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Long-term sequelae of COVID-19 can affect health-related quality of life (HRQOL). We examined the long-term impact of COVID-19 on HRQOL and elucidated factors associated with low HRQOL. Discharged COVID-19 patients were assessed at 3 and 6 months after disease onset. The patients completed a medical examination and SF-36 questionnaire at the two time points and underwent pulmonary function testing at 6 months. All had undergone computed tomography (CT) imaging upon hospital admission. Of the 74 included patients, 38% reported respiratory symptoms at 3 months and 26% at 6 months. The aggregated SF-36 scores declined in the role/social component summary (RCS), a category related to social activity. Patients with respiratory sequelae or impaired pulmonary function had lower RCS scores. There was a negative linear relation between the RCS score and the CT score, which reflected the extent of COVID-19 pneumonia (3 months, P = 0.0024; 6 months, P = 0.0464). A high CT score (≥ 10 points) predicted a low RCS score at 6 months (P = 0.026). This study highlights the long-term impairment of RCS and its associations with respiratory sequelae. The study also emphasizes the importance of radiological findings in predicting long-term HRQOL outcomes after COVID-19.

Shwachman-Diamond syndrome (SDS) is an autosomal recessive inherited disorder characterized by bone marrow failure, exocrine pancreatic dysfunction, and skeletal abnormalities. SDS is typically caused by a pathogenic mutation in the Shwachman-Bodian-Diamond Syndrome (SBDS) gene. Patients with SDS have an increased risk of developing acute myeloid leukemia (AML) and myelodysplastic syndromes. We identified germline biallelic SBDS mutations (p.K62X and p.I167M) in a 50-year-old AML patient who had never experienced the typical symptoms of SDS. The K62X mutation is one of the most common pathogenic mutations, whereas the significance of the I167M mutation was unclear. Based on cellular experiments, we concluded that the I167M mutation contributed to the development of AML, and chemotherapy including topoisomerase inhibitors, which induce DNA double-strand breaks, may have been toxic to this patient. Our experience indicates that some asymptomatic Shwachman-Bodian-Diamond syndrome mutations contribute to the development of leukemia, and that careful treatment selection may be warranted for patients harboring these mutations.

Introduction The detailed observations by the NASA Juno spacecraft has advanced Jupiter’s interior structure models which can be used to improve our understanding of Jupiter’s origin. In this study, we investigate the potential origin of Jupiter's enriched atmosphere. We revisit the planetesimal accretion during Jupiter’s formation: in previous studies, the planetesimal accretion rate is calculated using N-body simulations that model the swam of planetesimals around proto-Jupiter. It was concluded that the heavy-element enrichment in Jupiter's envelope can be explained by the planetesimal accretion if Jupiter formed in a planetesimal disk that is at least five times more massive than the minimum mass solar nebulae (MMSN). However, this conclusion was inferred under the assumption that the total mass of captured planetesimals linearly increases with the surface density of planetesimals. In reality, in such a massive disk the gravitational interactions between planetesimals and embryos becomes so strong that the initial eccentricity and inclination are excited to 〜0.1 at most. In this study, we investigate this scenario in detail accounting for the change of the eccentricity and inclination of the planetesimals and show its affect off Jupiter’s growth rate and final composition. Model Figure 1: The surface density of planetesimals used in this study. This surface density profile is obtained by Kobayashi & Tanaka (2021). We adopt a planetesimal disk obtained by Kobayashi & Tanaka (2021) where the collisional evolution of dust grains in the protoplanetary disk results in a dense-compact planetesimal disk because of pebble drift from the outer disk. Figure 1 shows the surface density profile of planetesimals we use in this study. We start the N-body simulations with a swam of planetesimals around proto-Jupiter which enters the runaway gas accretion phase and increases its mass from 10 M⊕ to 318 M⊕. During its formation, we assume that proto-Jupiter slightly migrates inward due to type II migration. If a planetesimal collides on the surface of proto-Jupiter or loses its escape energy from Jupiter's Hill sphere, we assume that the planetesimal is captured by proto-Jupiter. We set the initial eccentricities and inclinations of planetesimals as input parameters. Since the choice of the planetesimal’s size can significantly affect the accretion rate we consider various planetesimal sizes. Results Figure 2: The cumulative mass of captured planetesimals as a function of time. Black, red, green and blue lines show correspond to different assumed initial eccentricities of ‹e0›1/2=10-3,10-2,10-1, and 0.4, respectively. The initial inclination is set as ‹i0›1/2=0.5‹e0›1/2. In a massive planetesimal disk, proto-Jupiter accretes tens Earth-masses of heavy elements by the end of runaway gas accretion. Figure 2 shows the cumulative mass of captured planetesimals vs. time. We find that the increase of the initial eccentricity and inclination: weakens resonant trapping and leads to an enhancement of planetesimal accretion, reduces the capture probability of planetesimals. Due to the combination of these effects, the captured mass of planetesimals decreases with the increase of the initial eccentricity and inclination. Discussion Figure 3: Total mass of captured planetesimals as a function of planetesimal size and the initial eccentricity. The initial inclination is set as ‹i0›1/2=0.5‹e0›1/2. The solid and dashed black line shows the equilibrium eccentricity of planetesimals with and without embryos, respectively. The initial eccentricity and inclination of planetesimals are determined by the scattering from other planetesimals/embryos. In a massive planetesimal disk as assumed here, embryos other than proto-Jupiter would form and be in the “oligarchic regime”. Considering the eccentricity and inclination excitation from the embryos, we conclude that the total mass of captured planetesimals is about 5-10 M⊕, and is larger for larger planetesimals. The bulk metallicity of Jupiter is still a matter of debate (e.g., Stevenson 2020). Planetesimal accretion could explain structure models with ~10 M⊕ of heavy elements in Jupiter’s outer envelope. However, if Jupiter’s enrichment is found to be higher, as suggested by some structure models (e.g., Miguel et al. 2022), an additional enrichment mechanism would be required. Such an enrichment could be a result of giant impacts of embryos. Such impacts have been suggested by Liu et al. (2019) for the formation of Jupiter’s fuzzy core. We also compare our results with those presented by Shibata & Helled (2022), where planetesimal accretion was considered for the case of a migrating Jupiter from 20 au to 5 au. We find that the timing of planetesimal accretion must occur earlier for the in-situ formation case, which enriches Jupiter's interior rather than the outer envelope or atmosphere. We suggest that a determination of the heavy-element distribution in Jupiter’s envelope could constrain Jupiter’s formation location and formation history. References Kobayashi, H., & Tanaka, H. 2021, ApJ, 922, 16, doi: 10.3847/1538-4357/ac289c Liu, S.-F., Hori, Y., M ̈uller, S., et al. 2019, Nature, 572, 355, doi: 10.1038/s41586-019-1470-2 Miguel, Y., Bazot, M., Guillot, T., et al. 2022, arXiv e-prints, arXiv:2203.01866. https://arxiv.org/abs/2203.01866 Shibata, S., & Ikoma, M. 2019, MNRAS, 487, 4510, doi: 10.1093/mnras/stz1629 Shibata, S., & Helled, R. 2022, ApJL, 926, L37, doi: 10.3847/2041-8213/ac54b1 Stevenson, D. J. 2020, Annu. Rev. Earth Planet. Sci., 48, 465

Basophils, the rarest granulocytes, were identified by Paul Ehrlich more than 140 years ago, much earlier than the discovery of T and B cells. Unfortunately, basophils were often mixed up with tissue-resident mast cells because of some phenotypic similarities between them and considered erroneously as minor relatives or blood-circulating precursors of mast cells. Moreover, basophil research was hindered by the rarity of basophils and the paucity of useful analytical tools, and therefore basophils had often been neglected in immunological studies. A series of studies using newly developed tools, including basophil-depleting antibodies and genetically engineered mice deficient only in basophils, have clearly defined previously unrecognized roles of basophils, that are distinct from those played by tissue-resident mast cells. In this mini-review, we highlight recent advances in our understanding of basophil functions, particularly focusing on their roles in the regulation of innate and acquired immunity, allergic reactions, autoimmunity and protective immunity against parasitic infections, mainly based on animal studies. Further studies on human basophils would facilitate the development of new strategies for the treatment of basophil-associated disorders.

Hypersensitivity pneumonitis (HP) typically presents with interstitial inflammation and granulomas induced by an aberrant immune response to inhaled Ags in sensitized individuals. Although IL-17A is involved in the development of HP, the cellular sources of IL-17A and the mechanisms by which IL-17A contributes to granuloma formation remain unclear. Recent studies report that γδ T cells produce IL-17A and exhibit memory properties in various diseases. Therefore, we focused on IL-17A–secreting memory γδ T cells in the sensitization phase and aimed to elucidate the mechanisms by which IL-17A contributes to granuloma formation in HP. We induced a mouse model of HP using pigeon dropping extract (PDE) in wild-type and IL-17A knockout (IL-17A−/−) mice. IL-17A−/− mice exhibited reduced granulomatous areas, attenuated aggregation of CD11b+ alveolar macrophages, and reduced levels of CCL2, CCL4, and CCL5 in the bronchoalveolar lavage fluid. Among IL-17A+ cells, more γδ T cells than CD4+ cells were detected after intranasal PDE administration. Interestingly, the expansion of IL-17A–secreting Vγ4+ or Vγ1−Vγ4− cells of convalescent mice was enhanced in response to the sensitizing Ag. Additionally, coculture of macrophages with PDE and Vγ4+ cells purified from PDE-exposed convalescent mice produced significantly more IL-17A than coculture with Vγ4+ cells from naive mice. Our findings demonstrate that in the sensitization phase of HP, IL-17A–secreting memory γδ T cells play a pivotal role. Furthermore, we characterized the IL-17A/CCL2, CCL4, CCL5/CD11b+ alveolar macrophage axis, which underlies granuloma formation in HP. These findings may lead to new clinical examinations or therapeutic targets for HP.

TAFRO syndrome and POEMS syndrome are lymphoproliferative disorders with elevated interleukin-6 and vascular endothelial growth factor (VEGF) levels; however, their underlying pathogenic mechanisms remain unclear. Similarities have been reported in the pathological findings of the lymph nodes of TAFRO syndrome, Multicentric Castleman disease (MCD), and some cases of POEMS syndrome. However, there is no consensus on the relationship among them. We encountered a case of lymphoproliferative disorder that presented with manifestations of both TAFRO syndrome and POEMS syndrome. This case may be a subtype of idiopathic MCD and will be very important for establishing the disease concept of TAFRO syndrome and POEMS syndrome.

Methotrexate, hydrocortisone, vincristine, sobuzoxane, and etoposide (MTX-HOPE) chemotherapy was originally reported in 2007 as a salvage regimen for relapsed or refractory non-Hodgkin's lymphoma. To clarify the safety and efficacy of this regimen, we retrospectively analyzed patients at our institute. We analyzed 18 patients, including 16 with diffuse large B-cell lymphoma (DLBCL), one with follicular lymphoma (FL), and one with T-cell lymphoma. The median age at MTX-HOPE therapy was 79 (range: 68-87). Ten patients received more than 3 previous chemotherapy regimens. The median period from the initial treatment to the first MTX-HOPE administration was 53 months. No patient had severe renal dysfunction. The overall response rate was 78%, with 39% achieving CR and 39% achieving PR. The median OS and PFS after the initiation of MTX-HOPE were 10 months (range: 0.5-86 months) and 7 months (range: 0.2-86 months), respectively. The one-year OS rate was 44% and the two-year OS rate was 22%. The median number of treatment cycles was 7 (range: 1-46), and 6 patients received more than 10 cycles. Among eight patients who were over 80 years of age, 7 responded to the therapy, and the median OS and PFS of this subgroup were 19 months and 11 months, respectively. All patients tolerated the treatment well, mostly on an outpatient basis, except for one who died from infection and one who developed intracranial hemorrhage. MTX-HOPE may be a promising treatment option for elderly patients with refractory or relapsed malignant lymphoma.

This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made., The goal of the Ariel space mission is to observe a large and diversified population of transiting planets around a range of host star types to collect information on their atmospheric composition. The planetary bulk and atmospheric compositions bear the marks of the way the planets formed: Ariel’s observations will therefore provide an unprecedented wealth of data to advance our understanding of planet formation in our Galaxy. A number of environmental and evolutionary factors, however, can affect the final atmospheric composition. Here we provide a concise overview of which factors and effects of the star and planet formation processes can shape the atmospheric compositions that will be observed by Ariel, and highlight how Ariel’s characteristics make this mission optimally suited to address this very complex problem. © The Author(s) 2021., D.T., S.F., S.M., E.S., and A.N. acknowledge the support of the Italian Space Agency (ASI) through the ASI-INAF contract 2018-22-HH.0. D.T., C.C., D.F., and L.P. acknowledge the support of the PRIN-INAF 2016 “The Cradle of Life - GENESIS-SKA (General Conditions in Early Planetary Systems for the rise of life with SKA”. D.T., S.F., S.M. D.F, J.M., F.O., P.W. acknowledge the support of the Italian National Institute of Astrophysics (INAF) through the INAF Main Stream project “Ariel and the astrochemical link between circumstellar discs and planets” (CUP: C54I19000700005). S.M. acknowledges support from the European Research Council via the Horizon 2020 Framework Programme ERC Synergy “ECOGAL” Project GA-855130. M.K. acknowledges funding by the University of Tartu ASTRA project 2014-2020.4.01.16-0029 KOMEET “Benefits for Estonian Society from Space Research and Application”, financed by the EU European Regional Development Fund. J.M.D.K. gratefully acknowledges funding from the Deutsche Forschungsgemeinschaft (DFG, German Research Foundation) through an Emmy Noether Research Group (grant number KR4801/1-1) and the DFG Sachbeihilfe (grant number KR4801/2-1), as well as from the European Research Council (ERC) under the European Union’s Horizon 2020 research and innovation programme via the ERC Starting Grant MUSTANG (grant agreement number 714907). The research of O.P. is funded by the Royal Society, through Royal Society Dorothy Hodgkin Fellowship DH140243. M.P. thanks the support to NuGrid from STFC (through the University of Hull’s Consolidated Grant ST/R000840/1), and access to VIPER, the University of Hull High Performance Computing Facility. M.P. acknowledges the support from the ”Lendulet-2014” Program of the Hungarian Academy of Sciences (Hungary), from the ERC Consolidator Grant (Hungary) funding scheme (Project RADIOSTAR, G.A. n. 724560), by the National Science Foundation (NSF, USA) under grant No. PHY-1430152 (JINA Center for the Evolution of the Elements). M.P. also thanks the UK network BRIDGCE and the ChETEC COST Action (CA16117), supported by COST (European Cooperation in Science and Technology). M.I. thanks the support by JSPS KAKENHI 18H05439. C.D. acknowledges financial support from the State Agency for Research of the Spanish MCIU through the “Center of Excellence Severo Ochoa” award to the Instituto de Astrofísica de Andalucía (SEV-2017-0709), and the Group project Ref. PID2019-110689RB-I00/AEI/10.13039/501100011033.

The alkylating agent busulfan is commonly used as conditioning in allogeneic hematopoietic stem cell transplantation for acute myeloid leukemia (AML). However, a consensus has not yet been reached regarding the optimal busulfan dose in cord blood transplantation (CBT). Therefore, we conducted this large nationwide cohort study to retrospectively analyze the outcomes of CBT in patients with AML receiving busulfan at intermediate (6.4 mg/kg i.v.; BU2) or higher (12.8 mg/kg i.v.; BU4) doses within a fludarabine/i.v. busulfan (FLU/BU) regimen. Among 475 patients who underwent their first CBT following FLU/BU conditioning between 2007 and 2018, 162 received BU2 and 313 received BU4. Multivariate analysis identified BU4 as a significant factor for longer disease-free survival (hazard ratio [HR], .85; 95% confidence interval [CI], .75 to .97; P = .014) and a lower relapse rate (HR, .84; 95% CI, .72 to .98; P = .030). No significant differences were observed in non-relapse mortality between BU4 and BU2 (HR, 1.05; 95% CI, .88-1.26; P = .57). Subgroup analyses showed that BU4 provided significant benefits for patients who underwent transplantation while not in complete remission (CR) and those age

Background and Objectives: Obstructive sleep apnea (OSA) is known to be one of the common complications of interstitial lung disease (ILD). Although it is suspected that the incidence of OSA and the progression of ILD are closely related to each other, the clinical features of ILD with such complications are not fully understood. The aim of this study is to clarify specific clinical factors in ILD patients that predict the complication and the severity of OSA.Study Design and Method: ILD patients in our institute were prospectively investigated for the incidence of OSA by polysomnography (PSG).Results: All 33 patients were diagnosed with OSA. Univariate regression analysis showed a lower Diffusing capacity of the lung for carbon monoxide (DLco) and a lower respiratory rate (RR) predicted a higher HI and a higher AI, respectively. Multivariate regression analysis showed a lower DLco and a lower RR also predicted a higher apnea hypopnea index (AHI).Conclusions: A high prevalence of OSA was exhibited in our study of ILD patients. Lacking rapid breathing pattern and impaired diffusing capacity were predictive factors for the severity of OSA. The examination of sleep disorders should be actively considered for these patients.Short title: The relationship between ILD and OSA

Jupiter's atmosphere is enriched with heavy elements by a factor of about 3 compared to proto-solar. The origin of this enrichment and whether it represent the bulk composition of the planetary envelope remain unknown. Internal structure models of Jupiter suggest that its envelope is separated from the deep interior and that the planet is not fully mixed. This implies that Jupiter's atmosphere was enriched with heavy elements just before the end of its formation. Such enrichment can be a result of late planetesimal accretion. However, in-situ Jupiter formation models suggest the decreasing accretion rate with increasing planetary mass, which cannot explain Jupiter's atmospheric enrichment. In this study, we model Jupiter's formation and show that an migration of proto-Jupiter from $\sim$ 20 AU to its current location can lead to a late planetesimal accretion and atmospheric enrichment. Late planetesimal accretion does not occur if proto-Jupiter migrates only a few AU. We suggest that if Jupiter's outermost layer is fully-mixed and is relatively thin (up to $\sim$ 20\% of its mass), such late accretion can explain its measured atmospheric composition. It is therefore possible that Jupiter underwent significant orbital migration followed by late planetesimal accretion., 18 pages, 8 figures, Accepted for ApJL

Ariel, the Atmospheric Remote-sensing Infrared Exoplanet Large-survey, was adopted as the fourth medium-class mission in ESA's Cosmic Vision programme to be launched in 2029. During its 4-year mission, Ariel will study what exoplanets are made of, how they formed and how they evolve, by surveying a diverse sample of about 1000 extrasolar planets, simultaneously in visible and infrared wavelengths. It is the first mission dedicated to measuring the chemical composition and thermal structures of hundreds of transiting exoplanets, enabling planetary science far beyond the boundaries of the Solar System. The payload consists of an off-axis Cassegrain telescope (primary mirror 1100 mm x 730 mm ellipse) and two separate instruments (FGS and AIRS) covering simultaneously 0.5-7.8 micron spectral range. The satellite is best placed into an L2 orbit to maximise the thermal stability and the field of regard. The payload module is passively cooled via a series of V-Groove radiators; the detectors for the AIRS are the only items that require active cooling via an active Ne JT cooler. The Ariel payload is developed by a consortium of more than 50 institutes from 16 ESA countries, which include the UK, France, Italy, Belgium, Poland, Spain, Austria, Denmark, Ireland, Portugal, Czech Republic, Hungary, the Netherlands, Sweden, Norway, Estonia, and a NASA contribution., Comment: Ariel Definition Study Report, 147 pages. Reviewed by ESA Science Advisory Structure in November 2020. Original document available at: https://www.cosmos.esa.int/documents/1783156/3267291/Ariel_RedBook_Nov2020.pdf/

Chronic active Epstein-Barr virus infection (CAEBV) is a systemic T- or NK-lymphoproliferative disorder (LPD) caused by EBV. Allogenic hematopoietic stem cell transplantation (HSCT) is the only curative therapy for CAEBV, but relapse sometimes occurs. Relapse is generally attributed to proliferation of recipient-derived CAEBV cells. We herein report a case of donor-derived CAEBV-like NK-cell post-transplant lymphoproliferative disease (PTLD) in a 41-year-old female after the first allogenic HSCT for CAEBV from an HLA-matched sibling donor. A second HSCT from an HLA-matched unrelated donor successfully controlled the disease, but EBV infection of cells derived from the second donor continued to be detected. Although the mechanisms underlying CAEBV and CAEBV-like NK-cell PTLD have not yet been elucidated in detail, the findings of the present case imply that host genetic factors, including familial factors, may be important in disease development.

Studies of internal structure of gas giant planets suggest that their envelopes are enriched with heavier elements than hydrogen and helium relative to their central stars. Such enrichment likely occurred by solid accretion during late formation stages of gas giant planets in which gas accretion dominates protoplanetary growth. Some previous studies performed orbital integration of planetesimals around a growing protoplanet with the assumption of an uniform circumstellar disc to investigate how efficiently the protoplanet captures planetesimals. However, not only planetesimals but also disc gas are gravitationally perturbed by the protoplanet in its late formation stages, resulting in gap opening in the circumstellar disc. In this study, we investigate the effects of such gap formation on the capture of planetesimals by performing dynamical simulations of planetesimals around a growing proto-gas giant planet. Gap formation reduces the surface density of disc gas, makes a steep pressure gradient and limits the growth rate of the protoplanet. We find that the first effect enhances the capture of planetesimals, while the others reduce it. Consequently the amount of planetesimals captured during the gas accretion is estimated to be at most ~3 Mearth. We conclude that the in-situ capture of planetesimals needs the initial solid surface density more than five times higher than that of the minimum mass solar nebula for explaining the inferred large amount of heavy element in Jupiter. For highly dense warm Jupiters, we would need additional processes enhancing the capture and/or supply of planetesimals., Comment: 15 pages, 13 figures, this is a pre-copyedited, author-produced version of an article accepted for publication in MNRAS following peer review

Shwachman-Diamond syndrome (SDS) is an autosomal recessive inherited disorder characterized by bone marrow failure, exocrine pancreatic dysfunction, and skeletal abnormalities. SDS is typically caused by a pathogenic mutation in the Shwachman-Bodian-Diamond Syndrome (SBDS) gene. Patients with SDS have an increased risk of developing acute myeloid leukemia (AML) and myelodysplastic syndromes. We identified germline biallelic SBDS mutations (p.K62X and p.I167M) in a 50-year-old AML patient who had never experienced the typical symptoms of SDS. The K62X mutation is one of the most common pathogenic mutations, whereas the significance of the I167M mutation was unclear. Based on cellular experiments, we concluded that the I167M mutation contributed to the development of AML, and chemotherapy including topoisomerase inhibitors, which induce DNA double-strand breaks, may have been toxic to this patient. Our experience indicates that some asymptomatic Shwachman-Bodian-Diamond syndrome mutations contribute to the development of leukemia, and that careful treatment selection may be warranted for patients harboring these mutations.

We report a case of acquired hypofibrinogenemia with multiple myeloma presenting λ-type IgG monoclonal protein. The patient had anemia and renal deficiency, and also developed bleeding tendency due to severe coagulopathy. Her fibrinogen level was under the detectable limits in a functional assay. Enzyme-linked immunosorbent assay (ELISA) and immunoblotting analysis results were consistent with functional assay results, and deficiency patterns observed in cross-mixing tests for PT and aPTT confirmed the diagnosis of hypofibrinogenemia. To determine the cause of hypofibrinogenemia, we purified the patient’s immunoglobulin via protein A agarose, and confirmed that fibrinogen was included in the bound fraction, strongly indicating paraprotein interference with fibrinogen. As accelerated removal of fibrinogen was indicated, we incubated the patient’s plasma up to 48 h, but did not observe significant loss of fibrinogen. In sharp contrast, fibrinogen returned to below the detection level 12 h after infusion of fresh frozen plasma. These findings support leukocyte-mediated fibrinogen removal, rather than paraprotein-triggered fibrinogen instability. Surprisingly, the patient’s paraprotein was IgG2, but we speculate the amount of paraprotein (IgG 5346 mg/dL) compensated for lower affinity to Fcγ receptors.

In 2003, a 60-year-old man presenting with thrombocytosis was referred to our hospital. Laboratory tests revealed normal white blood cell count and hemoglobin level. Bone marrow examination showed an increased number of megakaryocytes with dysplasia. G-banded karyotype analysis revealed del (5q). Initially, the patient was diagnosed with myelodysplastic/myeloproliferative neoplasm (MDS/MPN), and it was treated with aspirin and hydroxyurea. During the treatment course, fluorescence in situ hybridization for CSF1R and EGR1 was performed to detect del (5q), which showed negative results. In 2017, the patient had increased platelet count despite receiving treatment. A comprehensive genomic profiling revealed that the deleted region in this case was present in 5q14-5q23, which was different from the common deleted region of 5q- syndrome (5q32-5q33, where CSF1R was present) and that of high-risk MDS or acute myeloid leukemia (5q31, where EGR1 was present). Moreover, a CALR mutation was also detected. This case met the diagnostic criteria of essential thrombocythemia. The platelet count decreased with the administration of anagrelide. In conclusion, comprehensive genetic profiling is very important, and it leads to accurate diagnosis and therapy.

A 61-year-old man was admitted to our hospital with fever and massive leukocytosis. A bone marrow smear revealed an increased density of myeloid cells in various stages of maturation as well as dysplasia in the neutrophils. There was no proliferation of blasts, eosinophils, or basophils. Genomic analysis of the bone marrow cells revealed no detectable abnormalities associated with myeloproliferative neoplasms, including BCR-ABL1. Therefore, the patient was diagnosed with atypical chronic myeloid leukemia (aCML). Chromosomal analysis revealed the presence of 1-17 double minute chromosomes (dmin) in 20 of 20 tumor cells examined. Multiple MYC signals were detected via interphase fluorescence in situ hybridization, indicating MYC gene amplification in the dmins. Three months after the oral administration of hydroxyurea, leukocytosis reoccurred. Therefore, induction therapy followed with umbilical cord blood transplantation was performed. However, MYC signals remained detectable in the bone marrow sample obtained immediately after neutrophil engraftment, indicating the presence of residual tumor cells. To the best of our knowledge, this is the first case report of aCML with dmin gene amplification, suggesting that the dmin MYC amplification exacerbated the patient's disease.

Despite the wide prevalence of [6, 6]-phenyl-C71-butyric acid methyl ester ([70]PCBM) as an electron acceptor in high-performance organic photovoltaic (OPV) devices, [70]PCBM has been generally used as a mixture of regioisomers. In this study, we utilized regioisomerically pure α- and β-[70]PCBM in combination with a crystalline conjugated polymer donor, poly(3-hexylthiophene) (P3HT) to investigate systematically the regioisomer effects of [70]PCBM on structures and electronic and photovoltaic properties of the composite films. Notably, the β-isomer induced a face-on P3HT packing in the blend film, whereas an edge-on alignment of P3HT was observed in the composite films with the α-isomer as well as the regioisomer mixture (mix-[70]PCBM). The hole mobility in a vertical direction to the substrate in the P3HT:β-[70]PCBM film was higher than those in P3HT:α-[70]PCBM and P3HT:mix-[70]PCBM due to the face-on P3HT packing. Reflecting the superior hole mobility, the OPV device based on the P3HT:β-[70]PCBM film showed a higher power conversion efficiency of 3.69% than the devices based on the other composite films (3.11–3.21%). The results obtained here demonstrate that the use of regioisomerically pure [70]fullerene mono-adducts can modulate the polymer packing direction in the blend film, which is an unprecedented approach to improve the device performances of OPVs.

Despite numerous organic semiconductors being developed during the past decade, C70 derivatives are predominantly used as electron acceptors in efficient polymer solar cells (PSCs). However, as-prepared C70 mono-adducts intrinsically comprise regioisomers that would mask individual device performances depending on the substituent position on C70. Herein, we separate the regioisomers of C70 mono-adducts for PSC applications for the first time. Systematic investigations of the substituent position effect using a novel symmetric C70 mono-adduct ([70]NCMA) and a prevalent, high-performance one ([70]PCBM) reveals that we can control the structures of the blend films with conjugated polymers and thereby improve the PSC performances by regioisomer separation. Our approach demonstrates the significance of exploring the best-matching regioisomer of C70 mono-adducts with high-performance conjugated polymers, which would achieve a remarkable progress in PSC devices.

To shed a light on fundamental molecular functions of photoinduced charge conductions by organic photovoltaic materials, it is important to directly observe molecular geometries of the intermediate charges just after the photoinduced electron-transfer reactions. However, highly inhomogeneous molecular environments at the bulk heteojunction interfaces in the photoactive layers have prevented us from understanding the mechanism of the charge conductions. We have herein investigated orbital geometries, electronic couplings, and hole-dissociation dynamics of photoinduced charge-separated (CS) states in a series of poly(3-hexylthiophene)-fullerene linked dyads bridged by rigid oligo-p-phenylene spacers by using time-resolved EPR spectroscopy. It has been revealed that one-dimensional intramolecular hole-dissociations exothermically take place from localized holes in initial CS states, following bridge-mediated, photoinduced charge-separations via triplet exciton diffusions in the conjugated polymer-backbones. This molecular wire property of the photoinduced charges in solution at room temperature demonstrates the potential utility of the covalently bridged polymer molecules applied for the molecular devices.

The α-type isomer of [6,6]-phenyl-C71-butyric acid methyl ester (α-[70]PCBM) has been separated into enantiomers. The structures of (R)- and (S)-α-[70]PCBM were unambiguously identified by X-ray crystallography. Systematic investigations on photovoltaic properties of devices based on the optically active/inactive α-[70]PCBM acceptor and a conjugated polymer donor revealed that the enantiomer separations and combinations have insignificant effects on the device performances.

Heavy chain disease (HCD) is a rare B-cell proliferative neoplasm that is characterised by the production of truncated monoclonal immunoglobulin heavy chains without light chains. Gamma HCD is a subgroup of HCD. A 67-year-old man was admitted to our hospital with dyspnoea and lower leg oedema. Based on the results of heart catheterisation, he was diagnosed with pulmonary hypertension. Laboratory tests revealed an elevated level of IgG, and serum immunoelectrophoresis showed that IgG was a monoclonal gamma heavy chain without light chains. Finally, he was diagnosed with gamma HCD complicated by pulmonary hypertension. Bortezomib and dexamethasone therapy was initiated, but became refractory within 8 months. Therefore, the treatment was switched to lenalidomide and dexamethasone therapy, and the disease has been stably controlled for more than 2 years. To the best of our knowledge, this is the first case of gamma HCD being successfully treated by lenalidomide and dexamethasone therapy.

Chronic obstructive pulmonary disease (COPD) is a leading cause of morbidity and mortality worldwide. It has generally been considered a non-Th2-type lung disorder, characterized by progressive airflow limitation with inflammation and emphysema, but its cellular and molecular mechanism remains ill defined, compared with that of asthma characterized by reversible airway obstruction. Here we show a previously unappreciated role for basophils at the initiation phase of emphysema formation in an elastase-induced murine model of COPD in that basophils represent less than 1% of lung-infiltrating cells. Intranasal elastase instillation elicited the recruitment of monocytes to the lung, followed by differentiation into interstitial macrophages (IMs) but rarely alveolar macrophages (AMs). Matrix metalloproteinase-12 (MMP-12) contributing to emphysema formation was highly expressed by IMs rather than AMs, in contrast to the prevailing assumption. Experiments using a series of genetically engineered mice suggested that basophil-derived IL-4, a Th2 cytokine, acted on lung-infiltrating monocytes to promote their differentiation into MMP-12–producing IMs that resulted in the destruction of alveolar walls and led to emphysema development. Indeed, mice deficient for IL-4 only in basophils failed to generate pathogenic MMP-12–producing IMs and hence develop emphysema. Thus, the basophil-derived IL-4/monocyte–derived IM/MMP-12 axis plays a crucial role in emphysema formation and therefore may be a potential target to slow down emphysema progression at the initiation phase of COPD.

Endoscopic retrograde cholangiopancreatography is difficult to perform in patients with gastrointestinal tract reconstruction.To evaluate the efficacy and safety of double-balloon endoscopy-assisted endoscopic papillary large-balloon dilatation for common bile duct stones in patients with gastrointestinal tract reconstruction.We conducted a retrospective case series with a comparison to historical controls. During the period 2009-2013, 11 postoperative patients underwent endoscopic papillary large-balloon dilatation (Group A). Procedure efficacy and safety were compared with patients who underwent endoscopic sphincterotomy without endoscopic papillary large-balloon dilatation, who served as historical controls (Group B).Group A consisted of 11 patients (63.6% males, mean age 78±10 years), and Group B consisted of 32 patients (78.1% males, mean age 75±7 years). The stone clearance rate was significantly higher in Group A than in Group B (100% vs. 65.6%, respectively; p0.05). Median procedure time was significantly shorter in Group A than in Group B (54min vs. 102min, respectively; p0.05), and the complication rate was not significantly different between groups (18% vs. 15.6%, respectively; p=0.586).Endoscopic papillary large-balloon dilatation may be an effective and safe treatment procedure in patients with gastrointestinal tract reconstruction.

This paper proposes the inrush current suppressor using an AC chopper in a large-capacity wind power generation system (WPGS) with two squirrel-cage induction machines (SCIMs), which are switched over depending on the wind speed. The input side of the AC chopper is connected to the source in parallel. The output side of the AC chopper is connected in series with the SCIM through matching transformers. In the proposed inrush current suppressor, the output voltage of the AC chopper is the same as the receiving-end voltage before connecting the SCIM. By gradually decreasing the output voltage of the AC chopper, the applied voltage of the SCIM is gradually increased without the inrush current. The basic principle of the proposed inrush current suppressor is discussed in detail. A computer simulation is implemented to confirm the validity and practicability of the proposed inrush current suppressor using a power system computer-aided design/electromagnetic transients including DC (PSCAD/EMTDC). Simulation results demonstrate that the proposed inrush current suppressor can suppress the inrush current.

Infection with Helicobacter pylori (HP) is common in many parts of the world. While most patients are asymptomatic, it causes peptic ulcer disease and malignancy in some of them. Other rare conditions have occasionally been reported in association with this infection. We report a case of hypertrophic gastropathy caused by HP in a 52-year-old asymptomatic patient. He was found to have marked enlargement of the gastric mucosal folds on radiological imaging and endoscopy. A gastric mucosal biopsy showed HP colonization associated with neutrophilic inflammation. After exclusion of neoplasia, other infections and infiltrative disorders, HP was thought to be the cause of the gastric fold hypertrophy. The patient responded well to HP eradication therapy, with normalization of the gastric mucosal folds. HP infection should be considered in the differential diagnosis of hypertrophic gastropathy and treated accordingly.