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2.
Korean J Fam Med ; 2024 Jan 23.
Artigo em Inglês | MEDLINE | ID: mdl-38263902

RESUMO

Background: In patients with breast cancer, a healthy diet can help reduce breast cancer-specific recurrence, mortality, and comorbid chronic disease rates. There have been few studies on dietary habits immediately after breast cancer diagnosis, especially those involving the Asian population. Therefore, this study aimed to compare the nutritional habits of newly diagnosed patients with breast cancer and the general population without cancer in Korea using propensity score (PS) matching. Methods: We conducted a case-controlled study of 157 patients with breast cancer and 2,363 cancer-free control participants from the Korea National Health and Nutrition Examination Survey. The PS values for the predicted probability of patients with breast cancer and the general population were estimated using logistic regression analysis, including age and body mass index. The dietary patterns were assessed using a 24-hour recall of 1 day and the Food Frequency Questionnaire. Results: PS matching showed that patients with breast cancer consumed fewer calories and carbohydrates; however, they consumed more protein and fat compared to the general population. Compared to the general population, patients with breast cancer consumed more healthy foods such as fish, seaweed, vegetables, fruit, mixed-grain rice, and nuts; however, they also consumed more soup, stew, and red meat. Conclusion: Newly diagnosed patients with breast cancer have some healthy dietary habits compared to the general population. However, there is considerable room for improvement in their diet quality. Our results support the need to develop tailored dietary recommendations for patients with breast cancer during the diagnostic and posttreatment periods to improve their diet quality.

3.
ACS Nano ; 17(17): 17372-17382, 2023 Sep 12.
Artigo em Inglês | MEDLINE | ID: mdl-37624768

RESUMO

Organic solid electrolytes compatible with all-solid-state Li metal batteries (LMBs) are essential to ensuring battery safety, high energy density, and long-term cycling performance. However, it remains a challenge to develop an approach to provide organic solid electrolytes with capabilities for the facile dissociation of strong Li-ion pairs and fast transport of ionic components. Herein, a diethylene glycol-modified pyridinium covalent organic framework (DEG-PMCOF) with a well-defined periodic structure is prepared as a multicomponent solid electrolyte with a cationic moiety of high polarity, an additional flexible ion-transporter, and an ordered ionic channel for all-solid-state LMBs. The DEG-containing pyridinium groups of DEG-PMCOF allow a lower dissociation energy of Li salts and a smaller energy barrier of Li-ion transport, leading to high ion conductivity (1.71 × 10-4 S cm-1) and a large Li-ion transfer number (0.61) at room temperature in the solid electrolyte. The DEG-PMCOF solid electrolyte exhibits a wide electrochemical stability window and effectively suppresses the formation of Li dendrites and dead Li in all-solid-state LMBs. Molecular dynamics and density functional theory simulations provide insights into the mechanisms for the enhanced Li-ion transport driven by the integrated diffusion process based on hopping motion, vehicle motion, and free diffusion of DEG-PMCOF. The all-solid-state LMB assembled with a DEG-PMCOF solid electrolyte displays a high specific capacity with a retention of 99% and an outstanding Coulombic efficiency of 99% at various C-rates during long-term cycling. This DEG-PMCOF approach can offer an effective route to design various solid-state Li batteries.

4.
Am J Physiol Cell Physiol ; 325(2): C509-C518, 2023 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-37486067

RESUMO

Sepsis is a life-threatening inflammatory response to infection, often accompanied by skeletal muscle atrophy. A previous study demonstrated that the administration of microRNA-140 (miR-140) attenuated lipopolysaccharide (LPS)-induced muscle atrophy, whereas miR-140 knockdown with siRNA promoted atrophy. Therefore, we investigated whether miR-140 is involved in LPS-induced muscle atrophy using a genetic model, miR-140-/- mice. We found that a single injection of LPS induced atrophy both in slow-twitch and fast-twitch muscles. The muscle weights and fiber cross-sectional areas were significantly reduced in both the wild-type (WT) and miR-140-/- mice, with no difference between genotypes. The expression of several proteolysis markers, muscle-specific RING-finger 1 (MuRF1) and MAFbx/atrogin-1, increased in both groups after LPS injection. The ubiquitinated proteins in the miR-140-/- mice were similar to those in the WT mice. Therefore, the deletion of miR-140 did not affect LPS-induced muscle atrophy.NEW & NOTEWORTHY We used miR-140-/- mice to determine the function of miR-140 in LPS-induced skeletal muscle atrophy. To our knowledge, this study is the first to examine slow-twitch muscles in LPS-induced muscle wasting after miR-140 manipulation.


Assuntos
MicroRNAs , Sepse , Animais , Camundongos , Lipopolissacarídeos , MicroRNAs/genética , MicroRNAs/metabolismo , Músculo Esquelético/metabolismo , Atrofia Muscular/metabolismo , Sepse/complicações , Sepse/genética , Sepse/metabolismo
5.
Adv Mater ; 35(30): e2301308, 2023 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-37068790

RESUMO

Organic solid electrolytes offer an effective route for safe and high-energy-density all-solid-state Li metal batteries. However, it remains a challenge to devise a new strategy to promote the dissociation of strong ion pairs and the transport of ionic components in organic solid electrolytes. Herein, a zwitterionic covalent organic framework (Zwitt-COF) with well-defined chemical and pore structures is prepared as a solid electrolyte capable of accelerating the dissociation and transport of Li ions. The Zwitt-COF solid electrolyte exhibits a high room-temperature ionic conductivity of 1.65 × 10-4  S cm-1 with a wide electrochemical stability window. Besides, the Zwitt-COF solid electrolyte displays stable Li plating/stripping behavior via effective inhibition of the formation of Li dendrites and dead Li, leading to superior long-term cycle performance with retention of 99% discharge capacity and 98% Coulombic efficiency in an all-solid-state Li-metal battery. Theoretical simulations reveal that the incorporation of zwitterionic groups into COF can facilitate the dissociation of strong ion pairs and reconstruct the AA-stacking configuration by dissociative adsorption of Li+ ions on Zwitt-COF producing linear hexagonal ion channels in the Zwitt-COF solid electrolyte. This strategy based on Zwitt-COF can provide an alternative way to construct various solid-state Li batteries.

6.
Mod Pathol ; 36(3): 100082, 2023 03.
Artigo em Inglês | MEDLINE | ID: mdl-36788099

RESUMO

Although venous invasion (VI) is common in colorectal cancers (CRCs) and is associated with distant metastasis, the 3-dimensional (3D) microscopic features and associated mechanisms of VI are not well elucidated. To characterize the patterns of VI, 103 tissue slabs were harvested from surgically resected CRCs with ≥pT2. They were cleared using the modified immunolabeling-enabled 3D imaging of solvent-cleared organs method, labeled with multicolor fluorescent antibodies, including antibodies against cytokeratin 19, desmin, CD31, and E-cadherin, and visualized by confocal laser scanning microscopy. VI was classified as intravasation, intraluminal growth, and/or extravasation, and 2-dimensional and 3D microscopic features were compared. VI was detected more frequently in 3D (56/103 [54.4%]) than in conventional 2-dimensional hematoxylin and eosin-stained slides (33/103 [32%]; P < .001). When VI was present, it was most commonly in the form of intraluminal growth (51/56), followed by extravasation (13/56) and intravasation (5/56). The mean length of intraluminal growth was 334.0 ± 212.4 µm. Neoplastic cell projections extended from cancer cell clusters in the connective tissue surrounding veins, penetrated the smooth muscle layer, and then grew into and filled the venous lumen. E-cadherin expression changed at each invasion phase; intact E-cadherin expression was observed in the cancer cells in the venous walls, but its expression was lost in small clusters of intraluminal neoplastic cells. In addition, reexpression of E-cadherin was observed when cancer cells formed well-oriented tubular structures and accumulated and grew along the luminal side of the venous wall. In contrast, singly scattered cancer cells and cancer cells with poorly defined tubular structures showed loss of E-cadherin expression. E-cadherin expression was intact in the large cohesive clusters of extravasated cancer cells. However, singly scattered cells and smaller projections of neoplastic cells in the stroma outward of venous wall showed a loss of E-cadherin expression. In conclusion, VI was observed in more than half of the CRCs analyzed by 3D histopathologic image reconstruction. Once inside a vein, neoplastic cells can grow intraluminally. The epithelial-mesenchymal transition is not maintained during VI of CRCs.


Assuntos
Caderinas , Neoplasias Colorretais , Humanos , Caderinas/metabolismo , Transição Epitelial-Mesenquimal , Linhagem Celular Tumoral , Neoplasias Colorretais/cirurgia , Neoplasias Colorretais/patologia
7.
J Nucl Med ; 64(1): 137-144, 2023 01.
Artigo em Inglês | MEDLINE | ID: mdl-35981900

RESUMO

For the past several decades, chimeric antigen receptor T-cell therapies have shown promise in the treatment of cancers. These treatments would greatly benefit from companion imaging biomarkers to follow the trafficking of T cells in vivo. Methods: Using synthetic biology, we engineered T cells with a chimeric receptor synthetic intramembrane proteolysis receptor (SNIPR) that induces overexpression of an exogenous reporter gene cassette on recognition of specific tumor markers. We then applied a SNIPR-based PET reporter system to 2 cancer-relevant antigens, human epidermal growth factor receptor 2 (HER2) and epidermal growth factor receptor variant III (EGFRvIII), commonly expressed in breast and glial tumors, respectively. Results: Antigen-specific reporter induction of the SNIPR PET T cells was confirmed in vitro using green fluorescent protein fluorescence, luciferase luminescence, and the HSV-TK PET reporter with 9-(4-18F-fluoro-3-[hydroxymethyl]butyl)guanine ([18F]FHBG). T cells associated with their target antigens were successfully imaged using PET in dual-xenograft HER2+/HER2- and EGFRvIII+/EGFRvIII- animal models, with more than 10-fold higher [18F]FHBG signals seen in antigen-expressing tumors versus the corresponding controls. Conclusion: The main innovation found in this work was PET detection of T cells via specific antigen-induced signals, in contrast to reporter systems relying on constitutive gene expression.


Assuntos
Neoplasias da Mama , Glioblastoma , Animais , Humanos , Feminino , Linfócitos T , Neoplasias da Mama/diagnóstico por imagem , Neoplasias da Mama/genética , Linhagem Celular Tumoral , Tomografia por Emissão de Pósitrons/métodos , Genes Reporter
8.
ACS Appl Mater Interfaces ; 14(21): 24404-24414, 2022 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-35584866

RESUMO

Covalent organic frameworks (COFs) are promising candidates for the controllable design of electrocatalysts. However, bifunctional electrocatalytic activities for the oxygen reduction reaction (ORR) and oxygen evolution reaction (OER) remain challenging in COFs. In this study, imidazolium-rich COFs (IMCOFs) with well-defined active sites and characteristic three-dimensional assembly structures were readily prepared, and their electronic structures were tuned by Co incorporation to elicit bifunctional electrocatalytic activities for the ORR and OER. The Co nanoparticle-incorporated spherical IMCOF-derived electrocatalyst (CoNP-s-IMCOF) exhibited lower overpotentials for the ORR and OER compared with the atomic Co-incorporated planar IMCOF-derived electrocatalyst (Co-p-IMCOF). Computational simulations revealed that the imidazole carbon sites of CoNP-s-IMCOF rather than the triazine carbons were the active sites for the ORR and OER, and its p-band center downshifted via charge transfer, facilitating the chemisorption of oxygen intermediates during the reactions. A Zn-air battery with CoNP-s-IMCOF exhibited a small voltage gap of 1.3 V with excellent durability for 935 cycles. This approach for control over the three-dimensional assembly and electronic structures of IMCOFs can be extended to the development of diverse catalytic nanomaterials for applications of interest.

9.
Nano Converg ; 9(1): 17, 2022 Apr 12.
Artigo em Inglês | MEDLINE | ID: mdl-35415763

RESUMO

N-Doped carbon electrocatalysts are a promising alternative to precious metal catalysts to promote oxygen reduction reaction (ORR). However, it remains a challenge to design the desired active sites on carbon skeletons in a controllable manner for ORR. Herein, we developed a facile approach based on oxygen-mediated solvothermal radical reaction (OSRR) for preparation of N-doped carbon electrocatalysts with a pre-designed active site and modulated catalytic activity for ORR. In the OSRR, 2-methylimidazole reacted with Co and Mn salts to form an active site precursor (MnCo-MIm) in N-methyl-2-pyrrolidone (NMP) at room temperature. Then, the reaction temperature increased to 140 °C under an oxygen atmosphere to generate NMP radicals, followed by their polymerization with the pre-formed MnCo-MIm to produce Mn-coupled Co nanoparticle-embedded N-doped carbon framework (MnCo-NCF). The MnCo-NCF showed uniform dispersion of nitrogen atoms and Mn-doped Co nanoparticles on the carbon skeleton with micropores and mesopores. The MnCo-NCF exhibited higher electrocatalytic activity for ORR than did a Co nanoparticle only-incorporated carbon framework due to the improved charge transfer from the Mn-doped Co nanoparticles to the carbon skeleton. In addition, the Zn-air battery assembled with MnCo-NCF had superior performance and durability to the battery using commercial Pt/C. This facile approach can be extended for designing carbon electrocatalysts with desired active sites to promote specific reactions.

10.
Lancet Oncol ; 23(2): e75-e87, 2022 02.
Artigo em Inglês | MEDLINE | ID: mdl-35114134

RESUMO

Radionuclide therapy is a rapidly expanding oncological treatment method. Overwhelmingly, the application of radionuclide therapy in clinical practice relies on fixed or empirical dosing strategies. In principle, the application of dosimetry promises to improve patient outcomes by tailoring administered radionuclide therapy activities to each patient's unique tumour burden and tumour uptake. However, robust prospective data are scarce due to few prospective randomised clinical trials investigating the use of dosimetry in radionuclide therapy. In this Review, we describe the role of dosimetry as it has been applied historically and in modern clinical practice and its potential future applications. We further emphasise areas of future growth and a potential pathway to optimised personalised activity modulation of radionuclide therapy.


Assuntos
Neoplasias/radioterapia , Neoplasias da Próstata/radioterapia , Radioisótopos/uso terapêutico , Dosagem Radioterapêutica , Humanos , Neoplasias Hepáticas/radioterapia , Masculino , Neuroblastoma/radioterapia , Neoplasias da Glândula Tireoide/radioterapia
11.
J Pathol Transl Med ; 56(3): 152-156, 2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-35073631

RESUMO

Yolk sac tumors (YSTs), which are also called endodermal sinus tumors, are malignant tumors of germ cell origin. These tumors usually occur in the gonads, but 20% of cases have been reported at extragonadal sites. The head and neck is a rarely affected region that accounts for just 1% of all malignant tumors of germ cell origin. In addition, YSTs arise mostly in childhood. We present a rare pathologically pure case of primary adult YST in the sinonasal area. A 45-year-old male patient presented with a rapidly growing mass in the nasal cavity, which caused nasal obstruction and bloody post-nasal drip. The histopathologic features indicated pure YST, and immunohistochemical analysis revealed positive reactivity for Sal-like protein 4 and alpha-fetoprotein. Herein, we discuss the clinical, radiologic, and histologic features of this YST and review other cases of sinonasal YST in adults.

12.
Langenbecks Arch Surg ; 407(3): 1091-1097, 2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-35013798

RESUMO

BACKGROUND: Although surgery is the primary treatment for ampullary cancer (AC), the benefit of adjuvant chemotherapy (CTx) has not yet been confirmed. METHODS: AC patients who were administered 5-fluorouracil(FU)/leucovorin(LV)-based CTx after curative intent surgery between 2011 and 2019 were included. Prognosis was compared between the observation (OB) and CTx groups after propensity score matching (PSM) using perioperative variables to control differences in patient characteristics. RESULTS: Before PSM, of 475 patients, those in the CTx group (n = 281) had worse 5-year overall survival (OS) (82.1% vs. 78.5%, p = 0.017) and worse 5-year recurrence-free survival (RFS) (54.9% vs. 75.7%, p < 0.001) than those in the OB group (n = 194). In addition, the CTx group had a higher rate of poor prognostic factors such as a high T stage (p < 0.001), node metastasis (p < 0.001), and poor differentiation (p < 0.001). After PSM, perioperative outcomes were comparable. In addition, there were no significant differences in OS (hazard ratio [HR], 1.085; 95% confidence interval [CI], 0.688-1.710; p = 0.726) or RFS (HR, 0.883; 95% CI, 0.613 1.272; p = 0.505) between the CTx (n = 123) and OB (n = 123) groups even after stratification by TNM stage. Intestinal subtype showed better 5-year OS (83.7% vs 33.2%, p = 0.015) and RFS (46.5% vs 24.9%, p = 0.035) rate compared with pancreatobiliary/mixed subtype. CONCLUSION: Patients who received adjuvant chemotherapy based on 5-FU/LV showed comparable oncologic outcomes to patients in the OB group even after stratification by tumor stage. The patients with intestinal subtype showed oncologic benefit for adjuvant 5-FU/LV CTx compared with pancreatobiliary or mixed subtypes.


Assuntos
Ampola Hepatopancreática , Neoplasias do Ducto Colédoco , Ampola Hepatopancreática/patologia , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Quimioterapia Adjuvante , Neoplasias do Ducto Colédoco/tratamento farmacológico , Neoplasias do Ducto Colédoco/cirurgia , Fluoruracila/administração & dosagem , Humanos , Leucovorina/administração & dosagem , Estadiamento de Neoplasias , Pontuação de Propensão
13.
Sci Rep ; 11(1): 19361, 2021 09 29.
Artigo em Inglês | MEDLINE | ID: mdl-34588544

RESUMO

Muscle atrophy occurs in a variety of physiological and pathological conditions. Specific molecular networks that govern protein synthesis and degradation play important roles in controlling muscle mass under diverse catabolic states. MicroRNAs (miRNAs) were previously found to be regulators of protein synthesis and degradation, and their expressions in skeletal muscle were altered in muscle wasting conditions. However, functional roles of miRNAs in muscle atrophy are poorly understood. In this study, we generated tamoxifen-inducible Dicer knockout (iDicer KO) mice and subjected them to 2 weeks of single hindlimb denervation. The expression of Dicer mRNA was significantly reduced in muscle of the iDicer KO mice compared to that of WT mice. The loss of Dicer moderately reduced levels of muscle-enriched miRNAs, miR-1, miR-133a and miR-206 in both innervated and denervated muscles of the iDicer KO mice. We also found that the extent of denervation-induced muscle atrophy as well as changes of signaling molecules related to protein synthesis/degradation pathways in the iDicer KO mice were comparable to these in WT mice. Taken together, Dicer knockout in adult skeletal muscle did not affect denervation-induced muscle atrophy.


Assuntos
MicroRNAs/metabolismo , Músculo Esquelético , Atrofia Muscular/metabolismo , Animais , Modelos Animais de Doenças , Camundongos , Camundongos Knockout , Músculo Esquelético/metabolismo , Músculo Esquelético/patologia
14.
Liver Int ; 41(4): 764-776, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-33548061

RESUMO

BACKGROUND: The heterogeneous immune landscapes of intrahepatic cholangiocarcinoma (ICC) remain largely unknown. Here we aimed to investigate the implications of tissue-resident memory (TRM)-related features of tumour-infiltrating CD8+ T cells (CD8+ TILs) from ICC patients. METHODS: From ICC patients, we obtained blood samples and ICC surgical specimens (n = 33). We performed multicolour flow cytometry, multiplexed immunohistochemistry and RNA sequencing. RESULTS: When compared to peripheral CD8+ T cells, the CD8+ TILs included significantly higher proportions of the CD69+ CD103- and CD69+ CD103+ TRM-like subsets (P < .001 for both). Relative to CD69- and CD69+ CD103- cells, the CD69+ CD103+ CD8+ TILs harboured higher levels of T-cell markers representing tumour specificity (ie CD39), proliferation (ie Ki-67) and T-cell activation (ie HLA-DR and CD38) (all P < .001). Moreover, compared to the stroma, the tumour margin and core density each had a significantly higher density of CD103+ CD8+ TILs (P < .001 for both). ICCs with high proportions of CD69+ CD103+ cells displayed higher levels of parameters associated with response to immune checkpoint inhibitors (ICIs)-including number of CD8+ TIL infiltrates (P = .019), PD-L1 expression in the tumour (P = .046) and expression of the T cell-inflamed gene signature (P < .001). ICCs with lower proportions of CD69+ CD103+ CD8+ TILs exhibited significant enrichment of genes related to the Wnt/ß-catenin (P < .001) and TGF-ß pathways (P = .002). CONCLUSION: CD69+ CD103+ TRM-like CD8+ TILs represent prominent tumour-specific immune responses and hold promise as a potential therapeutic target in ICC patients. Differential TRM-related features of ICCs may help develop future immunotherapeutic strategies such as maximizing TRM responses or inhibiting pathways contributing to immune evasion.


Assuntos
Linfócitos T CD8-Positivos , Colangiocarcinoma , Humanos , Memória Imunológica , Imunoterapia , Ativação Linfocitária , Linfócitos do Interstício Tumoral
15.
J Physiol Sci ; 71(1): 4, 2021 Jan 19.
Artigo em Inglês | MEDLINE | ID: mdl-33468054

RESUMO

Discovery of blood biomarkers to evaluate exercise-induced muscle damage have attracted many researchers and coaches. This study aimed to determine changes in circulating myomesin 3 fragments as a novel biomarker for exercise-induced muscle damage. Nine healthy males performed 10 sets of 40 repetitions of one-leg calf-raise exercise by the load corresponding to the half of their body weight. Muscle symptoms were evaluated by a visual analog scale (VAS). Blood samples were collected before and 2, 4, 24, 48, 72, and 96 h post-exercise. Plasma myomesin 3 fragments levels were significantly increased at 96 h after the eccentric exercise. The myomesin 3 fragments levels were correlated with other biomarkers of muscle damage and the muscle symptoms. These results suggest that the circulating myomesin 3 fragments levels are potential biomarkers reflecting eccentric exercise-induced muscle damage.


Assuntos
Conectina/metabolismo , Exercício Físico/fisiologia , Adulto , Conectina/química , Conectina/genética , Regulação da Expressão Gênica/fisiologia , Humanos , Masculino , Adulto Jovem
16.
Cancer Res Treat ; 53(1): 162-171, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-32878426

RESUMO

PURPOSE: The clinical implications of tumor-infiltrating T cell subsets and their spatial distribution in biliary tract cancer (BTC) patients treated with gemcitabine plus cisplatin were investigated. MATERIALS AND METHODS: A total of 52 BTC patients treated with palliative gemcitabine plus cisplatin were included. Multiplexed immunohistochemistry was performed on tumor tissues, and immune infiltrates were separately analyzed for the stroma, tumor margin, and tumor core. RESULTS: The density of CD8+ T cells, FoxP3- CD4+ helper T cells, and FoxP3+ CD4+ regulatory T cells was significantly higher in the tumor margin than in the stroma and tumor core. The density of LAG3- or TIM3-expressing CD8+ T cell and FoxP3- CD4+ helper T cell infiltrates was also higher in the tumor margin. In extrahepatic cholangiocarcinoma, there was a higher density of T cell subsets in the tumor core and regulatory T cells in all regions. A high density of FoxP3- CD4+ helper T cells in the tumor margin showed a trend toward better progression-free survival (PFS) (p=0.092) and significantly better overall survival (OS) (p=0.012). In multivariate analyses, a high density of FoxP3- CD4+ helper T cells in the tumor margin was independently associated with favorable PFS and OS. CONCLUSION: The tumor margin is the major site for the active infiltration of T cell subsets with higher levels of LAG3 and TIM3 expression in BTC. The density of tumor margin-infiltrating FoxP3- CD4+ helper T cells may be associated with clinical outcomes in BTC patients treated with gemcitabine plus cisplatin.


Assuntos
Neoplasias do Sistema Biliar/genética , Linfócitos T CD4-Positivos/metabolismo , Fatores de Transcrição Forkhead/metabolismo , Linfócitos do Interstício Tumoral/imunologia , Neoplasias do Sistema Biliar/patologia , Feminino , Humanos , Masculino , Prognóstico
17.
J Pathol Transl Med ; 54(5): 387-395, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32683855

RESUMO

BACKGROUND: Although lymph node metastasis is a poor prognostic factor in patients with pancreatic ductal adenocarcinoma (PDAC), our understanding of lymph node size in association with PDAC is limited. Increased nodal size in preoperative imaging has been used to detect node metastasis. We evaluated whether lymph node size can be used as a surrogate preoperative marker of lymph node metastasis. METHODS: We assessed nodal size and compared it to the nodal metastatic status of 200 patients with surgically resected PDAC. The size of all lymph nodes and metastatic nodal foci were measured along the long and short axis, and the relationships between nodal size and metastatic status were compared at six cutoff points. RESULTS: A total of 4,525 lymph nodes were examined, 9.1% of which were metastatic. The mean size of the metastatic nodes (long axis, 6.9±5.0 mm; short axis, 4.3±3.1 mm) was significantly larger than that of the non-metastatic nodes (long axis, 5.0±4.0 mm; short axis, 3.0±2.0 mm; all p<.001). Using a 10 mm cutoff, the sensitivity, specificity, positive predictive value, overall accuracy, and area under curve was 24.8%, 88.0%, 17.1%, 82.3%, and 0.60 for the long axis and 7.0%, 99.0%, 40.3%, 90.6%, and 0.61 for the short axis, respectively. CONCLUSIONS: The metastatic nodes are larger than the non-metastatic nodes in PDAC patients. However, the difference in nodal size was too small to be identified with preoperative imaging. The performance of preoperative radiologic imaging to predict lymph nodal metastasis was not good. Therefore, nodal size cannot be used a surrogate preoperative marker of lymph node metastasis.

18.
Neuroimage Clin ; 23: 101871, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31174103

RESUMO

Numerous brain disorders are associated with ventriculomegaly, including both neuro-degenerative diseases and cerebrospinal fluid disorders. Detailed evaluation of the ventricular system is important for these conditions to help understand the pathogenesis of ventricular enlargement and elucidate novel patterns of ventriculomegaly that can be associated with different diseases. One such disease is normal pressure hydrocephalus (NPH), a chronic form of hydrocephalus in older adults that causes dementia. Automatic parcellation of the ventricular system into its sub-compartments in patients with ventriculomegaly is quite challenging due to the large variation of the ventricle shape and size. Conventional brain labeling methods are time-consuming and often fail to identify the boundaries of the enlarged ventricles. We propose a modified 3D U-Net method to perform accurate ventricular parcellation, even with grossly enlarged ventricles, from magnetic resonance images (MRIs). We validated our method on a data set of healthy controls as well as a cohort of 95 patients with NPH with mild to severe ventriculomegaly and compared with several state-of-the-art segmentation methods. On the healthy data set, the proposed network achieved mean Dice similarity coefficient (DSC) of 0.895 ±â€¯0.03 for the ventricular system. On the NPH data set, we achieved mean DSC of 0.973 ±â€¯0.02, which is significantly (p < 0.005) higher than four state-of-the-art segmentation methods we compared with. Furthermore, the typical processing time on CPU-base implementation of the proposed method is 2 min, which is much lower than the several hours required by the other methods. Results indicate that our method provides: 1) highly robust parcellation of the ventricular system that is comparable in accuracy to state-of-the-art methods on healthy controls; 2) greater robustness and significantly more accurate results on cases of ventricular enlargement; and 3) a tool that enables computation of novel imaging biomarkers for dilated ventricular spaces that characterize the ventricular system.


Assuntos
Aprendizado Profundo , Hidrocefalia de Pressão Normal/diagnóstico por imagem , Interpretação de Imagem Assistida por Computador/métodos , Imageamento Tridimensional/métodos , Neuroimagem/métodos , Adulto , Idoso , Idoso de 80 Anos ou mais , Ventrículos Cerebrais/diagnóstico por imagem , Ventrículos Cerebrais/patologia , Feminino , Humanos , Hidrocefalia de Pressão Normal/patologia , Masculino , Pessoa de Meia-Idade
20.
Nat Neurosci ; 20(3): 476-483, 2017 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-28166220

RESUMO

Neuronal activity-induced gene expression modulates the function and plasticity of the nervous system. It is unknown whether and to what extent neuronal activity may trigger changes in chromatin accessibility, a major mode of epigenetic regulation of gene expression. Here we compared chromatin accessibility landscapes of adult mouse dentate granule neurons in vivo before and after synchronous neuronal activation using an assay for transposase-accessible chromatin using sequencing (ATAC-seq). We found genome-wide changes 1 h after activation, with enrichment of gained-open sites at active enhancer regions and at binding sites for AP1-complex components, including c-Fos. Some changes remained stable for at least 24 h. Functional analysis further implicates a critical role of c-Fos in initiating, but not maintaining, neuronal activity-induced chromatin opening. Our results reveal dynamic changes of chromatin accessibility in adult mammalian brains and suggest an epigenetic mechanism by which transient neuronal activation leads to dynamic changes in gene expression via modifying chromatin accessibility.


Assuntos
Cromatina/metabolismo , Giro Denteado/metabolismo , Neurônios/fisiologia , Animais , Eletrochoque , Epigênese Genética , Regulação da Expressão Gênica/genética , Masculino , Camundongos , Neurônios/metabolismo , Fatores de Tempo , Fator de Transcrição AP-1/metabolismo
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