Quantum oscillations with magnetic hysteresis observed in CeTe3_{3} thin films

We have performed magnetotransport measurements in CeTe$_{3}$ thin films down to $0.2~{\rm K}$. It is known that CeTe$_{3}$ has two magnetic transitions at $T_{\rm N1} \approx 3~{\rm K}$ and $T_{\rm N2} \approx 1~{\rm K}$. A clear Shubnikov-de-Haas (SdH) oscillation was observed at $4~{\rm K}$, demonstrating the strong two-dimensional nature in this material. Below $T_{\rm N2}$, the SdH oscillation has two frequencies, indicating that the Fermi surface could be slightly modulated due to the second magnetic transition. We also observed a magnetic hysteresis in the SdH oscillation below $T_{\rm N1}$. Especially, there is a unique spike in the magnetoresistance at $B \approx 0.6~{\rm T}$ only when the magnetic field is swept from a high enough field (more than $2~{\rm T}$) to zero field.Comment: 5 pages, 4 figures, accepted for publication in Applied Physics Letter

Butterfly-shaped magnetoresistance in van der Waals ferromagnet Fe5GeTe2

We have performed magnetoresistance (MR) measurements on van der Waals ferromagnetic devices using quenched- (Q-) and nonquenched- (NQ-) Fe₅GeTe₂ crystals. A clear butterfly-shaped hysteresis has been observed for thin-film (less than 6 unit-cell layer) Q- and NQ-Fe₅GeTe₂ devices, but not for thicker film ones. The switching field of the butterfly-shaped MR is consistent with the coercive filed obtained from the Hall measurements. The MR ratio of the butterfly peak reaches about 10% at maximum, which is much larger than that observed with conventional magnetic materials. Such a large MR ratio would be related to magnetic fluctuations due to the complicated magnetic structure in this material

Quantum oscillations with magnetic hysteresis observed in CeTe3 thin films

We have performed magnetotransport measurements in CeTe3 thin films down to 0.2K. It is known that CeTe3 has two magnetic transitions at TN 1 approximate to 3K and TN 2 approximate to 1K. A clear Shubnikov-de-Haas (SdH) oscillation was observed at 4K, demonstrating the strong two-dimensional nature in this material. BelowTN 2, the SdH oscillation has two frequencies, indicating that the Fermi surface could be slightly modulated due to the second magnetic transition. We also observed a magnetic hysteresis in the SdH oscillation below TN 1. Specifically, there is a unique spike in the magnetoresistance at B approximate to 0.6T only when the magnetic field is swept from a high enough field (more than 2T) to zero field

Shubnikov-de-Haas oscillation and possible modification of effective mass in CeTe3 thin films

Magnetoresistance measurements have been performed in CeTe3 thin film devices in a temperature range from 2.1 to 20 K up to 8 T. A clear Shubnikov-de-Haas oscillation was observed in the whole temperature range. The temperature dependence of the oscillation amplitude was found to deviate from the Lifshitz-Kosevich formula below the magnetic transition temperature at T-N1 approximate to 3 K. This indicates a significant interplay between the magnetic ordering and the conduction electrons, which could lead to a modification of the effective cyclotron mass. By analyzing the temperature dependence of the oscillation amplitude, we have estimated the effective mass, quantum lifetime and quantum mobility of the material both in the paramagnetic and antiferromagnetic states

Safety and tolerability of bosutinib in patients with amyotrophic lateral sclerosis (iDReAM study) : A multicentre, open-label, dose-escalation phase 1 trial

Background: Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease caused by the loss of motor neurons, and development of effective medicines is urgently required. Induced pluripotent stem cell (iPSC)-based drug repurposing identified the Src/c-Abl inhibitor bosutinib, which is approved for the treatment of chronic myelogenous leukemia (CML), as a candidate for the molecular targeted therapy of ALS. Methods: An open-label, multicentre, dose-escalation phase 1 study using a 3 + 3 design was conducted in 4 hospitals in Japan to evaluate the safety and tolerability of bosutinib in patients with ALS. Furthermore, the exploratory efficacy was evaluated using Revised ALS Functional Rating Scale (ALSFRS-R), predictive biomarkers including plasma neurofilament light chain (NFL) were explored, and single-cell RNA sequencing of iPSC-derived motor neurons was conducted. Patients, whose total ALSFRS-R scores decreased by 1–3 points during the 12 week, received escalating doses starting from 100 mg quaque die (QD) up to 400 mg QD based on dose-limiting toxicity (DLT) occurrence, and all participants who received one dose of the study drug were included in the primary analysis. This trial is registered with ClinicalTrials.gov, NCT04744532, as Induced pluripotent stem cell-based Drug Repurposing for Amyotrophic Lateral Sclerosis Medicine (iDReAM) study. Findings: Between March 29, 2019 and May 7, 2021, 20 patients were enrolled, 13 of whom received bosutinib treatment and 12 were included in the safety and efficacy analyses. No DLTs were observed up to 300 mg QD, but DLTs were observed in 3/3 patients of the 400 mg QD cohort. In all patients receiving 100 mg–400 mg, the prevalent adverse events (AEs) were gastrointestinal AEs in 12 patients (92.3%), liver function related AEs in 7 patients (53.8%), and rash in 3 patients (23.1%). The safety profile was consistent with that known for CML treatment, and ALS-specific AEs were not observed. A subset of patients (5/9 patients) was found to respond well to bosutinib treatment over the 12-week treatment period. It was found that the treatment-responsive patients could be distinguished by their lower levels of plasma NFL. Furthermore, single-cell RNA sequencing of iPSC-derived motor neurons revealed the pathogenesis related molecular signature in patients with ALS showing responsiveness to bosutinib. Interpretation: This is the first trial of a Src/c-Abl inhibitor, bosutinib, for patients with ALS. The safety and tolerability of bosutinib up to 300 mg, not 400 mg, in ALS were described, and responsiveness of patients on motor function was observed. Since this was an open-label trial within a short period with a limited number of patients, further clinical trials will be required

Safety and tolerability of bosutinib in patients with amyotrophic lateral sclerosis (iDReAM study): A multicentre, open-label, dose-escalation phase 1 trial

筋萎縮性側索硬化症（ALS）患者さんを対象とした ボスチニブ第1相試験；iDReAM試験の成果報告 （論文発表）. 京都大学プレスリリース. 2022-10-26.Phase I clinical trial of bosutinib for amyotrophic lateral sclerosis (ALS); iDReAM study. 京都大学プレスリリース. 2022-11-28.[Background] Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease caused by the loss of motor neurons, and development of effective medicines is urgently required. Induced pluripotent stem cell (iPSC)-based drug repurposing identified the Src/c-Abl inhibitor bosutinib, which is approved for the treatment of chronic myelogenous leukemia (CML), as a candidate for the molecular targeted therapy of ALS. [Methods] An open-label, multicentre, dose-escalation phase 1 study using a 3 + 3 design was conducted in 4 hospitals in Japan to evaluate the safety and tolerability of bosutinib in patients with ALS. Furthermore, the exploratory efficacy was evaluated using Revised ALS Functional Rating Scale (ALSFRS-R), predictive biomarkers including plasma neurofilament light chain (NFL) were explored, and single-cell RNA sequencing of iPSC-derived motor neurons was conducted. Patients, whose total ALSFRS-R scores decreased by 1–3 points during the 12-week, received escalating doses starting from 100 mg quaque die (QD) up to 400 mg QD based on dose-limiting toxicity (DLT) occurrence, and all participants who received one dose of the study drug were included in the primary analysis. This trial is registered with ClinicalTrials.gov, NCT04744532, as Induced pluripotent stem cell-based Drug Repurposing for Amyotrophic Lateral Sclerosis Medicine (iDReAM) study. [Findings] Between March 29, 2019 and May 7, 2021, 20 patients were enrolled, 13 of whom received bosutinib treatment and 12 were included in the safety and efficacy analyses. No DLTs were observed up to 300 mg QD, but DLTs were observed in 3/3 patients of the 400 mg QD cohort. In all patients receiving 100 mg–400 mg, the prevalent adverse events (AEs) were gastrointestinal AEs in 12 patients (92.3%), liver function related AEs in 7 patients (53.8%), and rash in 3 patients (23.1%). The safety profile was consistent with that known for CML treatment, and ALS-specific AEs were not observed. A subset of patients (5/9 patients) was found to respond well to bosutinib treatment over the 12-week treatment period. It was found that the treatment-responsive patients could be distinguished by their lower levels of plasma NFL. Furthermore, single-cell RNA sequencing of iPSC-derived motor neurons revealed the pathogenesis related molecular signature in patients with ALS showing responsiveness to bosutinib. [Interpretation] This is the first trial of a Src/c-Abl inhibitor, bosutinib, for patients with ALS. The safety and tolerability of bosutinib up to 300 mg, not 400 mg, in ALS were described, and responsiveness of patients on motor function was observed. Since this was an open-label trial within a short period with a limited number of patients, further clinical trials will be required