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1.
Nature ; 578(7794): 251-255, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-32015545

RESUMO

Solid-state lithium metal batteries require accommodation of electrochemically generated mechanical stress inside the lithium: this stress can be1,2 up to 1 gigapascal for an overpotential of 135 millivolts. Maintaining the mechanical and electrochemical stability of the solid structure despite physical contact with moving corrosive lithium metal is a demanding requirement. Using in situ transmission electron microscopy, we investigated the deposition and stripping of metallic lithium or sodium held within a large number of parallel hollow tubules made of a mixed ionic-electronic conductor (MIEC). Here we show that these alkali metals-as single crystals-can grow out of and retract inside the tubules via mainly diffusional Coble creep along the MIEC/metal phase boundary. Unlike solid electrolytes, many MIECs are electrochemically stable in contact with lithium (that is, there is a direct tie-line to metallic lithium on the equilibrium phase diagram), so this Coble creep mechanism can effectively relieve stress, maintain electronic and ionic contacts, eliminate solid-electrolyte interphase debris, and allow the reversible deposition/stripping of lithium across a distance of 10 micrometres for 100 cycles. A centimetre-wide full cell-consisting of approximately 1010 MIEC cylinders/solid electrolyte/LiFePO4-shows a high capacity of about 164 milliampere hours per gram of LiFePO4, and almost no degradation for over 50 cycles, starting with a 1× excess of Li. Modelling shows that the design is insensitive to MIEC material choice with channels about 100 nanometres wide and 10-100 micrometres deep. The behaviour of lithium metal within the MIEC channels suggests that the chemical and mechanical stability issues with the metal-electrolyte interface in solid-state lithium metal batteries can be overcome using this architecture.

2.
Hepatology ; 2024 Apr 23.
Artigo em Inglês | MEDLINE | ID: mdl-38652643

RESUMO

BACKGROUND AND AIMS: Noninvasive tools assessing steatosis, such as ultrasonography-based 2D-attenuation imaging (ATI), are needed to tackle the worldwide burden of steatotic liver disease. This one-stage individual patient data (IPD) meta-analysis aimed to create an ATI-based steatosis grading system. APPROACH AND RESULTS: A systematic review (EMBASE + MEDLINE, 2018-2022) identified studies, including patients with histologically or magnetic resonance imaging proton-density fat fraction (MRI-PDFF)-verified ATI for grading steatosis (S0 to S3). One-stage IPD meta-analyses were conducted using generalized mixed models with a random study-specific intercept. Created ATI-based steatosis grading system (aS0 to aS3) was externally validated on a prospective cohort of patients with type 2 diabetes and metabolic dysfunction-associated steatotic liver disease (n=174, histologically and MRI-PDFF-verified steatosis). Eleven enrolled studies included 1374 patients, classified into S0, S1, S2, and S3 in 45.4%, 35.0%, 9.3%, and 10.3% of the cases. ATI was correlated with histological steatosis ( r = 0.60; 95% CI: 0.52, 0.67; p < 0.001) and MRI-PDFF ( r = 0.70; 95% CI: 0.66, 0.73; p < 0.001) but not with liver stiffness ( r = 0.03; 95% CI: -0.04, 0.11, p = 0.343). Steatosis grade was an independent factor associated with ATI (coefficient: 0.24; 95% CI: [0.22, 0.26]; p < 0.001). ATI marginal means within S0, S1, S2, and S3 subpopulations were 0.59 (95% CI: [0.58, 0.61]), 0.69 (95% CI [0.67, 0.71]), 0.78 (95% CI: [0.76, 0.81]), and 0.85 (95% CI: [0.83, 0.88]) dB/cm/MHz; all contrasts between grades were significant ( p < 0.0001). Three ATI thresholds were calibrated to create a new ATI-based steatosis grading system (aS0 to aS3, cutoffs: 0.66, 0.73, and 0.81 dB/cm/MHz). Its external validation showed Obuchowski measures of 0.84 ± 0.02 and 0.82 ± 0.02 with histologically based and MRI-PDFF-based references. CONCLUSIONS: ATI is a reliable, noninvasive marker of steatosis. This validated ATI-based steatosis grading system could be valuable in assessing patients with metabolic dysfunction-associated steatotic liver disease.

3.
Nano Lett ; 2024 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-38619226

RESUMO

Halide perovskite-based resistive switching memory (memristor) has potential in an artificial synapse. However, an abrupt switch behavior observed for a formamidinium lead triiodide (FAPbI3)-based memristor is undesirable for an artificial synapse. Here, we report on the δ-FAPbI3/atomic-layer-deposited (ALD)-SnO2 bilayer memristor for gradual analogue resistive switching. In comparison to a single-layer δ-FAPbI3 memristor, the heterojunction δ-FAPbI3/ALD-SnO2 bilayer effectively reduces the current level in the high-resistance state. The analog resistive switching characteristics of δ-FAPbI3/ALD-SnO2 demonstrate exceptional linearity and potentiation/depression performance, resembling an artificial synapse for neuromorphic computing. The nonlinearity of long-term potentiation and long-term depression is notably decreased from 12.26 to 0.60 and from -8.79 to -3.47, respectively. Moreover, the δ-FAPbI3/ALD-SnO2 bilayer achieves a recognition rate of ≤94.04% based on the modified National Institute of Standards and Technology database (MNIST), establishing its potential in an efficient artificial synapse.

4.
Radiology ; 312(3): e231525, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-39254451

RESUMO

Background There are insufficient data comparing resorbable microspheres (RMs) with permanent trisacryl gelatin microspheres (TAGMs) for uterine artery embolization (UAE). Purpose To compare therapeutic efficacy and clinical outcomes in participants with symptomatic fibroids after UAE with RMs or TAGMs. Materials and Methods This randomized controlled trial included participants undergoing UAE for symptomatic fibroids at a single institution (from May 2021 to May 2023). Participants were randomized one-to-one to undergo UAE with either RMs or TAGMs. Numeric rating scale pain scores and cumulative fentanyl consumption were assessed for 24 hours after undergoing UAE. Anti-Mullerian hormone was measured to assess effects of UAE on ovarian function. MRI was performed before and 3 months after UAE to evaluate fibroid necrosis and uterine artery recanalization. Repeated variables such as pain were analyzed using Mann-Whitney U test with post hoc Bonferroni correction. Results Sixty female participants (mean age, 45.7 years ± 3.6 [SD]) completed the study, with 30 in each group. No evidence of a difference in pain scores was observed between groups (P > .99). Moreover, there was no evidence of a difference in the total fentanyl consumption at 24 hours after UAE between groups (median: RMs, 423 [IQR, 330-530] vs TAGMs, 562 [IQR, 437-780]; P = .15). Serum anti-Mullerian hormone 3 months after UAE showed no evidence of a difference between groups (RMs vs TAGMs, 0.71 ng/mL ± 0.73 vs 0.49 ng/mL ± 0.45, respectively; P = .09). No evidence of a difference in the rate of complete necrosis of the dominant fibroid was observed between groups (97% [29 of 30] for both groups; P > .99). The rate of uterine artery recanalization was higher in RM versus TAGM groups (70% [21 of 30] vs 17% [five of 30], respectively; P < .001). Conclusion UAE with RMs, compared with UAE with TAGMs, showed no evidence of a difference in terms of therapeutic effectiveness or postprocedural pain scores in participants with symptomatic fibroids. Clinical trial registration no. NCT05086770 © RSNA, 2024 See also the editorial by Spies in this issue.


Assuntos
Resinas Acrílicas , Gelatina , Leiomioma , Embolização da Artéria Uterina , Humanos , Feminino , Embolização da Artéria Uterina/métodos , Gelatina/uso terapêutico , Pessoa de Meia-Idade , Leiomioma/terapia , Leiomioma/diagnóstico por imagem , Resinas Acrílicas/uso terapêutico , Adulto , Microesferas , Neoplasias Uterinas/terapia , Neoplasias Uterinas/diagnóstico por imagem , Resultado do Tratamento , Medição da Dor
5.
Radiology ; 310(2): e231501, 2024 02.
Artigo em Inglês | MEDLINE | ID: mdl-38376399

RESUMO

Background The independent contribution of each Liver Imaging Reporting and Data System (LI-RADS) CT or MRI ancillary feature (AF) has not been established. Purpose To evaluate the association of LI-RADS AFs with hepatocellular carcinoma (HCC) and malignancy while adjusting for LI-RADS major features through an individual participant data (IPD) meta-analysis. Materials and Methods Medline, Embase, Cochrane Central Register of Controlled Trials, and Scopus were searched from January 2014 to January 2022 for studies evaluating the diagnostic accuracy of CT and MRI for HCC using LI-RADS version 2014, 2017, or 2018. Using a one-step approach, IPD across studies were pooled. Adjusted odds ratios (ORs) and 95% CIs were derived from multivariable logistic regression models of each AF combined with major features except threshold growth (excluded because of infrequent reporting). Liver observation clustering was addressed at the study and participant levels through random intercepts. Risk of bias was assessed using a composite reference standard and Quality Assessment of Diagnostic Accuracy Studies 2. Results Twenty studies comprising 3091 observations (2456 adult participants; mean age, 59 years ± 11 [SD]; 1849 [75.3%] men) were included. In total, 89% (eight of nine) of AFs favoring malignancy were associated with malignancy and/or HCC, 80% (four of five) of AFs favoring HCC were associated with HCC, and 57% (four of seven) of AFs favoring benignity were negatively associated with HCC and/or malignancy. Nonenhancing capsule (OR = 3.50 [95% CI: 1.53, 8.01]) had the strongest association with HCC. Diffusion restriction (OR = 14.45 [95% CI: 9.82, 21.27]) and mild-moderate T2 hyperintensity (OR = 10.18 [95% CI: 7.17, 14.44]) had the strongest association with malignancy. The strongest negative associations with HCC were parallels blood pool enhancement (OR = 0.07 [95% CI: 0.01, 0.49]) and marked T2 hyperintensity (OR = 0.18 [95% CI: 0.07, 0.45]). Seventeen studies (85%) had a high risk of bias. Conclusion Most LI-RADS AFs were independently associated with HCC, malignancy, or benignity as intended when adjusting for major features. © RSNA, 2024 Supplemental material is available for this article. See also the editorial by Crivellaro in this issue.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Imageamento por Ressonância Magnética , Tomografia Computadorizada por Raios X , Humanos , Carcinoma Hepatocelular/diagnóstico por imagem , Neoplasias Hepáticas/diagnóstico por imagem , Imageamento por Ressonância Magnética/métodos , Tomografia Computadorizada por Raios X/métodos , Fígado/diagnóstico por imagem , Sistemas de Informação em Radiologia , Pessoa de Meia-Idade , Masculino
6.
Liver Transpl ; 2024 Aug 26.
Artigo em Inglês | MEDLINE | ID: mdl-39177538

RESUMO

Hepatic steatosis (HS) criteria for living donor liver transplantation (LDLT) donor eligibility should be based on large droplet fat as per Banff consensus recommendations. We aimed to establish MRI PDFF cut-offs for HS assessment in potential LDLT donors. This retrospective study included consecutive potential LDLT donors who underwent MRI and liver biopsy between 2013 and 2023 at two tertiary institutions, each as development (n=3062; 2015 men; median [interquartile range] age of 32 [25-38] years) and external validation (n=472; 287 men; 35 [26-44] years) datasets. PDFF was measured using dedicated MRI sequences. Histologic HS defined as large droplet fat fraction was used as the reference standard. Dual PDFF cut-offs aimed at 95% sensitivity or 95% specificity, for diagnosing histologic HS of ≥10%, ≥20%, ≥30%, and ≥40%, were determined in the development dataset using ten-fold cross validation. The cut-offs were then validated in the external validation dataset. Equation for estimating histologic HS from PDFF was also derived using linear regression. The PDFF cut-offs for histologic HS of ≥10%, ≥20%, ≥30%, and ≥40%, targeting 95% sensitivity, were 3.7%, 5.5%, 8.0%, and 10.0%, respectively. External validation demonstrated high sensitivities ≥ 97.9% with specificities ranging from 60.9% to 95.1%. The PDFF cut-offs targeting 95% specificity were 6.3%, 8.0%, 9.1%, and 10.1%, respectively. External validation rendered high specificities ranging from 88.5% to 95.3% with sensitivities ranging from 76.6% to 100%. For diagnosing histologic HS ≥30%, which is the most prevalently used threshold for LDLT donor eligibility assessment, the PDFF cut-offs achieved sensitivities and specificities of both over 90%. The equation of (Histologic HS=-2.95 + 1.93 * PDFF) was derived.

7.
Eur Radiol ; 34(3): 1578-1586, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-37646813

RESUMO

OBJECTIVES: To compare the safety and efficacy of RFA for single HCCs ≤ 3 cm in subcapsular versus nonsubcapsular locations using a propensity score matched analysis. MATERIALS AND METHODS: This retrospective study included patients with solitary HCCs ≤ 3 cm in size who underwent percutaneous RFA from 2005 to 2015 as initial treatment at two large-volume liver centers. Patients were divided into two groups, consisting of those with subcapsular and nonsubcapsular tumor locations. Complications, local tumor progression (LTP), and overall survival (OS) were compared in these two groups before and after propensity score matching (PSM). RESULTS: The study population consisted of 964 patients (712 men [74%]) of mean age 58.3 years. Of these 964 patients, 561 (58%) had nonsubcapsular and 403 (42%) had subcapsular HCCs. PSM generated 402 pairs of patients. Major complication rate was low, but significantly higher in the subcapscular group (p = 0.047). Rates of technical effectiveness in these two groups were 99% and 98%, respectively (p = 0.315). However, during follow-up, cumulative 1-, 3-, 5-, and 10-year LTP and OS rates did significantly differ in both entire and PSM cohorts, resulting in the latter 8%, 15%, 20%, and 26% in the nonsubcapsular group vs. 13%, 24%, 30%, and 31% in the subcapsular group (p = 0.015), and 99%, 91%, 80%, and 59% vs. 98%, 85%, 73%, and 50% in the two groups (p = 0.004), respectively. CONCLUSION: Rates of major complications, LTP, and OS differed significantly following first-line RFA treatment of single HCCs ≤ 3 cm in favor of the nonsubcapsular locations. CLINICAL RELEVANCE STATEMENT: This large-scale study provides evidence that radiofrequency ablation for small (≤ 3 cm) hepatocellular carcinomas is safer and more effective in nonsubcapsular location than in subcapsular location. KEY POINTS: • There exist conflicting outcomes on the effectiveness of RFA for early HCC depending on tumor location. • Rate of local tumor progression was significantly higher in the subcapsular hepatocellular carcinomas. • Overall survival rate was significantly poorer in the subcapsular hepatocellular carcinomas.


Assuntos
Carcinoma Hepatocelular , Ablação por Cateter , Neoplasias Hepáticas , Ablação por Radiofrequência , Masculino , Humanos , Pessoa de Meia-Idade , Carcinoma Hepatocelular/patologia , Neoplasias Hepáticas/diagnóstico por imagem , Neoplasias Hepáticas/cirurgia , Estudos Retrospectivos , Resultado do Tratamento , Ablação por Cateter/métodos
8.
Eur Radiol ; 34(9): 5517-5528, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-38329504

RESUMO

OBJECTIVES: To compare the efficacy of transarterial chemoembolization (TACE) and radiofrequency ablation (RFA) for patients with single small (≤ 3 cm) hepatocellular carcinoma (HCC) and preserved liver function (Child-Pugh class A). MATERIALS AND METHODS: The clinical features of treatment-naïve patients who underwent TACE and RFA as first-line treatment were balanced through propensity score matching (PSM). The primary endpoint was overall survival (OS), and the secondary endpoints were local tumor recurrence (LTR) and recurrence-free survival (RFS). RESULTS: The analysis included 440 patients who received TACE, and 430 patients who received RFA. After PSM adjustment (323 pairs), the 5- and 10-year OS rates were 81% and 61%, respectively, in patients who underwent RFA, and 77% and 51%, respectively, for patients who underwent TACE (p = 0.021). Subgroup analyses showed that OS, LTR, and RFS were homogeneously better in the RFA group. CONCLUSION: RFA was associated with better survival outcomes than TACE in patients with single small HCC and preserved liver function. CLINICAL RELEVANCE STATEMENT: This large-scale comparative study provides evidence that radiofrequency ablation has a better overall survival rate than chemoembolization for small (≤ 3 cm) hepatocellular carcinomas. KEY POINTS: • The relative effectiveness of transarterial chemoembolization (TACE) and radiofrequency ablation (RFA) for early HCC is unclear. • Overall survival rate was significantly higher in the RFA group. • The effects of RFA on overall survival, local tumor recurrence, and recurrence-free survival were homogeneously better in all subgroups.


Assuntos
Carcinoma Hepatocelular , Quimioembolização Terapêutica , Neoplasias Hepáticas , Pontuação de Propensão , Ablação por Radiofrequência , Humanos , Carcinoma Hepatocelular/terapia , Carcinoma Hepatocelular/cirurgia , Neoplasias Hepáticas/terapia , Neoplasias Hepáticas/cirurgia , Quimioembolização Terapêutica/métodos , Masculino , Feminino , Pessoa de Meia-Idade , Ablação por Radiofrequência/métodos , Resultado do Tratamento , Idoso , Estudos Retrospectivos , Recidiva Local de Neoplasia , Taxa de Sobrevida
9.
Acta Radiol ; 65(3): 302-306, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-36600596

RESUMO

BACKGROUND: There have been conflicting outcomes regarding the use of lidocaine to reduce pain after uterine artery embolization (UAE). PURPOSE: To investigate the efficacy of intra-arterial lidocaine injection for pain and inflammatory response control within 24 h of UAE for symptomatic uterine fibroids. MATERIAL AND METHODS: Of 1530 patients who underwent UAE for uterine fibroids in 2007-2021, 5 mL of 1% lidocaine was injected into each uterine artery immediately after UAE in 23 patients. A disease-matched control group (n = 23) who did not receive intra-arterial lidocaine was generated from the same registry. The pain score, white blood cell (WBC) count, C-reactive protein (CRP), neutrophil/lymphocyte ratio (NLR), and fentanyl consumption were compared before and after UAE. Complete infarction of the dominant fibroid was assessed using magnetic resonance imaging. RESULTS: Significantly lower WBC count, CRP level, and NLR were noted 24 h after UAE in the lidocaine group. No statistically significant difference was noted in the pain score between groups at 0-24 h. The cumulative fentanyl dose administered during the first 24 h after UAE was not significantly different. After embolization, fibroid-related symptoms resolved in all patients. No significant difference was observed in the rate of complete infarction of the dominant fibroid. CONCLUSION: Lidocaine administration immediately after UAE resulted in a significant reduction in the inflammatory response. However, such a difference in the inflammatory reaction did not contribute to significant reductions in pain scores or fentanyl consumption.


Assuntos
Leiomioma , Embolização da Artéria Uterina , Neoplasias Uterinas , Feminino , Humanos , Lidocaína/uso terapêutico , Embolização da Artéria Uterina/métodos , Neoplasias Uterinas/terapia , Leiomioma/terapia , Dor , Fentanila , Infarto , Resultado do Tratamento
10.
Proc Natl Acad Sci U S A ; 118(1)2021 01 05.
Artigo em Inglês | MEDLINE | ID: mdl-33443222

RESUMO

Effective therapies for alcohol-associated liver disease (ALD) are limited; therefore, the discovery of new therapeutic agents is greatly warranted. Toll-like receptor 7 (TLR7) is a pattern recognition receptor for single-stranded RNA, and its activation prevents liver fibrosis. We examined liver and intestinal damage in Tlr7-/- mice to determine the role of TLR7 in ALD pathogenesis. In an alcoholic hepatitis (AH) mouse model, hepatic steatosis, injury, and inflammation were induced by chronic binge ethanol feeding in mice, and Tlr7 deficiency exacerbated these effects. Because these results demonstrated that endogenous TLR7 signaling activation is protective in the AH mouse model, we hypothesized that TLR7 activation may be an effective therapeutic strategy for ALD. Therefore, we investigated the therapeutic effect of TLR7 agonistic agent, 1Z1, in the AH mouse model. Oral administration of 1Z1 was well tolerated and prevented intestinal barrier disruption and bacterial translocation, which thus suppressed ethanol-induced hepatic injury, steatosis, and inflammation. Furthermore, 1Z1 treatment up-regulated the expression of antimicrobial peptides, Reg3b and Reg3g, in the intestinal epithelium, which modulated the microbiome by decreasing and increasing the amount of Bacteroides and Lactobacillus, respectively. Additionally, 1Z1 up-regulated intestinal interleukin (IL)-22 expression. IL-22 deficiency abolished the protective effects of 1Z1 in ethanol-induced liver and intestinal damage, suggesting intestinal IL-22 as a crucial mediator for 1Z1-mediated protection in the AH mouse model. Collectively, our results indicate that TLR7 signaling exerts protective effects in the AH mouse model and that a TLR7 ligand, 1Z1, holds therapeutic potential for the treatment of AH.


Assuntos
Etanol/toxicidade , Interleucinas/metabolismo , Mucosa Intestinal/metabolismo , Hepatopatias Alcoólicas/tratamento farmacológico , Glicoproteínas de Membrana/metabolismo , Transdução de Sinais/efeitos dos fármacos , Receptor 7 Toll-Like/metabolismo , Administração Oral , Animais , Bacteroides/efeitos dos fármacos , Modelos Animais de Doenças , Fígado Gorduroso/complicações , Fígado Gorduroso/genética , Fígado Gorduroso/metabolismo , Feminino , Microbioma Gastrointestinal/efeitos dos fármacos , Inflamação/complicações , Inflamação/genética , Inflamação/metabolismo , Mucosa Intestinal/efeitos dos fármacos , Lactobacillus/efeitos dos fármacos , Ligantes , Hepatopatias Alcoólicas/genética , Hepatopatias Alcoólicas/metabolismo , Hepatopatias Alcoólicas/fisiopatologia , Glicoproteínas de Membrana/agonistas , Glicoproteínas de Membrana/genética , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , MicroRNAs , Proteínas Associadas a Pancreatite/genética , Proteínas Associadas a Pancreatite/metabolismo , Polietilenoglicóis/química , Polietilenoglicóis/farmacologia , Proteínas Citotóxicas Formadoras de Poros/genética , Proteínas Citotóxicas Formadoras de Poros/metabolismo , Transdução de Sinais/genética , Junções Íntimas/efeitos dos fármacos , Junções Íntimas/patologia , Receptor 7 Toll-Like/agonistas , Receptor 7 Toll-Like/genética , Interleucina 22
11.
Ecotoxicol Environ Saf ; 276: 116294, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38574646

RESUMO

Particulate matter (PM), released into the air by a variety of natural and human activities, is a key indicator of air pollution. Although PM is known as the extensive health hazard to affect a variety of illness, few studies have specifically investigated the effects of PM10 exposure on schizophrenic development. In the present study, we aimed to investigate the impact of PM10 on MK-801, N-methyl-D-aspartate (NMDA) receptor antagonist, induced schizophrenia-like behaviors in C57BL/6 mouse. Preadolescent mice were exposed PM10 to 3.2 mg/m3 concentration for 4 h/day for 2 weeks through a compartmentalized whole-body inhalation chamber. After PM10 exposure, we conducted behavioral tests during adolescence and adulthood to investigate longitudinal development of schizophrenia. We found that PM10 exacerbated schizophrenia-like behavior, such as psychomotor agitation, social interaction deficits and cognitive deficits at adulthood in MK-801-induced schizophrenia animal model. Furthermore, the reduced expression levels of brain-derived neurotrophic factor (BDNF) and the phosphorylation of BDNF related signaling molecules, extracellular signal-regulated kinase (ERK) and cAMP response element-binding protein (CREB), were exacerbated by PM10 exposure in the adult hippocampus of MK-801-treated mice. Thus, our present study demonstrates that exposure to PM10 in preadolescence exacerbates the cognitive impairment in animal model of schizophrenia, which are considered to be facilitated by the decreased level of BDNF through reduced ERK-CREB expression.


Assuntos
Fator Neurotrófico Derivado do Encéfalo , Proteína de Ligação ao Elemento de Resposta ao AMP Cíclico , Maleato de Dizocilpina , Camundongos Endogâmicos C57BL , Material Particulado , Esquizofrenia , Transdução de Sinais , Animais , Fator Neurotrófico Derivado do Encéfalo/metabolismo , Esquizofrenia/induzido quimicamente , Material Particulado/toxicidade , Maleato de Dizocilpina/farmacologia , Camundongos , Masculino , Transdução de Sinais/efeitos dos fármacos , Proteína de Ligação ao Elemento de Resposta ao AMP Cíclico/metabolismo , Poluentes Atmosféricos/toxicidade , Comportamento Animal/efeitos dos fármacos , MAP Quinases Reguladas por Sinal Extracelular/metabolismo , Modelos Animais de Doenças , Hipocampo/efeitos dos fármacos , Hipocampo/metabolismo
12.
Sensors (Basel) ; 24(16)2024 Aug 08.
Artigo em Inglês | MEDLINE | ID: mdl-39204828

RESUMO

Wireless local area networks (WLANs) have recently evolved into technologies featuring extremely high throughput and ultra-high reliability. As WLANs are predominantly utilized in Internet of Things (IoT) and Wi-Fi-enabled sensor applications powered by coin cell batteries, these high-efficiency, high-performance technologies often cause significant battery depletion. The introduction of the trigger frame-based uplink transmission method, designed to enhance network throughput, lacks adequate security measures, enabling attackers to manipulate trigger frames. Devices receiving such frames must respond immediately; however, if a device receives a fake trigger frame, it fails to enter sleep mode, continuously sending response signals and thereby increasing power consumption. This problem is specifically acute in next-generation devices that support multi-link operation (MLO), capable of simultaneous transmission and reception across multiple links, rendering them more susceptible to battery draining attacks than conventional single-link devices. To address this, this paper introduces a Secure Triggering Frame-Based Dynamic Power Saving Mechanism (STF-DPSM) specifically designed for multi-link environments. Experimental results indicate that even in a multi-link environment with only two links, the STF-DPSM improves energy efficiency by an average of approximately 55.69% over conventional methods and reduces delay times by an average of approximately 44.7% compared with methods that consistently utilize encryption/decryption and integrity checks.

13.
Int J Mol Sci ; 25(17)2024 Sep 05.
Artigo em Inglês | MEDLINE | ID: mdl-39273565

RESUMO

Exosomes are nanovesicles 30-150 nm in diameter released extracellularly. Those isolated from human body fluids reflect the characteristics of their cells or tissues of origin. Exosomes carry extensive biological information from their parent cells and have significant potential as biomarkers for disease diagnosis and prognosis. However, there are limited studies utilizing exosomes in postmortem diagnostics. In this study, we extended our initial research which identified the presence and established detection methodologies for exosomes in postmortem fluids. We analyzed exosomal miRNA extracted from plasma and pericardial fluid samples of a control group (n = 13) and subjects with acute myocardial infarction (AMI; n = 24). We employed next-generation sequencing (NGS) to investigate whether this miRNA could serve as biomarkers for coronary atherosclerosis leading to acute myocardial infarction. Our analysis revealed 29 miRNAs that were differentially expressed in the AMI group compared to the control group. Among these, five miRNAs exhibited more than a twofold increase in expression across all samples from the AMI group. Specifically, miR-486-5p levels were significantly elevated in patients with high-grade (type VI or above) atherosclerotic plaques, as per the American Heart Association criteria, highlighting its potential as a predictive biomarker for coronary atherosclerosis progression. Our results indicate that postmortem-derived exosomal microRNAs can serve as potential biomarkers for various human diseases, including cardiovascular disorders. This finding has profound implications for forensic diagnostics, a field critically lacking diagnostic markers.


Assuntos
Biomarcadores , Exossomos , MicroRNAs , Humanos , Exossomos/metabolismo , Exossomos/genética , MicroRNAs/genética , MicroRNAs/metabolismo , Masculino , Feminino , Pessoa de Meia-Idade , Idoso , Infarto do Miocárdio/diagnóstico , Infarto do Miocárdio/metabolismo , Infarto do Miocárdio/genética , Autopsia , Isquemia Miocárdica/diagnóstico , Isquemia Miocárdica/genética , Isquemia Miocárdica/metabolismo , Líquido Pericárdico/metabolismo , Sequenciamento de Nucleotídeos em Larga Escala
14.
Int J Mol Sci ; 25(11)2024 May 22.
Artigo em Inglês | MEDLINE | ID: mdl-38891805

RESUMO

Plasmodium knowlesi is the only Plasmodium that causes zoonotic disease among the Plasmodium that cause infection in humans. It is fatal due to its short asexual growth cycle within 24 h. Lactate dehydrogenase (LDH), an enzyme that catalyzes the final step of glycolysis, is a biomarker for diagnosing infection by Plasmodium spp. parasite. Therefore, this study aimed to efficiently produce the soluble form of P. knowlesi LDH (PkLDH) using a bacterial expression system for studying malaria caused by P. knowlesi. Recombinant pET-21a(+)-PkLDH plasmid was constructed by inserting the PkLDH gene into a pET-21a(+) expression vector. Subsequently, the recombinant plasmid was inserted into the protein-expressing Escherichia coli Rosetta(DE3) strain, and the optimal conditions for overexpression of the PkLDH protein were established using this strain. We obtained a yield of 52.0 mg/L PkLDH from the Rosetta(DE3) strain and confirmed an activity of 483.9 U/mg through experiments. This methodology for high-efficiency PkLDH production can be utilized for the development of diagnostic methods and drug candidates for distinguishing malaria caused by P. knowlesi.


Assuntos
Clonagem Molecular , L-Lactato Desidrogenase , Malária , Plasmodium knowlesi , Plasmodium knowlesi/genética , Plasmodium knowlesi/enzimologia , L-Lactato Desidrogenase/genética , L-Lactato Desidrogenase/metabolismo , Clonagem Molecular/métodos , Malária/parasitologia , Malária/diagnóstico , Proteínas Recombinantes/genética , Proteínas Recombinantes/metabolismo , Escherichia coli/genética , Escherichia coli/metabolismo , Animais , Humanos , Expressão Gênica , Proteínas de Protozoários/genética , Proteínas de Protozoários/metabolismo
15.
Radiology ; 309(1): e231208, 2023 10.
Artigo em Inglês | MEDLINE | ID: mdl-37906011

RESUMO

Background The value of CT in assessment of clinically significant portal hypertension (CSPH) has not been well determined. Purpose To evaluate the performance of CT features that have been associated with portal hypertension for diagnosing CSPH in patients with chronic liver disease (CLD). Materials and Methods This retrospective study included patients with CLD who underwent contrast-enhanced CT and subsequent hepatic venous pressure gradient (HVPG) measurement within 3 months at two tertiary institutions from January 2001 to December 2019. Two readers independently evaluated the presence of gastroesophageal varix, spontaneous portosystemic shunt (SPSS), and ascites on CT images. Splenomegaly at CT was determined using three methods, as follows: personalized or fixed volume criteria, based on spleen volume as measured by a deep learning algorithm, or manually measured spleen diameter. The diagnostic performance of these findings alone or in combination for detecting CSPH (HVPG ≥10 mm Hg) was evaluated. Results A total of 235 patients (mean age, 53.2 years ± 13.0 [SD]; 155 male patients), including 110 (46.8%) with CSPH, were included. Detection of CSPH according to the presence of both splenomegaly and at least one other CT feature (ie, gastroesophageal varix, SPSS, and ascites) achieved specificities of 94.4%-97.6%, whereas detection of CSPH according to the presence of any feature (ie, splenomegaly, gastroesophageal varix, SPSS, or ascites) achieved sensitivities of 94.5%-98.2%. When employing the former as rule-in criteria with the absence of splenomegaly, gastroesophageal varix, SPSS, and ascites as rule-out criteria for CSPH, 171-185 (range, 72.8%-78.7%) of 235 patients were correctly classified as either having CSPH or not, seven to 13 (range, 3%-5.5%) of 235 patients were incorrectly classified, and 42-54 (range, 17.9%-23%) of 235 patients were unclassified. Conclusion The presence or absence of splenomegaly, gastroesophageal varix, SPSS, and/or ascites on CT images may be useful for ruling in and ruling out CSPH in patients with CLD. © RSNA, 2023 Supplemental material is available for this article. See also the editorial by Fraum in this issue.


Assuntos
Hipertensão Portal , Varizes , Humanos , Masculino , Pessoa de Meia-Idade , Esplenomegalia/diagnóstico por imagem , Ascite , Estudos Retrospectivos , Hipertensão Portal/diagnóstico por imagem , Tomografia Computadorizada por Raios X
16.
Radiology ; 306(1): 140-149, 2023 01.
Artigo em Inglês | MEDLINE | ID: mdl-35997607

RESUMO

Background Deep learning (DL) may facilitate the diagnosis of various pancreatic lesions at imaging. Purpose To develop and validate a DL-based approach for automatic identification of patients with various solid and cystic pancreatic neoplasms at abdominal CT and compare its diagnostic performance with that of radiologists. Materials and Methods In this retrospective study, a three-dimensional nnU-Net-based DL model was trained using the CT data of patients who underwent resection for pancreatic lesions between January 2014 and March 2015 and a subset of patients without pancreatic abnormality who underwent CT in 2014. Performance of the DL-based approach to identify patients with pancreatic lesions was evaluated in a temporally independent cohort (test set 1) and a temporally and spatially independent cohort (test set 2) and was compared with that of two board-certified radiologists. Performance was assessed using receiver operating characteristic analysis. Results The study included 852 patients in the training set (median age, 60 years [range, 19-85 years]; 462 men), 603 patients in test set 1 (median age, 58 years [range, 18-82 years]; 376 men), and 589 patients in test set 2 (median age, 63 years [range, 18-99 years]; 343 men). In test set 1, the DL-based approach had an area under the receiver operating characteristic curve (AUC) of 0.91 (95% CI: 0.89, 0.94) and showed slightly worse performance in test set 2 (AUC, 0.87 [95% CI: 0.84, 0.89]). The DL-based approach showed high sensitivity in identifying patients with solid lesions of any size (98%-100%) or cystic lesions measuring 1.0 cm or larger (92%-93%), which was comparable with the radiologists (95%-100% for solid lesions [P = .51 to P > .99]; 93%-98% for cystic lesions ≥1.0 cm [P = .38 to P > .99]). Conclusion The deep learning-based approach demonstrated high performance in identifying patients with various solid and cystic pancreatic lesions at CT. © RSNA, 2022 Online supplemental material is available for this article.


Assuntos
Aprendizado Profundo , Cisto Pancreático , Neoplasias Pancreáticas , Masculino , Humanos , Pessoa de Meia-Idade , Estudos Retrospectivos , Neoplasias Pancreáticas/cirurgia , Tomografia Computadorizada por Raios X/métodos
17.
Radiology ; 309(3): e231656, 2023 12.
Artigo em Inglês | MEDLINE | ID: mdl-38112549

RESUMO

Background A simplification of the Liver Imaging Reporting and Data System (LI-RADS) version 2018 (v2018), revised LI-RADS (rLI-RADS), has been proposed for imaging-based diagnosis of hepatocellular carcinoma (HCC). Single-site data suggest that rLI-RADS category 5 (rLR-5) improves sensitivity while maintaining positive predictive value (PPV) of the LI-RADS v2018 category 5 (LR-5), which indicates definite HCC. Purpose To compare the diagnostic performance of LI-RADS v2018 and rLI-RADS in a multicenter data set of patients at risk for HCC by performing an individual patient data meta-analysis. Materials and Methods Multiple databases were searched for studies published from January 2014 to January 2022 that evaluated the diagnostic performance of any version of LI-RADS at CT or MRI for diagnosing HCC. An individual patient data meta-analysis method was applied to observations from the identified studies. Quality Assessment of Diagnostic Accuracy Studies version 2 was applied to determine study risk of bias. Observations were categorized according to major features and either LI-RADS v2018 or rLI-RADS assignments. Diagnostic accuracies of category 5 for each system were calculated using generalized linear mixed models and compared using the likelihood ratio test for sensitivity and the Wald test for PPV. Results Twenty-four studies, including 3840 patients and 4727 observations, were analyzed. The median observation size was 19 mm (IQR, 11-30 mm). rLR-5 showed higher sensitivity compared with LR-5 (70.6% [95% CI: 60.7, 78.9] vs 61.3% [95% CI: 45.9, 74.7]; P < .001), with similar PPV (90.7% vs 92.3%; P = .55). In studies with low risk of bias (n = 4; 1031 observations), rLR-5 also achieved a higher sensitivity than LR-5 (72.3% [95% CI: 63.9, 80.1] vs 66.9% [95% CI: 58.2, 74.5]; P = .02), with similar PPV (83.1% vs 88.7%; P = .47). Conclusion rLR-5 achieved a higher sensitivity for identifying HCC than LR-5 while maintaining a comparable PPV at 90% or more, matching the results presented in the original rLI-RADS study. © RSNA, 2023 Supplemental material is available for this article. See also the editorial by Sirlin and Chernyak in this issue.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/patologia , Neoplasias Hepáticas/patologia , Estudos Retrospectivos , Imageamento por Ressonância Magnética/métodos , Meios de Contraste , Sensibilidade e Especificidade , Estudos Multicêntricos como Assunto
18.
PLoS Pathog ; 17(1): e1009213, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-33465148

RESUMO

Viral hemorrhagic septicemia virus (VHSV) is a rhabdovirus that causes high mortality in cultured flounder. Naturally occurring VHSV strains vary greatly in virulence. Until now, little has been known about genetic alterations that affect the virulence of VHSV in flounder. We recently reported the full-genome sequences of 18 VHSV strains. In this study, we determined the virulence of these 18 VHSV strains in flounder and then the assessed relationships between differences in the amino acid sequences of the 18 VHSV strains and their virulence to flounder. We identified one amino acid substitution in the phosphoprotein (P) (Pro55-to-Leu substitution in the P protein; PP55L) that is specific to highly virulent strains. This PP55L substitution was maintained stably after 30 cell passages. To investigate the effects of the PP55L substitution on VHSV virulence in flounder, we generated a recombinant VHSV carrying PP55L (rVHSV-P) from rVHSV carrying P55 in the P protein (rVHSV-wild). The rVHSV-P produced high level of viral RNA in cells and showed increased growth in cultured cells and virulence in flounder compared to the rVHSV-wild. In addition, rVHSV-P significantly inhibited the induction of the IFN1 gene in both cells and fish at 6 h post-infection. An RNA-seq analysis confirmed that rVHSV-P infection blocked the induction of several IFN-related genes in virus-infected cells at 6 h post-infection compared to rVHSV-wild. Ectopic expression of PP55L protein resulted in a decrease in IFN induction and an increase in viral RNA synthesis in rVHSV-wild-infected cells. Taken together, our results are the first to identify that the P55L substitution in the P protein enhances VHSV virulence in flounder. The data from this study add to the knowledge of VHSV virulence in flounder and could benefit VHSV surveillance efforts and the generation of a VHSV vaccine.


Assuntos
Doenças dos Peixes/virologia , Linguado/virologia , Novirhabdovirus/genética , Fosfoproteínas/genética , Infecções por Rhabdoviridae/virologia , Proteínas Virais/genética , Virulência/genética , Sequência de Aminoácidos , Substituição de Aminoácidos , Animais , Genoma Viral , Novirhabdovirus/metabolismo , Novirhabdovirus/patogenicidade , Fosfoproteínas/metabolismo , RNA-Seq , Homologia de Sequência , Transcriptoma , Proteínas Virais/metabolismo , Fatores de Virulência/genética , Fatores de Virulência/metabolismo
19.
Ann Surg Oncol ; 30(9): 5870-5880, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37261564

RESUMO

BACKGROUND: Disruption of the endothelial glycocalyx (EG) is associated with a poor prognosis in various clinical settings. This study aimed to determine the association between immediate postoperative serum syndecan-1 levels, a representative marker for EG degradation, and major postoperative morbidity and mortality in patients undergoing robot-assisted esophagectomy. METHODS: Patients who underwent robot-assisted esophagectomy between 2018 and 2022 were prospectively enrolled. The primary outcome was the association between immediate postoperative syndecan-1 levels and the occurrence of major postoperative morbidity and mortality within 30 days of surgery. Patients were classified into low and high syndecan-1 groups based on the optimal cut-off value of syndecan-1 for predicting major morbidity and mortality. A multivariable logistic regression analysis was performed to investigate the risk factors for major morbidity and mortality. RESULTS: A total of 207 patients were analyzed. Patients with high syndecan-1 levels (≥48 ng/mL) showed a significantly greater incidence of unexpected returns to the operating room and anastomotic leaks and longer durations of hospital and intensive care unit stays than patients with low syndecan-1 levels (<48 ng/mL). Immediate postoperative syndecan-1 levels ≥48 ng/mL (odds ratio [OR] 2.32, 95% confidence interval [CI] 1.23-4.76), American Society of Anesthesiologists physical status ≥III (OR 3.36, 95% CI 1.56-7.22), and current smoker (OR 4.02, 95% CI 1.52-10.61) were independently associated with major morbidity and mortality within 30 days of esophagectomy. CONCLUSIONS: Immediate postoperative syndecan-1 levels ≥48 ng/mL could be used for the early detection of patients at high risk of complications after robot-assisted esophagectomy.


Assuntos
Neoplasias Esofágicas , Robótica , Humanos , Sindecana-1 , Esofagectomia/efeitos adversos , Neoplasias Esofágicas/cirurgia , Incidência , Complicações Pós-Operatórias/epidemiologia
20.
J Magn Reson Imaging ; 2023 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-38038346

RESUMO

BACKGROUND: LI-RADS version 2018 (v2018) is used for non-invasive diagnosis of hepatocellular carcinoma (HCC). A recently proposed modification (known as mLI-RADS) demonstrated improved sensitivity while maintaining specificity and positive predictive value (PPV) of LI-RADS category 5 (definite HCC) for HCC. However, mLI-RADS requires multicenter validation. PURPOSE: To evaluate the performance of v2018 and mLI-RADS for liver lesions in a large, heterogeneous, multi-national cohort of patients at risk for HCC. STUDY TYPE: Systematic review and meta-analysis using individual participant data (IPD) [Study Protocol: https://osf.io/duys4]. POPULATION: 2223 observations from 1817 patients (includes all LI-RADS categories; females = 448, males = 1361, not reported = 8) at elevated risk for developing HCC (based on LI-RADS population criteria) from 12 retrospective studies. FIELD STRENGTH/SEQUENCE: 1.5T and 3T; complete liver MRI with gadoxetate disodium, including axial T2w images and dynamic axial fat-suppressed T1w images precontrast and in the arterial, portal venous, transitional, and hepatobiliary phases. Diffusion-weighted imaging was used when available. ASSESSMENT: Liver observations were categorized using v2018 and mLI-RADS. The diagnostic performance of each system's category 5 (LR-5 and mLR-5) for HCC were compared. STATISTICAL TESTS: The Quality Assessment of Diagnostic Accuracy Studies version 2 (QUADAS-2 was applied to determine risk of bias and applicability. Diagnostic performances were assessed using the likelihood ratio test for sensitivity and specificity and the Wald test for PPV. The significance level was P < 0.05. RESULTS: 17% (2/12) of the studies were considered low risk of bias (244 liver observations; 164 patients). When compared to v2018, mLR-5 demonstrated higher sensitivity (61.3% vs. 46.5%, P < 0.001), similar PPV (85.3% vs. 86.3%, P = 0.89), and similar specificity (85.8% vs. 90.8%, P = 0.16) for HCC. DATA CONCLUSION: This study confirms mLR-5 has higher sensitivity than LR-5 for HCC identification, while maintaining similar PPV and specificity, validating the mLI-RADS proposal in a heterogeneous, international cohort. LEVEL OF EVIDENCE: 3 TECHNICAL EFFICACY: Stage 2.

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