Germline mutations in
CDH1
, encoding E-cadherin, are known to be the causative mechanism of hereditary diffuse gastric cancer (HDGC). We encountered two cases of gastric cancer in a Japanese family ...with HDGC. A 28-year-old man (Case 1) died of advanced gastric cancer. His younger sister aged 27 (Case 2) was diagnosed with intramucosal signet ring cell carcinoma (SRCC). Both had identical germline
CDH1
mutations, but Case 1 was positive for
Helicobacter pylori
infection, whereas Case 2 was negative. Case 2 underwent total gastrectomy. Whole-exome sequencing of an intramucosal SRCC in Case 2 revealed seven somatic mutations including one in
CDH1
. The six non-
CDH1
mutations were classified as non-driver mutations. Decreased expression of E-cadherin in intramucosal SRCC was confirmed by immunohistochemistry. Our report demonstrated that
CDH1
mutation was the only active driver mutation in
Helicobacter pylori
-uninfected intramucosal SRCC.
To develop and internally validate a preoperative clinical prediction model for acute adjacent vertebral fracture (AVF) after vertebral augmentation to support preoperative decision-making, named the ...after vertebral augmentation (AVA) score.
In this prognostic study, a multicentre, retrospective single-level vertebral augmentation cohort of 377 patients from six Japanese hospitals was used to derive an AVF prediction model. Backward stepwise selection (p < 0.05) was used to select preoperative clinical and imaging predictors for acute AVF after vertebral augmentation for up to one month, from 14 predictors. We assigned a score to each selected variable based on the regression coefficient and developed the AVA scoring system. We evaluated sensitivity and specificity for each cut-off, area under the curve (AUC), and calibration as diagnostic performance. Internal validation was conducted using bootstrapping to correct the optimism.
Of the 377 patients used for model derivation, 58 (15%) had an acute AVF postoperatively. The following preoperative measures on multivariable analysis were summarized in the five-point AVA score: intravertebral instability (≥ 5 mm), focal kyphosis (≥ 10°), duration of symptoms (≥ 30 days), intravertebral cleft, and previous history of vertebral fracture. Internal validation showed a mean optimism of 0.019 with a corrected AUC of 0.77. A cut-off of ≤ one point was chosen to classify a low risk of AVF, for which only four of 137 patients (3%) had AVF with 92.5% sensitivity and 45.6% specificity. A cut-off of ≥ four points was chosen to classify a high risk of AVF, for which 22 of 38 (58%) had AVF with 41.5% sensitivity and 94.5% specificity.
In this study, the AVA score was found to be a simple preoperative method for the identification of patients at low and high risk of postoperative acute AVF. This model could be applied to individual patients and could aid in the decision-making before vertebral augmentation. Cite this article:
2022;104-B(1):97-102.
Treatment outcomes for children with relapsed and refractory acute lymphoblastic leukemia (R/R-ALL) remain poor, and the optimal induction therapy has not been determined. Bortezomib is a proteasome ...inhibitor that acts synergistically and additively with standard chemotherapy for ALL. We evaluated the efficacy and safety of combination chemotherapy with bortezomib in children with R/R-ALL. This single-arm, multicenter, phase 2 study was conducted in Japan between 2016 and 2020. Eligible patients were divided into two cohorts: a high-risk first-relapse cohort of untreated patients with high-risk first-relapsed ALL and an expansion cohort of patients with refractory ALL, including multiple relapses, relapse after allogeneic hematopoietic cell transplantation, and induction failure. All patients received a single course of chemotherapy as induction therapy. Sixteen patients (10 in the high-risk first-relapse cohort, six in the expansion cohort) were evaluable. The overall remission rate after induction therapy was 60% in the high-risk first-relapse cohort and 16.7% in the expansion cohort. All patients had minimal residual disease. Adverse events were acceptable except for interstitial lung disease and hypoxia in a patient in the expansion cohort, but addition of bortezomib to conventional chemotherapy did not produce obvious improvement in children with R/R-ALL.
Hepatic venous outflow obstruction (HVOO) is a critical complication after living donor liver transplantation (LDLT). This study aimed to evaluate the incidence of HVOO and the risk factors for HVOO ...in adults. From 2005 to 2015, 430 adult LDLT patients (right lobe RL graft, 270 patients; left lobe LL graft, 160 patients) were enrolled and divided into no HVOO (n = 413) and HVOO (n = 17) groups. Patient demographics and surgical data were compared, and risk factors for HVOO were analyzed. Furthermore, the longterm outcomes of percutaneous interventions as treatment for HVOO were assessed. HVOO occurred in 17 (4.0%) patients. The incidence of HVOO in patients receiving a LL graft was significantly higher than in those receiving a RL graft (8.1% versus 1.5%; P = 0.001). The body weight and caliber of hepatic vein anastomosis in the HVOO group were significantly lower compared with the no HVOO group (P = 0.02 and P = 0.008, respectively). Multivariate analysis revealed that only LL graft was an independent risk factor for HVOO (OR, 4.782; 95% CI, 1.387‐16.488; P = 0.01). Among 17 patients with HVOO, 7 patients were treated with single balloon angioplasty, and 9 patients who developed recurrence were treated with repeated interventions. Overall, 6 patients underwent stent placement: 1 at the initial procedure, 3 at the second procedure for early recurrence, and 2 following repeated balloon angioplasty (≥3 interventions). These 6 patients experienced no recurrence. Overall graft survival was not significantly different between the HVOO and no HVOO groups (P = 0.99). In conclusion, the use of a LL graft was associated with HVOO, and percutaneous interventions were effective for treating adult HVOO after LDLT. Liver Transplantation 22 785–795 2016 AASLD.
Background
The treatment of duplicated thoracic ducts (TDs) injury after esophagectomy generally requires a bilateral transthoracic approach. We present the cases of two patients with postoperative ...chylothorax who underwent transhiatal bilateral TD ligation for duplicated TDs.
Case presentation
Two patients diagnosed with chylothorax after esophagectomy performed for thoracic esophageal cancer underwent transhiatal TD ligation. Although supradiaphragmatic mass ligation was performed on the fat tissue of the right side of the aorta containing the TD, chyle leakage persisted. To tackle this, the fat tissue of the left side of the aorta was ligated, after which the chyle leakage stopped.
Conclusion
Compared to the conventional transthoracic approach, the transhiatal approach enables the ligation of both left- and right-sided TD in a single surgical operation, without the need to change the patient’s posture. This approach may be appropriate for the treatment of chylothorax after esophagectomy, considering the possibility of duplicated TDs.
Intermpl: Momentum Pseudo-Labeling With Intermediate CTC Loss Higuchi, Yosuke; Ogawa, Tetsuji; Kobayashi, Tetsunori ...
ICASSP 2023 - 2023 IEEE International Conference on Acoustics, Speech and Signal Processing (ICASSP),
2023-June-4
Conference Proceeding
Odprti dostop
This paper presents InterMPL, a semi-supervised learning method of end-to-end automatic speech recognition (ASR) that performs pseudo-labeling (PL) with intermediate supervision. Momentum PL (MPL) ...trains a connectionist temporal classification (CTC)-based model on unlabeled data by continuously generating pseudo-labels on the fly and improving their quality. In contrast to autoregressive formulations, such as the attention-based encoder-decoder and transducer, CTC is well suited for MPL, or PL-based semi-supervised ASR in general, owing to its simple/fast inference algorithm and robustness against generating collapsed labels. However, CTC generally yields inferior performance than the autoregressive models due to the conditional independence assumption, thereby limiting the performance of MPL. We propose to enhance MPL by introducing intermediate loss, inspired by the recent advances in CTC-based modeling. Specifically, we focus on self-conditional and hierarchical conditional CTC, that apply auxiliary CTC losses to intermediate layers such that the conditional independence assumption is explicitly relaxed. We also explore how pseudo-labels should be generated and used as supervision for intermediate losses. Experimental results in different semi-supervised settings demonstrate that the proposed approach outperforms MPL and improves an ASR model by up to a 12.1% absolute performance gain. In addition, our detailed analysis validates the importance of the intermediate loss.
Abstract
The corrugated horn is a high-performance feed often used in radio telescopes. There has been a growing demand for wideband optics and corrugated horns in millimeter- and submillimeter-wave ...receivers as they improve observation efficiency and allow us to observe important emission lines such as CO in multiple excited states simultaneously. However, in the millimeter/submillimeter band, it has been challenging to create a conical corrugated horn with a fractional bandwidth of ∼60% because the wavelength is very short, making it difficult to make narrow corrugations. In this study we designed a conical corrugated horn with good return loss, low cross-polarization, and symmetric beam pattern in the 210–375 GHz band (56% fractional bandwidth) by optimizing the dimensions of the corrugations. The corrugated horn was installed on the Osaka 1.85 m mm–submm telescope with matched frequency-independent optics, and simultaneous observations of 12CO, 13CO, and C18O (J = 2–1, 3–2) were successfully made. We describe the new design of the corrugated horn and report the performance evaluation results including the optics.
Herpes simplex virus (HSV)-2 shedding is associated with increased risk for sexually acquiring HIV. Because Langerhans cells (LCs), the mucosal epithelium resident dendritic cells, are suspected to ...be one of the initial target cell types infected by HIV following sexual exposure, we examined whether and how HSV-2 affects HIV infection of LCs. Although relatively few HSV-2/HIV-coinfected LCs were detected, HSV-2 dramatically enhanced the HIV susceptibility of LCs within skin explants. HSV-2 stimulated epithelial cell production of antimicrobial peptides (AMPs), including human β defensins and LL-37. LL-37 strongly upregulated the expression of HIV receptors in monocyte-derived LCs (mLCs), thereby enhancing their HIV susceptibility. Culture supernatants of epithelial cells infected with HSV-2 enhanced HIV susceptibility in mLCs, and this effect was abrogated by blocking LL-37 production. These data suggest that HSV-2 enhances sexual transmission of HIV by increasing HIV susceptibility of LCs via epithelial cell production of LL-37.
► HSV-2 enhances HIV susceptibility of epithelial tissue resident Langerhans cells ► HSV-2 stimulates production of antimicrobial peptides by epithelial cells ► LL-37, but not other AMPs, enhances HIV infection of LCs ► LL-37 upregulates LC surface expression of the HIV receptors CD4 and CCR5
Azacitidine, an inhibitor of DNA methyltransferase, is reported to have antileukemic efficacy and is approved for the treatment of myelodysplastic syndromes in Western countries. We have conducted a ...Phase I/II study of azacitidine in Japanese patients with myelodysplastic syndromes to evaluate its pharmacokinetics, efficacy, and safety. In all, 53 patients received 75 mg/m2 azacitidine subcutaneously or intravenously once daily for seven consecutive days on a 28‐day cycle. The Cmax following intravenous administration was approximately 3.7‐fold higher than that following subcutaneous administration, whereas the area under the plasma concentration–time curve from time zero to infinity was comparable for subcutaneous and intravenous administration. The bioavailability of azacitidine following subcutaneous administration was 91.1%, indicating that azacitidine is nearly completely absorbed after subcutaneous administration. The hematologic improvement and hematologic response rates were 54.9% (28/51) and 28.3% (15/53), respectively, and there were no differences between the two routes of administration. Azacitidine was generally well tolerated and clinically manageable in Japanese patients with myelodysplastic syndromes. Adverse events occurred in ≥20% of patients included hematologic toxicity, gastrointestinal events, and general disorders, such as malaise. Grade 3/4 adverse events that occurred in ≥50% of patients were all due to hematologic toxicity. The safety profile of azacitidine was generally similar for both routes of administration, with the exception of injection site reactions observed following subcutaneous administration. These results indicate that azacitidine can be expected to be a useful therapeutic agent in Japanese patients with myelodysplastic syndromes. (Cancer Sci 2011; 102: 1680–1686)
We recently reported that cardiomyocytes could be differentiated from bone marrow mesenchymal stem cells in vitro by 5-azacytidine treatment. In native cardiomyocytes, adrenergic and muscarinic ...receptors play crucial roles in mediating heart rate, conduction velocity, contractility, and cardiac hypertrophy. We investigated whether these receptors are expressed in differentiated CMG cells, and if so, whether they have downstream signaling systems.
Reverse transcription-polymerase chain reaction revealed that CMG cells had already expressed alpha(1A)-, alpha(1B)-, and alpha(1D)-adrenergic receptor mRNA before 5-azacytidine treatment, whereas expression of beta(1)-, beta(2)-adrenergic and M(1)-, M(2)-muscarinic receptors was first detected at 1 day. Phenylephrine dose-dependently induced phosphorylation of ERK1/2, which was completely inhibited by prazosin, and significantly increased cell size. Isoproterenol augmented cAMP by 38-fold, which was fully inhibited by propranolol. Isoproterenol (10(-7) mol/L) increased the spontaneous beating rate by 47.6% (basal, 127+/-16 bpm), and propranolol and CGP20712A (beta(1)-selective blocker) reduced it by 79.0% and 71.0%, respectively, whereas ICI118551 (beta(2)-selective blocker) induced slight reduction. Cell motion, percent shortening, and contractile velocity were increased by 37.5%, 26.9%, and 50.6%, respectively, in response to isoproterenol. Phenylephrine and isoproterenol augmented ANP and BNP gene expressions. Carbachol increased IP(3) by 32-fold, which was markedly inhibited by atropine as well as AFDX116 (M(2)-selective blocker) measured by radioimmunoassay.
These findings indicate that CMG cells expressed alpha(1A), alpha(1B), and alpha(1D) receptors before differentiation and expressed beta(1), beta(2), M(1), and M(2) receptors after they obtained the cardiomyocyte phenotype. These receptors had functional signal transduction pathways and could modulate cell function.
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