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Nanodrugs, which utilise nanomaterials in disease prevention and therapy, have attracted considerable interest since their initial conceptualisation in the 1990s. Substantial efforts have been made to develop nanodrugs for overcoming the limitations of conventional drugs, such as low targeting efficacy, high dosage and toxicity, and potential drug resistance. Despite the significant progress that has been made in nanodrug discovery, the precise design or screening of nanomaterials with desired biomedical functions prior to experimentation remains a significant challenge. This is particularly the case with regard to personalised precision nanodrugs, which require the simultaneous optimisation of the structures, compositions, and surface functionalities of nanodrugs. The development of powerful computer clusters and algorithms has made it possible to overcome this challenge through in silico methods, which provide a comprehensive understanding of the medical functions of nanodrugs in relation to their physicochemical properties. In addition, machine learning techniques have been widely employed in nanodrug research, significantly accelerating the understanding of bio-nano interactions and the development of nanodrugs. This review will present a summary of the computational advances in nanodrug discovery, focusing on the understanding of how the key interfacial interactions, namely, surface adsorption, supramolecular recognition, surface catalysis, and chemical conversion, affect the therapeutic efficacy of nanodrugs. Furthermore, this review will discuss the challenges and opportunities in computer-aided nanodrug discovery, with particular emphasis on the integrated "computation + machine learning + experimentation" strategy that can potentially accelerate the discovery of precision nanodrugs.
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During biomedical applications, nanozymes, exhibiting enzyme-like characteristics, inevitably come into contact with biological fluids in living systems, leading to the formation of a protein corona on their surface. Although it is acknowledged that molecular adsorption can influence the catalytic activity of nanozymes, there is a dearth of understanding regarding the impact of the protein corona on nanozyme activity and its determinant factors. In order to address this gap, we employed the AuNR@Pt@PDDAC [PDDAC, poly(diallyldimethylammonium chloride)] nanorod (NR) as a model nanozyme with multiple activities, including peroxidase, oxidase, and catalase-mimetic activities, to investigate the inhibitory effects of the protein corona on the catalytic activity. After the identification of major components in the plasma protein corona on the NR, we observed that spherical proteins and fibrous proteins induced distinct inhibitory effects on the catalytic activity of nanozymes. To elucidate the underlying mechanism, we uncovered that the adsorbed proteins assembled on the surface of the nanozymes, forming protein networks (PNs). Notably, the PNs derived from fibrous proteins exhibited a screen mesh-like structure with smaller pore sizes compared to those formed by spherical proteins. This structural disparity resulted in a reduced efficiency for the permeation of substrate molecules, leading to a more robust inhibition in activity. These findings underscore the significance of the protein shape as a crucial factor influencing nanozyme activity. This revelation provides valuable insights for the rational design and application of nanozymes in the biomedical fields.
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Nanoestruturas , Coroa de Proteína , Escleroproteínas , Peroxidase , Adsorção , Corantes , CatáliseRESUMO
BACKGROUND: The present research aims to investigate the clinical diagnostic value of LncRNA HOXA distal transcript antisense RNA (HOTTIP) in acute respiratory distress syndrome (ARDS) of sepsis and its predictive significance for mortality. METHODS: One hundred eighteenth patients with sepsis and 96 healthy individuals were enrolled. RT-qPCR to examine HOTTIP levels. The incidence of ARDS and death was recorded. The diagnostic significance of HOTTIP in sepsis ARDS was examined using ROC and logistic regression analysis. The correlation between HOTTIP and disease severity was evaluated using Pearson's coefficients. Kaplan-Meier analysis and COX regression were employed to examine the predictive significance of mortality. Validation of HOTTIP target miRNA by dual-luciferase assay. RESULTS: HOTTIP was persistently up-regulated in patients with ARDS sepsis than in patients without ARDS patients (P < 0.05). HOTTIP was a risk factor for the development of ARDS, which could be diagnosed in ARDS patients from non-ARDS patients (AUC = 0.847). Both the SOFA score (r = 0.6793) and the APACHE II score (r = 0.6384) were positively correlated with the HOTTIP levels. Furthermore, serum HOTTIP was an independent predictor of short-term mortality (HR = 4.813. 95%CI: 1.471-15.750, P = 0.009) and noticeably predicted the occurrence of short-term death (log rank = 0.020). miR-574-5p, a target miRNA for HOTTIP, was reduced in patients with sepsis ARDS and negatively correlated with HOTTIP. CONCLUSIONS: The presence of HOTTIP serves as a diagnostic biomarker for the occurrence of ARDS, exhibits correlation with disease severity, and provides predictive value of short-term mortality in sepsis patients. HOTTIP may be involved in ARDS progression by targeting miR-574-5p.
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MicroRNAs , RNA Longo não Codificante , Síndrome do Desconforto Respiratório , Sepse , Humanos , Biomarcadores , Estudos de Casos e Controles , MicroRNAs/genética , Prognóstico , Síndrome do Desconforto Respiratório/diagnóstico , Síndrome do Desconforto Respiratório/epidemiologia , RNA Longo não Codificante/genética , Curva ROC , Sepse/diagnóstico , Sepse/genéticaRESUMO
BACKGROUND: Neutrophil-to-lymphocyte ratio (NLR) has been suggested to be a prognostic marker for various diseases, but whether NLR dynamics (ΔNLR) is related to mortality and disease severity in patients with septic acute kidney injury (AKI) has not been determined. METHODS: Between August 2013 and August 2021, septic AKI patients at our center were retrospectively enrolled. ΔNLR was defined as the difference between the NLR at septic AKI diagnosis and at hospital admission. The relationship between the ΔNLR and mortality was evaluated by Kaplan-Meier curves, Cox proportional hazards, and cubic spline analyses. The prediction values were compared by area under the receiver-operating characteristic curve (AUROC), net reclassification improvement (NRI), and integrated discrimination improvement (IDI) analyses. RESULTS: Of the 413 participants, the mean age was 63 ± 17 years, and 134 were female (32.4%). According to the median value, patients in the high-ΔNLR group had significantly greater 90-d mortality (74.4% vs. 46.6%, p < 0.001). After adjustment for potential confounders, high ΔNLR remained an independent predictor of 90-d mortality (HR = 2.80; 95% CI = 1.74-4.49, p < 0.001). Furthermore, ΔNLR had the highest AUROC for 90-d mortality (0.685) among the various biomarkers and exhibited an improved NRI (0.314) and IDI (0.027) when incorporated with PCT and CRP. For secondary outcomes, patients with high ΔNLR had increased risk of 30-d mortality (p = 0.004), need for renal replacement therapy (p = 0.011), and developing stage-3 AKI (p = 0.040) according to the adjusted models. CONCLUSIONS: High ΔNLR is independently associated with increased risk of patient mortality and adverse outcomes. ΔNLR might be utilized to facilitate risk stratification and optimize septic AKI management.
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Injúria Renal Aguda , Neutrófilos , Humanos , Feminino , Pessoa de Meia-Idade , Idoso , Idoso de 80 Anos ou mais , Masculino , Prognóstico , Estudos de Coortes , Estudos Retrospectivos , Linfócitos , Injúria Renal Aguda/etiologiaRESUMO
Photodynamic molecular beacons (PMBs) are highly appealing for activatable photodynamic therapy (PDT), but their applications are hindered by limited therapeutic efficacy. Here, by molecular engineering of enzyme-responsive units in the loop region of DNA-based PMBs, we present for the first time the modular design of an enzyme/microRNA dual-regulated PMB (D-PMB) to achieve cancer-cell-selective amplification of PDT efficacy. In the design, the "inert" photosensitizers in D-PMB could be repeatedly activated in the presence of both tumor-specific enzyme and miRNA, leading to amplified generation of cytotoxic singlet oxygen species and therefore enhanced PDT efficacy in vitro and in vivo. By contrast, low photodynamic activity could be observed in healthy cells, as D-PMB activation has been largely avoided by the dual-regulatable design. This work presents a cooperatively activated PDT strategy, which enables enhanced therapeutic efficacy with improved tumor-specificity and thus conceptualizes an approach to expand the repertoire of designing smart tumor treatment modality.
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MicroRNAs , Neoplasias , Fotoquimioterapia , Humanos , MicroRNAs/genética , MicroRNAs/uso terapêutico , Fármacos Fotossensibilizantes/farmacologia , Fármacos Fotossensibilizantes/uso terapêutico , Oxigênio Singlete , Neoplasias/tratamento farmacológico , Neoplasias/genética , Neoplasias/patologia , Linhagem Celular TumoralRESUMO
DNAzymes exhibit tremendous application potentials in the field of biosensing and gene regulation due to its unique catalytic function. However, spatiotemporally controlled regulation of DNAzyme activity remains a daunting challenge, which may cause nonspecific signal leakage or gene silencing of the catalytic systems. Here, we report a photochemical approach via modular weaving active DNAzyme into the skeleton of tetrahedral DNA nanocages (TDN) for light-triggered on-demand liberation of DNAzyme and thus conditional control of gene regulation activity. We demonstrate that the direct encoding of DNAzyme in TDN could improve the biostability of DNAzyme and ensure the delivery efficiency, comparing with the conventional surface anchoring strategy. Furthermore, the molecular weaving of the DNA nanostructures allows remote control of DNAzyme-mediated gene regulation with high spatiotemporal precision of light. In addition, we demonstrate that the approach is applicable for controlled regulation of the gene editing functions of other functional nucleic acids.
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Técnicas Biossensoriais , DNA Catalítico , DNA Catalítico/metabolismo , DNA/química , Regulação da Expressão Gênica , Esqueleto/metabolismoRESUMO
Acute kidney injury (AKI) is characterized by a rapid reduction in kidney function caused by various etiologies. Tubular epithelial cell dysregulation plays a pivotal role in the pathogenesis of AKI. Tight junction (TJ) is the major molecular structure that connects adjacent epithelial cells and is critical in maintaining barrier function and determining the permeability of epithelia. TJ proteins are dysregulated in various types of AKI, and some reno-protective drugs can reverse TJ changes caused by insult. An in-depth understanding of TJ regulation and its causality with AKI will provide more insight to the disease pathogenesis and will shed light on the potential role of TJs to serve as novel therapeutic targets in AKI.
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Injúria Renal Aguda , Junções Íntimas , Humanos , Junções Íntimas/metabolismo , Epitélio/metabolismo , Células Epiteliais/metabolismo , Proteínas de Junções Íntimas/metabolismo , Injúria Renal Aguda/patologiaRESUMO
How to optimize the enzyme-like catalytic activity of nanozymes to improve their applicability has become a great challenge. Herein, we present an l-cysteine (l-Cys) coordination-driven self-assembly strategy to activate polyvinylpyrrolidone (PVP)-modified Cu single-atom nanozymes MoOx-Cu-Cys (denoted as MCCP SAzymes) aiming at catalytic tumor-specific therapy. The Cu single atom content of MCCP can be rationally modulated to 10.10 wt %, which activates the catalase (CAT)-like activity of MoOx nanoparticles to catalyze the decomposition of H2O2 in acidic microenvironments to increase O2 production. Excitingly, the maximized CAT-like catalytic efficiency of MCCP is 138-fold higher than that of typical MnO2 nanozymes and exhibits 14.3-fold higher affinity than natural catalase, as demonstrated by steady-state kinetics. We verify that the well-defined l-Cys-Cu···O active sites optimize CAT-like activity to match the active sites of natural catalase through an l-Cys bridge-accelerated electron transfer from Cys-Cu to MoOx disclosed by density functional theory calculations. Simultaneously, the high loading Cu single atoms in MCCP also enable generation of â¢OH via a Fenton-like reaction. Moreover, under X-ray irradiation, MCCP converts O2 to 1O2 for cascading radiodynamic therapy, thereby facilitating the multiple reactive oxygen species (ROS) for radiosensitization to achieve substantial antitumor.
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Three-dimensional nondestructive, nanoresolution, and in situ visualization of protein spatial localization in a large, thick single cell remains challenging. In this study, we designed a multifunctional iron oxide (Fe@BFK) nanoprobe that possesses fluorescence and hard X-ray imaging signals. This probe can specifically target the human epidermal growth factor receptor 2 (HER2) protein and help optimize the label condition and selection of suitable samples for X-ray imaging. Combining 30 nm resolution synchrotron radiation hard X-ray nanocomputed tomography and the X-ray-sensitive Fe@BFK nanoprobe, a 3D localization of HER2 on SK-BR-3 cells was obtained for the first time. HER2 was mainly localized and cluster-distributed on the cell membrane with a heterogeneous pattern. This study provides a novel method for the in situ and nondestructive synchrotron radiation imaging of the desired protein localization in large, thick cells and evaluation of the true cellular distribution of a nanoprobe with high resolution.
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Tomografia por Raios X , Humanos , FluorescênciaRESUMO
BACKGROUND: Blood pressure variability (BPV) is a risk factor for poor prognosis including cardiovascular events, chronic kidney disease, and mortality, independent of elevated BP. METHODS: We searched PubMed/Medline, EMBASE, and the Cochrane Central Register of Controlled Trials (CENTRAL) from inception to November 23, 2022. Cohort studies reporting the association between BPV and chronic kidney disease (CKD) progression were selected. Hazard ratios were pooled using a random-effects model. Meta-regression, subgroup analyses, and sensitivity analyses were conducted. RESULTS: A total of 23 studies were included in this systematic review and meta-analysis. Increased BPV was associated with progression of CKD (HR: 1.21, 95% CI: 1.09-1.33) and incidence of ESRD (HR: 1.08, 95% CI: 1.08-1.30). Among the different BPV metrics, high variation independent of mean (VIM), coefficient of variation (CV), standard deviation (SD), and average real variability (ARV) were indicated as predictors of CKD progression. DISCUSSION: Increased BPV was associated with CKD progression.
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Falência Renal Crônica , Insuficiência Renal Crônica , Humanos , Pressão Sanguínea , Insuficiência Renal Crônica/diagnóstico , Insuficiência Renal Crônica/epidemiologia , Insuficiência Renal Crônica/complicações , Fatores de Risco , Estudos de Coortes , Monitorização Ambulatorial da Pressão Arterial , Progressão da Doença , Falência Renal Crônica/epidemiologiaRESUMO
BACKGROUND: Norovirus is a leading cause of acute gastroenteritis among children. Previous studies based on symptomatic infections indicated that mutations, rather than recombination drove the evolution of the norovirus ORF2. These characteristics were found in hospital-based symptomatic infections, whereas, asymptomatic infections are frequent and contribute significantly to transmission. METHODS: We conducted the first norovirus molecular epidemiology analysis covering both symptomatic and asymptomatic infections derived from a birth cohort study in the northern China. RESULTS: During the study, 14 symptomatic and 20 asymptomatic norovirus infections were detected in 32 infants. Out of the 14 strains that caused symptomatic infections, 12 strains were identified as GII.3[P12], and others were GII.4[P31]. Conversely, 17 asymptomatic infections were caused by GII.4[P31], two by GII.2[P16], and one by GII.4[P16]. Regardless of symptomatic and asymptomatic infections, the mutations were detected frequently in the ORF2 region, and almost all recombination were identified in the RdRp-ORF2 region. The majority of the mutations were located around the predefined epitope regions of P2 subdomain indicating a potential for immune evasion. CONCLUSION: The role of symptomatic as well as asymptomatic infections in the evolution of norovirus needs to be evaluated continuously.
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Infecções por Caliciviridae , Norovirus , Humanos , Lactente , Infecções Assintomáticas/epidemiologia , Infecções por Caliciviridae/epidemiologia , Estudos de Coortes , População do Leste Asiático , Fezes , Genótipo , Epidemiologia Molecular , Norovirus/genética , FilogeniaRESUMO
OBJECTIVE: Bariatric surgery (BS) is considered one of the most effective treatments for obese individuals with Obstructive Sleep Apnea (OSA). However, otolaryngologists have raised concerns about the structural alterations caused by BS on the upper respiratory tract, especially, on the pharyngeal cavity. METHODS: In this study, we recruited 42 individuals who underwent BS at our hospital. They were divided into two groups based on apnea-hypopnea index (AHI): mild group (5 ≤ AHI < 15) and moderate-severe group (AHI ≥ 15). The participants were followed up for 12 months and several indicators, including body mass index (BMI), polysomnography (PSG), and acoustic pharyngometry (APh), were assessed repeatedly before surgery and at 3, 6, and 12 months (m) after surgery. RESULTS: Participants exhibited significant decreases in BMI (F = 128.1, P = 0.001) and total weight loss (F = 176.7, P < 0.001) after BS. The AHI value among obese patients with mild OSA decreased significantly within three months after surgery (0 day vs. 3 months, P < 0.01), and decreased significantly more than 12 months with moderate-to-severe patients (0 day vs. 3 months, 3 months vs. 6 months, 6 months vs. 12 months, P < 0.01). The therapeutic effect of OSA of the mild group was significantly better compared with that of the moderate-severe group at 6 months (mean rank = 28.13 vs. 14.21, P < 0.001) and 12 m (mean rank = 26.75 vs. 15.52, P = 0.001). The APh results revealed that the pharyngeal volume of the two groups increased significantly between 0 day and 6 months after surgery (P < 0.01). The oropharyngeal junction (OPJ) area and the glottal area were increased significantly between 0 day and 6 m after surgery (P < 0.01). CONCLUSION: BS can relieve apnea and OSA symptoms among obese patients with OSA, especially in the early postoperative period. Moreover, OSA severity was closely associated with OPJ and glottal areas, rather than pharyngeal cavity volume.
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Cirurgia Bariátrica , Apneia Obstrutiva do Sono , Humanos , Obesidade/complicações , Obesidade/cirurgia , Apneia Obstrutiva do Sono/complicações , Apneia Obstrutiva do Sono/cirurgia , Apneia Obstrutiva do Sono/diagnóstico , Cirurgia Bariátrica/efeitos adversos , Faringe/cirurgia , Período Pós-OperatórioRESUMO
Autophagy is an evolutionarily conserved mechanism for degrading and recycling various cellular components, functioning in both normal development and stress conditions. This process is tightly regulated by a set of autophagy-related (ATG) proteins, including ATG2 in the ATG9 cycling system and ATG5 in the ATG12 conjugation system. Our recent research demonstrated that autophagy-mediated compartmental cytoplasmic deletion is essential for pollen germination. However, the precise mechanisms through which autophagy regulates pollen germination, ensuring its fertility, remain largely unknown. Here, we applied multi-omics analyses, including transcriptomic and metabolomic approaches, to investigate the downstream pathways of autophagy in the process of pollen germination. Although ATG2 and ATG5 play similar roles in regulating pollen germination, high-throughput transcriptomic analysis reveals that silencing ATG5 has a greater impact on the transcriptome than silencing ATG2. Cross-comparisons of transcriptome and proteome analysis reveal that gene expression at the mRNA level and protein level is differentially affected by autophagy. Furthermore, high-throughput metabolomics analysis demonstrates that pathways related to amino acid metabolism and aminoacyl-tRNA biosynthesis were affected by both ATG2 and ATG5 silencing. Collectively, our multi-omics analyses reveal the central role of autophagy in cellular metabolism, which is critical for initiating pollen germination and ensuring pollen fertility.
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Autofagia , Multiômica , Proteínas Relacionadas à Autofagia/genética , Autofagia/genética , Proteína 12 Relacionada à Autofagia/genética , Pólen/genética , Pólen/metabolismo , Germinação/genéticaRESUMO
Despite significant progress in DNA self-assembly for interfacing with biology, spatiotemporally controlled regulation of biological process via in situ dynamic DNA assembly remains an outstanding challenge. Here, we report an optically triggered DNA assembly and disassembly strategy that enables on-demand activation and termination of the cyclic GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING) signaling pathway. In the design, an activatable DNA hairpin is engineered with a photocleavable group at defined site to modulate its self-assembly activity. Light activation induces the configurational switching and consequent self-assembly of the DNA hairpins to form long linear double-stranded structures, allowing to stimulate cGAS protein to synthesize 2',3'-cyclic-GMP-AMP (cGAMP) for STING stimulation. Furthermore, by endowing the pre-assembled DNA scaffold with a built-in photolysis feature, we demonstrate that the cGAS-STING stimulation can be efficiently terminated through remote photo-triggering, providing for the first time a route to control the temporal "dose" on-demand for such a stimulation. We envision that this regulation strategy will benefit and inspire both fundamental research and therapeutic applications regarding the cGAS-STING pathway.
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Fenômenos Biológicos , Transdução de Sinais , Nucleotidiltransferases/metabolismo , DNARESUMO
Reconstituting and probing exosome-cell interactions is critical for elucidating exosome-related cell biology and advancing their diagnostic and therapeutic potential. We report here an exosomal engineering strategy to achieve controlled regulation of exosome-cell interactions with activatable sensing capability. The approach relies on membrane-protein directed, programmable DNA self-assembly to construct a DNA polymeric scaffold with multivalent display of structure-switchable aptamer sensing probes on exosome surfaces. The engineered exosomes exhibit enhanced cancer cell targeting ability compared to exosomes modified with monovalent aptamers. Furthermore, the anchored aptamer probes could be activated by specific membrane protein targeting, followed by structural switching to report an output fluorescence signal, thus allowing dynamic monitoring of exosome-cell interactions both in vitro and in vivo. We envision this will provide a complementary tool for specific regulation and monitoring of exosome-cell docking interactions and will advance the development of exosome-based biomedical applications.
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Aptâmeros de Nucleotídeos , Exossomos , Aptâmeros de Nucleotídeos/química , DNA/análise , Exossomos/química , Fluorescência , Oligonucleotídeos/análise , Transporte ProteicoRESUMO
One of the persistent obstacles for high-power laser diodes (LDs) has been the catastrophic optical mirror damage (COMD), which limits the operating power level and lifetime of commercial high-power LDs. The output facet of LD reaches a critical temperature resulting in COMD, which is an irreversible device failure. Here, we fabricate multi-section LDs by tailoring the waveguide structure along the cavity that separates the output facet from the heat-generating lasing region. In this method, the LD waveguide is divided into electrically isolated laser and window sections along the cavity. The laser section is pumped at a high current to achieve high output power, and the window is biased at a low current with negligible heat generation. This design restricts the thermal impact of the laser section on the facet, and the window section allows lossless transport of the laser to the output facet. The lasers were operated continuous-wave up to the maximum achievable power. While standard LDs show COMD failures, the multi-section waveguide LDs are COMD-free. Our technique and results provide a pathway for high-reliability LDs, which would find diverse applications in semiconductor lasers.
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BACKGROUND: Obstructive sleep apnea (OSA) is a common disease that seriously affects human health and daily life. However, the gold standard for its diagnosis, polysomnography (PSG), is expensive resulting in inadequate diagnosis of this disease in primary clinics. Therefore, a simple and rapid method for initial screening for OSA is needed. Acoustic pharyngometry (APh) is an FDA-approved noninvasive method that is gradually being applied to screening for OSA. MATERIALS AND METHODS: In this study, we applied analysis with receiver operating characteristic (ROC) curves to explore how APh may play a greater role in the screening of subjects with suspected OSA. Patients admitted into the departments of otolaryngology at our hospital from March 2017 to May 2019 were recruited into the study. All subjects underwent PSG monitor and were separated into two groups according to the apnea-hypopnea index (AHI) from the PSG results: OSA group (AHI ≥ 5) and control group (AHI < 5). APh measurements and other indicators of the subjects, including age, height, and weight; Epworth Sleepiness Scale (ESS) score; and the pharynx examination, including the degree of tonsil enlargement and tongue hypertrophy, were also be recorded. RESULTS: The t-test results showed that almost all indicators except age and height have significant differences between the OSA group and control group. Subjects with OSA had greater weight, BMI, ESS, higher degree of tonsil enlargement, and tongue hypertrophy, while they had smaller minimal cross-sectional area (mCSA) and pharyngeal volume than the subjects in control group. The correlation analysis revealed that pharyngeal volume and mCSA were two helpful indicators to screen for OSA. Furthermore, we established the ROC curve and calculated the combining predictors (combining predictors = pharyngeal volume + mCSA * (- 2.347)/(- 0.225)). The area under the ROC curve (AUC) of combining predictors was 0.917 (95% CI 0.842-0.991, P < 0.001), which was higher than combinations of other two independent indicators. The cutoff point of combining predictors was found to be 59.84 (AUC = 0.917, sensitivity = 0.80, 1-specificity = 0.06, P < 0.001). CONCLUSIONS: These findings suggest that APh is a simple, rapid, and economical detection method which may be useful in screening for OSA, especially in communities and primary clinics where PSG cannot be performed.
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Faringe/patologia , Apneia Obstrutiva do Sono/diagnóstico , Adulto , Feminino , Humanos , Masculino , Tamanho do ÓrgãoRESUMO
OBJECTIVE: To explore the diagnostic efficacy of pepsin concentration in saliva for laryngopharyngeal reflux (LPR) disease. METHODS: In this study, we recruited 40 participants with abnormal sensation of throat into the study who visited our hospital from March 2020 to December 2020. The 24 h multichannel intraluminal impedance and pH monitoring (24 h MII-pH), reflux symptom index (RSI) and reflux finding score (RFS), pepsin concentration in saliva were collected. The Cohen's kappa test and receiver-operating characteristic (ROC) curves were performed to determine and compare the sensitivity and specificity of five diagnostic methods: RSI; RFS, pepsin concentration, RSI + RFS, RSI + RFS + pepsin concentration. RESULTS: The area under the curve (AUC) of RSI, RFS, pepsin concentration, RSI + RFS, RSI + RFS + pepsin concentration were 0.767, 0.733, 0.870, 0.750,0.867, respectively. That is, the pepsin concentration has maximum AUC (the cutoff point is 219.47 (ng/mL); the sensitivity and 1-specificity is 0.300, 0.933, respectively.). The positive predictive value was 90.3% (28/31), and the negative predictive value was 77.8% (7/9). The Cohen's kappa coefficients of the five diagnostic subgroups were: RSI 0.486 (95% CI 0.207-0.764, P = 0.001); RFS 0.333 (95% CI 0.021-0.644, P = 0.032); RSI + RFS: 0.517 (95% CI 0.205-0.829, P = 0.001); pepsin concentration: 0.699 (95% CI 0.379-0.931, P = 0.001); RSI + RFS + pepsin concentration: 0.500 (95% CI 0.181-0.819, P < 0.001). CONCLUSION: The pepsin concentration has the maximum AUC area and highest consistency with the 24 h MII-pH. Therefore, it has certain value in the screening and diagnosis of diseases related to LPR disease.
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Refluxo Laringofaríngeo , Humanos , Refluxo Laringofaríngeo/diagnóstico , Pepsina A , Monitoramento do pH Esofágico , Saliva , Impedância Elétrica , Concentração de Íons de HidrogênioRESUMO
The recognition of abnormal gait behavior is important in the field of motion assessment and disease diagnosis. Currently, abnormal gait behavior is primarily recognized by pressure and inertial data obtained from wearable sensors. However, the data drift and wearing difficulties for patients have impeded the application of these wearable sensors. Here, we propose a contactless abnormal gait behavior recognition method that captures human pose data using a monocular camera. A lightweight OpenPose (OP) model is generated with Depthwise Separable Convolution to recognize joint points and extract their coordinates during walking in real time. For the walking data errors extracted in the 2D plane, a 3D reconstruction is performed on the walking data, and a total of 11 types of abnormal gait features are extracted by the OP model. Finally, the XGBoost algorithm is used for feature screening. The final experimental results show that the Random Forest (RF) algorithm in combination with 3D features delivers the highest precision (92.13%) for abnormal gait behavior recognition. The proposed scheme overcomes the data drift of inertial sensors and sensor wearing challenges in the elderly while reducing the hardware requirements for model deployment. With excellent real-time and contactless capabilities, the scheme is expected to enjoy a wide range of applications in the field of abnormal gait measurement.
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Marcha , Caminhada , Idoso , Algoritmos , Humanos , Movimento (Física)RESUMO
Small defects on the rails develop fast under the continuous load of passing trains, and this may lead to train derailment and other disasters. In recent years, many types of wireless sensor systems have been developed for rail defect detection. However, there has been a lack of comprehensive reviews on the working principles, functions, and trade-offs of these wireless sensor systems. Therefore, we provide in this paper a systematic review of recent studies on wireless sensor-based rail defect detection systems from three different perspectives: sensing principles, wireless networks, and power supply. We analyzed and compared six sensing methods to discuss their detection accuracy, detectable types of defects, and their detection efficiency. For wireless networks, we analyzed and compared their application scenarios, the advantages and disadvantages of different network topologies, and the capabilities of different transmission media. From the perspective of power supply, we analyzed and compared different power supply modules in terms of installation and energy harvesting methods, and the amount of energy they can supply. Finally, we offered three suggestions that may inspire the future development of wireless sensor-based rail defect detection systems.