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Material decomposition (MD) is an application of dual-energy computed tomography (DECT) that decomposes DECT images into specific material images. However, the direct inversion method used in MD often amplifies noise in the decomposed material images, resulting in lower image quality. To address this issue, we propose an image-domain MD method based on the concept of deep image prior (DIP). DIP is an unsupervised learning method that can perform different tasks without using a large training dataset with known targets (i.e., basis material images). We retrospectively recruited patients who underwent non-contrast brain DECT scans and investigated the feasibility of using the proposed DIP-based method to decompose DECT images into two (i.e., bone and soft tissue) and three (i.e., bone, soft tissue, and fat) basis materials. We evaluated the decomposed material images in terms of signal-to-noise ratio (SNR) and modulation transfer function (MTF). The proposed DIP-based method showed greater improvement in SNR in the decomposed soft-tissue images compared to the direct inversion method and the iterative method. Moreover, the proposed method produced similar MTF curves in both two- and three-material decompositions. Additionally, the proposed DIP-based method demonstrated better separation ability than the other two studied methods in the case of three-material decomposition. Our results suggest that the proposed DIP-based method is capable of unsupervisedly generating high-quality basis material images from DECT images., (© 2023. Australasian College of Physical Scientists and Engineers in Medicine.)

Parametric imaging obtained from kinetic modeling analysis of dynamic positron emission tomography (PET) data is a useful tool for quantifying tracer kinetics. However, pixel-wise time-activity curves have high noise levels which lead to poor quality of parametric images. To solve this limitation, we proposed a new image denoising method based on deep image prior (DIP). Like the original DIP method, the proposed DIP method is an unsupervised method, in which no training dataset is required. However, the difference is that our method can simultaneously denoise all dynamic PET images. Moreover, we propose a modified version of the DIP method called double DIP (DDIP), which has two DIP architectures. The additional DIP model is used to generate high-quality input data for the second DIP model. Computer simulations were performed to evaluate the performance of the proposed DIP-based methods. Our simulation results showed that the DDIP method outperformed the single DIP method. In addition, the DDIP method combined with data augmentation could generate PET parametric images with superior image quality compared to the spatiotemporal-based non-local means filtering and high constrained backprojection. Our preliminary results show that our proposed DDIP method is a novel and effective unsupervised method for simultaneously denoising dynamic PET images., (© 2022. The Author(s) under exclusive licence to Society for Imaging Informatics in Medicine.)

Deep learning (DL) has shown great potential in conversions between various imaging modalities. Similarly, DL can be applied to synthesize a high-kV computed tomography (CT) image from its corresponding low-kV CT image. This indicates the feasibility of obtaining dual-energy CT (DECT) images without purchasing a DECT scanner. In this study, we investigated whether a low-to-high kV mapping was better than a high-to-low kV mapping. We used a U-Net model to perform conversions between different kV CT images. Moreover, we proposed a double U-Net model to improve the quality of original single-energy CT images. Ninety-eight patients who underwent brain DECT scans were used to train, validate, and test the proposed DL-based model. The results showed that the low-to-high kV conversion was better than the high-to-low kV conversion. In addition, the DL-based DECT images had better signal-to-noise ratios (SNRs) than the true (original) DECT images, but at the expense of a slight loss in spatial resolution. The mean CT number differences between the true and DL-based DECT images were within [Formula: see text] 1 HU. No statistically significant difference in CT number measurements was found between the true and DL-based DECT images (p > 0.05). The DL-based DECT images with improved SNR could produce low-noise virtual monoenergetic images. Our preliminary results indicate that DL has the potential to generate brain DECT images using single-energy brain CT images.

Chronic myeloid leukemia (CML) is a hematopoietic malignancy caused by the constitutive activation of Bcr-Abl tyrosine kinase. The Bcr-Abl inhibitor imatinib and other second-generation tyrosine kinase inhibitors such as dasatinib and nilotinib have remarkable efficacy in CML treatment. However, gene mutation-mediated drug resistance remains a critical problem. Among point mutations, the Bcr-Abl T315I mutation confers resistance to these Bcr-Abl inhibitors. Previously, we have synthesized the compound (1-methyl-1H-indol-5-yl)-(3,4,5-trimethoxy-phenyl)-methanone (MPT0B002) as a novel microtubule inhibitor. In this study, we evaluated its effects on the proliferation, cell cycle, and apoptosis of K562 CML cells and BaF3 cells expressing either wild-type Bcr-Abl (BaF3/p210) or T315I-mutated Bcr-Abl (BaF3/T315I). MPT0B002 inhibited cell viability in a dose-dependent manner in these cells but did not affect the proliferation of human umbilical vein endothelial cells. It disrupted tubulin polymerization and arrested cell cycle at the G2/M phase. Treatment with MPT0B002 induced apoptosis, and this induction was associated with increased levels of cleaved caspase-3 and cleaved PARP. Furthermore, MPT0B002 can downregulate both Bcr-Abl and Bcr-Abl-T315I mRNA expressions and protein levels and the downstream signaling pathways. Taken together, our findings suggest that MPT0B002 may be considered a promising compound to downregulate not only wild type Bcr-Abl but also the T315I mutant to overcome Bcr-Abl-T315I mutation-mediated resistance in CML cells.

Imatinib, a Bcr-Abl-specific inhibitor, is effective for treating chronic myeloid leukemia (CML), but drug resistance has emerged for this disease. In this study, we synthesized a novel tubulin polymerization inhibitor, MPT0B206 (N-[1-(4-methoxy-benzenesulfonyl)-2,3-dihydro-1H-indol-7-yl]-formamide), and demonstrated its apoptotic effect and mechanism in imatinib-sensitive K562 and imatinib-resistant K562R CML cells. Western blotting and immunofluorescence microscopy showed that MPT0B206 induced microtubule depolymerization in K562 and K562R cells. MPT0B206 inhibited the growth of these cells in a concentration- and time-dependent manner. It did not affect the viability of normal human umbilical vein endothelial cells. MPT0B206 induced G2/M cell cycle arrest and the appearance of the mitotic marker MPM-2 in K562 and K562R cells, which is associated with the upregulation of cyclin B1 and the dephosphorylation of Cdc2. Treatment of K562 and K562R cells with MPT0B206 induced apoptosis and reduced the protein levels of procaspase-9 and procaspase-3 and increased caspase-3 activity and PARP cleavage. MPT0B206 also reduced the levels of the antiapoptotic proteins Mcl-1 and Bcl-2 and increased the level of the apoptotic protein Bax. Additional experiments showed that MPT0B206 markedly downregulated Bcr-Abl mRNA expression and total and phosphorylated Bcr-Abl protein levels and inhibited the phosphorylation of its downstream proteins STAT5, MAPK, and AKT, and the protein level of c-Myc in K562 and K562R cells. Furthermore, MPT0B206 triggered viability reduction and apoptosis in CML cells carrying T315I-mutated Bcr-Abl. Together, these results suggest that MPT0B206 is a promising alternative for treating imatinib-resistant CML.

Thiamine dependent enzymes are diminished in Alzheimer's disease (AD). Thiamine deficiency in vitro and in rodents is a useful model of this reduction. Thiamine interacts with cellular calcium stores. To directly test the relevance of the thiamine dependent changes to dynamic processes in AD, the interactions must be studied in cells from patients with AD. These studies employed fibroblasts. Mitochondrial dysfunction including reductions in thiamine dependent enzymes and abnormalities in calcium homeostasis and oxidative processes occur in fibroblasts from Alzheimer's Disease (AD) patients. Bombesin-releasable calcium stores (BRCS) from the endoplasmic reticulum (ER) are exaggerated in fibroblasts from patients with AD bearing a presenilin-1 (PS-1) mutation and in control fibroblasts treated with oxidants. ER calcium regulates calcium entry into the cell through capacitative calcium entry (CCE), which is reduced in fibroblasts and neurons from mice bearing PS-1 mutations. Under physiological conditions, mitochondria and ER play important and interactive roles in the regulation of Ca(2+) homeostasis. Thus, the interactions of mitochondria and oxidants with CCE were tested. Inhibition of ER Ca(2+)-ATPase by cyclopiazonic acid (CPA) stimulates CCE. CPA-induced CCE was diminished by inhibition of mitochondrial Ca(2+) export (-60%) or import (-40%). Different aspects of mitochondrial Ca(2+) coupled to CPA-induced-CCE were sensitive to select oxidants. The effects were very different when CCE was examined in the presence of InsP3, a physiological regulator of ER calcium release, and subsequent CCE. CCE under these conditions was only mildly reduced (20-25%) by inhibition of mitochondrial Ca(2+) export, and inhibition of mitochondrial Ca(2+) uptake exaggerated CCE (+53%). However, t-BHP reversed both abnormalities. The results suggest that in the presence of InsP3, mitochondria buffer the local Ca(2+) released from ER following rapid activation of InsP3R and serve as a negative feedback to the CCE. The results suggest that mitochondrial Ca(2+) modifies the depletion and refilling mechanism of ER Ca(2+) stores.

Extranodal natural killer/T cell lymphomas, nasal type (ENKLs), which are a group of non-Hodgkin lymphomas with poor prognoses, are much more common in China than in Western countries. Here, we retrospectively assessed the impact of two treatment regimens on clinical response and survival among 42 ENKL patients. All patients were diagnosed with stage IV, relapsed, or refractory ENKL. Twenty patients received modified SMILE (consisting of L-asparaginase, methotrexate, ifosphamide, etoposide, and dexamethasone) chemotherapy, and 22 control patients received CHOP (consisting of cyclophosphamide, doxorubicin, vincristine, and prednisone) treatment. Higher complete response (CR) and overall response rates (ORR) (CR 45.0 vs. 13%, ORR 70 vs. 36%) were observed among the patients treated with the modified SMILE regimen (Fisher's exact = 0.040, Pearson χ(2) P = 0.030). Similarly, a higher ORR rate was observed among Epstein-Barr virus-positive patients (ORR 50.0 vs. 18.0%, Fisher's exact = 0.049). The treatment group was also significantly associated with longer overall survival (OS) and progression-free survival (PFS) (Log-rank, P = 0.0341, P = 0.0142, respectively), but OS did not seem to be longer. Treatment-related toxicity was monitored in all patients throughout the protocol. There were no significant differences in the incidence of hematological and non-hematological toxicities between the two groups (P < 0.05), with the exception of peripheral neuropathy (treatment = 0 control = 5, Fisher's exact = 0.049).

Purpose: The aim of this study was to investigate whether physical evaluations could be used for predicting the presence and severity of obstructive sleep apnea (OSA) in non-obese snoring patients., Methods: This is a retrospective study, and a total of 244 non-obese (body mass index, BMI, <27 kg/m(2)) snoring patients (178 men and 66 women; mean age = 43.1 ± 12.1 years) were included. Each patient underwent polysomnography and a thorough physical examination, including flexible nasopharyngoscopy and Müller maneuver. Patients were divided into four groups based on apnea-hypopnea index (AHI) scores: normal (simple snoring), AHI < 5; mild OSA, 5 ≦ AHI < 15; moderate OSA, 15 ≦ AHI < 30; severe OSA, AHI ≧ 30. Logistic regression was used to identify risk factors for OSA severity., Results: Fifty-nine patients (24%) were simple snorers. The prevalence of sleep apnea (mild, moderate, or severe OSA) for our non-obese snoring patients was 76%. Univariate logistic analyses showed that higher BMI, male gender and retropalatal Müller grades were significantly associated with OSA severity. Multivariate logistic regression analysis identified male gender and retropalatal Müller grade as risk factors for OSA in non-obese snoring patients., Conclusions: Physical examination may be useful for studying the upper airway in non-obese snoring patients. Flexible nasopharyngoscopy with Müller maneuver appears to be useful for evaluating the severity of OSA in non-obese patients. Retropalatal Müller grade is highly related to both the presence and severity of OSA, particularly in males.

To improve the biological activity of titanium, by using of glow discharge plasma (GDP), albumin-grafted titanium disk have been implemented and carefully studied. Titanium disks were pre-treated with GDP in an environment filled with argon and allylamine gas. Glutaraldehyde was used as a cross-linking agent for albumin grafting. Then, the surface of the albumin-grafted titanium was examined using scanning electron microscopy and X-ray photoelectron spectroscopy. In addition, the static water contact angles of the albumin-grafted titanium disks were measured using goniometry. To observe the effects of albumin adsorption on cell behavior, MG-63 osteoblast-like cells were cultured on the surface-modified titanium disks. Blood coagulation resistance of the modified titanium was monitored and compared to the control titanium disks. The results demonstrated that MG-63 osteoblast-like cells cultured on the albumin-grafted titanium disks expressed better-differentiated morphology compare to cells grown on the control disks. Furthermore, albumin-grafting treatment significantly improved the surface wettability of the titanium disks and resulted in a significantly negative effect on thrombus formation. Based on these results, it was believed that the GDP can potentially improve the biofunctionality of titanium surfaces.

This study investigated the effects of static magnetic fields on the differentiation of MG63 cells cultured on the surface of poly-L-lactide (PLLA) substrates. The cells were continuously exposed to a 4,000 Gauss-static magnetic field (SMF) for 5 days. The proliferation effects of the SMF were measured by MTT assay. Morphologic changes and extracellular matrix release were observed by scanning electron microscopy. The effects of the SMF on alkaline phosphatase activity levels were compared between exposed and unexposed cells. The SMF-exposed cells exhibited decreased MTT values after 1 and 3 days of culture. In addition, SMF exposure promoted the expression of extracellular matrix in MG63 cells on the PLLA substrate. After 1 day, the alkaline phosphatase-specific activity of SMF-exposed MG63 cells was significantly increased (P < 0.05) with a ratio of 1.5-fold. These results show that MG63 cells, seeded on a PLLA disc and treated with SMF, had a more differentiated phenotype.

Nickel-titanium (NiTi) instruments are extensively used in endodontic treatment because of their outstanding mechanical properties. However, unexpected fracture of NiTi rotary instruments occurs during endodontic procedures. Therefore, a reliable method to detect the structural status of a used NiTi instrument is needed. The aim of this study is to use natural frequency for monitoring structural changes of a NiTi instrument during and after the instrumentation process. In this study, laboratory modal testing experiments were performed on cyclic fatigue-loaded NiTi rotary instruments with a natural frequency detecting device. In addition, three-dimensional finite element (FE) models were established for assessing the structural changes that take place in repeatedly loaded NiTi instruments. Repeated rotational loading resulted in a significant decrease (p < 0.05) in natural frequency (with a decreasing ratio of 5.6%) when the tested instruments reached 77-85% of their total life limit. In FE analysis, a strong correlation between natural frequency and change in elastic modulus of the NiTi instrument was found. These findings indicated that natural frequency may represent an effective parameter for evaluating the micro-structural status of NiTi rotary instruments subjected to fatigue loadings.

Recently, the term tensotaxis was proposed to describe the phenomenon that tensile stress or strain affects cell migration. Even so, less attention has been paid to the effects of compressive stress on cell behavior. In this study, by using an injection-molded method combined with photoelastic technology, we developed residual stress gradient-controlled poly-L-lactide discs. After culturing NIH-3T3 fibroblasts on the stress gradient substrate, the cell distributions for high- and low-stress regions were measured and compared. Our results showed that there were significantly more cells in the low-compressive stress region relative to their high-stress analogs (p < 0.05). In addition, NIH-3T3 fibroblasts in the low-compressive stress region expressed more abundant extensive filopodia. These findings provide greater insight into the interaction between cells and substrates, and could serve as a useful reference for connective tissue development and repair.

The aim of this study was to evaluate the effectiveness of vibrational assessment of the mandible fracture patterns. Measurement of natural frequencies and associated vibrational mode shapes was performed to determine the relationship between the dynamic behavior of the human mandible and incidence of mandibular fractures using both in vitro modal testing and finite element analysis. Our results show that the natural frequencies of the human mandible in dry and wet conditions are 567 Hz and 501 Hz, respectively. The first vibrational mode of human mandible is a bending vibration with nodes located at the mandibular body where bone fracture is less likely to occur. By contrast, high vibration amplitudes were identified in the symphysis/parasymphysis and subcondyle regions where bone fractures tend occur. These findings indicate that the vibrational characteristics of the mandible are potential parameters for assessment of the mechanisms of injury.

Considerable evidence indicates that oxidative stress accompanies age-related neurodegenerative diseases. Specific mechanisms by which oxidative stress leads to neurodegeneration are unknown. Two targets of oxidative stress that are known to change in neurodegenerative diseases are the mitochondrial enzyme alpha-ketoglutarate dehydrogenase complex (KGDHC) and endoplasmic reticulum calcium stores. KGDHC activities are diminished in all common neurodegenerative diseases and the changes are particularly well documented in Alzheimer's disease (AD). A second change that occurs in cells from AD patients is an exaggerated endoplasmic reticulum calcium store [i.e., bombesin-releasable calcium stores (BRCS)]. H(2)O(2), a general oxidant, changes both variables in the same direction as occurs in disease. Other oxidants selectively alter these variables. Various antioxidants were used to help define the critical oxidant species that modifies these responses. All of the antioxidants diminish the oxidant-induced carboxy-dichlorofluorescein (cDCF) detectable reactive oxygen species (ROS), but have diverse actions on these cellular processes. For example, alpha-keto-beta-methyl-n-valeric acid (KMV) diminishes the H(2)O(2) effects on BRCS, while trolox and DMSO exaggerate the response. Acute trolox treatment does not alter H(2)O(2)-induced changes in KGDHC, whereas chronic treatment with trolox increases KGDHC almost threefold. The results suggest that KGDHC and BRCS provide targets by which oxidative stress may induce neurodegeneration and a useful tool for selecting antioxidants for reversing age-related neurodegeneration.

The aim of the study was to evaluate the potential for using natural frequency (NF) as an indicator for assessing the stability of a magnetic keeper device used in prosthodontic treatment. A three-dimensional finite element (FE) model of a root keeper-cement-dentine system was established for NF analysis. The model was first validated against a series of in vitro experiments. Then, NF values of the first vibrational mode of the FE model with various boundary conditions were calculated. The in vitro results showed that the measured NF values of the root keeper-incisor units decreased significantly (p<0.01) from 9.07 +/- 0.37 to 5.73 +/- 0.10 kHz when the units were embedded in simulated bony tissue. Results obtained from FE simulations demonstrated that the root keeper would fully loosen when the constant values of the spring elements were lower than 10(4) N-m(-1). Furthermore, a linear increase in the NF values of the model was observed from 6.16 to 15.52 kHz, when the constant was increased from 10(4) to 10(7) N-m(-1), and the values then reached a plateau. The results indicate that the NF value of a root keeper has the potential to be used for monitoring the stability of such a device.

A new optode membrane for the sensitive determination of berberine based on fluorescence quenching of a conjugated polymer, poly(2,5-dimethoxy-phenyldiacetylene) (PDPA), is proposed. Incorporated in a membrane composed of plasticized poly(vinyl chloride) (PVC), the conjugated polymer exhibits better stability than those small sensing molecules regarding its excellent optical properties and lipophilic characteristics. Moreover, upon the introduction of a negatively charged lipophilic additive (tetraphenylborate salt) into a PVC membrane, the optode displayed enhanced sensitivity. In addition, satisfactory analytical sensing characteristics for determining beberine were obtained in terms of the selectivity, reversibility and reproducibility with a detecting range of between 7.5 x 10(-7) mol l(-1) and 7.5 x 10(-4) mol l(-1). The optode membrane has been applied to determine berberine in commercial tablets. The results showed a good agreement with those obtained by the pharmacopoeial method.

Modal analysis is carried out to test the natural frequencies of certain human teeth, including central incisors (CIs), canines (CAs), first premolars (FPs) and first molars (FMs). A total number of 1007 teeth are tested, taking into account tooth type, oral location, age and gender, to analyse the effects of the above-mentioned factors on the natural frequency of the sample teeth. The results reveal that no significant difference in the natural frequency is noted among teeth in the four different intra-oral quadrants. Nevertheless, tooth type and age elicit an effect upon the value of the natural frequency of teeth. On the other hand, the mean value for the natural frequency of CIs (1.27 +/- 0.15 kHz), CAs (1.30 +/- 0.15 kHz), FPs (1.27 +/- 0.15 kHz) and FMs (1.16 +/- 0.12 kHz) for males are significantly lower (p < 0.01) than the analogous figure for females (1.41 +/- 0.21 kHz for CIs, 1.40 +/- 0.18 kHz for CAs, 1.37 +/- 0.20 kHz for FPs, and 1.25 +/- 0.16 kHz for FMs). Moreover, the natural frequency of teeth in male subjects varies with age (p < 0.05). The highest mean frequency of CIs, CAs and FPs for the male subjects is found for the group aged between 40 and 49 years. On the other hand, the natural frequency for the similar set of teeth for the female subjects is shown to be in no way associated with age.

The mechanism of brain contusion has been investigated using a series of three-dimensional (3D) finite element analyses. A head injury model was used to simulate forward and backward rotation around the upper cervical vertebra. Intracranial pressure and shear stress responses were calculated and compared. The results obtained with this model support the predictions of cavitation theory that a pressure gradient develops in the brain during indirect impact. Contrecoup pressure-time histories in the parasagittal plane demonstrated that an indirect impact induced a smaller intracranial pressure (-53.7 kPa for backward rotation, and -65.5 kPa for forward rotation) than that caused by a direct impact. In addition, negative pressures induced by indirect impact to the head were not high enough to form cavitation bubbles, which can damage the brain tissue. Simulations predicted that a decrease in skull deformation had a large effect in reducing the intracranial pressure. However, the areas of high shear stress concentration were consistent with those of clinical observations. The findings of this study suggest that shear strain theory appears to better account for the clinical findings in head injury when the head is subjected to an indirect impact.