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Calcineurin inhibitor-based graft-versus-host disease (GVHD) prophylaxis is standard in allogeneic hematopoietic stem cell transplantation (HCT) but fails to induce long-term tolerance without chronic GVHD in a considerable number of patients. In this study, we addressed this long-standing question in mouse models of HCT. After HCT, alloreactive donor T cells rapidly differentiated into PD-1+ TIGIT+ terminally exhausted T cells (terminal-Tex). GVHD prophylaxis with cyclosporine (CSP) suppressed donor T-cell expression of TOX, a master regulator to promote differentiation of transitory exhausted T cells (transitory-Tex), expressing both inhibitory receptors and effector molecules, into terminal-Tex, and inhibited tolerance induction. Adoptive transfer of transitory-Tex, but not terminal-Tex, into secondary recipients developed chronic GVHD. Transitory-Tex maintained alloreactivity and thus PD-1 blockade restored graft-versus-leukemia (GVL) activity of transitory-Tex, not terminal-Tex. In conclusion, CSP inhibits tolerance induction by suppressing the terminal exhaustion of donor T cells, while maintaining GVL effects to suppress leukemia relapse.

Allogeneic hematopoietic stem cell transplantation (allo-SCT) is a potentially curative therapy for FLT3 internal tandem duplication mutant (FLT3-ITD+) acute myeloid leukemia, but relapse rate is high. A recent study showed that sorafenib, a first generation FLT3 and multikinase inhibitor, enhanced graft-versus-leukemia (GVL) effects against FLT3-ITD+ leukemia via interleukin-15 (IL-15) production. However, it remains to be clarified whether this effect could be mediated by selective FLT3 inhibition. We investigated whether gilteritinib, a selective FLT3 inhibitor, could enhance GVL effects against FLT3-ITD transfected Ba/F3 leukemia (Ba/F3-FLT3-ITD) in mice. Oral administration of gilteritinib from day +5 to +14 after allo-SCT reduced expression of the co-inhibitory receptors PD-1 and TIGIT on donor CD8(+) T cells and enhanced IL-15 expression in Ba/F3-FLT3-ITD. Bioluminescent imaging using luciferase-transfected Ba/F3-FLT3-ITD demonstrated that gilteritinib significantly suppressed leukemia expansion after allo-SCT, whereas it did not impact the morbidity or mortality of graft-versus-host disease (GVHD), resulting in significant improvement of overall survival. In conclusion, short-term administration of gilteritinib after allo-SCT enhanced GVL effects against FLT3-ITD+ leukemia without exacerbating GVHD.

Purpose The purpose of this study was to investigate the incidence of multiple organ calcification and the correlation between multiple organ calcification and clinical severity in patients with thrombocytopenia, anasarca, fever, reticulin fibrosis, renal dysfunction, and organomegaly (TAFRO) syndrome. Methods We retrospectively identified 13 patients with TAFRO syndrome who were treated at our hospital between February 2019 and March 2021. Computed tomography (CT) images of TAFRO patients, which were acquired at admission and one month after admission, were evaluated. Additionally, clinical and laboratory data related to organ calcification and severity classification of TAFRO syndrome were investigated. The correlation between the presence of organ calcification on CT and TAFRO syndrome-severity classification was evaluated. Results One month after admission, calcification of the myocardium, adrenal glands, gallbladder wall, pancreas, kidney, skeletal muscle, and skin were observed in 38%, 46%, 15%, 15%, 15%, 23%, and 15% of the thirteen patients, respectively. The occurrence rate of calcifications in the myocardium, adrenal glands, and skeletal muscle was significantly higher in patients with a grade 4 or higher clinical severity than in those with a level up to grade 3 (p = 0.001, p = 0.005, and p = 0.035, respectively). Conclusions Our results suggest that the higher the clinical severity in patients with TAFRO syndrome, the higher is the frequency of calcification in the myocardium, adrenal glands, and skeletal muscle; therefore, the assessment of these organ calcifications on CT images may be useful in predicting the severity of TAFRO syndrome.

An optical wave microphone, which is well designed based on Fraunhofer diffraction of a laser beam, is expected to be applied to various acoustic fields where conventional microphones cannot be used due to strong electric and/or magnetic field. The authors have developed this technique and applied it to detect discharge sounds emitted from plasmas such as micro plasma, gliding arc plasma and plasma jet. An improved optical wave microphone with regard to signal-to-noise ratio uses single mode optical fibers for laser transformation. In this study, detailed characteristics of the fiber-type optical wave microphone were evaluated according to the theory of the optical wave microphone. Furthermore, the fiber-type optical wave microphone was combined with computer tomography (CT). The fiber-type optical wave microphone CT succeeded to visualize and quantify 2-D acoustic field generated by an ultrasonic transducer, and the obtained sound pressure distribution showed good similarity to that measured with a condenser microphone. Furthermore, the technique was applied to surface barrier discharge with different applied voltage frequencies and the distribution of acoustic waves above the discharge was quantified.

Granulopoiesis in the bone marrow adjusts cellular output as demand for neutrophils changes. Reactive granulopoiesis is induced by profound neutropenia, but its mechanism remains to be clarified. We herein explored its mechanisms using mouse models of syngeneic hematopoietic stem cell transplantation (SCT) and 5-fluorouracil-induced neutropenia. After SCT, T cell production of IL-17A was up-regulated. Neutrophil recovery was significantly delayed in IL-17A-deficient or T cell-deficient RAG1 −/− mice, and adoptive transfer of wild-type ( WT ) T cells facilitated neutrophil engraftment. Gut decontamination with oral antibiotics suppressed T cell production of IL-17A and impaired neutrophil recovery. Transplantation of fecal microbiota collected from neutropenic, not naive, mice promoted neutrophil recovery in these mice, suggesting that neutropenia-associated microbiota had a potential to stimulate reactive granulopoiesis. Our study uncovered a cross talk between gut microbiota and neutropenia after SCT and chemotherapy.

The excitation temperature of the high-current vacuum arc was measured based on the intensity ratio of two Cu I spectra of 510.6 and 515.3 nm. Diffuse mode vacuum arcs with the peak current of 2 kA, igniting between 5-mm gap, 10-mm phi electrodes, Cu100, Cu80Cr20, and Cu50Cr50 wt.% contacts were measured by a multiple-imaging optical system and high-speed video camera. It turns out that the excitation temperature was almost evenly distributed in the gap. The excitation temperature at the current peak depended on the electrode material and took higher in the order of Cu100, Cu80Cr20, and Cu50Cr50. The excitation temperature was also measured by a spectroscopic approach, and it showed the same tendencies as the measurement using multiple-imaging optical systems and a high-speed video camera. The current decreasing phase of dc interruption was simulated by using semiconductor switches at the peak of ac 50-Hz current, and as a result, the current zero with a decreasing ratio of 30 A/ $\mu \text{s}$ was realized. The excitation temperature for the Cu100 electrode decreased with the decreasing current, whereas those for Cu80Cr20 and Cu50Cr50 increased. This difference suggests that developing direct current vacuum circuit breakers needs the optimization of the electrode materials, current waveform, and plasma parameters in the gap.

The excitation temperature is a widely measured plasma parameter. In this article, the validity of an excitation temperature measurement is verified using a transition simulation between excited levels based on a collisional-radiative model. The collisional-radiative model calculation was validated by comparing it with the results of a spectroscopic measurement for a 2-kA peak vacuum arc ignited between the Cu100, Cu80Cr20, and Cu50Cr50 electrodes, whose diameter and gap length are 10 and 5 mm, respectively. As a result, the experimental result of the spectroscopy can be well simulated using the collisional-radiative model when the electron temperature and electron density are set to approximately 1.1–1.2 eV and 1.3– $2.1\times 10^{20}\,\,\text{m}^{-3}$ , respectively. It was found that the excitation temperature can be obtained from only two lines (510.6- and 515.3-nm lines) of the Cu I spectra with an accuracy comparable to that obtained from many line spectra of Cu neutrals. In addition, the relaxation times of the two lines are shorter than 100 ns. The excitation temperature, the electron temperature, and the electron density of the Cu100 electrodes were slightly higher than those of Cu50Cr50 electrodes. Such dependence on electrode material is caused by the difference in the density of the neutrals and ions. A comparison of the deposition ratio of Cu and Cr on the viewing port glass measured using energy-dispersive X-ray spectroscopy and a comparison of the cathode spot number suggest that the difference in the density of the neutrals and ions is caused by the difference in the cathode spot current.

Interelectrode phenomena related to intense-mode vacuum arc interruption were systematically compared between CuCr and AgWC electrodes by using various optical techniques mainly including two-color pyrometry for anode temperature determination after current zero, optical emission spectroscopy for the plasma composition assessment, and a Shack–Hartmann method for simultaneous 2-D electron and metal vapor density imaging. At the current peak, the widths of the radial electron density distributions for CuCr were narrower than those for AgWC. The electron density for CuCr was 3–5 times higher than that for AgWC. At current zero, the metal vapor density for CuCr was slightly lower than that for AgWC, which was specifically demonstrated for CuCr by a locally reduced metal vapor density below the minimum detectable limit of 1020 m−3. During and after the arcing time, mixing ratios of the copper vapor existing in the CuCr gap was about two times higher than expected from the CuCr electrode composition. After current zero, the decaying time constants of the metal vapor densities on the anode surfaces were Cr < Cu < Ag. This order was consistent with the decaying time constants of the anode evaporation rates estimated from the anode temperature measurement. The consistency suggests that the supplying process of the metal vapor after the intense vacuum arc interruption was the evaporation of the anode surfaces.

Highlights • The prognosis of atypical pulmonary carcinoid with liver metastases is poor, and the patients are often treated using non-surgical therapies. • We successfully treated multiple liver metastases from atypical pulmonary carcinoid by using two-stage hepatectomy combined with embolization of portal vein branches. • Two-stage hepatectomy may be a good option for bilobar multiple liver metastases of atypical pulmonary carcinoid., Introduction The prognosis of atypical pulmonary carcinoid with liver metastases is extremely poor, and patients with multiple liver metastases are often treated using non-surgical therapies. We report a case with multiple liver metastases from atypical pulmonary carcinoid that was successfully treated using two-stage hepatectomy combined with embolization of portal vein branches. Presentation of case A 48-year-old man was referred to our department after multiple liver tumors were detected in both liver lobes on computed tomography. He had undergone right upper lobectomy of the lung for atypical pulmonary carcinoid (T2a, N0, M0; Stage IB) 2 years previously. Positron emission tomography-computed tomography showed no extrahepatic tumor manifestations. The tumors were located in segment 2, 3, 5/8 and the right hepatic vein drainage area. We planned complete resection of metastases in a two-stage hepatectomy. The first stage comprised concomitant left lateral segmentectomy, partial hepatectomy of segment 5/8 and portal vein embolization of the posterior segmental branches. The second stage comprised resection of the right hepatic vein drainage area, performed 21 days after the first surgery. Histopathological diagnosis was liver metastases of atypical pulmonary carcinoid. Postoperative bile leak developed, which was treated with endoscopic retrograde biliary drainage and percutaneous bile leak drainage. He has been followed for 24 months postoperatively without tumor recurrence. Discussion Two-stage hepatectomy may represent an option for bilobar multiple liver metastases from atypical pulmonary carcinoid. Conclusion We successfully treated a patient with multiple liver metastases of atypical pulmonary carcinoid using a two-stage hepatectomy combined with portal vein embolization of the posterior segmental branches.