We successfully fabricate a transversely disordered optical fiber made of AsSe
and As
S
glasses for high-resolution mid-infrared image transport. By using the fabricated fiber, we experimentally ...observe transverse Anderson localization of mid-infrared light at the wavelength of 3 µm. Moreover, we numerically evaluate the localization in the fiber by using a cross-sectional image of the fiber.
Objective
Non-simple nodules in hepatocellular carcinoma (HCC) correlate with poor prognosis. Therefore, we examined the diagnostic ability of gadolinium-ethoxybenzyl-diethylenetriamine pentaacetic ...acid-enhanced magnetic resonance imaging (EOB-MRI) and contrast-enhanced ultrasound (CEUS) for diagnosing the macroscopic classification of small HCCs.
Methods
A total of 85 surgically resected nodules (≤30 mm) were analyzed.
HCCs were pathologically classified as simple nodular (SN) and non-SN. By evaluating hepatobiliary phase (HBP) of EOB-MRI and Kupffer phase of CEUS, the diagnostic abilities of both modalities to correctly distinguish between SN and non-SN were compared.
Results
Forty-six nodules were diagnosed as SN and the remaining 39 nodules as non-SN. The area under the ROC curve (AUROCs, 95 % confidence interval) for the diagnosis of non-SN were EOB-MRI, 0.786 (0.682–0.890): CEUS, 0.784 (0.679–0.889), in combination, 0.876 (0.792–0.959). The sensitivity, specificity, and accuracy were 64.1 %, 95.7 %, and 81.2 % in EOB-MRI, 56.4 %, 97.8 %, and 78.8 % in CEUS, and 84.6 %, 95.7 %, and 90.6 % in combination, respectively. High diagnostic ability was obtained when diagnosed in both modalities combined. The sensitivity was especially statistically significant compared to CEUS.
Conclusion
Combined diagnosis by EOB-MRI and CEUS can provide high-quality imaging assessment for determining non-SN in small HCCs.
Key Points
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Non-SN has a higher frequency of MVI and intrahepatic metastasis than SN.
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Macroscopic classification is useful to choose the treatment strategy for small HCCs.
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Diagnostic ability for macroscopic findings of EOB-MRI and CEUS were statistically equal.
•
The diagnosis of macroscopic findings by individual modality has limitations.
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Combined diagnosis of EOB-MRI and CEUS provides high diagnostic ability.
In humans, insulin resistance has been linked to an impaired metabolic transition from fasting to feeding (metabolic flexibility; MetFlex). Previous studies suggest that mitochondrial dynamics ...response is a putative determinant of MetFlex; however, this has not been studied in humans. Thus, the aim of this study was to investigate the mitochondrial dynamics response in the metabolic transition from fasting to feeding in human peripheral blood mononuclear cells (PBMCs). Six male subjects fasted for 16 h (fasting), immediately after which they consumed a 75‐g oral glucose load (glucose). In both fasting and glucose conditions, blood samples were taken to obtain PBMCs. Mitochondrial dynamics were assessed by electron microscopy images. We exposed in vitro acetoacetate‐treated PBMCs to the specific IP3R inhibitor Xestospongin B (XeB) to reduce IP3R‐mediated mitochondrial Ca2+ accumulation. This allowed us to evaluate the role of ER‐mitochondria Ca2+ exchange in the mitochondrial dynamic response to substrate availability. To determine whether PBMCs could be used in obesity context (low MetFlex), we measured mitochondrial dynamics in mouse spleen‐derived lymphocytes from WT and ob/ob mice. We demonstrated that the transition from fasting to feeding reduces mitochondria‐ER interactions, induces mitochondrial fission and reduces mitochondrial cristae density in human PBMCs. In addition, we demonstrated that IP3R activity is key in the mitochondrial dynamics response when PBMCs are treated with a fasting‐substrate in vitro. In murine mononuclear‐cells, we confirmed that mitochondria‐ER interactions are regulated in the fasted‐fed transition and we further highlight mitochondria‐ER miscommunication in PBMCs of diabetic mice. In conclusion, our results demonstrate that the fasting/feeding transition reduces mitochondria‐ER interactions, induces mitochondrial fission and reduces mitochondrial cristae density in human PBMCs, and that IP3R activity may potentially play a central role.
Recent advancements in electron microscope volume imaging, such as serial imaging using scanning electron microscopy (SEM), have facilitated the acquisition of three-dimensional ultrastructural ...information of biological samples. These advancements help build a comprehensive understanding of the functional structures in entire organelles, cells, organs and organisms, including large-scale wiring maps of neural circuitry in various species. Advanced volume imaging of biological specimens has often been limited by artifacts and insufficient contrast, which are partly caused by problems in staining, serial sectioning and electron beam irradiation. To address these issues, methods of sample preparation have been modified and improved in order to achieve better resolution and higher signal-to-noise ratios (SNRs) in large tissue volumes. These improvements include the development of new embedding media for electron microscope imaging that have desirable physical properties such as less deformation in the electron beam and higher stability for sectioning. The optimization of embedding media involves multiple resins and filler materials including biological tissues, metallic particles and conductive carbon black. These materials alter the physical properties of the embedding media, such as conductivity, which reduces specimen charge, ameliorates damage to sections, reduces image deformation and results in better ultrastructural data. These improvements and further studies to improve electron microscope volume imaging methods provide options for better scale, quality and throughput in the three-dimensional ultrastructural analyses of biological samples. These efforts will enable a deeper understanding of neuronal circuitry and the structural foundation of basic and higher brain functions.
Cassette-electrode microbial fuel cells (CE-MFCs) have been developed for the conversion of biomass wastes into electric energy. The present study modified CE-MFC for its application to wastewater ...treatment and examined its utility in a long-term (240 days) experiment to treat a synthetic wastewater, containing starch, yeast extract, peptone, plant oil, and a detergent (approximately 500 mg of total chemical oxygen demand COD per liter). A test MFC reactor (1 l in capacity) was equipped with 10 cassette electrodes with total anode and cathode projection areas of 1440 cm2, and the operation was initiated by inoculating with rice paddy-field soil. It was demonstrated that CE-MFC achieved COD removal rates of 80% at hydraulic-retention times of 6 h or greater, and electricity was generated at a maximum power density of 150 mW m−2 and Coulombic efficiency of 20%. Microbial communities established on anodes of CEs were analyzed by pyrosequencing of PCR-amplified 16S rRNA gene fragments, showing that Geobacter, Clostridium, and Geothrix were abundantly detected in anode biofilms. These results demonstrate the utility of CE-MFC for wastewater treatment, in which Geobacter and Geothrix would be involved in the electricity generation.
Attention-deficit hyperactivity disorder (ADHD) and autism spectrum disorder (ASD) are associated with attentional impairments, with both commonalities and differences in the nature of their ...attention deficits. This study aimed to investigate the neural correlates of ADHD and ASD traits in healthy individuals, focusing on the functional connectivity (FC) of attention-related large-scale brain networks (LSBNs). The participants were 61 healthy individuals (30 men; age, 21.9 ± 1.9 years). The Adult ADHD Self-Report Scale (ASRS) and Autism Spectrum Quotient (AQ) were administered as indicators of ADHD and ASD traits, respectively. Performance in the continuous performance test (CPT) was used as a behavioural measure of sustained attentional function. Functional magnetic resonance imaging scans were performed during the resting state (Rest) and auditory oddball task (Odd). Considering the critical role in attention processing, we focused our analyses on the default mode (DMN), frontoparietal (FPN), and salience (SN) networks. Region of interest (ROI)-to-ROI analyses (false discovery rate < 0.05) were performed to determine relationships between psychological measures with within-network FC (DMN, FPN, and SN) as well as with between-network FC (DMN-FPN, DMN-SN, and FPN-SN). ASRS scores, but not AQ scores, were correlated with less frequent commission errors and shorter reaction times in the CPT. During Odd, significant positive correlations with ASRS were demonstrated in multiple FCs within DMN, while significant positive correlations with AQ were demonstrated in multiple FCs within FPN. AQs were negatively correlated with FPN-SN FCs. During Rest, AQs were negatively and positively correlated with one FC within the SN and multiple FCs between the DMN and SN, respectively. These findings of the ROI-to-ROI analysis were only partially replicated in a split-half replication analysis, a replication analysis with open-access data sets, and a replication analysis with a structure-based atlas. The better CPT performance by individuals with subclinical ADHD traits suggests positive effects of these traits on sustained attention. Differential associations between LSBN FCs and ASD/ADHD traits corroborate the notion of differences in sustained and selective attention between clinical ADHD and ASD.
In the present study, we report a human-inherited, impaired, adaptive immunity disorder, which predominantly manifested as a B cell differentiation defect, caused by a heterozygous IKZF3 missense ...variant, resulting in a glycine-to-arginine replacement within the DNA-binding domain of the encoded AIOLOS protein. Using mice that bear the corresponding variant and recapitulate the B and T cell phenotypes, we show that the mutant AIOLOS homodimers and AIOLOS-IKAROS heterodimers did not bind the canonical AIOLOS-IKAROS DNA sequence. In addition, homodimers and heterodimers containing one mutant AIOLOS bound to genomic regions lacking both canonical motifs. However, the removal of the dimerization capacity from mutant AIOLOS restored B cell development. Hence, the adaptive immunity defect is caused by the AIOLOS variant hijacking IKAROS function. Heterodimeric interference is a new mechanism of autosomal dominance that causes inborn errors of immunity by impairing protein function via the mutation of its heterodimeric partner.
Skeletal muscle stem cells (MuSCs) have been proposed as suitable candidates for cell therapy to muscular disorders since they exhibit a good capacity for myogenic regeneration. However, for better ...therapeutic outcomes, it is necessary to isolate human MuSCs from a suitable tissue source that possess high myogenic differentiation. In this context, isolated CD56+CD82+ cells from extra eyelid tissues were tested in vitro myogenic differentiation potential. Primary human myogenic cells derived from extra eyelids including orbicularis oculi, might be good candidates for human muscle stem cell-based research.
Cancer-type organic anion transporting polypeptide 1B3 (Ct-OATP1B3) mRNA is a variant isoform of the liver-type OATP1B3. Because Ct-OATP1B3 mRNA shows an excellent cancer-specific expression profile ...in colorectal cancer (CRC), and that its expression levels are associated with CRC prognosis, it holds the potential to become a useful CRC detection and diagnosis biomarker. While the potential is currently justified only at the tissue level, if existence of Ct-OATP1B3 mRNA in CRC-derived extracellular vesicles (EVs) is validated, the findings could enhance its translational potential as a CRC detection and diagnosis biomarker. Therefore, this study aims at proving that Ct-OATP1B3 mRNA exists in CRC-derived EVs, and can be detected using serum specimens. To examine the possibility of Ct-OATP1B3 mRNA being existed in extracellular milieu, we isolated EVs from the human CRC (HCT116, HT-29, and SW480) cell lines, and prepared their cDNAs. The RT-PCR results showed that Ct-OATP1B3 mRNA was clearly present in EVs derived from the human CRC cell lines. Then, in order to further explore the possibility that Ct-OATP1B3 mRNA in CRC-derived EVs can be detected in serum, we isolated serum EVs derived from human CRC xenograft mice, and then performed RT-PCR. The results showed that Ct-OATP1B3 mRNA could be found in all serum EV and CRC tissue samples of the mice examined. Collectively, our findings, which show that Ct-OATP1B3 mRNA exists in EVs and can be detected in (at least) mouse serum, strengthen the potential use of Ct-OATP1B3 mRNA as a serum-based CRC biomarker.
To investigate the safety and efficacy of cultured human corneal endothelial cell (hCEC) injection therapy with mature differentiated (mature) cell subpopulations (SPs) for corneal endothelial ...failure (CEF).
Comparative, interventional case series.
This study involved 18 eyes with CEF that underwent cultured hCEC injection therapy, categorized into 2 groups: (1) 11 eyes administered a relatively lower proportion (0.1 to 76.3%) of mature cell SPs (group 1 Gr1), and (2) 7 eyes administered a relatively higher proportion (>90%) of mature cell SPs (group 2 Gr2). From 1 week to 3 years postoperation, corneal endothelial cell (CEC) density (CECD), central corneal thickness (CCT), and best-corrected visual acuity (BCVA) were recorded, and the CEC parameter's “spring constant” was calculated. The proportion of mature SPs was evaluated by fluorescence-activated cell sorting analysis based on cell-surface markers.
At 3 years postoperation, corneal restoration with improved BCVA was attained in 10 of the 11 Gr1 eyes and all Gr2 eyes, the median CECD in Gr2 (3083 cells/mm2; range, 2182-4417 cells/mm2) was higher than that in Gr1 (1349 cells/mm2; range, 746-2104 cells/mm2) (P < .001), and the spring constant verified the superiority of the mature cultured hCECs. From 24 weeks through 3 years postoperation, the median percentage of CECD decrease was 3.2% in Gr2 and 23.6% in Gr1 (P < .005). CCT recovery was prompt and constant in Gr2, while diverse in Gr1. No adverse events were observed.
Our findings showed that mature cell SPs for hCEC injection therapy provide rapid recovery of CCT, better CECD, and low CECD attrition over 3 years postsurgery.
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