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We herein report a 67-year-old Japanese woman with liver cirrhosis caused by primary biliary cholangitis. The patient was admitted to the hospital with loss of consciousness. Hepatic encephalopathy (HE) was diagnosed after diagnostic imaging and symptom assessments. Molecular biology tests were performed on oral saliva and stool samples. The test results indicated sequence similarity between urease-positive S. salivarius in both oral saliva and stool, as revealed by the signals in the overlapping peaks. This bacterium can potentially increase ammonia production in the gut, leading to HE in patients with liver cirrhosis.

Competing Interests: None.

A novel NH 3 gas sensor is introduced, employing polyaniline (PANI) with a unique structure called a graft film. The preparation method was simple: polydopamine (PD) was coated on a flexible polyethylene terephthalate (PET) film and PANI graft chains were grown on its surface. This distinctive three-layer sensor showed a response value of 12 for 50 ppm NH 3 in a dry atmosphere at 50 °C. This value surpasses those of previously reported sensors using structurally controlled PANI films. Additionally, it is on par with sensors that combine PANI with metal oxide semiconductors or carbon materials, the high sensitivity of which have been reported. To confirm our film's potential as a flexible sensor, the effect of bending on the its characteristics was investigated. This revealed that although bending decreased the response value, it had no effect on the response time or recovery. This indicated that the sensor film itself was not broken by bending and had sufficient mechanical strength.

Body movements influence brain-wide neuronal activities. In the sensory cortex, thalamocortical bottom-up inputs and motor-sensory top-down inputs are thought to affect the dynamics of membrane potentials ( V m ) of neurons and change their processing of sensory information during movements. However, direct perturbation of the axons projecting to the sensory cortex from other remote areas during movements has remained unassessed, and therefore the interareal circuits generating motor-related signals in sensory cortices remain unclear. Using a G i/o -coupled opsin, eOPN3, we here inhibited interareal signals incoming to the whisker primary somatosensory barrel cortex (wS1) of awake male mice and tested their effects on whisking-related changes in neuronal activities in wS1. Spontaneous whisking in air induced the changes in spike rates of a subset of wS1 neurons, which were accompanied by depolarization and substantial reduction of slow-wave oscillatory fluctuations of V m Despite an extensive innervation, inhibition of inputs from the whisker primary motor cortex (wM1) to wS1 did not alter the spike rates and V m dynamics of wS1 neurons during whisking. In contrast, inhibition of axons from the whisker-related thalamus (wTLM) and the whisker secondary somatosensory cortex (wS2) to wS1 largely attenuated the whisking-related supra- and sub-threshold V m dynamics of wS1 neurons. Notably, silencing inputs from wTLM markedly decreased the modulation depth of whisking phase-tuned neurons in wS1, while inhibiting wS2 inputs did not impact the whisking variable tuning of wS1 neurons. Thus, sensorimotor integration in wS1 during spontaneous whisking is predominantly facilitated by direct synaptic inputs from wTLM and wS2 rather than from wM1., (Copyright © 2024 Kawatani et al.)

Background: Lenvatinib is appropriate for reducing the production of nitric oxide (NO) and facilitating as block angiogenesis. However, to our knowledge, there are no data that support the correlation between NO and clinical response in patients who received lenvatinib therapy for HCC. Therefore, we investigated the correlation between the change rate of NO levels and clinical responses including adverse events (AEs) after lenvatinib therapy for unresectable hepatocellular carcinoma (HCC)., Methods: This study was conducted using previously collected data from another study. We enrolled 70 patients who received lenvatinib for advanced or unresectable HCC. NO was measured by converting nitrate (NO 3 - ) to nitrite (NO 2 - ) with nitrate reductase, followed by quantitation of NO 2 - based on Griess reagent. To determine whether lenvatinib influences NO in unresectable HCC, we evaluated the influence of the change rate of NO from baseline after administration of lenvatinib on maximal therapeutic response and SAE., Results: After lenvatinib administration, a change rate in the NO from 0.27 to 4.16 was observed. There was no difference between the clinical response to lenvatinib and the change rate of NO (p = 0.632). However, the change rate of NO was significantly lower in patients with AEs than in those without AEs (p = 0.030). When a reduction in NO rate of < 0.8 was defined as a clinically significant reduction of NO (CSRN), the CSRN group had significantly worse progression-free survival (PFS) and overall survival (OS) than the non-CSRN group (p = 0.029 and p = 0.005, respectively)., Conclusion: Decreased NO levels were associated with the occurrence of AEs and worse prognosis after lenvatinib administration. Change rate in serum NO can be used as predictive markers in patients receiving lenvatinib therapy for HCC., (© 2022. The Author(s).)

Purpose: Promoter DNA methylation of various genes has been associated with metachronous gastric cancer (MGC). The cancer-specific methylation gene, cysteine dioxygenase type 1 (CDO1) , has been implicated in the occurrence of residual gastric cancer. We evaluated whether DNA methylation of CDO1 could be a predictive biomarker of MGC using specimens of MGC developing on scars after endoscopic submucosal dissection (ESD)., Materials and Methods: CDO1 methylation values (TaqMeth values) were compared between 33 patients with early gastric cancer (EGC) with no confirmed metachronous lesions at >3 years after ESD (non-MGC: nMGC group) and 11 patients with MGC developing on scars after ESD (MGCSE groups: EGC at the first ESD [MGCSE-1 group], EGC at the second ESD for treating MGC developing on scars after ESD [MGCSE-2 group]). Each EGC specimen was measured at five locations (at tumor [T] and the 4-point tumor-adjacent noncancerous mucosa [TAM])., Results: In the nMGC group, the TaqMeth values for T were significantly higher than that for TAM (P=0.0006). In the MGCSE groups, TAM (MGCSE-1) exhibited significantly higher TaqMeth values than TAM (nMGC) (P<0.0001) and TAM (MGCSE-2) (P=0.0041), suggesting that TAM (MGCSE-1) exhibited CDO1 hypermethylation similar to T (P=0.3638). The area under the curve for discriminating the highest TaqMeth value of TAM (MGCSE-1) from that of TAM (nMGC) was 0.81, and using the cut-off value of 43.4, CDO1 hypermethylation effectively enriched the MGCSE groups (P<0.0001)., Conclusions: CDO1 hypermethylation has been implicated in the occurrence of MGC, suggesting its potential as a promising MGC predictor., Competing Interests: Conflict of Interest: No potential conflict of interest relevant to this article was reported., (Copyright © 2021. Korean Gastric Cancer Association.)

Objective The standard treatment for chronic myeloid leukemia (CML) is the continuous use of tyrosine kinase inhibitors (TKIs), which results in a favorable prognosis for the majority of patients. Recent studies have identified cardiovascular diseases (CVDs) as late adverse events (AEs) related to TKIs. In this study, we evaluated the long-term efficacy and AEs of TKIs, focusing on CVDs. Methods We performed a retrospective survey of CML patients (diagnosed from 2001 to 2016) treated with TKIs in Nagasaki Prefecture. Clinical data were obtained from their medical records. We analyzed the survival, estimated cumulative incidence of CVDs, and risk factors for CVD among CML patients treated with TKIs. Results The overall survival rate of 264 CML patients treated with TKIs (median age 58 years old) was 89.6% [95% confidence interval (CI), 84.9-92.9%], and 80.5% (95% CI, 73.4-85.9%) at 5 and 10 years after the CML diagnosis, respectively. CVD events occurred in 26 patients (9.8%, median age 67.5 years old) with a median 65.5 months of TKI treatment. The cumulative incidences at 2 and 5 years was 2.4% (95% CI, 1.0-4.8%) and 5.2% (95% CI, 2.8-8.6%), respectively. Hypertension and a high SCORE chart risk at the diagnosis of CML were associated with CVD events during TKI treatment. Conclusion TKI treatment contributed to the long-term survival of CML patients in Nagasaki Prefecture in a "real-world" setting, but the incidence of CVDs seemed to be increased in these patients. A proper approach to managing risk factors for CVD is warranted to reduce CVD events during TKI treatment.

Recently, we developed an in situ mRNA detection method termed RNase H-assisted rolling circle amplification-fluorescence in situ hybridization (RHa-RCA-FISH), which can detect even short mRNA in a bacterial cell. However, because this FISH method is sensitive to the sample condition, it is necessary to find a suitable cell permeabilization and collection protocol. Here, we demonstrate its further applicability for detecting intrinsic mRNA expression using lactic acid bacteria (LAB) as a model consortium. Our results show that this method can visualize functional gene expression in LAB cells and can be used for monitoring the temporal transition of gene expression. In addition, we also confirmed that data obtained from bulk analyses such as RNA-seq or microarray do not always correspond to gene expression in individual cells. RHa-RCA-FISH will be a powerful tool to compensate for insufficient data from metatranscriptome analyses while clarifying the carriers of function in microbial consortia. By extending this technique to capture spatiotemporal microbial gene expression at the single-cell level, it will be able to characterize microbial interactions in phytoplankton-bacteria interactions.

Meta-analyses using next generation sequencing is a powerful strategy for studying microbiota; however, it cannot clarify the role of individual microbes within microbiota. To know which cell expresses what gene is important for elucidation of the individual cell's function in microbiota. In this report, we developed novel fluorescence in situ hybridization (FISH) procedure using RNase-H-assisted rolling circle amplification to visualize mRNA of interest in microbial cells without reverse transcription. Our results show that this method is applicable to both Gram-negative and Gram-positive microbes without any noise from DNA, and it is possible to visualize the target mRNA expression directly at the single-cell level. Therefore, our procedure, when combined with data of meta-analyses, can help to understand the role of individual microbes in the microbiota.

Isosteric heat of adsorption is exquisitely sensitive to structural changes in carbon surfaces based on the energetic behavior of the interactions between adsorbates and carbon materials. We discuss the relationships between porous structures, oxygen functional groups, and heat of adsorption based on the behavior of the heat of adsorption of polar and non-polar fluids on porous carbon materials with oxygen functional groups. The porosity and functional groups of porous carbon materials were estimated from N 2 adsorption isotherms at 77 K and temperature-programmed desorption. High-resolution adsorption isotherms of water, acetonitrile (polar fluid), and n-hexane (non-polar fluid) were measured on porous carbon materials with different pore size distributions and amounts of oxygen functional groups at various temperatures. The heats of adsorption were determined by applying the Clausius-Clapeyron equation to the adsorption isotherms. The heat of adsorption curves directly reflect the effects of interactions of fluid-oxygen functional groups, fluid-basal planes of pore walls, and fluid-fluid interfaces. In particular, the heat of adsorption curve of water is very sensitive to surface oxygen functional groups. This finding indicates the possibility of estimating the relative amounts of oxygen functional groups on porous carbon materials based on the amounts of water adsorbed at specific relative pressures., (Copyright © 2019 Elsevier Inc. All rights reserved.)

The presence or absence of metastasis has critical implications for therapeutic decision-making in urothelial cancer (UC). Conventional magnetic resonance imaging (MRI) utilizing anatomic T1- and T2-weighted images has modest efficacy in detecting lymph node and distant metastases in UC. However, incorporation of functional techniques including diffusion weighted imaging and dynamic contrast-enhanced imaging, may improve the accuracy of lesion detection and staging. Multiparametric (mp)MRI is widely used in the imaging of prostate and breast cancers, though its usefulness in UC has yet to be fully elucidated. The present study reports on mpMRI in the context of two cases of bladder and ureteral cancer, and imaging results with pathological diagnosis.

This paper presents a novel approach to predicting self-calibration in a pressure sensor using a proposed Levenberg Marquardt Back Propagation Artificial Neural Network (LMBP-ANN) model. The self-calibration algorithm should be able to fix major problems in the pressure sensor such as hysteresis, variation in gain and lack of linearity with high accuracy. The traditional calibration process for this kind of sensor is a time-consuming task because it is usually done through manual and repetitive identification. Furthermore, a traditional computational method is inadequate for solving the problem since it is extremely difficult to resolve the mathematical formula among multiple confounding pressure variables. Accordingly, this paper describes a new self-calibration methodology for nonlinear pressure sensors based on an LMBP-ANN model. The proposed method was achieved using a collected dataset from pressure sensors in real time. The load cell will be used as a reference for measuring the applied force. The proposed method was validated by comparing the output pressure of the trained network with the experimental target pressure (reference). This paper also shows that the proposed model exhibited a remarkable performance than traditional methods with a max mean square error of 0.17325 and an R-value over 0.99 for the total response of training, testing and validation. To verify the proposed model's capability to build a self-calibration algorithm, the model was tested using an untrained input data set. As a result, the proposed LMBP-ANN model for self-calibration purposes is able to successfully predict the desired pressure over time, even the uncertain behaviour of the pressure sensors due to its material creep. This means that the proposed model overcomes the problems of hysteresis, variation in gain and lack of linearity over time. In return, this can be used to enhance the durability of the grasping mechanism, leading to a more robust and secure grasp for paralyzed hands. Furthermore, the exposed analysis approach in this paper can be a useful methodology for the user to evaluate the performance of any measurement system in a real-time environment.

RNA-primed rolling circle amplification (RPRCA) is a useful laboratory method for RNA detection; however, the detection of RNA is limited by the lack of information on 3'-terminal sequences. We uncovered that conventional RPRCA using pre-circularized probes could potentially detect the internal sequence of target RNA molecules in combination with RNase H. However, the specificity for mRNA detection was low, presumably due to non-specific hybridization of non-target RNA with the circular probe. To overcome this technical problem, we developed a method for detecting a sequence of interest in target RNA molecules via RNase H-assisted RPRCA using padlocked probes. When padlock probes are hybridized to the target RNA molecule, they are converted to the circular form by SplintR ligase. Subsequently, RNase H creates nick sites only in the hybridized RNA sequence, and single-stranded DNA is finally synthesized from the nick site by phi29 DNA polymerase. This method could specifically detect at least 10 fmol of the target RNA molecule without reverse transcription. Moreover, this method detected GFP mRNA present in 10 ng of total RNA isolated from Escherichia coli without background DNA amplification. Therefore, this method can potentially detect almost all types of RNA molecules without reverse transcription and reveal full-length sequence information.

The expression of H1 receptor has been reported in amacrine cells of mouse and rat retinae. However, we assumed that other types of histamine receptors also function in amacrine cells. In order to confirm that histamine modulates the membrane potential in mouse amacrine cells, we measured voltage-gated currents using whole-cell configuration. Under voltage-clamp conditions, the amplitude of voltage-gated outward currents was enhanced by the application of 100 µM histamine in 65% of amacrine cells. Histamine also increased the amplitudes of voltage-gated inward currents in 72% of amacrine cells. When antagonists of the histamine H1, H2, or H3 receptors were applied to histamine-sensitive amacrine cells, all three types of these inhibitors reduced the effect of histamine. Moreover, we classified recorded cells into seven types based on their morphological characteristics. Two of the seven types, diffuse multistratified cells and AII amacrine cells, responded significantly to histamine. These results indicate that histamine affected the membrane potential via three types of histamine receptors. Furthermore, there were differences in the responses to histamine among types of amacrine cells. Histamine may be one of the important neurotransmitters and/or neuromodulators in the visual processing.

Tyrosine kinase inhibitors (TKIs), including imatinib, dasatinib and nilotinib are primarily used in the initial treatment of chronic phase (CP)-chronic myeloid leukemia (CML), as CMLs harbor the BCR-ABL fusion product. An increased number of lymphocytes and large granular lymphocytes (LGLs) have been observed in patients treated with dasatinib, but not other TKIs. The LGLs have been reported to be primarily natural killer (NK) cells and cytotoxic T lymphocytes (CTLs). In the present study, a CP-CML patient who has maintained molecular response 5 for >2.4 years after stopping dasatinib was reported. Memory and effector CTLs and NK cells, were observed after 2.4 years of treatment-free remission, despite the fact that lymphocyte counts are not elevated in the patient. These results suggest that dasatinib may induce cellular immunity, including NK cells and CTLs and this cellular immunity may be maintained for a long period following cessation of dasatinib. The results suggest that this cellular immunity may provide a long-term cure without the need for continued TKI treatment.

Background: The QT variability index (QTVI) is a noninvasive index of repolarization lability that has been applied to subjects with cardiovascular disease. QTVI provides a ratio of normalized QT variability to normalized heart rate variability, and therefore includes an assessment of autonomic nervous activity. However, measurement of QT time is particularly difficult in children, who exhibit physiologically high heart rates compared with adults. In this study, we developed a set of standard values of J-point to Tpeak interval (JTp) for infants by age, and assessed the correlation of QTVI with the JTp variability index (JTpVI)., Methods: Subjects included 623 infants and children (0-7 years of age) without heart disease and 57 healthy university students. All subjects were divided into three groups by age. QTVI and JTpVI were calculated based on an electrocardiogram, and age-specific standard values, a gender-specific classification, and a standard growth curve were constructed., Results: JTpVI markedly decreased in infancy and slowly decreased thereafter, reaching adult values by school age. There was also a strong correlation of JTpVI with QTVI (r = .856)., Conclusions: JTp can be used to evaluate the variability of the repolarization time in healthy infants, and may be useful for detection of early repolarization abnormalities., (© 2017 Wiley Periodicals, Inc.)

There is evidence that radiation exposure is a causative factor of myelodysplastic syndromes (MDS). However, little is known about whether radiation exposure is also a prognostic factor of MDS. We investigated the impact of radiation exposure on the prognosis of MDS in Nagasaki atomic bomb survivors using the International Prognostic Scoring System (IPSS) and the revised version (IPSS-R). Subjects were 140 patients with primary MDS diagnosed between 1985 and 2011 and evaluable for IPSS, IPSS-R, and exposure distance. Of those, 31 were exposed at <1.5 km, 35 at 1.5-2.99 km, and 74 at ≥3.0 km. By the end of March 2014, 47 patients (34%) progressed to overt leukemia and 106 (75.7%) died. By comparing with patients exposed at ≥3.0 km, those exposed at <1.5 km had significantly higher frequencies of abnormal chromosome (P = 0.02), intermediate/poor IPSS, and intermediate/poor/very poor IPSS-R cytogenetic category (P = 0.0001, and P < 0.0001, respectively). As with de novo MDS, multivariate Cox regression analyses revealed that cytogenetic abnormalities, IPSS karyotype, and IPSS-R cytogenetics were significantly associated with poor survival, and cumulative incidence of leukemic transformation in MDS among atomic bomb survivors, but exposure distance was not associated with any poor outcomes. These suggest that exposure to the greater dose of atomic bomb radiation is associated with developing poor cytogenetic abnormalities in MDS, which might consequently lead to overt leukemia among atomic bomb survivors., (© 2016 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.)

Primary mediastinal large B-cell lymphoma (PMLBCL) is one of the subtypes of diffuse large B-cell lymphoma. We experienced a rare case of PMLBCL that exhibited endobronchial involvement. A 33-year-old Japanese female with the chief complaints of epigastralgia, back pain, and nausea visited a primary care hospital. Computed tomography of the chest and abdomen demonstrated a bulky mass in the left anterior mediastinum, multiple pulmonary nodules, axillary lymph node swelling, and a pancreatic tumor. Fiberoptic bronchoscopy showed a white-tinged irregularly shaped endobronchial tumor accompanied by capillary vessel dilation in the left upper lobar bronchus. Taken together, these findings resulted in a diagnosis of PMLBCL.