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PURPOSE: We investigated the vertical implantation of a toric implantable collamer lens (ICL) and compared the rotational stability with that of horizontal implantation. METHODS: This matched comparative study retrospectively reviewed and analyzed data from patients who underwent ICL implantation from 2003-2022 by 1:1 matching vertical and horizontal (V and H toric groups, respectively) implantation patients according to preoperative astigmatism, spherical equivalent, sulcus-to-sulcus, anterior chamber depth, and ICL size. Visual acuity, manifest refraction, vaulting, and rotation were measured 3 months postoperatively. RESULTS: We included 646 eyes (323 each in the V and H toric groups). No statistically significant difference was observed between groups in postoperative visual acuity, refractive error, and astigmatism. Vaulting was lower in the V toric group. (P < 0.001). The mean lens rotation in the V toric group was less than that in the H toric group (1.11 ± 2.84° versus 3.02 ± 10.34°, P = 0.001). The proportion of eyes in the V and H toric groups showing ≥10° of rotation was 2.5% (8 eyes) and 6.5% (21 eyes), respectively (P = 0.014). Despite repositioning from rotation, three (0.9%) and eight (2.5%) eyes required removal owing to lens re-rotation in the V and H toric groups, respectively. CONCLUSION: Toric ICL vertical implantation showed good rotational stability, and appropriate visual acuity correction results with relatively low vaulting. This procedure therefore presents an effective novel method that could replace horizontal toric ICL implantation.
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Astigmatismo , Implantación de Lentes Intraoculares , Lentes Intraoculares Fáquicas , Agudeza Visual , Humanos , Masculino , Femenino , Implantación de Lentes Intraoculares/métodos , Adulto , Estudios Retrospectivos , Agudeza Visual/fisiología , Astigmatismo/cirugía , Astigmatismo/fisiopatología , Rotación , Refracción Ocular/fisiología , Persona de Mediana Edad , Adulto Joven , Miopía/cirugía , Miopía/fisiopatologíaRESUMEN
PURPOSE: This study was conducted to evaluate the effects of plasma treatment of sandblasted and acid-etched (SLA) titanium implants on surface cleansing and osseointegration in a beagle model. MATERIALS AND METHODS: For morphological analysis and XPS analysis, scanning electron microscope and x-ray photoelectron spectroscopy were used to analyze the surface topography and chemical compositions of implant before and after plasma treatment. For this animal experiment, twelve SLA titanium implants were divided into two groups: a control group (untreated implants) and a plasma group (implants treated with plasma). Each group was randomly located in the mandibular bone of the beagle dog (n = 6). After 8 weeks, the beagle dogs were sacrificed, and volumetric analysis and histometric analysis were performed within the region of interest. RESULTS: In morphological analysis, plasma treatment did not alter the implant surface topography or cause any physical damage. In XPS analysis, the atomic percentage of carbon at the inspection point before the plasma treatment was 34.09%. After the plasma treatment, it was reduced to 18.74%, indicating a 45% reduction in carbon. In volumetric analysis and histometric analysis, the plasma group exhibited relatively higher mean values for new bone volume (NBV), bone to implant contact (BIC), and inter-thread bone density (ITBD) compared to the control group. However, there was no significant difference between the two groups (P > .05). CONCLUSION: Within the limits of this study, plasma treatment effectively eliminated hydrocarbons without changing the implant surface.
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The proliferation of data has facilitated global accessibility, which demands escalating amounts of power for data storage and processing purposes. In recent years, there has been a rise in research in the field of neuromorphic electronics, which draws inspiration from biological neurons and synapses. These electronics possess the ability to perform in-memory computing, which helps alleviate the limitations imposed by the 'von Neumann bottleneck' that exists between the memory and processor in the traditional von Neumann architecture. By leveraging their multi-bit non-volatility, characteristics that mimic biology, and Kirchhoff's law, neuromorphic electronics offer a promising solution to reduce the power consumption in processing vector-matrix multiplication tasks. Among all the existing nonvolatile memory technologies, NAND flash memory is one of the most competitive integrated solutions for the storage of large volumes of data. This work provides a comprehensive overview of the recent developments in neuromorphic computing based on NAND flash memory. Neuromorphic architectures using NAND flash memory for off-chip learning are presented with various quantization levels of input and weight. Next, neuromorphic architectures for on-chip learning are presented using standard backpropagation and feedback alignment algorithms. The array architecture, operation scheme, and electrical characteristics of NAND flash memory are discussed with a focus on the use of NAND flash memory in various neural network structures. Furthermore, the discrepancy of array architecture between on-chip learning and off-chip learning is addressed. This review article provides a foundation for understanding the neuromorphic computing based on the NAND flash memory and methods to utilize it based on application requirements.
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N6-adenosine methylation (m6A) is critical for controlling cancer cell growth and tumorigenesis. However, the function and detailed mechanism of how m6A methyltransferases modulate m6A levels on specific targets remain unknown. In the current study, we identified significantly elevated levels of RBM15, an m6A writer, in basal-like breast cancer (BC) patients compared to nonbasal-like BC patients and linked this increase to worse clinical outcomes. Gene expression profiling revealed correlations between RBM15 and serine and glycine metabolic genes, including PHGDH, PSAT1, PSPH, and SHMT2. RBM15 influences m6A levels and, specifically, the m6A levels of serine and glycine metabolic genes via direct binding to target RNA. The effects of RBM15 on cell growth were largely dependent on serine and glycine metabolism. Thus, RBM15 coordinates cancer cell growth through altered serine and glycine metabolism, suggesting that RBM15 is a new therapeutic target in BC.
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Proliferación Celular , Regulación Neoplásica de la Expresión Génica , Glicina , Proteínas de Unión al ARN , Serina , Neoplasias de la Mama Triple Negativas , Humanos , Serina/metabolismo , Glicina/metabolismo , Femenino , Proteínas de Unión al ARN/metabolismo , Proteínas de Unión al ARN/genética , Línea Celular Tumoral , Neoplasias de la Mama Triple Negativas/metabolismo , Neoplasias de la Mama Triple Negativas/genética , Neoplasias de la Mama Triple Negativas/patología , Metilación , Adenosina/metabolismo , Adenosina/análogos & derivadosRESUMEN
Smart healthcare systems integrated with advanced deep neural networks enable real-time health monitoring, early disease detection, and personalized treatment. In this work, a novel 3D AND-type flash memory array with a rounded double channel for computing-in-memory (CIM) architecture to overcome the limitations of conventional smart healthcare systems: the necessity of high area and energy efficiency while maintaining high classification accuracy is proposed. The fabricated array, characterized by low-power operations and high scalability with double independent channels per floor, exhibits enhanced cell density and energy efficiency while effectively emulating the features of biological synapses. The CIM architecture leveraging the fabricated array achieves high classification accuracy (93.5%) for electrocardiogram signals, ensuring timely detection of potentially life-threatening arrhythmias. Incorporated with a simplified spike-timing-dependent plasticity learning rule, the CIM architecture is suitable for robust, area- and energy-efficient in-memory arrhythmia detection systems. This work effectively addresses the challenges of conventional smart healthcare systems, paving the way for a more refined healthcare paradigm.
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Arritmias Cardíacas , Electrocardiografía , Procesamiento de Señales Asistido por Computador , Arritmias Cardíacas/diagnóstico , Humanos , Electrocardiografía/métodos , Electrocardiografía/instrumentación , Redes Neurales de la Computación , Diseño de EquipoRESUMEN
Surface reconstruction, reorganizing the surface atoms or structure, is a promising strategy to manipulate materials' electrical, electrochemical, and surface catalytic properties. Herein, a rapid surface reconstruction of indium sulfide (In2S3) is demonstrated via a high-temperature flame treatment to improve its charge collection properties. The flame process selectively transforms the In2S3 surface into a diffusionless In2O3 layer with high crystallinity. Additionally, it controllably generates bulk sulfur vacancies within a few seconds, leading to surface-reconstructed In2S3 (sr-In2S3). When using those sr-In2S3 as photoanode for photoelectrochemical water splitting devices, these dual functions of surface In2O3/bulk In2S3 reduce the charge recombination in the surface and bulk region, thus improving photocurrent density and stability. With optimized surface reconstruction, the sr-In2S3 photoanode demonstrates a significant photocurrent density of 8.5 mA cm-2 at 1.23 V versus a reversible hydrogen electrode (RHE), marking a 2.5-fold increase compared to pristine In2S3 (3.5 mA cm-2). More importantly, the sr-In2S3 photoanode exhibits an impressive photocurrent density of 7.3 mA cm-2 at 0.6 V versus RHE for iodide oxidation reaction. A practical and scalable surface reconstruction is also showcased via flame treatment. This work provides new insights for surface reconstruction engineering in sulfide-based semiconductors, making a breakthrough in developing efficient solar-fuel energy devices.
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Arteriovenous malformations (AVMs) are congenital vascular anomalies with a poor prognosis. AVMs are considered intractable diseases, as there is no established approach for early diagnosis and treatment. Therefore, this study aimed to provide new evidence by analyzing microRNAs (miRNAs) associated with AVM. We present fundamental evidence for the early diagnosis and treatment of AVM by analyzing miRNAs in the endothelial cells of AVMs. This study performed sequencing and validation of miRNAs in endothelial cells from normal and AVM tissues. Five upregulated and two downregulated miRNAs were subsequently analyzed under hypoxia and vascular endothelial growth factor (VEGF) treatment by one-way analysis of variance (ANOVA). Under hypoxic conditions, miR-135b-5p was significantly upregulated in the AVM compared to that under normal conditions, corresponding to increased endothelial activity (p-value = 0.0238). VEGF treatment showed no significant increase in miR-135b-5p under normal conditions, however, a surge in AVM was observed. Under both hypoxia and VEGF treatment, comparison indicated a downregulation of miR-135b-5p in AVM. Therefore, miR-135b-5p was assumed to affect the pathophysiological process of AVM and might play a vital role as a potential biomarker of AVMs for application related to diagnosis and treatment.
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Malformaciones Arteriovenosas , Biomarcadores , Células Endoteliales , MicroARNs , Factor A de Crecimiento Endotelial Vascular , MicroARNs/genética , MicroARNs/metabolismo , Humanos , Malformaciones Arteriovenosas/genética , Malformaciones Arteriovenosas/metabolismo , Malformaciones Arteriovenosas/patología , Malformaciones Arteriovenosas/diagnóstico , Células Endoteliales/metabolismo , Células Endoteliales/patología , Factor A de Crecimiento Endotelial Vascular/metabolismo , Factor A de Crecimiento Endotelial Vascular/genética , Masculino , Femenino , Adulto , Hipoxia de la Célula/genéticaRESUMEN
The pursuit of sub-1-nm field-effect transistor (FET) channels within 3D semiconducting crystals faces challenges due to diminished gate electrostatics and increased charge carrier scattering. 2D semiconductors, exemplified by transition metal dichalcogenides, provide a promising alternative. However, the non-idealities, such as excess low-frequency noise (LFN) in 2D FETs, present substantial hurdles to their realization and commercialization. In this study, ideal LFN characteristics in monolayer MoS2 FETs are attained by engineering the metal-2D semiconductor contact and the subgap density of states (DOS). By probing non-ideal contact resistance effects using CuS and Au electrodes, it is uncovered that excess contact noise in the high drain current (ID) region can be substantially reduced by forming a van der Waals junction with CuS electrodes. Furthermore, thermal annealing effectively mitigates sulfur vacancy-induced subgap density of states (DOS), diminishing excess noise in the low ID region. Through meticulous optimization of metal-2D semiconductor contacts and subgap DOS, alignment of 1/f noise with the pure carrier number fluctuation model is achieved, ultimately achieving the sought-after ideal LFN behavior in monolayer MoS2 FETs. This study underscores the necessity of refining excess noise, heralding improved performance and reliability of 2D electronic devices.
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The demand for gas sensing systems that enable fast and precise gas recognition is growing rapidly. However, substantial challenges arise from the complex fabrication process of sensor arrays, time-consuming data transmission to an external processor, and high energy consumption in multi-stage data processing. In this study, a gas sensing system using on-chip annealing for fast and power-efficient gas detection is proposed. By utilizing a micro-heater embedded in the gas sensor, the sensing material of adjacent sensors in the same substrate can be easily varied without further fabrication steps. The response to oxidizing gas is constrained in metal oxide (MOX) sensing material with small grain sizes, as the depletion width of grain cannot extend beyond the grain size during the gas reaction. On the other hand, the response to reducing gases and humidity, which decrease the depletion width, is less affected by grain sizes. A readout circuit integrating a differential amplifier and dual FET-type gas sensors effectively emphasizes the response to oxidizing gases by canceling the response to reducing gases and humidity. The selective on-chip annealing method is applicable to various MOX sensing materials, demonstrating its potential for application in commercial fields due to its simplicity and expandability.
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In this study, we identified a new strain of the genus Neocypholaelaps from the beehives of Apis mellifera colonies in the Republic of Korea (ROK). The Neocypholaelap sp. KOR23 mites were collected from the hives of honeybee apiaries in Wonju, Gangwon-do, in May 2023. Morphological and molecular analyses based on 18S and 28S rRNA gene regions conclusively identified that these mites belong to the genus Neocypholaelaps, closely resembling Neocypholaelaps sp. APGD-2010 that was first isolated from the United States. The presence of 9 of 25 honeybee pathogens in these mite samples suggests that Neocypholaelaps sp. KOR23 mite may act as an intermediate vector and carrier of honeybee diseases. The identification of various honeybee pathogens within this mite highlights their significance in disease transmission among honeybee colonies. This comprehensive study provides valuable insights into the taxonomy and implications of these mites for bee health management and pathogen dissemination.
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Ácaros , Varroidae , Abejas , Animales , República de CoreaRESUMEN
OBJECTIVES: Temporomandibular disorder (TMD) is a common condition that affects the temporomandibular joint (TMJ) and the muscles of the jaw, resulting in pain and dysfunction. TMD is affected by both behavioral and psychological factors. Digital therapeutics (DTx) can exert therapeutic effects by controlling behavioral factors through the delivery of appropriate interventions. Here, we report an open-label randomized control trial to evaluate the efficacy of DTx for TMD. METHODS: We recruited 40 participants diagnosed with TMD. Participants were randomly divided into an intervention group (DTx use, n = 20) and a control group (n = 20). The intervention group received the usual treatment process for TMD in addition to the use of the DTx. The control group received the usual treatments only. Patients in both groups were followed up for 3-4 weeks, and outcome data were collected and analyzed. RESULT: The intervention group showed a significant reduction in pain scores as measured by the numerical rating scale (NRS) (p = 0.016). Additionally, the intervention group showed a statistically significant increase in maximal mouth opening compared to the control group (p = 0.0079). However, there were no significant differences in improvement in the Jaw Functional Limitation Scale, Oral Behavior Checklist, and Patient Health Questionnaire-4 between the two groups (p = 0503, = 0.820, and = 0.943, respectively). CONCLUSION: This RCT reveals DTx potential in TMD, showing pain and mouth opening improvements with conventional treatment. But no significant changes were noted in other outcomes. The findings advocate for more extensive, long-term research to solidify DTx's role in TMD management. CLINICAL SIGNIFICANCE: This research underlines DTx potential to improve pain outcomes in TMD therapy, reinforcing its value as a complementary treatment modality.
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Dolor Facial , Dimensión del Dolor , Trastornos de la Articulación Temporomandibular , Humanos , Femenino , Masculino , Proyectos Piloto , Trastornos de la Articulación Temporomandibular/terapia , Adulto , Dolor Facial/terapia , Resultado del Tratamiento , Persona de Mediana Edad , Rango del Movimiento Articular/fisiología , Adulto Joven , Articulación Temporomandibular/fisiopatología , Terapia Asistida por Computador/métodosRESUMEN
Background: Metformin, a drug prescribed for patients with type 2 diabetes, has potential efficacy in enhancing antitumor immunity; however, the detailed underlying mechanisms remain to be elucidated. Therefore, we aimed to identify the inhibitory molecular mechanisms of metformin on programmed death ligand 1 (PD-L1) expression in cancer cells and programmed death 1 (PD-1) expression in immune cells. Methods: We employed a luciferase reporter assay, quantitative real-time PCR, immunoblotting analysis, immunoprecipitation and ubiquitylation assays, and a natural killer (NK) cell-mediated tumor cell cytotoxicity assay. A mouse xenograft tumor model was used to evaluate the effect of metformin on tumor growth, followed by flow-cytometric analysis using tumor-derived single-cell suspensions. Results: Metformin decreased AKT-mediated ß-catenin S552 phosphorylation and subsequent ß-catenin transactivation in an adenosine monophosphate-activated protein kinase (AMPK) activation-dependent manner, resulting in reduced CD274 (encoding PD-L1) transcription in cancer cells. Tumor-derived soluble factors enhanced PD-1 protein stability in NK and T cells via dissociation of PD-1 from ubiquitin E3 ligases and reducing PD-1 polyubiquitylation. Metformin inhibited the tumor-derived soluble factor-reduced binding of PD-1 to E3 ligases and PD-1 polyubiquitylation, resulting in PD-1 protein downregulation in an AMPK activation-dependent manner. These inhibitory effects of metformin on both PD-L1 and PD-1 expression ameliorated cancer-reduced cytotoxic activity of immune cells in vitro and decreased tumor immune evasion and growth in vivo. Conclusions: Metformin blocks both PD-L1 and PD-1 within the tumor microenvironment. This study provided a mechanistic insight into the efficacy of metformin in improving immunotherapy in human cancer.
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Antígeno B7-H1 , Células Asesinas Naturales , Metformina , Receptor de Muerte Celular Programada 1 , beta Catenina , Metformina/farmacología , Receptor de Muerte Celular Programada 1/metabolismo , Receptor de Muerte Celular Programada 1/antagonistas & inhibidores , Receptor de Muerte Celular Programada 1/genética , Humanos , Antígeno B7-H1/metabolismo , Antígeno B7-H1/genética , Animales , Línea Celular Tumoral , Ratones , Células Asesinas Naturales/efectos de los fármacos , Células Asesinas Naturales/inmunología , Células Asesinas Naturales/metabolismo , beta Catenina/metabolismo , Ensayos Antitumor por Modelo de Xenoinjerto , Proteínas Quinasas Activadas por AMP/metabolismo , Ratones Endogámicos BALB C , Fosforilación/efectos de los fármacos , Ratones Desnudos , Linfocitos T/efectos de los fármacos , Linfocitos T/metabolismo , Linfocitos T/inmunología , Proteínas Proto-Oncogénicas c-akt/metabolismo , Neoplasias/patología , Neoplasias/metabolismo , Neoplasias/tratamiento farmacológico , Ubiquitinación/efectos de los fármacosRESUMEN
PURPOSE: Complications of implant prostheses have direct correlation with the increased use of implants for dental rehabilitation. In this study, we present cases of peri-implant oral malignancies (PIOM) around dental implants and a retrospective analysis of patients treated for PIOM. METHODS: The retrospective analysis was performed with patients treated for PIOM at the Department of Oral and Maxillofacial Surgery of the Seoul National University Dental Hospital between 2006 and 2014. The patient records were thoroughly screened for previous medical issues, human papilloma virus infections, and other clinical data with a focus on relevant information such as localization, time from implant insertion to the development of the carcinoma, implant type and prosthetic rehabilitation. RESULTS: Twenty-one patients were diagnosed with PIOM. The male-to-female ratio was 1.625. The mean age of the patients was 60.42 ± 9.35 years old. Three patients reported ongoing alcohol/tobacco consumption. Five patients had a history of previous oral cancer surgery or exhibited mucosal lesions. The time from implant placement until carcinoma diagnosis was 49.13 ± 33.63 months on average. Most PIOM patients (95.2%) were diagnosed with SCC. All patients had previously been treated for peri-implantitis. In 85.7% of the patients, prostheses were observed on the opposing teeth where PIOM occurred. CONCLUSION: Based on the review of these cases, it can be deduced that there is a possibility that implant treatment and galvanic currents between prosthesis may constitute an irritant and/or inflammatory cofactor which contributes to the formation and/or development of malignant tumors. Patients at potential risk may benefit from individualized recall intervals and careful evaluations.
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Carcinoma , Implantes Dentales , Neoplasias de la Boca , Periimplantitis , Humanos , Masculino , Femenino , Persona de Mediana Edad , Anciano , Implantes Dentales/efectos adversos , Estudios Retrospectivos , Neoplasias de la Boca/inducido químicamente , Neoplasias de la Boca/complicaciones , Carcinoma/inducido químicamente , Carcinoma/complicacionesRESUMEN
Chronic myeloid leukemia (CML) is characterized by the Philadelphia (Ph) chromosome resulting from the translocation of t(9;22)(q34;q11), producing the BCR::ABL1 fusion gene. Variant Ph chromosome translocations, involving rearrangements in chromosomes other than 9 and 22, occur in 5-10% of CML cases. Herein, we report a unique case of a 36-year-old male with a four-way variant Ph chromosome. Conventional chromosomal analysis performed on bone marrow aspirate samples showed 46, XY, t(1;9;22;16)(q21;q34;q11.2;q24). Nested RT-PCR of the BCR::ABL1 gene revealed a major BCR::ABL rearrangement. The treatment with nilotinib achieved a complete hematologic, cytogenetic, and molecular response after 12 months.
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Ridge resorption can result in insufficient bone volume for implant surgery, necessitating bone substitutes to restore the resorption area. Recent advances in computer-aided design and manufacturing enable the use of alloplastic bone graft materials with customizable compositions or shapes. This randomized study evaluated the clinical effectiveness of a customized three-dimensional (3D) printed alloplastic bone material. Sixty patients requiring guided bone regeneration for implant installation following tooth extraction due to alveolar bone resorption were recruited at two institutions. The participants were randomly allocated to either a group that received 3D-printed patient-customized bone graft material or a group that received conventional block bone graft material. Implant installation with bone harvesting was performed approximately 5 months after bone grafting. Histological and radiological assessments of the harvested bone area were performed. The experimental group had a significantly higher percent bone volume and a smaller tissue surface than the control group. Bone volume, bone surface, bone surface/volume ratio, bone surface density (bone surface/total volume), and bone mineral density did not differ significantly between groups. Patient-customized bone graft materials offer convenience and reduce patient discomfort. The findings suggest 3D-printed patient-customized bone graft materials could be used as an alternative for simpler bone grafting procedures.
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Pérdida de Hueso Alveolar , Sustitutos de Huesos , Humanos , Trasplante Óseo/métodos , Estudios Prospectivos , Pérdida de Hueso Alveolar/diagnóstico por imagen , Pérdida de Hueso Alveolar/cirugía , Regeneración Ósea , CerámicaRESUMEN
This study presents findings indicating that the ferroelectric tunnel junction (FTJ) or resistive random-access memory (RRAM) in one cell can be intentionally selected depending on the application. The HfAlO film annealed at 700 °C shows stable FTJ characteristics and can be converted into RRAM by forming a conductive filament inside the same cell, that is, the process of intentionally forming a conductive filament is the result of defect generation and redistribution, and applying compliance current prior to a hard breakdown event of the dielectric film enables subsequent RRAM operation. The converted RRAM demonstrated good memory performance. Through current-voltage fitting, it was confirmed that the two resistance states of the FTJ and RRAM had different transport mechanisms. In the RRAM, the 1/f noise power of the high-resistance state (HRS) was about ten times higher than that of the low-resistance state (LRS). This is because the noise components increase due to the additional current paths in the HRS. The 1/f noise power according to resistance states in the FTJ was exactly the opposite result from the case of the RRAM. This is because the noise component due to the Poole-Frenkel emission is added to the noise component due to the tunneling current in the LRS. In addition, we confirmed the potentiation and depression characteristics of the two devices and further evaluated the accuracy of pattern recognition through a simulation by considering a dataset from the Modified National Institute of Standards and Technology.
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BACKGROUND: Oral potentially malignant disorders (OPMDs) are associated with an increased risk of cancer of the oral cavity including the tongue. The early detection of oral cavity cancers and OPMDs is critical for reducing cancer-specific morbidity and mortality. Recently, there have been studies to apply the rapidly advancing technology of deep learning for diagnosing oral cavity cancer and OPMDs. However, several challenging issues such as class imbalance must be resolved to effectively train a deep learning model for medical imaging classification tasks. The aim of this study is to evaluate a new technique of artificial intelligence to improve the classification performance in an imbalanced tongue lesion dataset. METHODS: A total of 1,810 tongue images were used for the classification. The class-imbalanced dataset consisted of 372 instances of cancer, 141 instances of OPMDs, and 1,297 instances of noncancerous lesions. The EfficientNet model was used as the feature extraction model for classification. Mosaic data augmentation, soft labeling, and curriculum learning (CL) were employed to improve the classification performance of the convolutional neural network. RESULTS: Utilizing a mosaic-augmented dataset in conjunction with CL, the final model achieved an accuracy rate of 0.9444, surpassing conventional oversampling and weight balancing methods. The relative precision improvement rate for the minority class OPMD was 21.2%, while the relative [Formula: see text] score improvement rate of OPMD was 4.9%. CONCLUSIONS: The present study demonstrates that the integration of mosaic-based soft labeling and curriculum learning improves the classification performance of tongue lesions compared to previous methods, establishing a foundation for future research on effectively learning from imbalanced data.
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Aprendizaje Profundo , Neoplasias de la Boca , Humanos , Inteligencia Artificial , Curriculum , LenguaRESUMEN
Exposure to ambient ultrafine particulate matter (UPM) causes respiratory disorders; however, the underlying molecular mechanisms remain unclear. In this study, we synthesized simulated UPM (sUPM) with controlled physicochemical properties using the spark-discharge method. Subsequently, we investigated the biological effects of sUPM using BEAS-2B human bronchial epithelial cells (HBECs) and a mouse intratracheal instillation model. High throughput RNA-sequencing and bioinformatics analyses revealed that dysregulation of the glycolytic metabolism is involved in the inhibited proliferation and survival of HBECs by sUPM treatment. Furthermore, signaling pathway and enzymatic analyses showed that the treatment of BEAS-2B cells with sUPM induces the inactivation of extracellular signal-regulated kinase (ERK) and protein kinase B (PKB, also known as AKT), resulting in the downregulation of phosphofructokinase 2 (PFK2) S483 phosphorylation, PFK enzyme activity, and aerobic glycolysis in HBECs in an oxidative stress-independent manner. Additionally, intratracheal instillation of sUPM reduced the phosphorylation of ERK, AKT, and PFK2, decreased proliferation, and increased the apoptosis of bronchial epithelial cells in mice. The findings of this study imply that UPM induces pulmonary toxicity by disrupting aerobic glycolytic metabolism in lung epithelial cells, which can provide novel insights into the toxicity mechanisms of UPM and strategies to prevent their toxic effects.
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Contaminantes Atmosféricos , Material Particulado , Humanos , Animales , Ratones , Material Particulado/análisis , Proteínas Proto-Oncogénicas c-akt/metabolismo , Fosforilación , Células Epiteliales , Glucólisis , Fosfofructoquinasas/análisis , Fosfofructoquinasas/metabolismo , Contaminantes Atmosféricos/análisisRESUMEN
BACKGROUND: Cancer cells undergo cellular adaptation through metabolic reprogramming to sustain survival and rapid growth under various stress conditions. However, how brain tumors modulate their metabolic flexibility in the naturally serine/glycine (S/G)-deficient brain microenvironment remain unknown. METHODS: We used a range of primary/stem-like and established glioblastoma (GBM) cell models in vitro and in vivo. To identify the regulatory mechanisms of S/G deprivation-induced metabolic flexibility, we employed high-throughput RNA-sequencing, transcriptomic analysis, metabolic flux analysis, metabolites analysis, chromatin immunoprecipitation (ChIP), luciferase reporter, nuclear fractionation, cycloheximide-chase, and glucose consumption. The clinical significances were analyzed in the genomic database (GSE4290) and in human GBM specimens. RESULTS: The high-throughput RNA-sequencing and transcriptomic analysis demonstrate that the de novo serine synthesis pathway (SSP) and glycolysis are highly activated in GBM cells under S/G deprivation conditions. Mechanistically, S/G deprivation rapidly induces reactive oxygen species (ROS)-mediated AMP-activated protein kinase (AMPK) activation and AMPK-dependent hypoxia-inducible factor (HIF)-1α stabilization and transactivation. Activated HIF-1α in turn promotes the expression of SSP enzymes phosphoglycerate dehydrogenase (PHGDH), phosphoserine aminotransferase 1 (PSAT1), and phosphoserine phosphatase (PSPH). In addition, the HIF-1α-induced expression of glycolytic genes (GLUT1, GLUT3, HK2, and PFKFB2) promotes glucose uptake, glycolysis, and glycolytic flux to fuel SSP, leading to elevated de novo serine and glycine biosynthesis, NADPH/NADP+ ratio, and the proliferation and survival of GBM cells. Analyses of human GBM specimens reveal that the levels of overexpressed PHGDH, PSAT1, and PSPH are positively correlated with levels of AMPK T172 phosphorylation and HIF-1α expression and the poor prognosis of GBM patients. CONCLUSION: Our findings reveal that metabolic stress-enhanced glucose-derived de novo serine biosynthesis is a critical metabolic feature of GBM cells, and highlight the potential to target SSP for treating human GBM.
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Proteínas Quinasas Activadas por AMP , Glioblastoma , Humanos , Glioblastoma/patología , Serina , Glucosa/metabolismo , Glicina , ARN , Subunidad alfa del Factor 1 Inducible por Hipoxia/genética , Línea Celular Tumoral , Microambiente Tumoral , Fosfofructoquinasa-2RESUMEN
Odontogenic ghost cell carcinoma (OGCC), a malignant counterpart of the odontogenic ghost cell tumor (OGCT),with aggressive growth characteristics, is exceedingly rare. A painful swelling in the jaw with local paresthesia isthe most common symptom.We described a case of 47-year Korean woman who had a rare central epithelial odontogenic ghost cell carcinomawhich recurred at reconstructed fibular flap. Immunohistochemical differences between OGCT and OGCC analyzedusing primary and recurred surgical specimen. On the basis of this case, the tumor started as an OGCT andtransformed into OGCC with highly aggressive, rapidly growing, infiltrative tumors. Our findings suggest thatsome of the cytokines produced by ghost cells may play important roles in causing extensive bone resorption inthe odontogenic ghost cell carcinoma.Wide local excision with histologically clean margins is the treatment mode of selection. Also, we recommendclose long-term surveillance of OGCT because of high recurrence and potential for malignancy transformation (AU)