinical trials. J. Med. Invest. 68 : 71-75, February, 2021.

Hydroxyamide-functionalized azolium salt (NHC•HI 4) was evaluated for dual enantioselective control in a Cu-catalyzed asymmetric conjugate addition (ACA) reaction. This investigation was based on our previously reported ACA reaction catalyzed using CuOTf combined with NHC•AgI complex 1. It was revealed that the stereocontrol of the catalytic ACA reaction depended on the order of the addition of the substrates. Additionally, the chiral NHC ligand precursors, substrates, the relationship between the catalyst ee (eecat) and product ee (eepro), and halogen counter anion were completely evaluated. These results suggested that the catalytic performance of the CuOTf/4 system was comparable with that of the CuOTf/1 system. Furthermore, to gain knowledge of the Cu species generated using CuOTf and NHC ligand precursor, the reaction of CuOTf with 1 was investigated. Although obtaining the corresponding NHC•CuX species failed, the corresponding NHC•AuCl complex 11 could be synthesized by allowing 1 to react with AuCl•SMe2.

A kinematically complete quasifree (p,pn) experiment in inverse kinematics was performed to study the structure of the Borromean nucleus ^{17}B, which had long been considered to have a neutron halo. By analyzing the momentum distributions and exclusive cross sections, we obtained the spectroscopic factors for 1s_{1/2} and 0d_{5/2} orbitals, and a surprisingly small percentage of 9(2)% was determined for 1s_{1/2}. Our finding of such a small 1s_{1/2} component and the halo features reported in prior experiments can be explained by the deformed relativistic Hartree-Bogoliubov theory in continuum, revealing a definite but not dominant neutron halo in ^{17}B. The present work gives the smallest s- or p-orbital component among known nuclei exhibiting halo features and implies that the dominant occupation of s or p orbitals is not a prerequisite for the occurrence of a neutron halo.

The formation of a dineutron in the nucleus $^{11}$Li is found to be localized to the surface region. The experiment measured the intrinsic momentum of the struck neutron in $^{11}$Li via the $(p,pn)$ knockout reaction at 246 MeV/nucleon. The correlation angle between the two neutrons is, for the first time, measured as a function of the intrinsic neutron momentum. A comparison with reaction calculations reveals the localization of the dineutron at $r\sim3.6$ fm. The results also support the density dependence of dineutron formation as deduced from Hartree-Fock-Bogoliubov calculations for nuclear matter.

Background With the global proliferation of the novel COVID-19 disease, conventionally conducting institutional review board (IRB) meetings has become a difficult task. Amid concerns about the suspension of drug development due to delays within IRBs, it has been suggested that IRB meetings should be temporarily conducted via the internet. Objective This study aimed to elucidate the current status of IRB meetings conducted through web conference systems. Methods A survey on conducting IRB meetings through web conference systems was administered to Japanese national university hospitals. Respondents were in charge of operating IRB offices at different universities. This study was not a randomized controlled trial. Results The survey was performed at 42 facilities between the end of May and early June, 2020, immediately after the state of emergency was lifted in Japan. The survey yielded a response rate of 74% (31/42). Additionally, while 68% (21/31) of facilities introduced web conference systems for IRB meetings, 13% (4/31) of the surveyed facilities postponed IRB meetings. Therefore, we conducted a further survey of 21 facilities that implemented web conference systems for IRB meetings. According to 71% (15/21) of the respondents, there was no financial burden for implementing these systems, as they were free of charge. In 90% (19/21) of the facilities, IRB meetings through web conference systems were already being conducted with personal electronic devices. Furthermore, in 48% (10/21) of facilities, a web conference system was used in conjunction with face-to-face meetings. Conclusions Due to the COVID-19 pandemic, the number of reviews in clinical trial core hospitals has decreased. This suggests that the development of pharmaceuticals has stagnated because of COVID-19. According to 71% (15/21) of the respondents who conducted IRB meetings through web conference systems, the cost of introducing such meetings was US $0, showing a negligible financial burden. Moreover, it was shown that online deliberations could be carried out in the same manner as face-to-face meetings, as 86% (18/21) of facilities stated that the number of comments made by board members did not change. To improve the quality of IRB meetings conducted through web conference systems, it is necessary to further examine camera use and the content displayed on members’ screens during meetings. Further examination of all members who use web conference systems is required. Our measures for addressing the requests and problems identified in our study could potentially be considered protocols for future IRB meetings, when the COVID-19 pandemic has passed and face-to-face meetings are possible again. This study also highlights the importance of developing web conference systems for IRB meetings to respond to future unforeseen pandemics.

BACKGROUND With the global proliferation of the novel COVID-19 disease, conventionally conducting institutional review board (IRB) meetings has become a difficult task. Amid concerns about the suspension of drug development due to delays within IRBs, it has been suggested that IRB meetings should be temporarily conducted via the internet. OBJECTIVE This study aimed to elucidate the current status of IRB meetings conducted through web conference systems. METHODS A survey on conducting IRB meetings through web conference systems was administered to Japanese national university hospitals. Respondents were in charge of operating IRB offices at different universities. This study was not a randomized controlled trial. RESULTS The survey was performed at 42 facilities between the end of May and early June, 2020, immediately after the state of emergency was lifted in Japan. The survey yielded a response rate of 74% (31/42). Additionally, while 68% (21/31) of facilities introduced web conference systems for IRB meetings, 13% (4/31) of the surveyed facilities postponed IRB meetings. Therefore, we conducted a further survey of 21 facilities that implemented web conference systems for IRB meetings. According to 71% (15/21) of the respondents, there was no financial burden for implementing these systems, as they were free of charge. In 90% (19/21) of the facilities, IRB meetings through web conference systems were already being conducted with personal electronic devices. Furthermore, in 48% (10/21) of facilities, a web conference system was used in conjunction with face-to-face meetings. CONCLUSIONS Due to the COVID-19 pandemic, the number of reviews in clinical trial core hospitals has decreased. This suggests that the development of pharmaceuticals has stagnated because of COVID-19. According to 71% (15/21) of the respondents who conducted IRB meetings through web conference systems, the cost of introducing such meetings was US $0, showing a negligible financial burden. Moreover, it was shown that online deliberations could be carried out in the same manner as face-to-face meetings, as 86% (18/21) of facilities stated that the number of comments made by board members did not change. To improve the quality of IRB meetings conducted through web conference systems, it is necessary to further examine camera use and the content displayed on members’ screens during meetings. Further examination of all members who use web conference systems is required. Our measures for addressing the requests and problems identified in our study could potentially be considered protocols for future IRB meetings, when the COVID-19 pandemic has passed and face-to-face meetings are possible again. This study also highlights the importance of developing web conference systems for IRB meetings to respond to future unforeseen pandemics.

The structure of a neutron-rich ^{25}F nucleus is investigated by a quasifree (p,2p) knockout reaction at 270A MeV in inverse kinematics. The sum of spectroscopic factors of π0d_{5/2} orbital is found to be 1.0±0.3. However, the spectroscopic factor with residual ^{24}O nucleus being in the ground state is found to be only 0.36±0.13, while those in the excited state is 0.65±0.25. The result shows that the ^{24}O core of ^{25}F nucleus significantly differs from a free ^{24}O nucleus, and the core consists of ∼35% ^{24}O_{g.s.}. and ∼65% excited ^{24}O. The result may infer that the addition of the 0d_{5/2} proton considerably changes neutron structure in ^{25}F from that in ^{24}O, which could be a possible mechanism responsible for the oxygen dripline anomaly.

Spectroscopy of 16B plays an essential role in understanding the halo structure in 17B, but very limited knowledge has so far been obtained. We have carried out a kinematically complete measurement on the spectroscopy of 16B by using quasi-free (p,pn) reaction on 17B. The level scheme of 16B up to 5 MeV was made clear for the first time.

This study aims to propose a simple procedure for the development of enantioselective hydrosilylation of a ketone using catalytic amounts of [Ir(cod)2]BF4 and chiral azolium salt. Previously, catalytic asymmetric hydrosilylation reactions have used well-defined metal-N-heterocyclic carbene (NHC) complexes. The proposed method offers an important advantage of avoiding preparation of NHC-metal species. Several reaction parameters including the amount of reductant, solvent, catalyst loading and ligand structure were evaluated. In addition, the investigation of the reaction progress as a function of time revealed that an iridium species, which was generated after 5 h of reaction time, catalyzed the stereoselective reduction with almost perfect facial selection of the ketone. An attempt to obtain a catalytic active species from the reaction of [Ir(cod)2]BF4 and chiral azolium salt has been made. The newly obtained iridium species promoted the hydrosilylation of a ketone with high yield and enantioselectivity.

Objectives The clinical benefit of chemotherapy and the appropriate regimen for non-small-cell lung cancer (NSCLC) patients with interstitial lung disease (ILD) remain unclear. To fulfill this unmet medical need, we conducted a phase II study to elucidate the efficacy of S-1 in combination with carboplatin (CBDCA) in NSCLC patients with ILD. Materials and methods A total of 33 advanced or recurrent NSCLC patients with ILD were prospectively enrolled in this multicenter, open-label, phase II study. Every 4 weeks, CBDCA at a dose of AUC 5 on day 1 and S-1 at a dose of 80 mg/m2 daily for 14 days were administered. The primary endpoint was the investigator-assessed objective response rate. Results The median age at initiating chemotherapy was 70. Sixteen patients (48.5%) had squamous cell carcinoma histology. With respect to the types of ILD, the usual interstitial pneumonia pattern was dominant (66.7%). The median number of cycles administered was 3, and the overall response rate and disease control rate were 33.3% and 78.8%, respectively. The median progression-free survival, the median survival time and the 1-year survival rate were 4.8 months, 12.8 months and 51.4%, respectively. Acute exacerbation of ILD caused by chemotherapy was noted in 2 patients (6.1%). Conclusion This is the first prospective study designed to evaluate the efficacy of a specific chemotherapeutic regimen as the primary endpoint in patients with advanced NSCLC with ILD. The combination of S-1 with CBDCA may be a treatment option for advanced NSCLC patients with ILD (The clinical trial registration number: UMIN000011046).

We discuss heavy-ion fusion reactions of a well-deformed odd-mass nucleus at energies around the Coulomb barrier. To this end, we consider the $^{16}$O+$^{165}$Ho reaction and take into account the effect of deformation of $^{165}$Ho using the orientation average formula. We show that fusion cross sections are sensitive to magnetic substates of the target nucleus, and cross sections for the side collision, which are relevant to a synthesis of superheavy elements, may be enhanced by a factor of around two by aligning the deformed target nuclei. We also discuss the effect of alignment on the fusion barrier distribution. We find that, for a particular choice of alignment, the shape of barrier distribution becomes similar to a typical shape of barrier distribution for a deformed nucleus with a negative hexadecapole deformation parameter, $\beta_4$, even if the intrinsic $\beta_4$ is positive in the target nucleus., Comment: 6 pages, 5 eps figures

The triple alpha reaction is one of the most important reactions in the nuclear astrophysics. However, its reaction rate in high temperature environments at T 9 > 2 was still uncertain. One of the major origins of the uncertainty was that the radiative-decay probability of the 3 1 − state in 12C was unknown. In the present work, we have determined the radiative-decay probability of the 3 1 − state to be 1.3 − 1.1 + 1.2 × 10 − 6 by measuring the 1H(12C,12Cp) reaction for the first time, and derived the triple alpha reaction rate in high temperature environments from the measured radiative-decay probability. The present result suggests that the 3 1 − state noticeably enhances the triple alpha reaction rate although the contribution from the 3 1 − state had been assumed to be small.

A 60-year-old man was admitted to our hospital with non-small cell lung cancer (NSCLC). Imaging and pathological studies revealed NSCLC, not otherwise specified (NOS), at clinical stage T3N1M0 stage IIIA. We started radiotherapy alone because of obstructive pneumonia and end-stage renal disease, but the tumors progressed rapidly and resulted in death due to air obstruction by pharyngeal metastasis. The cancer was diagnosed as pleomorphic carcinoma in an autopsy. Viable lung tumor cells, which were resistant to radiotherapy, and the pharyngeal metastasis had mesenchymal phenotypes and expressed ZEB1 but not SNAI1. These observations indicated that ZEB1-associated epithelial-mesenchymal transition has malignant features including resistance to radiotherapy and aggressive metastatic potential. ZEB1-associated EMT may be an important mechanism to understand the pathophysiology of pleomorphic carcinoma. Keywords: Pulmonary pleomorphic carcinoma, Epithelial-mesenchymal transition (EMT), ZEB1

We present an investigation of the structure of 13Be obtained via a kinematically complete measurement of the (p,pn) reaction in inverse kinematics at 265 MeV/nucleon. The relative energy spectrum of 13Be is compared to Transfer-to-the-Continuum calculations which use as structure inputs the overlaps of the 14Be ground-state wave function, computed in a three-body model, with the unbound states of the 13Be residual nucleus. The key role of neutron p-wave orbital in the interpretation of the low-relative-energy part of the spectrum is discussed. Keywords: Quasi-free scattering, Borromean nuclei, Three-body model, Resonances

We report three different transformations in the reaction of the hydroxyamide-functionalized azolium chloride 1 with Ag2O. These transformations were controlled by the N-substituent at the azolium ring of 1. Treatment of 1c (R = Me, alkyl) with Ag2O afforded the corresponding monodentate NHC-Ag (NHC represents N-heterocyclic carbene) complex, 6c, in 95% yield. In contrast, the reaction of 1b (R = Ph, aryl) with Ag2O yielded the corresponding 2-hydroxyoxazolidine-substituted azolium hydroxide, 7b, in 90% yield. In this transformation, perhaps the cyclization of the hydroxyamide moiety of 1b to 2-hydroxyoxazolidine occurred under the influence of the hydroxide counter anion. Several aryl-substituted azolium chlorides, 1d-f, were also converted into the corresponding cyclization products, 7d-f. However, the reaction of 1h (R = 2,4,6-Me3C6H2, aryl) with Ag2O afforded the corresponding NHC-Ag complex, 6h, in 93% yield, whereas the reaction of 1i (R = 4-MeOC6H4, aryl) with Ag2O provided a mixture of 6i and 7i in 56% and 32% yields, respectively. Moreover, the reaction of azolium chloride, 1j (R = 2,6-iPr2C6H3, aryl), which has a more sterically hindered substituent at the ortho-position of the aryl side-arm, was investigated. Treatment of 1j with Ag2O gave unexpected urea derivative, 8j, in 99% yield.

Enantioselective reduction of ketones with (EtO) 2 MeSiH catalyzed by an in-situ generated N -heterocyclic carbene (NHC) Ir complex at room temperature has been developed. A series of benzimidazolium salts were synthesized and screened in the asymmetric hydrosilylation reaction. As a result, propiophenone was efficiently reduced by the combined catalytic system of [IrCl(cod)] 2 and NHC–Ag complex derived from N -(1-naphthalenylmethyl)-substituted benzimidazolium salt L12 , affording the corresponding alcohol in 92% yield and with 92% ee. Moreover, the evaluation of an Ir catalyst precursor showed that cationic [Ir(cod) 2 ]BF 4 complex could be used. Furthermore, the introduction of a chiral hydroxyamide side arm into the benzimidazolium salt was critical for the successful design of the NHC ligand.

We have combined the low-energy neutron detector WINDS (Wide-angle Inverse-kinematics Neutron Detectors for SHARAQ) and the SAMURAI spectrometer at RIKEN Nishina Center RI Beam Factory (RIBF) in order to perform ( p , n ) reactions in inverse kinematics for unstable nuclei in the mass region around A ∼ 100 . In this setup, WINDS is used for detecting recoil neutrons and the SAMURAI spectrometer is used for tagging decay channel of heavy residue. The first experiment by using the setup was performed to study Gamow–Teller transitions from 132 Sn in April 2014. The atomic number Z and mass-to-charge ratio A / Q of the beam residues were determined from the measurements of time of flight, magnetic rigidity and energy loss. The obtained A / Q and Z resolutions were σ A / Q = 0.14 % and σ Z = 0.22 , respectively. Furthermore, owing to the large momentum acceptance ( 50 % ) of SAMURAI, the beam residues associated with the γ , 1n and 2n decay channel were measured in the same magnetic field setting. The kinematic loci of the measured recoil neutron energy and laboratory angle are clearly seen. It shows that the excitation energy up to about 20 MeV can be reconstructed.

The asymmetric 1,4-addition of Et2Zn to 2-cyclohexen-1-one using a Cu(I) salt/N-heterocyclic carbene (NHC)–Ag complex catalytic system afforded optically active 3-ethylcyclohexanone. The reversal of enantioselectivity using the same catalytic system was achieved by changing the order of the addition of substrates.

The key parameter to discuss the possibility of the pion condensation in nuclear matter, i.e., the so-called Landau-Migdal parameter g^{'}, was extracted by measuring the double-differential cross sections for the (p,n) reaction at 216 MeV/u on a neutron-rich doubly magic unstable nucleus, ^{132}Sn with the quality comparable to data taken with stable nuclei. The extracted strengths for Gamow-Teller (GT) transitions from ^{132}Sn leading to ^{132}Sb exhibit the GT giant resonance (GTR) at the excitation energy of 16.3±0.4(stat)±0.4(syst) MeV with the width of Γ=4.7±0.8 MeV. The integrated GT strength up to E_{x}=25 MeV is S_{GT}^{-}=53±5(stat)_{-10}^{+11}(syst), corresponding to 56% of Ikeda's sum rule of 3(N-Z)=96. The present result accurately constrains the Landau-Migdal parameter as g^{'}=0.68±0.07, thanks to the high sensitivity of the GTR energy to g^{'}. In combination with previous studies on the GTR for ^{90}Zr and ^{208}Pb, the result of this work shows the constancy of this parameter in the nuclear chart region with (N-Z)/A=0.11 to 0.24 and A=90 to 208.

International audience; Dineutron decay is a forefront topic in nuclear structure that still lacks a firm experimental claim. The spontaneous emission of a dineutron should be favored in nuclei that are unbound with respect to two-neutron emission but bound with respect to single-neutron emission. A very interesting candidate can be found by adding two neutrons to the most neutron-rich Beryllium isotope,$^{14}$Be, a well-known 2n-halo nucleus. The intriguing nature of the phenomenon has motivated recent theoretical calculations and a new experimental campaign at RIKEN RIBF. In this work, the decay properties of$^{16}$Be and the structure of$^{15}$Be have been probed via the proton-knockout reaction from a$^{17}$B beam.

Background Older patients with lung cancer have increased over the past decades. Several standard treatments for older patients were established, but their clinical features in real world clinics remain unknown. Thus, we performed a retrospective study to clarify the clinical features of them. Methods The patients with lung cancer who were admitted to our hospital between April 1, 2012 and March 31, 2015 were retrospectively analyzed. Patients older than 75 years were defined as older patients. Standard treatments were based on the guidelines. Results In total, 333 patients were analyzed. The older patients had a poor performance status (PS), more comorbidities, and fewer opportunities to receive standard treatments. The prognosis of the older patients who received standard treatments was superior to that of those who did not. The therapeutic efficacy of standard treatments for older patients with stages I and II diseases was similar to their younger counterparts. However, the prognosis of older patients with advanced stage, especially stage III disease, was poor. The tolerability of first-line chemotherapy by older patients was comparable with their younger counterparts, but the older patients had fewer opportunities to receive several chemotherapy regimens, even second line chemotherapy. Conclusions We should positively consider standard treatments for older patients. However, not only their shorter life expectancy but also their poor PS and multiple comorbidities that sometimes render patients unable to receive standard treatments and several chemotherapy regimens, make their prognosis poor. The standard treatments for older patients, especially in locally advanced stages, require modification.

International audience; Differential cross sections of p–6He elastic scattering were measured in inverse kinematics at an incident energy of 200 A MeV, covering the high momentum transfer region of 1.7–2.7 fm−1. The sensitivity of the elastic scattering at low and high momentum transfers to the density distribution was investigated quantitatively using relativistic impulse approximation calculations. In the high momentum transfer region, where the present data were taken, the differential cross section has an order of magnitude higher sensitivity to the inner part of the 6He density relative to the peripheral part (15:1). This feature makes the obtained data valuable for the deduction of the inner part of the 6He density. The data were compared to a set of calculations assuming different proton and neutron density profiles of 6He. The data are well reproduced by the calculation assuming almost the same profiles of proton and neutron densities around the center of 6He, and a proton profile reproducing the known point-proton radius of 1.94 fm. This finding is consistent with the assumption that the 6He nucleus consists of a rigid α-like core with a two-neutron halo.

The (^{12}N, ^{12}C) charge-exchange reaction at 175 MeV/u was developed as a novel probe for studying the isovector spin giant monopole resonance (IVSMR), whose properties are important for better understanding the bulk properties of nuclei and asymmetric nuclear matter. This probe, now available through the production of ^{12}N as a secondary rare-isotope beam, is exothermic, is strongly absorbed at the surface of the target nucleus, and provides selectivity for spin-transfer excitations. All three properties enhance the excitation of the IVSMR compared to other, primarily light-ion, probes, which have been used to study the IVSMR thus far. The ^{90}Zr(^{12}N,^{12}C) reaction was measured and the excitation energy spectra up to about 70 MeV for both the spin-transfer and non-spin-transfer channels were deduced separately by tagging the decay by γ emission from the ^{12}C ejectile. Besides the well-known Gamow-Teller and isobaric analog transitions, a clear signature of the IVSMR was identified. By comparing with the results from light-ion reactions on the same target nucleus and theoretical predictions, the suitability of this new probe for studying the IVSMR was confirmed.

We systematically measured the differential cross sections of inelastic $\ensuremath{\alpha}$ scattering off self-conjugate $A=4n$ nuclei at two incident energies ${E}_{\ensuremath{\alpha}}=130\phantom{\rule{0.28em}{0ex}}\mathrm{MeV}$ and $386\phantom{\rule{0.28em}{0ex}}\mathrm{MeV}$ at Research Center for Nuclear Physics, Osaka University. The measured cross sections were analyzed by the distorted-wave Born-approximation (DWBA) calculation using the single-folding potentials, which are obtained by folding macroscopic transition densities with the phenomenological $\ensuremath{\alpha}N$ interaction. The DWBA calculation with the density-dependent $\ensuremath{\alpha}N$ interaction systematically overestimates the cross sections for the $\mathrm{\ensuremath{\Delta}}L=0$ transitions. However, the DWBA calculation using the density-independent $\ensuremath{\alpha}N$ interaction reasonably well describes all the transitions with $\mathrm{\ensuremath{\Delta}}L=0$--4. We examined uncertainties in the present DWBA calculation stemming from the macroscopic transition densities, distorting potentials, phenomenological $\ensuremath{\alpha}N$ interaction, and coupled channel effects in $^{12}\mathrm{C}$. It was found that the DWBA calculation is not sensitive to details of the transition densities nor the distorting potentials, and the phenomenological density-independent $\ensuremath{\alpha}N$ interaction gives reasonable results. The coupled-channel effects are negligibly small for the ${2}_{1}^{+}$ and ${3}_{1}^{\ensuremath{-}}$ states in $^{12}\mathrm{C}$, but not for the ${0}_{2}^{+}$ state. However, the DWBA calculation using the density-independent interaction at ${E}_{\ensuremath{\alpha}}=386\phantom{\rule{0.28em}{0ex}}\mathrm{MeV}$ is still reasonable even for the ${0}_{2}^{+}$ state. We concluded that the macroscopic DWBA calculations using the density-independent interaction are reliably applicable to the analysis of inelastic $\ensuremath{\alpha}$ scattering at ${E}_{\ensuremath{\alpha}}\ensuremath{\sim}100\phantom{\rule{0.28em}{0ex}}\mathrm{MeV}/\mathrm{u}$.

International audience; The dependence of the single-particle strength on the difference between proton and neutron separation energies is studied for oxygen isotopes in a wide range of isospins. The cross sections of the quasi-free (p, 2p) reaction on 14,16,18,22,24O were measured at intermediate energies. The measured cross sections are compared to predictions based on the distorted wave impulse approximation and shell-model psd valence-space spectroscopic factors. The reduction factors, which are the ratio of the experimental cross sections to the theoretical predictions, show no apparent dependence on the proton–neutron separation energy difference. The result is compatible with the result of the (e, e p) reaction on stable targets and with the predictions of recent ab initio calculations.

C 2 -symmetric ester-amide functionalized azolium salt was synthesized from readily available α-amino ester such as L -serine methyl ester. The combination of a Cu salt and the chiral azolium salt promoted the asymmetric conjugate addition reaction of enones with dialkylzincs. Thus, treatment of acyclic enone such as chalcone with Et 2 Zn afforded the corresponding 1,4-adduct with up to 85% ee. An excellent ee value of 93% was obtained when 3-nonen-2-one was reacted with Et 2 Zn. The present catalytic system was found to be useful for the 1,4-addition reaction of cyclic enone. For example, the reaction of 2-cyclohepten-1-one with Et 2 Zn produced ( R )-3-ethylcycloheptanone with 80% ee.

We have measured a complete set of deuteron analyzing powers in deuteron–proton elastic scattering at 190, 250, and 294 MeV/nucleon. The obtained data are compared with the Faddeev calculations based on the modern nucleon–nucleon forces together with the Tucson-Melbourne’99, and UrbanaIX three nucleon forces. The data are also presented with the calculations based on the N4LO NN potentials of the chiral effective field theory.

A hydroxyamide-functionalized azolium salt as the precursor of a (±)-trans-1,2-cyclohexanediamine-based bis(NHC) ­ligand was designed and synthesized from readily accessible l -leucinol. The combination of a Cu salt with this chiral ligand precursor promoted the asymmetric conjugate addition of Et2Zn to 2-cyclohexen-1-one at room temperature without the need for temperature control to afford the corresponding 1,4-adduct with up to 95% ee.

The effects of three nucleon force (3NF) have been actively studied via the nucleon–deuteron (Nd) scattering states. The differential cross sections and the vector analyzing powers A y of the 2H(p, n) inclusive breakup reaction at 170 MeV were measured for the study of 3NF effects in the intermediate energy region. The polarized proton beam of 170 MeV was injected to the deuterated polyethylene (CD2) target and the energy of scattered neutrons were measured by using TOF method. The data were compared with the Faddeev calculations based on modern nucleon–nucleon (NN) forces with and without the 3NF. Concerning the differential cross sections, we can see large discrepancies between the data and the calculations in the region of scattered neutron energies are low, which is similar to the results of the 2H(p, p) inclusive breakup reaction at 250 MeV.