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The ELISA is the most worldwide method for immunoassay. However, the ELISA is losing ground due to low reproducibility of manual experimental processes in both R&D and IVD areas. An automated platform is a good solution, but there are still limitations owning to extremely high cost and requiring large space to set up especially for a small size laboratory. Here, we present a novel all-in-one platform called "VEUS" settable on the laboratory table that offers comprehensive automation of the entire multiplex immunoassay process by exploiting antibody conjugated magnetic particles, quality control and then immunoanalytical reaction, thereby enhancing detection sensitivity and high reproducibility. As a proof of concept, the system exhibits a sensitive LOD of 0.6 and 3.1 pg mL-1 within 1 h run, comparable precision that of molecular diagnostic systems based on PCR method, enabling rapid multiplex diagnosis of Influenza A, Influenza B, and COVID-19 viruses with similar symptoms. Through automation by the all-in-one system, it can be used by novice users, something innovative for immunoassays, relying heavily on user experience. Furthermore, it can contribute to streamline entire immunoassay processes of diverse biomarkers with high reproducibility and convenience in laboratories.
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SARS-CoV-2 , Humanos , Imunoensaio/métodos , SARS-CoV-2/imunologia , SARS-CoV-2/isolamento & purificação , Anticorpos Imobilizados/imunologia , Anticorpos Imobilizados/química , Reprodutibilidade dos Testes , COVID-19/diagnóstico , COVID-19/virologia , Ensaio de Imunoadsorção Enzimática/métodos , Vírus da Influenza A/imunologia , Vírus da Influenza B/imunologia , Automação Laboratorial/métodos , Limite de DetecçãoRESUMO
BACKGROUND: Avascular necrosis (AVN) is a medical condition characterized by the destruction of bone tissue due to a diminished blood supply. When the rate of tissue destruction surpasses the rate of regeneration, effective treatment becomes challenging, leading to escalating pain, arthritis, and bone fragility as the disease advances. A timely diagnosis is imperative to prevent and initiate proactive treatment for osteonecrosis. We explored the potential of differentially expressed proteins in serum-derived extracellular vesicles (EVs) as biomarkers for AVN of the femoral head in humans. We analyzed the genetic material contained in serum-derived exosomes from patients for early diagnosis, treatment, and prognosis of avascular necrosis. METHODS: EVs were isolated from the serum of both patients with AVN and a control group of healthy individuals. Proteomic analyses were conducted to compare the expression patterns of these proteins by proteomic analysis using LC-MS/MS. RESULTS: Our results show that the levels of IGHV3-23, FN1, VWF, FGB, PRG4, FCGBP, and ZSWIM9 were upregulated in the EVs of patients with AVN compared with those of healthy controls. ELISA results showed that VWF and PRG4 were significantly upregulated in the patients with AVN. CONCLUSIONS: These findings suggest that these EV proteins could serve as promising biomarkers for the early detection and diagnosis of AVN. Early diagnosis is paramount for effective treatment, and the identification of new osteonecrosis biomarkers is essential to facilitate swift diagnosis and proactive intervention. Our study provides novel insights into the identification of AVN-related biomarkers that can enhance clinical management and treatment outcomes.
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This study presents an innovative solution for the enhanced tracking and security of pharmaceuticals through the development of microstructures incorporating environmentally responsive, coded microparticles. Utilizing maskless photolithography, we engineered these microparticles with a degradable masking layer with 30 µm thickness that undergoes controlled dissolution. Quantitative analysis revealed that the protective layer's degradation, monitored by red fluorescence intensity, diminishes predictably over 144 h in phosphate-buffered saline under physiological conditions. This degradation not only confirms the microparticles' integrity but also allows the extraction of encoded information, which can serve as a robust indicator of medicinal shelf life and a deterrent to tampering. These findings indicate the potential for applying this technology in real-time monitoring of pharmaceuticals, ensuring quality and authenticity in the supply chain.
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Physical unclonable functions (PUFs) have attracted interest in demonstrating authentication and cryptographic processes for Internet of Things (IoT) devices. We demonstrated four-dimensional PUFs (4D PUFs) to realize time-varying chaotic phosphorescent randomness on MoS2 atomic seeds. By forming hybrid states involving more than one emitter with distinct lifetimes in 4D PUFs, irregular lifetime distribution throughout patterns functions as a time-varying disorder that is impossible to replicate. Moreover, we established a bit extraction process incorporating multiple 64 bit-stream challenges and experimentally obtained physical features of 4D PUFs, producing countless random 896 bit-stream responses. Furthermore, the weak and strong PUF models were conceptualized and demonstrated based on 4D PUFs, exhibiting superior cryptological performances, including randomness, uniqueness, degree of freedom, and independent bit ratio. Finally, the data encryption and decryption in pictures were performed by a single 4D PUF. Therefore, 4D PUFs could enhance the counterfeiting deterrent of existing optical PUFs and be used as an anticounterfeiting security strategy for advanced authentication and cryptographic processes of IoT devices.
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Efforts have been made to develop bromodomain inhibitors as cancer treatments. Sub-pathways, particularly in ovarian cancer, affected by bromodomain-containing protein (BRD) remain unclear. This study verified the antitumor effects of a new drug that can overcome OPT-0139-chemoresistance to treat ovarian cancer. A mouse xenograft model of human ovarian cancer cells, SKOV3 and OVCAR3, was used in this study. Cell viability and proliferation were assessed using MTT and ATP assays. Cell cycle arrest and apoptosis were determined using flow cytometry. BRD4 and c-Myc expression and apoptosis-related molecules were detected using RT-PCR and real-time PCR and Western blot. We confirmed the OPT-0139 effect and mechanism of action in epithelial ovarian cancer. OPT-0139 significantly reduced cell viability and proliferation and induced apoptosis and cell cycle arrest. In the mouse xenograft model, significant changes in tumor growth, volume, weight, and BRD4-related gene expression were observed, suggesting the antitumor effects of BRD4 inhibitors. Combination therapy with cisplatin promoted apoptosis and suppressed tumor growth in vitro and in vivo. Our results suggest OPT-0139, a BRD4 inhibitor, as a promising anticancer drug for the treatment of ovarian cancer by inhibiting cell proliferation, decreasing cell viability, arresting cell cycle, and inducing apoptosis.
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OBJECTIVES: The relationship between volar fragment size and postoperative volar tilt loss in complete articular distal radius fracture is not well known. In this study, we measured precise radiological parameters to help identify other factors that might contribute to volar tilt loss. MATERIAL AND METHODS: We retrospectively reviewed the radiological examinations and charts of 256 patients with distal radial fracture who underwent volar locking plate fixation between March 2014 and July 2022. Radiological parameters were measured based on preoperative CT and immediate postoperative radiographs. Univariate and multivariate linear regression analysis was performed to identify relevant factors associated with volar tilt loss following volar locking plate fixation. The receiver operating characteristic curve was used to identify the cutoff value of the independent parameters. RESULTS: On univariate analysis, 2 radiologic parameters on preoperative CT (volar fragment length at the lunate fossa, and teardrop angle) and 4 on immediate postoperative X-ray (radial inclination, radial length, capitate shift, and volar tilt) were significantly associated with postoperative volar tilt loss. On multivariate linear regression analysis, the risk of volar tilt loss increased as the capitate moved toward the back of the radial shaft. The cut-off for anteroposterior length in the lunate fossa was 6.5 mm. CONCLUSIONS: AO/OTA type-C distal radius fractures with <6.5 mm anteroposterior length in the lunate fossa had significantly higher rates of malunion with dorsal deformity. In addition, preoperative teardrop angle <37.2 ° and immediate postoperative volar tilt <3.7º are also predictors of postoperative volar tilt loss.
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Placas Ósseas , Fixação Interna de Fraturas , Fraturas do Rádio , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Osso Semilunar/diagnóstico por imagem , Osso Semilunar/cirurgia , Complicações Pós-Operatórias/diagnóstico por imagem , Fraturas do Rádio/cirurgia , Fraturas do Rádio/diagnóstico por imagem , Estudos Retrospectivos , Tomografia Computadorizada por Raios XRESUMO
OBJECTIVE: Deep learning is an advanced machine-learning approach that is used in several medical fields. Here, we developed a deep learning model using an object detection algorithm to identify the L5 vertebra on anteroposterior lumbar spine radiographs, and assessed its detection accuracy. METHODS: We retrospectively recruited 150 participants for whom both anteroposterior whole-spine and lumbar spine radiographs were available. The anteroposterior lumbar spine radiographs of these patients were used as the input data. Of the 150 images, 105 (70%) were randomly selected as the training set, and the remaining 45 (30%) were assigned to the validation set. YOLOv5x, of the YOLOv5 family model, was used to detect the L5 vertebra area. RESULTS: The mean average precisions 0.5 and 0.75 of the trained L5 detection model were 99.2% and 96.9%, respectively. The model's precision was 95.7% and its recall was 97.8%. Furthermore, 93.3% of the validation data were correctly detected. CONCLUSION: Our deep learning model showed an outstanding ability to identify L5 vertebrae.
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Aprendizado Profundo , Humanos , Estudos Retrospectivos , Vértebras Lombares/diagnóstico por imagem , Região Lombossacral , RadiografiaRESUMO
A noncontact sensor field is an innovative device that can detect, measure, or monitor physical properties or conditions without direct physical contact with the subject or object under examination. These sensors use a variety of methods, including electromagnetic, optical, and acoustic technique, to collect information about the target without physical interaction. Noncontact sensors find wide-ranging applications in various fields such as manufacturing, robotics, automobiles, security, environmental monitoring, space industry, agriculture, and entertainment. In particular, they are used in the medical field, where they provide continuous monitoring of patient conditions and offer opportunities in rehabilitation medicine. This article introduces the potential of noncontact sensors in the field of rehabilitation medicine.
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Researchers are increasingly interested in cell therapy using mesenchymal stem cells (MSCs) as an alternative remedy for osteoporosis, with fewer side effects. Thus, we isolated and characterized extracellular vesicles (EVs) from human adipose tissue-derived MSCs (hMSCs) and investigated their inhibitory effects on RANKL-induced osteoclast differentiation. Purified EVs were collected from the supernatant of hMSCs by tangential flow filtration. Characterization of EVs included typical evaluation of the size and concentration of EVs by nanoparticle tracking analysis and morphology analysis using transmission electron microscopy. hMSC-EVs inhibited RANKL-induced differentiation of bone marrow-derived macrophages (BMDMs) into osteoclasts in a dose-dependent manner. F-actin ring formation and bone resorption were also reduced by EV treatment of osteoclasts. In addition, EVs decreased RANKL-induced phosphorylation of p38 and JNK and expression of osteoclastogenesis-related genes in BMDMs treated with RANKL. To elucidate which part of the hMSC-EVs plays a role in the inhibition of osteoclast differentiation, we analyzed miRNA profiles in hMSC-EVs. The results showed that has-miR122-5p was present at significantly high read counts. Overexpression of miR122-5p in BMDMs significantly inhibited RANKL-induced osteoclast differentiation and induced defects in F-actin ring formation and bone resorption. Our results also revealed that RANKL-induced phosphorylation of p38 and JNK and osteoclast-specific gene expression was decreased by miR122-5p transfection, which was consistent with the results of hMSC-EVs. These findings suggest that hMSC-EVs containing miR122-5p inhibit RANKL-induced osteoclast differentiation via the downregulation of molecular mechanisms and could be a preventive candidate for destructive bone diseases.
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Background: Cage subsidence after oblique lumbar interbody fusion (OLIF) induces restenosis and adversely affects patient outcomes. Many studies have investigated the causes of subsidence, one of which is endplate fracture (EF). This study aimed to identify predictors of EF after OLIF. Methods: This retrospective study reviewed consecutive patients who underwent OLIF at a single institute between August 2019 and February 2022. A total of 104 patients were enrolled. The patients' demographic data and surgical details were collected through chart reviews. Radiographic variables were measured. Related variables were also analyzed using binomial logistic regression, dividing each group into those with versus without EF. Results: EF occurred at 30 of 164 levels (18.3%), and the binary logistic analysis revealed that sex (odds ratio [OR], 11.07), inferior endplate concave depth (OR, 1.95), disc wedge angle (OR, 1.22), lumbar lordosis (OR, 1.09), pelvic incidence (OR, 1.07), sagittal vertical axis (OR, 1.02), sacral slope (OR, 0.9), L3-4 level (OR, 0.005), and L4-5 level (OR, 0.004) were significantly related to EF. Conclusions: OLIF in older Asian patients should be performed carefully after recognizing the high possibility of EF and confirming the factors that should be considered preoperatively.
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Fraturas Ósseas , Lordose , Fusão Vertebral , Humanos , Idoso , Estudos Retrospectivos , Resultado do Tratamento , Região Lombossacral , Vértebras Lombares/diagnóstico por imagem , Vértebras Lombares/cirurgia , Fusão Vertebral/efeitos adversosRESUMO
As an urgent international challenge, the sudden change in climate due to global warming needs to be addressed in the near future. This can be achieved through a reduction in fossil fuel utilization and through carbon sequestration, which reduces the concentration of CO2 in the atmosphere. In this study, a self-sustainable impact sensor is proposed through implementing a triboelectric nanogenerator with a CaCO3 contact layer fabricated via a CO2 absorption method. The triboelectric polarity of CaCO3 with the location between the polyimide and the paper and the effects of varying the crystal structure are investigated first. The impact sensing characteristics are then confirmed at various input frequencies and under applied forces. Further, the high mechanical strength and strong adherence of CaCO3 on the surface of the device are demonstrated through enhanced durability compared to the unmodified device. For the intended application, the as-fabricated sensor is used to detect the turning state of the paper Ddakji in a slap match game using a supervised learning algorithm based on a support vector machine presenting a high classification accuracy of 95.8%. The robust CaCO3-based triboelectric device can provide an eco-friendly advantage due to its self-powered characteristics for impact sensing and carbon sequestration.
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Sarcopenia is a condition in which muscle mass and strength are decreased and muscle function is impaired. It is an indicator of frailty and loss of independence in older adults. It is also associated with increased physical disability, which increases the risk of falls. As a multifactorial disease, sarcopenia is caused by a combination of factors including aging, hormonal changes, nutritional deficiencies, and physical inactivity. Understanding the underlying pathophysiology of sarcopenia and identifying its different causes is critical to developing effective prevention and treatment strategies. This review summarizes the pathophysiology, consequences, diagnostic methods, and multidisciplinary approaches to sarcopenia.
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RATIONALE: Ischemic monomelic neuropathy (IMN) is a disease that occurs after acute arterial occlusion or steal phenomenon in an extremity that results in single or multiple axonal mononeuropathies in the distal limb without the classical features of limb ischemia, including a skin color change, limb swelling, and ischemic claudication. IMN can easily be misdiagnosed as any other neuropathic disorder. Here we present a case of IMN that was misdiagnosed as spinal epidural hematoma. PATIENT CONCERNS: A 77-year-old man presented with sudden motor weakness and pain in his left foot and calf 5 days after a bilateral L4 to 5 posterior decompression for lumbar spinal stenosis. His symptoms progressed over the next 5 days. The strengths of the left ankle dorsiflexors, first toe extensors, and ankle plantar flexors were Medical Research Council 0. On brain and whole-spine magnetic resonance imaging, no specific abnormalities correlated with his symptoms were observed. Computed tomography angiography of the lower extremities revealed segmental occlusion of the left common femoral artery and multifocal severe stenoses in the bilateral anterior and posterior tibial arteries of the left leg. No skin color change or swelling was observed in the left lower extremity. DIAGNOSIS: Based on his clinical features and imaging findings, he was diagnosed with IMN. INTERVENTION: The patient underwent thrombectomy of the left femoral artery. OUTCOMES: After the treatment, his pain almost completely disappeared. LESSONS: When patients exhibit acute-onset pain in the unilateral limb with or without motor weakness but no correlated abnormality on spinal magnetic resonance imaging or computed tomography, clinicians should consider the possibility of IMN.
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Arteriopatias Oclusivas , Hematoma Epidural Craniano , Hematoma Epidural Espinal , Masculino , Humanos , Idoso , Hematoma Epidural Espinal/complicações , Hematoma Epidural Espinal/diagnóstico , Hematoma Epidural Espinal/cirurgia , Perna (Membro)/irrigação sanguínea , Isquemia/diagnóstico , Isquemia/etiologia , Isquemia/cirurgia , Dor , Descompressão , Erros de DiagnósticoRESUMO
Neural diseases such as compressive, congenital, and traumatic injuries have diverse consequences, from benign mild sequelae to severe life-threatening conditions with associated losses of motor, sensory, and autonomic functions. Several approaches have been adopted to control neuroinflammatory cascades. Traditionally, mesenchymal stem cells (MSCs) have been regarded as therapeutic agents, as they possess growth factors and cytokines with potential anti-inflammatory and regenerative effects. However, several animal model studies have reported conflicting outcomes, and therefore, the role of MSCs as a regenerative source for the treatment of neural pathologies remains debatable. In addition, issues such as heterogeneity and ethical issues limited their use as therapeutic agents. To overcome the obstacles associated with the use of traditional agents, we explored the therapeutic potentials of extracellular vesicles (EVs), which contain nucleic acids, functional proteins, and bioactive lipids, and play crucial roles in immune response regulation, inflammation reduction, and cell-to-cell communication. EVs may surpass MSCs in size issue, immunogenicity, and response to the host environment. However, a comprehensive review is required on the therapeutic potential of EVs for the treatment of neural pathologies. In this review, we discuss the action mechanism of EVs, their potential for treating neural pathologies, and future perspectives regarding their clinical applications.
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Recently, considerable research efforts to achieve advanced design of promising electroactive materials as well as unique structures in supercapacitor electrodes have been explored for high-performance energy storage systems. We suggest the development of novel electroactive materials with an enlarged surface area for sandpaper materials. Based on the inherent micro-structured morphologies of the sandpaper substrate, nano-structured Fe-V electroactive material can be coated on it by facile electrochemical deposition technique. A hierarchically designed electroactive surface is covered with FeV-layered double hydroxide (LDH) nano-flakes on Ni-sputtered sandpaper as a unique structural and compositional material. The successful growth of FeV-LDH is clearly revealed by surface analysis techniques. Further, electrochemical studies of the suggested electrodes are carried out to optimize the Fe-V composition as well as the grit number of the sandpaper substrate. Herein, optimized Fe0.75V0.25 LDHs coated on #15000 grit Ni-sputtered sandpaper are developed as advanced battery-type electrodes. Finally, along with the negative electrode of activated carbon and the FeV-LDH electrode, it is utilized for hybrid supercapacitor (HSC) assembly. The fabricated flexible HSC device indicates high energy and power density by showing excellent rate capability. This study is a remarkable approach to improving the electrochemical performance of energy storage devices using facile synthesis.
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The purpose of this study was to identify the role of HOXB9 and associated molecular mechanism in acquiring chemoresistance to ovarian cancer cells. After establishing HOXB9-overexpressing cells (HOXB9-OE/SKOV3), cisplatin resistance-induced cells (Cis-R/SKOV3), and an ovarian cancer xenograft mouse model, the effects of HOXB9 were evaluated in vitro and in vivo. Expression levels of ERCC-1, MRP-2, XIAP, and Bax/Bcl-2 were assessed as putative mechanisms mediating chemoresistance. Cisplatin-induced apoptosis was significantly decreased in HOXB9-OE/SKOV3 compared to SKOV3. Cisplatin treatment of SKOV3 strongly induced ERCC-1, MRP-2, and XIAP, and apoptosis was strongly induced through the inhibition of Bcl-2 and activation of Bax. ERCC-1, MRP-2, XIAP, and Bcl-2 were also strongly induced in HOXB9 OE/SKOV3. In contrast to SKOV3, cisplatin treatment alone of HOXB9 OE/SKOV3 did not affect the expression of Bcl-2 and Bax, and consequently, there was no increase in apoptosis. HOXB9 knockdown suppressed the expression of ERCC-1 and XIAP, but did not affect MRP-2 and Bcl-2/Bax expression in HOXB9 OE/SKOV3 and Cis-R/SKOV3, and caused a small increase in apoptosis. Treatment of SKOV3 with both cisplatin and siRNA_HOXB9 led to complete suppression of ERCC-1, MRP-2, and XIAP, and significantly increased apoptosis through inhibition of Bcl-2 expression and activation of Bax. The results observed in Cis-R/SKOV3 were similar to that in HOXB9 OE/SKOV3. Our data suggest that HOXB9 overexpression may cause chemoresistance in ovarian cancer cells by differential induction of ERCC-1, MRP-2, and XIAP depending on the strength of HOXB9 expression through inhibition of the mitochondrial pathway of apoptosis, including Bax/Bcl-2.
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Antineoplásicos , Neoplasias Ovarianas , Feminino , Humanos , Animais , Camundongos , Cisplatino/farmacologia , Cisplatino/uso terapêutico , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Resistencia a Medicamentos Antineoplásicos/genética , Proteína X Associada a bcl-2/genética , Linhagem Celular Tumoral , Neoplasias Ovarianas/tratamento farmacológico , Neoplasias Ovarianas/genética , Neoplasias Ovarianas/metabolismo , Apoptose , Proteínas Proto-Oncogênicas c-bcl-2/genética , Proliferação de Células , Proteínas Inibidoras de Apoptose Ligadas ao Cromossomo X/metabolismo , Proteínas de Homeodomínio/farmacologiaRESUMO
BACKGROUND: Cervical spondylotic myelopathy (CSM) is a critical condition that results in significant neurologic deterioration. An accurate diagnosis is essential for determining its outcome and prognosis. The pathology is strongly associated with dynamic factors; therefore, dynamic magnetic resonance (MR) image could be crucial to accurately detect CSM. However, very few studies have evaluated the reliability and accuracy of dynamic MR in CSM. In this study, we aimed to compare intra- and interobserver reliabilities and accuracy of dynamic MR in detecting CSM using sagittal MR scans of the neck in the flexed, neutral, and extended position. METHODS: Out of 131 patients who underwent surgical treatments for CSM, 107 were enrolled in this study. The patient underwent three-types of sagittal MR scans that were obtained separately in different neck positions (neutral, flexion, and extension postures). The MR scans of the cervical spine were evaluated independently by three spine professionals, on the basis of tabled questionnaires. For accuracy, we performed a receiver operator characteristic analysis, and the overall discriminating ability of each method was measured by calculating the area under the ROC curve. The Cohen's kappa coefficient and the Fleiss-generalized kappa coefficient was used to the inter- and intra-observer reliabilities. RESULTS: The intraobserver reliability (using the Cohen's kappa coefficient) and interobserver reliability (using the Fless kappa coefficient) were respectively 0.64 and 0.52 for the neutral sagittal MR. The accuracy of neutral sagittal MR in detecting CSM was 0.735 (95% CI, 0.720 to 0.741) while that of extension sagittal MRI was 0.932 (96% CI, 0.921 to 0.948). CONCLUSIONS: Dynamic MR significantly showed better diagnostic reliability and accuracy in detecting CSM compared to conventional MR. In particular, extension MR scans could provide a more accurate diagnosis than other images.
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Doenças da Medula Espinal , Espondilose , Humanos , Reprodutibilidade dos Testes , Espondilose/cirurgia , Doenças da Medula Espinal/cirurgia , Imageamento por Ressonância Magnética/métodos , Vértebras Cervicais/cirurgiaRESUMO
Diagnostic techniques for spinal pathologies have been developed in accordance with advances in technology. Accurate diagnosis of spinal pathology is essential for appropriate management of spinal diseases. Since the development of X-rays in 1895 and computed tomography (CT) in 1967, several diagnostic imaging modalities have been utilized for detecting spinal pathologies, including radiography, CT, magnetic resonance imaging, and radionuclide imaging. In addition to diagnostic imaging technologies, electrodiagnostic tests, including electromyography and nerve conduction studies, play a significant role as diagnostic tools, as spinal diseases are mostly profoundly associated with pathologies of the neural structures, such as the spinal cord and nerve root, and extent of injury at the structure cannot be adequately detected by conventional imaging techniques. In patient-specific treatment strategies, usage of diagnostic modalities is of great importance; thus, we should be aware of the basic details and approaches of the different diagnostic modalities. In this review, the authors discuss the details of the technologies that aid in the diagnosis of spinal pathologies.
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In this study, we propose high similarity and multiple angular segment display-based encoded microparticle fabrication using omni- and unidirectional data unit photolithography systems. Uniform high-correlation values are obtained regardless of the decoding direction when an omnidirectional data unit is used. In addition, multiple display angles are analyzed based on unidirectional data units with varying slit widths. Finally, encoded microparticles for multiple angular segment displays are fabricated and selective information recognition is demonstrated.