A comparison between vertical winds in the lower thermosphere and magnetic field perturbations on the ground

Vertical winds in the lower thermosphere are estimated from OI557.7-nm Doppler shifts obtained with a Fabry-Perot interferometer at the Poker Flat Research Range (65.12N, 147.43W in geographic coordinate), Alaska. The temporal variation of vertical winds was compared with the horizontal component of the magnetic field obtained at Poker Flat and two other sites, Gakona (62.12N, 145.14W) and Fort Yukon (66.36N, 145.22W). Two nights of observations were examined and the results were shown here. The results showed that temporal variations of vertical winds were similar to that of magnetic field variation during each substorm. In some cases the results of cross correlation between these two parameters showed that the magnetic field perturbation leads vertical winds in the earlier period of the substorm. The difference increased gradually and reached a maximum at around the center of the recovery phase. From there, the differences decreased. The mechanism for the relation between the two parameters is still unclear, but this result suggests an intimate relation between ionospheric currents and vertical wind in the thermosphere

Successful stenting of the ductus venosus in 2 neonates with asplenia syndrome complicated by infracardiac type total anomalous pulmonary venous connection

SummaryIn the neonatal period, the surgical mortality of palliation is extremely high for asplenia syndrome complicated by single ventricle combined with total anomalous pulmonary venous connection (TAPVC). Recently, stent implantation for the pulmonary venous drainage route soon after birth has been used instead of surgery to prevent pulmonary venous occlusion and to maintain stable hemodynamics in the neonatal period or in early infancy. Here, we successfully implanted stents in the ductus venosus (DV) in 2 neonates with asplenia syndrome complicated by infracardiac type TAPVC. The first patient was a 3-day-old male neonate with severe cyanosis. Immediately after TAPVC was diagnosed, we implanted a stent in the DV. The second patient was a 0-day-old female neonate. She was diagnosed as TAPVC by fetal echocardiogram. After the scheduled delivery, a stent was successfully implanted. We believe that stent implantation in the DV in the neonatal period is effective and less invasive than surgery in patients with infracardiac type TAPVC

Label-free multiphoton excitation imaging as a promising diagnostic tool for breast cancer

Histopathological diagnosis is the ultimate method of attaining the final diagnosis; however, the observation range is limited to the two-dimensional plane, and it requires thin slicing of the tissue, which limits diagnostic information. To seek solutions for these problems, we proposed a novel imaging-based histopathological examination. We used the multiphoton excitation microscopy (MPM) technique to establish a method for visualizing unfixed/unstained human breast tissues. Under near-infrared ray excitation, fresh human breast tissues emitted fluorescent signals with three major peaks, which enabled visualizing the breast tissue morphology without any fixation or dye staining. Our study using human breast tissue samples from 32 patients indicated that experienced pathologists can estimate normal or cancerous lesions using only these MPM images with a kappa coefficient of 1.0. Moreover, we developed an image classification algorithm with artificial intelligence that enabled us to automatically define cancer cells in small areas with a high sensitivity of ≥0.942. Taken together, label-free MPM imaging is a promising method for the real-time automatic diagnosis of breast cancer.This is the pre-peer reviewed version of the following article:Matsui T., Iwasa A., Mimura M., et al. Label-free multiphoton excitation imaging as a promising diagnostic tool for breast cancer. Cancer Science 113, 2916 (2022), which has been published in final form at https://doi.org/10.1111/cas.15428. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Self-Archiving

Adiponectin/resistin levels and insulin resistance in children: a four country comparison study

There are few reports on the effects of ethnicity or gender in the association between adipocytokines and insulin resistance in children of different ages. This study assessed associations between serum concentrations of adiponectin/resistin and parameters of insulin resistance in children from 4 different countries. A total of 2,290 children were analyzed in this study; each was from one of 4 different countries (Japan, Thailand, Italy and USA), and grouped according to age (8–11 years old in Group 1 and 12–15 years old in Group 2). Adioponectin was higher in female than in male children, and in Group 1 than in Group 2. Generally, adiponectin was lower in Asian as compared to Italian and American children. These tendencies remained even after adjustment for body mass index (BMI) or waist circumstance (WC). Among older children (Group 2), resistin was higher in female than in male children. Significant correlations by non-parametric univariate correlation coefficients and Spearman’s rank correlation coefficients were found between adiponectin and homeostasis model assessment of insulin resistance (HOMA-IR), and fasting serum insulin levels in young Japanese, Italian, and American female children(p < 0.01, p < 0.05, p < 0.05, respectively). Correlations between serum adiponectin and HOMA-IR were also found among older male Italian, American, and Thai children (p < 0.05, p < 0.001, p < 0.001, respectively). In multiple regression analysis by forced entry method, adiponectin correlated with HOMA-IR in Italian and American male children, and in all older female children regardless of country of origin. There was no correlation between resistin and markers of insulin resistance in children from any of the countries. We conclude that serum adiponectin concentrations are lower in Asian as compared to Italian and American children, and that adiponectin but not resistin contributes to differences in markers for insulin resistance in children from different populations

Subtypes of Familial Hemophagocytic Lymphohistiocytosis in Japan Based on Genetic and Functional Analyses of Cytotoxic T Lymphocytes

BACKGROUND: Familial hemophagocytic lymphohistiocytosis (FHL) is a rare disease of infancy or early childhood. To clarify the incidence and subtypes of FHL in Japan, we performed genetic and functional analyses of cytotoxic T lymphocytes (CTLs) in Japanese patients with FHL. DESIGN AND METHODS: Among the Japanese children with hemophagocytic lymphohistiocytosis (HLH) registered at our laboratory, those with more than one of the following findings were eligible for study entry under a diagnosis of FHL: positive for known genetic mutations, a family history of HLH, and impaired CTL-mediated cytotoxicity. Mutations of the newly identified causative gene for FHL5, STXBP2, and the cytotoxicity and degranulation activity of CTLs in FHL patients, were analyzed. RESULTS: Among 31 FHL patients who satisfied the above criteria, PRF1 mutation was detected in 17 (FHL2) and UNC13D mutation was in 10 (FHL3). In 2 other patients, 3 novel mutations of STXBP2 gene were confirmed (FHL5). Finally, the remaining 2 were classified as having FHL with unknown genetic mutations. In all FHL patients, CTL-mediated cytotoxicity was low or deficient, and degranulation activity was also low or absent except FHL2 patients. In 2 patients with unknown genetic mutations, the cytotoxicity and degranulation activity of CTLs appeared to be deficient in one patient and moderately impaired in the other. CONCLUSIONS: FHL can be diagnosed and classified on the basis of CTL-mediated cytotoxicity, degranulation activity, and genetic analysis. Based on the data obtained from functional analysis of CTLs, other unknown gene(s) responsible for FHL remain to be identified

In vivo induction of activin A-producing alveolar macrophages supports the progression of lung cell carcinoma

Alveolar macrophages (AMs) are crucial for maintaining normal lung function. They are abundant in lung cancer tissues, but their pathophysiological significance remains unknown. Here we show, using an orthotopic murine lung cancer model and human carcinoma samples, that AMs support cancer cell proliferation and thus contribute to unfavourable outcome. Inhibin beta A (INHBA) expression is upregulated in AMs under tumor-bearing conditions, leading to the secretion of activin A, a homodimer of INHBA. Accordingly, follistatin, an antagonist of activin A is able to inhibit lung cancer cell proliferation. Single-cell RNA sequence analysis identifies a characteristic subset of AMs specifically induced in the tumor environment that are abundant in INHBA, and distinct from INHBA-expressing AMs in normal lungs. Moreover, postnatal deletion of INHBA/activin A could limit tumor growth in experimental models. Collectively, our findings demonstrate the critical pathological role of activin A-producing AMs in tumorigenesis, and provides means to clearly distinguish them from their healthy counterparts.Taniguchi S., Matsui T., Kimura K., et al. In vivo induction of activin A-producing alveolar macrophages supports the progression of lung cell carcinoma. Nature Communications 14, 143 (2023); https://doi.org/10.1038/s41467-022-35701-8

Targeting critical kinases and anti-apoptotic molecules overcomes steroid resistance in MLL-rearranged leukaemia.

BACKGROUND: Acute lymphoblastic leukaemia with mixed lineage leukaemia gene rearrangement (MLL-ALL) frequently affects infants and is associated with a poor prognosis. Primary refractory and relapsed disease due to resistance to glucocorticoids (GCs) remains a substantial hurdle to improving clinical outcomes. In this study, we aimed to overcome GC resistance of MLL-ALL. METHODS: Using leukaemia patient specimens, we performed bioinformatic analyses to identify target genes/pathways. To test inhibition of target pathways in vivo, we created pre-clinical therapeutic mouse patient-derived xenograft (PDX)-models by transplanting human MLL-ALL leukaemia initiating cells (LIC) into immune-deficient NSG mice. Finally, we conducted B-cell lymphoma-2 (BCL-2) homology domain 3 (BH3) profiling to identify BH3 peptides responsible for treatment resistance in MLL-leukaemia. FINDINGS: Src family kinases (SFKs) and Fms-like tyrosine kinase 3 (FLT3) signaling pathway were over-represented in MLL-ALL cells. PDX-models of infant MLL- ALL recapitulated GC-resistance in vivo but RK-20449, an inhibitor of SFKs and FLT3 eliminated human MLL-ALL cells in vivo, overcoming GC-resistance. Further, we identified BCL-2 dependence as a mechanism of treatment resistance in MLL-ALL through BH3 profiling. Furthermore, MLL-ALL cells resistant to RK-20449 treatment were dependent on the anti-apoptotic BCL-2 protein for their survival. Combined inhibition of SFKs/FLT3 by RK-20449 and of BCL-2 by ABT-199 led to substantial elimination of MLL-ALL cells in vitro and in vivo. Triple treatment combining GCs, RK-20449 and ABT-199 resulted in complete elimination of MLL-ALL cells in vivo. INTERPRETATION: SFKs/FLT3 signaling pathways are promising targets for treatment of treatment-resistant MLL-ALL. Combined inhibition of these kinase pathways and anti-apoptotic BCL-2 successfully eliminated highly resistant MLL-ALL and demonstrated a new treatment strategy for treatment-resistant poor-outcome MLL-ALL. FUNDING: This study was supported by RIKEN (RIKEN President\u27s Discretionary Grant) for FI, Japan Agency for Medical Research and Development (the Basic Science and Platform Technology Program for Innovative Biological Medicine for FI and by NIH CA034196 for LDS. The funders had no role in the study design, data collection, data analysis, interpretation nor writing of the report