A randomized, double-blind, placebo-controlled phase II study of olanzapine-based prophylactic antiemetic therapy for delayed and persistent nausea and vomiting in patients with HER2-positive or HER2-low breast cancer treated with trastuzumab deruxtecan: ERICA study (WJOG14320B).

BACKGROUND: Nausea and vomiting are common adverse events associated with trastuzumab deruxtecan (T-DXd). We evaluated the efficacy of an olanzapine-based triplet regimen for preventing nausea and vomiting in patients receiving their first cycle T-DXd. PATIENTS AND METHODS: This multi-institutional, randomized, double-blind, placebo-controlled (ERICA) phase II study enrolled patients with human epidermal growth factor receptor 2-positive/human epidermal growth factor receptor 2-low metastatic breast cancer receiving their first cycle of T-DXd. Patients were randomized to olanzapine 5 mg or placebo once daily (1 : 1 ratio) from day 1 to day 6, plus a 5-hydroxytryptamine type 3 receptor antagonist and dexamethasone 6.6 mg intravenously or 8 mg orally on day 1. The total observation period was 504 h (21 days) from the first T-DXd administration. The primary endpoint was complete response (CR), defined as no emetic events and no rescue medications, in the delayed phase (24-120 h after T-DXd), with the type I error rate of 0.2 (one-sided) for the comparison. Secondary endpoints included no nausea rate in the delayed and persistent phases (120-504 h), adverse event by Common Terminology Criteria for Adverse Events (CTCAE) and patient-reported outcomes version of the CTCAE (PRO-CTCAE). RESULTS: In total, 168 patients were enrolled at 43 sites in Japan (November 2021-September 2023) with 162 patients (olanzapine, n = 80; placebo, n = 82) included in the per protocol set. The primary endpoint was met as the delayed phase CR rate was significantly greater with olanzapine than placebo (70.0% versus 56.1%, P = 0.047). Efficacy was maintained in the persistent phase (63.9% versus 44.4%). No nausea rate was also greater with olanzapine (delayed phase: 57.5% versus 37.8%; persistent phase: 51.4% versus 31.9%). CR rates in the delayed phase favored olanzapine across subgroups. Appetite loss was also decreased with olanzapine. Hyperglycemia and somnolence were mostly of low-grade severity. CONCLUSION: Olanzapine 5 mg for 6 days with 5-hydroxytryptamine type 3 receptor antagonist and dexamethasone appears effective for T-DXd-treated patients to prevent delayed and persistent nausea and vomiting.

Precise Spectroscopy of the 3n and 3p Systems via the

To search for low-energy resonant structures in isospin T=3/2 three-body systems, we have performed the experiments ^{3}H(t,^{3}He)3n and ^{3}He(^{3}He,t)3p at intermediate energies. For the 3n experiment, we have newly developed a thick Ti-^{3}H target that has the largest tritium thickness among targets of this type ever made. The 3n experiment for the first time covered the momentum-transfer region as low as 15 MeV/c, which provides ideal conditions for producing fragile systems. However, in the excitation-energy spectra we obtained, we did not observe any distinct peak structures. This is in sharp contrast to tetraneutron spectra. The distributions of the 3n and 3p spectra are found to be similar, except for the displacement in energy due to Coulomb repulsion. Comparisons with theoretical calculations suggest that three-body correlations exist in the 3n and 3p systems, although not enough to produce a resonant peak.

Turbulence Transition in Magnetically Confined Hydrogen and Deuterium Plasmas.

In this study, we discovered a turbulence transition in a large helical device. The turbulence level and turbulence-driven energy transport decrease to a specific transition density and increase above it. The ruling turbulences below and above the transition density were ion-temperature gradient (ITG) and resistive-interchange (RI) turbulences, consistent with the predictions of gyrokinetic theory and two-fluid MHD model, respectively. Isotope experiments on hydrogen (H) and deuterium (D) clarified the role of transitions. In the ITG regime, turbulence levels and energy transport were comparable in the H and D plasmas. In contrast, in the RI regime, they were clearly suppressed in the D plasma. The results provide crucial knowledge for understanding isotope effects and future optimization of stellarator and heliotron devices.

Association between skin toxicity and efficacy of necitumumab in squamous non-small-cell lung cancer: a pooled analysis of two randomized clinical trials-SQUIRE and JFCM.

BACKGROUND: Efficacy of necitumumab [recombinant human monoclonal antibody that blocks the ligand binding epidermal growth factor receptor (EGFR)] in patients with squamous (SQ) non-small-cell lung cancer (NSCLC) has been confirmed in two randomized clinical trials (SQUIRE and JFCM). This study evaluated the association between efficacy and initial skin toxicity with necitumumab treatment by analyzing pooled data from two clinical trials (SQUIRE and JFCM). MATERIALS AND METHODS: Data of 635 patients with SQ-NSCLC (intent-to-treat population) treated with necitumumab plus gemcitabine and cisplatin (N + GC) were pooled from two clinical trials (SQUIRE and JFCM). The relationship between skin toxicities developed by the end of the second cycle and efficacy was evaluated. Efficacy endpoints included overall survival (OS), progression-free survival (PFS), and objective response rate (ORR). Univariate and multivariate analyses were carried out for these endpoints. RESULTS: OS and ORR were associated with skin toxicity, whereas PFS was not. Patients with grade ≥2 or grade 1 skin toxicity had significantly longer OS compared to patients without skin toxicity (grade 0) in the N + GC group [median = 15.0 (grade ≥2); 12.7 (grade 1); 9.4 (grade 0) months; hazard ratio (HR) = 0.51 (grade ≥2 to grade 0); 95% confidence interval (CI) 0.40-0.64, P < 0.001 and HR = 0.64 (grade 1 to grade 0); 95% CI 0.52-0.80, P < 0.001]. In multivariate analysis, OS was significantly associated with skin toxicity. CONCLUSIONS: A significant association was found between necitumumab-induced skin toxicity and efficacy. These results are consistent with the previously reported association between other EGFR inhibitors-induced skin toxicity and efficacy.

Quasi-2D Fermi surface in the anomalous superconductor UTe2.

The heavy fermion paramagnet UTe2 exhibits numerous characteristics of spin-triplet superconductivity. Efforts to understand the microscopic details of this exotic superconductivity have been impeded by uncertainty regarding the underlying electronic structure. Here we directly probe the Fermi surface of UTe2 by measuring magnetic quantum oscillations in pristine quality crystals. We find an angular profile of quantum oscillatory frequency and amplitude that is characteristic of a quasi-2D Fermi surface, which we find is well described by two cylindrical Fermi sheets of electron- and hole-type respectively. Additionally, we find that both cylindrical Fermi sheets possess considerable undulation but negligible small-scale corrugation, which may allow for their near-nesting and therefore promote magnetic fluctuations that enhance the triplet pairing mechanism. Importantly, we find no evidence for the presence of any 3D Fermi surface sections. Our results place strong constraints on the possible symmetry of the superconducting order parameter in UTe2.

Longitudinal Spin Fluctuations Driving Field-Reinforced Superconductivity in UTe_{2}.

Our measurements of ^{125}Te NMR relaxations reveal an enhancement of electronic spin fluctuations above µ_{0}H^{*}∼15 T, leading to their divergence in the vicinity of the metamagnetic transition at µ_{0}H_{m}≈35 T, below which field-reinforced superconductivity appears when a magnetic field (H) is applied along the crystallographic b axis. The NMR data evidence that these fluctuations are dominantly longitudinal, providing a key to understanding the peculiar superconducting phase diagram in H∥b, where such fluctuations enhance the pairing interactions.

Field Induced Multiple Superconducting Phases in UTe_{2} along Hard Magnetic Axis.

The superconducting (SC) phase diagram in uranium ditelluride is explored under magnetic fields (H) along the hard magnetic b axis using a high-quality single crystal with T_{c}=2.1 K. Simultaneous electrical resistivity and ac magnetic susceptibility measurements discern low- and high-field SC (LFSC and HFSC, respectively) phases with contrasting field-angular dependence. Crystal quality increases the upper critical field of the LFSC phase, but the H^{*} of ∼15 T, at which the HFSC phase appears, is always the same through the various crystals. A phase boundary signature is also observed inside the LFSC phase near H^{*}, indicating an intermediate SC phase characterized by small flux pinning forces.

Effect of uranium deficiency on normal and superconducting properties in unconventional superconductor UTe2.

Single crystals of the unconventional superconductor UTe2have been grown in various conditions which result in different superconducting transition temperature as well as normal state properties. Stoichiometry of the samples has been characterized by the single-crystal x-ray crystallography and electron microprobe analyses. Superconducting samples are nearly stoichiometric within an experimental error of about 1%, while non-superconducting sample significantly deviates from the ideal composition. The superconducting UTe2showed that the large density of states was partially gapped in the normal state, while the non-superconducting sample is characterized by the relatively large electronic specific heat as reported previously.

First-line nivolumab + ipilimumab in advanced NSCLC: CheckMate 227 subpopulation analyses in Asian patients.

BACKGROUND: Nivolumab plus ipilimumab demonstrated clinically meaningful improvement in efficacy versus chemotherapy with a manageable safety profile in patients with advanced non-small cell lung cancer (NSCLC) and tumor programmed death-ligand 1 (PD-L1) expression ≥1% or <1% in Part 1 of CheckMate 227. Here we report efficacy and safety results for the Asian subpopulation. METHODS: Patients with stage IV/recurrent NSCLC were randomized 1 : 1 : 1 to nivolumab plus ipilimumab, nivolumab monotherapy, or chemotherapy (PD-L1 ≥1%) or nivolumab plus ipilimumab, nivolumab plus chemotherapy, or chemotherapy (PD-L1 <1%). Overall survival (OS), progression-free survival, objective response rate, duration of response, and safety were evaluated among patients in Japan, South Korea, and Taiwan. RESULTS: In the Asian subpopulation with PD-L1 ≥1%, 81 patients received nivolumab plus ipilimumab and 81 received chemotherapy. Median OS was not reached with nivolumab plus ipilimumab versus 24.8 months with chemotherapy; 3-year OS rate was 53% versus 37% [hazard ratio (HR), 0.72; 95% confidence interval (CI) 0.47-1.11]. The 3-year progression-free survival rate was 26% versus 7% (HR, 0.65; 95% CI 0.45-0.96), objective response rate was 56% versus 37%, and median duration of response was 29.0 months (95% CI 15.0 months-not reached) versus 6.9 months (95% CI 3.9-11.1 months). Similar results were observed regardless of tumor PD-L1 expression and in Japanese patients. Grade 3-4 treatment-related adverse events occurred in 40% of patients receiving nivolumab plus ipilimumab and 36% receiving chemotherapy, in the overall Asian subpopulation (tumor PD-L1 expression ≥1% and <1%); no new safety signals were identified. CONCLUSIONS: At 3-year follow-up, nivolumab plus ipilimumab provided durable long-term efficacy benefits versus chemotherapy regardless of tumor PD-L1 expression in the Asian subpopulation, including Japanese patients. Consistent with findings for all randomized patients, these data support the use of nivolumab plus ipilimumab as first-line treatment of Asian patients with advanced NSCLC.

Dual-Task Training Combining Cognitive Tasks and Occupations among Japanese Community-Dwelling Older Adults: A Pilot Study.

This study investigated whether dual tasks comprising cognitive tasks and occupations related to daily living can improve the mental and cognitive function of Japanese community-dwelling older adults. Participants included 30 older adults, equally divided into intervention and control groups. The outcome measures were memory, attention, depression, and health-related quality of life. No adverse effects of the intervention were observed in any participant in the intervention group. Logical memory I, logical memory II, and Center for Epidemiologic Studies Depression Scale scores showed a significant interaction. Dual tasks combining cognitive tasks and occupations may help improve delayed recall and alleviate depression. A novel attempt to integrate cognitive stimulation and activities valued by individuals may help mediate age-related cognitive function decline and reduce depressive symptoms in community-dwelling older adults.

Gastrointestinal stromal tumour lacking mutations in the KIT and PDGFRA genes in a cat.

Molecular subtyping in gastrointestinal stromal tumours is a useful method for predicting the efficacy of treatment using tyrosine kinase inhibitors in humans. However, owing to the paucity of reports on mutational analyses, the association between genetic mutations and the therapeutic response to tyrosine kinase inhibitors remains unclear in feline gastrointestinal stromal tumours. In this report, we describe the case of a cat with a gastrointestinal stromal tumour which was unresponsive to tyrosine kinase inhibitors. A mutational analysis revealed that the cat lacked mutations in both the KIT and platelet-derived growth factor receptor-alpha (PDGFRA) genes. Our findings are consistent with the fact that KIT/PDGFRA wild-type gastrointestinal stromal tumours are less responsive to tyrosine kinase inhibitors in humans. This signifies the need for further evaluation and possibly individualised treatment for gastrointestinal stromal tumours in cats on the basis of mutational analyses.

First-line nivolumab plus ipilimumab with two cycles of chemotherapy versus chemotherapy alone (four cycles) in advanced non-small-cell lung cancer: CheckMate 9LA 2-year update.

BACKGROUND: To further characterize survival benefit with first-line nivolumab plus ipilimumab with two cycles of chemotherapy versus chemotherapy alone, we report updated data from the phase III CheckMate 9LA trial with a 2-year minimum follow-up. PATIENTS AND METHODS: Adult patients were treatment naïve, with stage IV/recurrent non-small-cell lung cancer, no known sensitizing EGFR/ALK alterations, and an Eastern Cooperative Oncology Group performance status ≤1. Patients were randomized 1 : 1 to nivolumab 360 mg every 3 weeks plus ipilimumab 1 mg/kg every 6 weeks with two cycles of chemotherapy, or four cycles of chemotherapy. Updated efficacy and safety outcomes are reported, along with progression-free survival (PFS) after next line of treatment (PFS2), treatment-related adverse events (TRAEs) by treatment cycle, and efficacy outcomes in patients who discontinued all treatment components in the experimental arm due to TRAEs. RESULTS: With a median follow-up of 30.7 months, nivolumab plus ipilimumab with chemotherapy continued to prolong overall survival (OS) versus chemotherapy. Median OS was 15.8 versus 11.0 months [hazard ratio 0.72 (95% confidence interval 0.61-0.86)]; 2-year OS rate was 38% versus 26%. Two-year PFS rate was 20% versus 8%. ORR was 38% versus 25%, respectively; 34% versus 12% of all responses were ongoing at 2 years. Median PFS2 was 13.9 versus 8.7 months. Improved efficacy outcomes in the experimental versus control arm were observed across most subgroups, including by programmed death-ligand 1 and histology. No new safety signals were observed; onset of grade 3/4 TRAEs was mostly observed during the first two treatment cycles in the experimental arm. In patients who discontinued all components of nivolumab plus ipilimumab with chemotherapy treatment due to TRAEs (n = 61) median OS was 27.5 months; 56% of responders had an ongoing response ≥1 year after discontinuation. CONCLUSIONS: With a 2-year minimum follow-up, nivolumab plus ipilimumab with two cycles of chemotherapy provided durable efficacy benefits over chemotherapy with a manageable safety profile and remains an efficacious first-line treatment of advanced non-small-cell lung cancer.

Systematic evaluation of magnetic sensitivities of anisotropic magnetoresistive sensors at liquid helium temperature for superconducting cavities.

Trapped magnetic flux in bulk superconductors reduces the quality factor Q in superconducting radio-frequency (SRF) cavities. However, the mechanisms underlying flux trapping and radio-frequency loss are not well understood. Detailed observation of the magnetic distributions is important for understanding such phenomena. Magnetic field mapping is useful for observing the magnetic field distribution around SRF cavities. Measuring the change in the magnetic field around the cavity elucidates the flux trapping behavior. Anisotropic magnetoresistive (AMR) sensors are inexpensive and small devices that can detect magnetic flux density. The magnetic sensitivities of AMR sensors need to be evaluated at liquid helium temperature for the magnetic field mapping of SRF cavities. In this study, a test stand was constructed to calibrate the magnetic sensitivities of AMR sensors in liquid helium, and 110 AMR sensors were tested using this stand. The magnetic sensitivities were evaluated systematically. A solenoid coil was used to control the uniform external magnetic field and to measure the magnetic sensitivity at low temperatures. All AMR sensors exhibited suitable sensitivities to the magnetic field around the SRF cavity. The variation in these sensitivities in all AMR sensors was ∼1%. The AMR sensors were found to have sufficient sensitivity for mapping the magnetic field around the exterior surface of the SRF cavity.

Three-dimensional conformal radiation therapy for canine aortic body tumour: 6 cases (2014-2019).

OBJECTIVE: To determine the feasibility of three-dimensional conformal radiation therapy for canine aortic body tumours. MATERIALS AND METHODS: Medical records of dogs that had undergone three-dimensional conformal radiation therapy with presumptive diagnosis of aortic body tumour were reviewed for clinical characteristics, treatment modality and outcomes. RESULTS: Eight dogs were diagnosed with aortic body tumour and were treated with three-dimensional conformal radiation therapy. One dog had proliferation of a mass in the right atrium during treatment and died of respiratory distress. Another dog did not undergo follow-up CT to evaluate the treatment response due to the increased blood urea nitrogen values. The remaining 6 dogs were included in the case series. Radiotherapy was performed using a median dose per fraction of 7 Gy (3.3-7.14 Gy), a median of seven divided doses (7-15) and a total median dose of 49 Gy (45-50 Gy). The median number of CT scans during the follow-up period was 5 (range: 3-8 times). CT revealed acute side effects in four dogs-grade 1 effects related to the lung (n = 4) and skin (n = 2). Self-limiting or asymptomatic late side effects (grade 1 lung-related effect) were observed in three dogs. After therapy, one dog demonstrated a complete response, another demonstrated a partial response and the disease remained stable in four animals. The median follow-up period was 514.5 (235-1219) days. After three-dimensional conformal radiation therapy, the aortic body tumour reduced gradually over time without regrowth in all these 6 dogs. CLINICAL SIGNIFICANCE: In this small case series, aortic body tumours responded to three-dimensional conformal radiation therapy. Transient and self-limiting side effects of the treatments were common. Further controlled studies are required to prove the effectiveness and the safety of this intervention.

A clinical investigation of the association between perioperative oral management and prognostic nutritional index in patients with digestive and urinary cancers.

Background: The prognostic nutritional index (pni) is a simple metric calculated using serum albumin and the peripheral lymphocyte count. It was reported that a low pni score is significantly associated with major postoperative complications and poor prognosis. The purpose of the present study was to investigate the effects of perioperative oral management (pom) on the perioperative pni profiles of patients with digestive system or urinary cancers. Study Design: The medical records of 181 patients with cancer who underwent surgery and for whom a pni could be calculated were retrospectively reviewed. Results: The intervention rate with pom was 34.8%. The median preoperative pni score was 48.25 in all patients with a pom intervention [25% to 75% interquartile range (iqr): 44.38-54.13] and 47.25 in those without an intervention (iqr: 42.0-53.5). Compared with patients not receiving pom, those who received pom had significantly higher pni scores from the early postoperative period (p < 0.05). Notably, of patients who could resume oral intake within 3 days after surgery, those who received pom intervention, compared with those who did not, had significantly higher pni scores from the early postoperative period (p < 0.05). Conclusions: Perioperative oral management interventions might have positive effects on the postoperative pni scores of patients with cancer.

Mapping of a New Deformation Region around

We performed the first direct mass measurements of neutron-rich scandium, titanium, and vanadium isotopes around the neutron number 40 at the RIKEN RI Beam Factory using the time-of-flight magnetic-rigidity technique. The atomic mass excesses of ^{58-60}Sc, ^{60-62}Ti, and ^{62-64}V were measured for the first time. The experimental results show that the two-neutron separation energies in the vicinity of ^{62}Ti increase compared to neighboring nuclei. This shows that the masses of Ti isotopes near N=40 are affected by the Jahn-Teller effect. Therefore, a development of Jahn-Teller stabilization appears below the Cr isotopes, and the systematics in Sc, Ti, and V isotopes suggest that ^{62}Ti is located close to the peak of the Jahn-Teller effect.

How Different is the Core of

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.

Switching of band inversion and topological surface states by charge density wave.

Topologically nontrivial materials host protected edge states associated with the bulk band inversion through the bulk-edge correspondence. Manipulating such edge states is highly desired for developing new functions and devices practically using their dissipation-less nature and spin-momentum locking. Here we introduce a transition-metal dichalcogenide VTe2, that hosts a charge density wave (CDW) coupled with the band inversion involving V3d and Te5p orbitals. Spin- and angle-resolved photoemission spectroscopy with first-principles calculations reveal the huge anisotropic modification of the bulk electronic structure by the CDW formation, accompanying the selective disappearance of Dirac-type spin-polarized topological surface states that exist in the normal state. Thorough three dimensional investigation of bulk states indicates that the corresponding band inversion at the Brillouin zone boundary dissolves upon the CDW formation, by transforming into anomalous flat bands. Our finding provides a new insight to the topological manipulation of matters by utilizing CDWs' flexible characters to external stimuli.