This paper reported a study on the 3-dimensional deep-learning-based automatic diagnosis of nasal fractures. (1) Background: The nasal bone is the most protuberant feature of the face; therefore, it ...is highly vulnerable to facial trauma and its fractures are known as the most common facial fractures worldwide. In addition, its adhesion causes rapid deformation, so a clear diagnosis is needed early after fracture onset. (2) Methods: The collected computed tomography images were reconstructed to isotropic voxel data including the whole region of the nasal bone, which are represented in a fixed cubic volume. The configured 3-dimensional input data were then automatically classified by the deep learning of residual neural networks (3D-ResNet34 and ResNet50) with the spatial context information using a single network, whose performance was evaluated by 5-fold cross-validation. (3) Results: The classification of nasal fractures with simple 3D-ResNet34 and ResNet50 networks achieved areas under the receiver operating characteristic curve of 94.5% and 93.4% for binary classification, respectively, both indicating unprecedented high performance in the task. (4) Conclusions: In this paper, it is presented the possibility of automatic nasal bone fracture diagnosis using a 3-dimensional Resnet-based single classification network and it will improve the diagnostic environment with future research.
Continuous monitoring of the present genetic status is essential to preserve the genetic resource of wild populations. In this study, we sequenced regional Pacific abalone Haliotis discus samples ...from three different locations around the Korean peninsula to assess population structure, utilizing Genotyping-by-Sequencing (GBS) method. Using PstI enzyme for genome reduction, we demonstrated the resultant library represented the whole genome region with even spacing, and as a result 16,603 single nucleotide variants (SNVs) were produced. Genetic diversity and population structure were investigated using several methods, and a strong genetic heterogeneity was observed in the Korean abalone populations. Additionally, by comparison of the variant sets among population groups, we were able to discover 26 Korean abalone population-specific SNVs, potentially associated with phenotype differences. This is the first study demonstrating the feasibility of GBS for population genetic study on H. discus. Our results will provide valuable data for the genetic conservation and management of wild abalone populations in Korea and help future GBS studies on the marine mollusks.
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•ALDH2 deficiency is associated with an increased risk of HCC from cirrhosis in those who drink alcohol.•Chronic CCl4+EtOH treatment induces greater hepatic mitochondrial DNA damage ...in Aldh2-deficient mice than WT mice.•Oxidized mitochondrial DNA is delivered to HCC cells via hepatocyte-derived extracellular vesicles.•Oxidized mitochondrial DNA and acetaldehyde synergistically promote ROS production and multiple oncogenic pathways.
Excessive alcohol consumption is one of the major causes of hepatocellular carcinoma (HCC). Approximately 30–40% of the Asian population are deficient for aldehyde dehydrogenase 2 (ALDH2), a key enzyme that detoxifies the ethanol metabolite acetaldehyde. However, how ALDH2 deficiency affects alcohol-related HCC remains unclear.
ALDH2 polymorphisms were studied in 646 patients with viral hepatitis B (HBV) infection, who did or did not drink alcohol. A new model of HCC induced by chronic carbon tetrachloride (CCl4) and alcohol administration was developed and studied in 3 lines of Aldh2-deficient mice: including Aldh2 global knockout (KO) mice, Aldh2*1/*2 knock-in mutant mice, and liver-specific Aldh2 KO mice.
We demonstrated that ALDH2 deficiency was not associated with liver disease progression but was associated with an increased risk of HCC development in cirrhotic patients with HBV who consumed excessive alcohol. The mechanisms underlying HCC development associated with cirrhosis and alcohol consumption were studied in Aldh2-deficient mice. We found that all 3 lines of Aldh2-deficient mice were more susceptible to CCl4 plus alcohol-associated liver fibrosis and HCC development. Furthermore, our results from in vivo and in vitro mechanistic studies revealed that after CCl4 plus ethanol exposure, Aldh2-deficient hepatocytes produced a large amount of harmful oxidized mitochondrial DNA via extracellular vesicles, which were then transferred into neighboring HCC cells and together with acetaldehyde activated multiple oncogenic pathways (JNK, STAT3, BCL-2, and TAZ), thereby promoting HCC.
ALDH2 deficiency is associated with an increased risk of alcohol-related HCC development from fibrosis in patients and in mice. Mechanistic studies reveal a novel mechanism that Aldh2-deficient hepatocytes promote alcohol-associated HCC by transferring harmful oxidized mitochondrial DNA-enriched extracellular vesicles into HCC and subsequently activating multiple oncogenic pathways in HCC.
Alcoholics with an ALDH2 polymorphism have an increased risk of digestive tract cancer development, however, the link between ALDH2 deficiency and hepatocellular carcinoma (HCC) development has not been well established. In this study, we show that ALDH2 deficiency exacerbates alcohol-associated HCC development both in patients and mouse models. Mechanistic studies revealed that after chronic alcohol exposure, Aldh2-deficient hepatocytes produce a large amount of harmful oxidized mitochondrial DNA via extracellular vesicles, which can be delivered into neighboring HCC cells and subsequently activate multiple oncogenic pathways, promoting HCC.
Parkinson disease (PD), progressive supranuclear palsy (PSP), and multiple-system atrophy (MSA) are known to affect dopaminergic neurons of the brain stem and striatum with different preferential ...involvement. Here we investigated differences in striatal subregional dopamine transporter loss in PD, PSP, and MSA and assessed the diagnostic value of (18)F-fluorinated-N-3-fluoropropyl-2-β-carboxymethoxy-3-β-(4-iodophenyl)nortropane ((18)F-FP-CIT) PET in differentiating PSP and MSA from PD.
Forty-nine patients with PD, 19 patients with PSP, 24 patients with MSA, and 21 healthy people (healthy controls) were examined with (18)F-FP-CIT PET. The PET images were spatially normalized and analyzed with 12 striatal subregional volume-of-interest (VOI) templates (bilateral ventral striatum VS, anterior caudate AC, posterior caudate, anterior putamen, posterior putamen PP, and ventral putamen VP) and 1 occipital VOI template. The nondisplaceable binding potential (BP(ND)) and intersubregional ratio (ISR; defined as the ratio of the BP(ND) of one striatal subregion to that of another striatal subregion) of subregional VOIs were calculated.
The BP(ND) of all VOIs in the PD, MSA, and PSP groups were significantly lower than those in the healthy controls (P < 0.05). The BP(ND) of AC and the AC/VS ISR in the PSP group were significantly lower than those in the PD group. The BP(ND) of VP was significantly lower, but the PP/VP ISR was significantly higher in the MSA group than in the PD group. At the cutoff value for the AC/VS ISR (<0.7), the sensitivity and specificity for differentiating PSP from PD were 94% and 92%, respectively. At the cutoff value for the PP/VP ISR (>0.65), the sensitivity and specificity for differentiating MSA from PD were 90% and 45%, respectively. The diagnostic accuracy of visual analysis was similar to that of quantitative analysis for differentiating PSP from PD but was significantly higher for differentiating MSA from PD.
Compared with PD, PSP and MSA showed more prominent and earlier dopamine transporter loss in the AC and VP, respectively. These findings could be useful for suggesting PSP or MSA in parkinsonian cases without characteristic atypical features.
The digestive system is gaining interest as a major regulator of various functions including immune defense, nutrient accumulation, and regulation of feeding behavior, aside from its conventional ...function as a digestive organ. The Drosophila midgut epithelium is completely renewed every 1-2 weeks due to differentiation of pluripotent intestinal stem cells in the midgut. Intestinal stem cells constantly divide and differentiate into enterocytes that secrete digestive enzymes and absorb nutrients, or enteroendocrine cells that secrete regulatory peptides. Regulatory peptides have important roles in development and metabolism, but study has mainly focused on expression and functions in the nervous system, and not much is known about the roles in endocrine functions of enteroendocrine cells. We systemically examined the expression of 45 regulatory peptide genes in the Drosophila midgut, and verified that at least 10 genes are expressed in the midgut enteroendocrine cells through RT-PCR, in situ hybridization, antisera, and 25 regulatory peptide-GAL transgenes. The Drosophila midgut is highly compartmentalized, and individual peptides in enteroendocrine cells were observed to express in specific regions of the midgut. We also confirmed that some peptides expressed in the same region of the midgut are expressed in mutually exclusive enteroendocrine cells. These results indicate that the midgut enteroendocrine cells are functionally differentiated into different subgroups. Through this study, we have established a basis to study regulatory peptide functions in enteroendocrine cells as well as the complex organization of enteroendocrine cells in the Drosophila midgut.
This study was a cost-effectiveness analysis of intensive blood pressure (BP) control among hypertensive patients in Korea. We constructed a Markov model comparing intensive versus standard BP ...control treatment and calculated the incremental cost-effectiveness ratio. The study population consisted of hypertensive patients over 50 years old with systolic blood pressures (SBPs) exceeding 140 mmHg and at high risk of cardiovascular disease. Treatment alternatives included lowering the SBP below 120 mmHg (intensive) and 140 mmHg (standard) for target BP. We assumed five scenarios with different medication adherence. The effectiveness variable was quality-adjusted life years (QALYs), and costs included medical costs related to hypertension (HT), complications, and nonmedical costs. In addition, we performed a sensitivity analysis to confirm the robustness of the results of this study. Scenario 5, with 100% medication adherence, showed the lowest incremental cost-effectiveness ratio (ICER) of $1,373 USD, followed by scenario 1 (first 15 years: 62.5%, 16-30 years: 65.2%, after 30 years: 59.5%), scenario 2 (first five years: 62.5% decrease by 5% every five years), and scenario 3 (first 10 years: 62.5% decrease by 10% every 10 years). The ICERs in all scenarios were lower than the willingness to pay (WTP) threshold of $9,492-$32,907 USD in Korea. Tornado analysis showed that the ICERs were changed greatly according to stroke incidence. Intensive treatment of HT prevents cardiovascular disease (CVD); therefore, intensive treatment is more cost-effective than standard treatment despite the consumption of more health resources. ICERs are considerably changed according to medication adherence, confirming the importance of patient adherence to treatment.
Abstract
Chemical short-range order in disordered solid solutions often emerges with specific heat treatments. Unlike thermally activated ordering, mechanically derived short-range order (MSRO) in a ...multi-principal-element Fe
40
Mn
40
Cr
10
Co
10
(at%) alloy originates from tensile deformation at 77 K, and its degree/extent can be tailored by adjusting the loading rates under quasistatic conditions. The mechanical response and multi-length-scale characterisation pointed to the minor contribution of MSRO formation to yield strength, mechanical twinning, and deformation-induced displacive transformation. Scanning and high-resolution transmission electron microscopy and the anlaysis of electron diffraction patterns revealed the microstructural features responsible for MSRO and the dependence of the ordering degree/extent on the applied strain rates. Here, we show that underpinned by molecular dynamics, MSRO in the alloys with low stacking-fault energies forms when loaded at 77 K, and these systems that offer different perspectives on the process of strain-induced ordering transition are driven by crystalline lattice defects (dislocations and stacking faults).
Abstract Introduction Mineral trioxide aggregate (MTA) materials have been used for many years as a pulp therapy material. The most widely used product, ProRoot MTA (Dentsply, Tulsa, OK), has a major ...drawback in that it causes tooth discoloration. Alternatives have recently been developed such as ENDOCEM Zr (MARUCHI, Wonju, Korea) and RetroMTA (BioMTA, Seoul, Korea). The purpose of this study was to compare the discoloration of these various MTA-based materials. Methods Discoloration of discs prepared from 4 different MTA-based materials (ProRoot MTA, MTA Angelus Angelus, Londrina, PR, Brazil, ENDOCEM Zr, and RetroMTA) were observed at 15 and 30 minutes after exposure to light at an intensity of 1000 mA/cm2 . In a tooth model, 12 premolars were used per each group to retrofill the pulp chamber with MTA-based materials. The degree of discoloration was measured over a 16-week period using a digital spectrophotometer. Results Distinct color changes were observed for discs made from ProRoot MTA and MTA Angelus, but no clear change was observed for those made from either ENDOCEM Zr or RetroMTA. In the tooth model, more distinct, time-dependent color changes were observed for teeth filled with ProRoot MTA and MTA Angelus than for those filled with ENDOCEM Zr and RetroMTA. Conclusions Less discoloration was observed with ENDOCEM Zr and RetroMTA (which contain zirconium oxide) than with ProRoot MTA and MTA Angelus (which contain bismuth oxide) in both of the test models used.
Addressing age-related immunological defects through therapeutic interventions is essential for healthy aging, as the immune system plays a crucial role in controlling infections, malignancies, and ...in supporting tissue homeostasis and repair. In our study, we show that stimulating toll-like receptor 5 (TLR5) via mucosal delivery of a flagellin-containing fusion protein effectively extends the lifespan and enhances the healthspan of mice of both sexes. This enhancement in healthspan is evidenced by diminished hair loss and ocular lens opacity, increased bone mineral density, improved stem cell activity, delayed thymic involution, heightened cognitive capacity, and the prevention of pulmonary lung fibrosis. Additionally, this fusion protein boosts intestinal mucosal integrity by augmenting the surface expression of TLR5 in a certain subset of dendritic cells and increasing interleukin-22 (IL-22) secretion. In this work, we present observations that underscore the benefits of TLR5-dependent stimulation in the mucosal compartment, suggesting a viable strategy for enhancing longevity and healthspan.
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