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1.
Anim Cells Syst (Seoul) ; 28(1): 453-465, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39268223

RESUMEN

Upregulation of CXC motif chemokine 10 (CXCL10) in melanoma patients has been found to be associated with melanoma progression. However, the role of endogenous CXCL10 from the host in melanoma tumor growth remains unclear. In the present study, we found that host-derived endogenous CXCL10 production was dramatically augmented during subcutaneous B16F10 melanoma tumor growth and that host ablation of CXCL10 in Cxcl10-/- mice showed a decrease in both angiogenesis and tumor growth of B16F10 melanoma in vivo. Several signaling pathways involved in production of pro-angiogenic factors and tumor growth were activated by CXCL10 in B16F10 melanoma cells. CXCL10 increased expression of pro-angiogenic factors, such as vascular endothelial growth factor (VEGF), platelet-derived growth factor subunit-B (PDGF-B), fibroblast growth factor 2 (FGF2), hepatocyte growth factor (HGF), and angiopoietin 2 (Angpt2), in B16F10 melanoma cells, resulting in enhanced tube formation and proliferation of human umbilical vein endothelial cells in vitro. In addition, CXCL10 directly enhanced B16F10 melanoma tumor growth in an in vitro three-dimensional cell culture system. Together, our findings reveal that amplified host-derived endogenous CXCL10 is critical for B16F10 melanoma angiogenesis and tumor growth. Therefore, CXCL10 might represent a therapeutic target for melanoma.

2.
NMR Biomed ; : e5226, 2024 Aug 20.
Artículo en Inglés | MEDLINE | ID: mdl-39162295

RESUMEN

Iron and myelin are primary susceptibility sources in the human brain. These substances are essential for a healthy brain, and their abnormalities are often related to various neurological disorders. Recently, an advanced susceptibility mapping technique, which is referred to as χ-separation (pronounced as "chi"-separation), has been proposed, successfully disentangling paramagnetic iron from diamagnetic myelin. This method provided a new opportunity for generating high-resolution iron and myelin maps of the brain. Utilizing this technique, this study constructs a normative χ-separation atlas from 106 healthy human brains. The resulting atlas provides detailed anatomical structures associated with the distributions of iron and myelin, clearly delineating subcortical nuclei, thalamic nuclei, and white matter fiber bundles. Additionally, susceptibility values in a number of regions of interest are reported along with age-dependent changes. This atlas may have direct applications such as localization of subcortical structures for deep brain stimulation or high-intensity focused ultrasound and also serve as a valuable resource for future research.

3.
Neurology ; 103(6): e209604, 2024 Sep 24.
Artículo en Inglés | MEDLINE | ID: mdl-39213476

RESUMEN

BACKGROUND AND OBJECTIVES: Myelin and iron play essential roles in remyelination processes of multiple sclerosis (MS) lesions. χ-separation, a novel biophysical model applied to multiecho T2*-data and T2-data, estimates the contribution of myelin and iron to the obtained susceptibility signal. We used this method to investigate myelin and iron levels in lesion and nonlesion brain areas in patients with MS and healthy individuals. METHODS: This prospective MS cohort study included patients with MS fulfilling the McDonald Criteria 2017 and healthy individuals, aged 18 years or older, with no other neurologic comorbidities. Participants underwent MRI at baseline and after 2 years, including multiecho GRE-(T2*) and FAST-(T2) sequences. Using χ-separation, we generated myelin-sensitive and iron-sensitive susceptibility maps. White matter lesions (WMLs), cortical lesions (CLs), surrounding normal-appearing white matter (NAWM), and normal-appearing gray matter were segmented on fluid-attenuated inversion recovery and magnetization-prepared 2 rapid gradient echo images, respectively. Cross-sectional group comparisons used Wilcoxon rank-sum tests, longitudinal analyses applied Wilcoxon signed-rank tests. Associations with clinical outcomes (disease phenotype, age, sex, disease duration, disability measured by Expanded Disability Status Scale [EDSS], neurofilament light chain levels, and T2-lesion number and volume) were assessed using linear regression models. RESULTS: Of 168 patients with MS (median [interquartile range (IQR)] age 47.0 [21.7] years; 101 women; 6,898 WMLs, 775 CLs) and 103 healthy individuals (age 33.0 [10.5] years, 57 women), 108 and 62 were followed for a median of 2 years, respectively (IQR 0.1; 5,030 WMLs, 485 CLs). At baseline, WMLs had lower myelin (median 0.025 [IQR 0.015] parts per million [ppm]) and iron (0.017 [0.015] ppm) than the corresponding NAWM (myelin 0.030 [0.012]; iron 0.019 [0.011] ppm; both p < 0.001). After 2 years, both myelin (0.027 [0.014] ppm) and iron had increased (0.018 [0.015] ppm; both p < 0.001). Younger age (p < 0.001, b = -5.111 × 10-5), lower disability (p = 0.04, b = -2.352 × 10-5), and relapsing-remitting phenotype (RRMS, 0.003 [0.01] vs primary progressive 0.002 [IQR 0.01], p < 0.001; vs secondary progressive 0.0004 [IQR 0.01], p < 0.001) at baseline were associated with remyelination. Increment of myelin correlated with clinical improvement measured by EDSS (p = 0.015, b = -6.686 × 10-4). DISCUSSION: χ-separation, a novel mathematical model applied to multiecho T2*-images and T2-images shows that young RRMS patients with low disability exhibit higher remyelination capacity, which correlated with clinical disability over a 2-year follow-up.


Asunto(s)
Imagen por Resonancia Magnética , Esclerosis Múltiple , Remielinización , Sustancia Blanca , Humanos , Femenino , Masculino , Adulto , Sustancia Blanca/diagnóstico por imagen , Sustancia Blanca/patología , Remielinización/fisiología , Persona de Mediana Edad , Esclerosis Múltiple/diagnóstico por imagen , Esclerosis Múltiple/patología , Estudios Prospectivos , Vaina de Mielina/patología , Hierro/metabolismo , Estudios Transversales , Corteza Cerebral/diagnóstico por imagen , Corteza Cerebral/patología , Estudios de Cohortes
4.
Water Res ; 261: 122021, 2024 Sep 01.
Artículo en Inglés | MEDLINE | ID: mdl-38986280

RESUMEN

Membrane distillation (MD) equipped with omniphobic (non-wetting) membranes has found a niche in water reclamation from hypersaline industrial wastewater. Here, we examined the efficacy of non-fluorinated materials as surface coating agents for omniphobic MD membrane fabrication, and identified necessary mechanisms to attain a maximized wetting resistance using fluorine-free materials. We first prepared MD membranes with different surface chemistries using a series of linear alkylsilanes and polydimethylsiloxane (PDMS) as representative fluorine-free, low surface energy materials. Membranes modified with a longer chain alkylsilane exhibited a lower surface energy and demonstrated a greater wetting resistance in direct contact MD experiments using feedwaters of various surface tensions. Despite the nearly identical surface energy measured for the longest alkylsilane and PDMS, PDMS-modified membrane exhibited an extended antiwetting performance as compared to the membrane treated with the longest alkylsilane. To elucidate the source of the distinctive wetting resistance, we examined the nucleation and condensation kinetics on the surfaces with the different surface chemistries via environmental scanning electron microscopy. Our analysis suggests that the membranes treated with long chain alkylsilanes contain surface defects (i.e., hydrophilic regions) whereas the high mobility of the PDMS effectively minimizes the defect exposure, slowing down the condensation and subsequent surface wetting.


Asunto(s)
Aguas Residuales , Purificación del Agua , Humectabilidad , Aguas Residuales/química , Purificación del Agua/métodos , Dimetilpolisiloxanos/química , Flúor/química , Solución Salina/química , Interacciones Hidrofóbicas e Hidrofílicas , Destilación
5.
Nanoscale Horiz ; 9(9): 1475-1492, 2024 Aug 19.
Artículo en Inglés | MEDLINE | ID: mdl-39015048

RESUMEN

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.

6.
J Adv Prosthodont ; 16(3): 189-199, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38957293

RESUMEN

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.

7.
Exp Mol Med ; 56(6): 1373-1387, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38825643

RESUMEN

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.


Asunto(s)
Proliferación Celular , Regulación Neoplásica de la Expresión Génica , Glicina , Proteínas de Unión al ARN , Serina , Neoplasias de la Mama Triple Negativas , Femenino , Humanos , Adenosina/metabolismo , Adenosina/análogos & derivados , Línea Celular Tumoral , Glicina/metabolismo , Metilación , Proteínas de Unión al ARN/metabolismo , Proteínas de Unión al ARN/genética , Serina/metabolismo , Neoplasias de la Mama Triple Negativas/metabolismo , Neoplasias de la Mama Triple Negativas/genética , Neoplasias de la Mama Triple Negativas/patología
8.
NMR Biomed ; 37(9): e5167, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-38697612

RESUMEN

Susceptibility source separation, or χ-separation, estimates diamagnetic (χdia) and paramagnetic susceptibility (χpara) signals in the brain using local field and R2' (= R2* - R2) maps. Recently proposed R2*-based χ-separation methods allow for χ-separation using only multi-echo gradient echo (ME-GRE) data, eliminating the need for additional data acquisition for R2 mapping. Although this approach reduces scan time and enhances clinical utility, the impact of missing R2 information remains a subject of exploration. In this study, we evaluate the viability of two previously proposed R2*-based χ-separation methods as alternatives to their R2'-based counterparts: model-based R2*-χ-separation versus χ-separation and deep learning-based χ-sepnet-R2* versus χ-sepnet-R2'. Their performances are assessed in individuals with multiple sclerosis (MS), comparing them with their corresponding R2'-based counterparts (i.e., R2*-χ-separation vs. χ-separation and χ-sepnet-R2* vs. χ-sepnet-R2'). The evaluations encompass qualitative visual assessments by experienced neuroradiologists and quantitative analyses, including region of interest analyses and linear regression analyses. Qualitatively, R2*-χ-separation tends to report higher χpara and χdia values compared with χ-separation, leading to less distinct lesion contrasts, while χ-sepnet-R2* closely aligns with χ-sepnet-R2'. Quantitative analysis reveals a robust correlation between both R2*-based methods and their R2'-based counterparts (r ≥ 0.88). Specifically, in the whole-brain voxels, χ-sepnet-R2* exhibits higher correlation and better linearity than R2*-χ-separation (χdia/χpara from R2*-χ-separation: r = 0.88/0.90, slope = 0.79/0.86; χdia/χpara from χ-sepnet-R2*: r = 0.90/0.92, slope = 0.99/0.97). In MS lesions, both R2*-based methods display comparable correlation and linearity (χdia/χpara from R2*-χ-separation: r = 0.90/0.91, slope = 0.98/0.91; χdia/χpara from χ-sepnet-R2*: r = 0.88/0.88, slope = 0.91/0.95). Notably, χ-sepnet-R2* demonstrates negligible offsets, whereas R2*-χ-separation exhibits relatively large offsets (0.02 ppm in the whole brain and 0.01 ppm in the MS lesions), potentially indicating the false presence of myelin or iron in MS lesions. Overall, both R2*-based χ-separation methods demonstrated their viability as alternatives to their R2'-based counterparts. χ-sepnet-R2* showed better alignment with its R2'-based counterpart with minimal susceptibility offsets, compared with R2*-χ-separation that reported higher χpara and χdia values compared with R2'-based χ-separation.


Asunto(s)
Imagen por Resonancia Magnética , Esclerosis Múltiple , Humanos , Esclerosis Múltiple/diagnóstico por imagen , Esclerosis Múltiple/patología , Femenino , Masculino , Adulto , Persona de Mediana Edad , Encéfalo/diagnóstico por imagen , Encéfalo/patología , Aprendizaje Profundo
9.
Adv Sci (Weinh) ; 11(26): e2308460, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38709909

RESUMEN

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.


Asunto(s)
Arritmias Cardíacas , Electrocardiografía , Procesamiento de Señales Asistido por Computador , Arritmias Cardíacas/diagnóstico , Humanos , Electrocardiografía/métodos , Electrocardiografía/instrumentación , Redes Neurales de la Computación , Diseño de Equipo
10.
Neurobiol Aging ; 141: 21-33, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-38810596

RESUMEN

INTRODUCTION: The "structural disconnection" hypothesis of cognitive aging suggests that deterioration of white matter (WM), especially myelin, results in cognitive decline, yet in vivo evidence is inconclusive. METHODS: We examined age differences in WM microstructure using Myelin Water Imaging and Diffusion Tensor Imaging in 141 healthy participants (age 20-79). We used the Virginia Cognitive Aging Project and the NIH Toolbox® to generate composites for memory, processing speed, and executive function. RESULTS: Voxel-wise analyses showed that lower myelin water fraction (MWF), predominantly in prefrontal WM, genu of the corpus callosum, and posterior limb of the internal capsule was associated with reduced memory performance after controlling for age, sex, and education. In structural equation modeling, MWF in the prefrontal white matter and genu of the corpus callosum significantly mediated the effect of age on memory, whereas fractional anisotropy (FA) did not. DISCUSSION: Our findings support the disconnection hypothesis, showing that myelin decline contributes to age-related memory loss and opens avenues for interventions targeting myelin health.


Asunto(s)
Imagen de Difusión Tensora , Envejecimiento Saludable , Memoria , Vaina de Mielina , Sustancia Blanca , Humanos , Anciano , Persona de Mediana Edad , Femenino , Masculino , Adulto , Sustancia Blanca/diagnóstico por imagen , Sustancia Blanca/patología , Envejecimiento Saludable/patología , Envejecimiento Saludable/psicología , Memoria/fisiología , Adulto Joven , Cuerpo Calloso/diagnóstico por imagen , Envejecimiento/patología , Envejecimiento/psicología , Envejecimiento/fisiología , Envejecimiento Cognitivo/fisiología , Envejecimiento Cognitivo/psicología
11.
Adv Sci (Weinh) ; 11(28): e2401821, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38738755

RESUMEN

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.

12.
Adv Sci (Weinh) ; 11(28): e2307196, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38773725

RESUMEN

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.

13.
PLoS One ; 19(4): e0300025, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38603704

RESUMEN

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.


Asunto(s)
Ácaros , Varroidae , Abejas , Animales , República de Corea
14.
J Dent ; 147: 105030, 2024 08.
Artículo en Inglés | MEDLINE | ID: mdl-38685341

RESUMEN

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.


Asunto(s)
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/métodos
15.
Magn Reson Med Sci ; 23(3): 291-306, 2024 Jul 01.
Artículo en Inglés | MEDLINE | ID: mdl-38644201

RESUMEN

In MRI, researchers have long endeavored to effectively visualize myelin distribution in the brain, a pursuit with significant implications for both scientific research and clinical applications. Over time, various methods such as myelin water imaging, magnetization transfer imaging, and relaxometric imaging have been developed, each carrying distinct advantages and limitations. Recently, an innovative technique named as magnetic susceptibility source separation has emerged, introducing a novel surrogate biomarker for myelin in the form of a diamagnetic susceptibility map. This paper comprehensively reviews this cutting-edge method, providing the fundamental concepts of magnetic susceptibility, susceptibility imaging, and the validation of the diamagnetic susceptibility map as a myelin biomarker that indirectly measures myelin content. Additionally, the paper explores essential aspects of data acquisition and processing, offering practical insights for readers. A comparison with established myelin imaging methods is also presented, and both current and prospective clinical and scientific applications are discussed to provide a holistic understanding of the technique. This work aims to serve as a foundational resource for newcomers entering this dynamic and rapidly expanding field.


Asunto(s)
Encéfalo , Imagen por Resonancia Magnética , Vaina de Mielina , Humanos , Imagen por Resonancia Magnética/métodos , Encéfalo/diagnóstico por imagen , Procesamiento de Imagen Asistido por Computador/métodos
16.
Ann Lab Med ; 44(5): 426-436, 2024 Sep 01.
Artículo en Inglés | MEDLINE | ID: mdl-38529546

RESUMEN

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.


Asunto(s)
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 fármacos
17.
Korean J Radiol ; 25(3): 267-276, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38413111

RESUMEN

OBJECTIVE: To evaluate the diagnostic performance of susceptibility map-weighted imaging (SMwI) taken in different acquisition planes for discriminating patients with neurodegenerative parkinsonism from those without. MATERIALS AND METHODS: This retrospective, observational, single-institution study enrolled consecutive patients who visited movement disorder clinics and underwent brain MRI and 18F-FP-CIT PET between September 2021 and December 2021. SMwI images were acquired in both the oblique (perpendicular to the midbrain) and the anterior commissure-posterior commissure (AC-PC) planes. Hyperintensity in the substantia nigra was determined by two neuroradiologists. 18F-FP-CIT PET was used as the reference standard. Inter-rater agreement was assessed using Cohen's kappa coefficient. The diagnostic performance of SMwI in the two planes was analyzed separately for the right and left substantia nigra. Multivariable logistic regression analysis with generalized estimating equations was applied to compare the diagnostic performance of the two planes. RESULTS: In total, 194 patients were included, of whom 105 and 103 had positive results on 18F-FP-CIT PET in the left and right substantia nigra, respectively. Good inter-rater agreement in the oblique (κ = 0.772/0.658 for left/right) and AC-PC planes (0.730/0.741 for left/right) was confirmed. The pooled sensitivities for two readers were 86.4% (178/206, left) and 83.3% (175/210, right) in the oblique plane and 87.4% (180/206, left) and 87.6% (184/210, right) in the AC-PC plane. The pooled specificities for two readers were 83.5% (152/182, left) and 82.0% (146/178, right) in the oblique plane, and 83.5% (152/182, left) and 86.0% (153/178, right) in the AC-PC plane. There were no significant differences in the diagnostic performance between the two planes (P > 0.05). CONCLUSION: There are no significant difference in the diagnostic performance of SMwI performed in the oblique and AC-PC plane in discriminating patients with parkinsonism from those without. This finding affirms that each institution may choose the imaging plane for SMwI according to their clinical settings.


Asunto(s)
Trastornos Parkinsonianos , Humanos , Imagen por Resonancia Magnética/métodos , Trastornos Parkinsonianos/diagnóstico por imagen , Estudios Retrospectivos , Tropanos
18.
Sci Rep ; 14(1): 3397, 2024 02 10.
Artículo en Inglés | MEDLINE | ID: mdl-38336901

RESUMEN

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.


Asunto(s)
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 , Cerámica
19.
BMC Oral Health ; 24(1): 161, 2024 Feb 01.
Artículo en Inglés | MEDLINE | ID: mdl-38302981

RESUMEN

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.


Asunto(s)
Aprendizaje Profundo , Neoplasias de la Boca , Humanos , Inteligencia Artificial , Curriculum , Lengua
20.
J Chem Phys ; 160(7)2024 Feb 21.
Artículo en Inglés | MEDLINE | ID: mdl-38375908

RESUMEN

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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