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1.
Sensors (Basel) ; 24(8)2024 Apr 16.
Article in English | MEDLINE | ID: mdl-38676175

ABSTRACT

The identification of multi-source signals with time-frequency aliasing is a complex problem in wideband signal reception. The traditional method of first separation and identification especially fails due to the significant separation error under underdetermined conditions when the degree of time-frequency aliasing is high. The single-mode recognition method does not need to be separated first. However, the single-mode features contain less signal information, making it challenging to identify time-frequency aliasing signals accurately. To solve the above problems, this article proposes a time-frequency aliasing signal recognition method based on multi-mode fusion (TRMM). This method uses the U-Net network to extract pixel-by-pixel features of the time-frequency and wave-frequency images and then performs weighted fusion. The multimodal feature scores are used as the classification basis to realize the recognition of the time-frequency aliasing signals. When the SNR is 0 dB, the recognition rate of the four-signal aliasing model can reach more than 97.3%.

2.
Article in English | MEDLINE | ID: mdl-38648130

ABSTRACT

In this article, we propose a set of transform-based neural network layers as an alternative to the 3 x 3 Conv2D layers in convolutional neural networks (CNNs). The proposed layers can be implemented based on orthogonal transforms, such as the discrete cosine transform (DCT), Hadamard transform (HT), and biorthogonal block wavelet transform (BWT). Furthermore, by taking advantage of the convolution theorems, convolutional filtering operations are performed in the transform domain using elementwise multiplications. Trainable soft-thresholding layers, that remove noise in the transform domain, bring nonlinearity to the transform domain layers. Compared with the Conv2D layer, which is spatial-agnostic and channel-specific, the proposed layers are location-specific and channel-specific. Moreover, these proposed layers reduce the number of parameters and multiplications significantly while improving the accuracy results of regular ResNets on the ImageNet-1K classification task. Furthermore, they can be inserted with a batch normalization (BN) layer before the global average pooling layer in the conventional ResNets as an additional layer to improve classification accuracy.

3.
Angew Chem Int Ed Engl ; 63(5): e202317549, 2024 Jan 25.
Article in English | MEDLINE | ID: mdl-38078819

ABSTRACT

Solid electrolyte interphase (SEI) makes the electrochemical window of aqueous electrolytes beyond the thermodynamics limitation of water. However, achieving the energetic and robust SEI is more challenging in aqueous electrolytes because the low SEI formation efficiency (SFE) only contributed from anion-reduced products, and the low SEI formation quality (SFQ) negatively impacted by the hydrogen evolution, resulting in a high Li loss to compensate for SEI formation. Herein, we propose a highly efficient strategy to construct Spatially-Temporally Synchronized (STS) robust SEI by the involvement of synergistic chemical precipitation-electrochemical reduction. In this case, a robust Li3 PO4 -rich SEI enables intelligent inherent growth at the active site of the hydrogen by the chemical capture of the OH- stemmed from the HER to trigger the ionization balance of dihydrogen phosphate (H2 PO4 - ) shift to insoluble solid Li3 PO4 . It is worth highlighting that the Li3 PO4 formation does not extra-consume lithium derived from the cathode but makes good use of the product of HER (OH- ), prompting the SEI to achieve 100 % SFE and pushing the HER potential into -1.8 V vs. Ag/AgCl. This energetic and robust SEI offers a new way to achieve anion/concentration-independent interfacial chemistry for the aqueous batteries.

4.
Sci Adv ; 9(36): eadg7481, 2023 Sep 08.
Article in English | MEDLINE | ID: mdl-37682993

ABSTRACT

Physically unclonable functions (PUFs) are a class of hardware-specific security primitives based on secret keys extracted from integrated circuits, which can protect important information against cyberattacks and reverse engineering. Here, we put forward an emerging type of PUF in the electromagnetic domain by virtue of the self-dual absorber-emitter singularity that uniquely exists in the non-Hermitian parity-time (PT)-symmetric structures. At this self-dual singular point, the reconfigurable emissive and absorptive properties with order-of-magnitude differences in scattered power can respond sensitively to admittance or phase perturbations caused by, for example, manufacturing imperfectness. Consequently, the entropy sourced from inevitable manufacturing variations can be amplified, yielding excellent PUF security metrics in terms of randomness and uniqueness. We show that this electromagnetic PUF can be robust against machine learning-assisted attacks based on the Fourier regression and generative adversarial network. Moreover, the proposed PUF concept is wavelength-scalable in radio frequency, terahertz, infrared, and optical systems, paving a promising avenue toward applications of cryptography and encryption.

5.
J Dent ; 138: 104721, 2023 11.
Article in English | MEDLINE | ID: mdl-37741504

ABSTRACT

OBJECTIVES: To determine the agreement of removable dental prosthesis cleanliness as assessed by a semi-automated planimetric method between images captured by a digital single-lens reflex camera (DSLR) and smartphone. METHODS: A total of 97 participants with removable prostheses were recruited for the quantification of the prosthesis plaque area coverage. The colour images of stained prosthesis plaque were obtained using both a DSLR camera and a smartphone. The prosthesis plaque area coverage was analysed in two ways: (i) prosthesis cleanliness index (PCI) and (ii) percentage plaque area coverage (PPC). The PPC (continuous data) was converted to the PCI (categorical data) to provide prevalence ordinal scales and the agreements in PCI ratings were determined using weighted Kappa statistics. Agreement of PPC scores was determined through assessing directional, standardised directional, and absolute differences and correlation analyses. RESULTS: Weighted Kappa values of agreement between PCI categories were excellent (> 0.80) for all comparisons. The mean PPC was 24.79 % as determined by DSLR and 25.37 % as determined by smartphone. There was no statistically significant difference in the means of PPC between the DSLR and smartphone (P = 0.149). The standardised directional difference was 0.15 ('small'). The mean absolute difference was 2.77. The interclass correlation coefficient was 0.98 ('excellent'). CONCLUSIONS: This method showed almost perfect agreements and allowed for threshold-based plaque segmentation on the removable prostheses. There was substantial agreement between DSLR and smartphone assessment of prosthesis plaque area coverage as determined by a semi-automated planimetric assessment. CLINICAL SIGNIFICANCE: This semi-automated planimetric assessment method has implications for monitoring removable prosthesis hygiene initiatives by offering a valid, reliable, and quantitative method of assessment with potential use in managed care and community settings.


Subject(s)
Dental Implants , Denture, Partial, Removable , Humans , Denture, Complete
6.
Natl Sci Rev ; 10(2): nwac226, 2023 Feb.
Article in English | MEDLINE | ID: mdl-36817832

ABSTRACT

A single-crystalline Ni-rich (SCNR) cathode with a large particle size can achieve higher energy density, and is safer, than polycrystalline counterparts. However, synthesizing large SCNR cathodes (>5 µm) without compromising electrochemical performance is very challenging due to the incompatibility between Ni-rich cathodes and high temperature calcination. Herein, we introduce Vegard's Slope as a guide for rationally selecting sintering aids, and we successfully synthesize size-controlled SCNR cathodes, the largest of which can be up to 10 µm. Comprehensive theoretical calculation and experimental characterization show that sintering aids continuously migrate to the particle surface, suppress sublattice oxygen release and reduce the surface energy of the typically exposed facets, which promotes grain boundary migration and elevates calcination critical temperature. The dense SCNR cathodes, fabricated by packing of different-sized SCNR cathode particles, achieve a highest electrode press density of 3.9 g cm-3 and a highest volumetric energy density of 3000 Wh L-1. The pouch cell demonstrates a high energy density of 303 Wh kg-1, 730 Wh L-1 and 76% capacity retention after 1200 cycles. SCNR cathodes with an optimized particle size distribution can meet the requirements for both electric vehicles and portable devices. Furthermore, the principle for controlling the growth of SCNR particles can be widely applied when synthesizing other materials for Li-ion, Na-ion and K-ion batteries.

7.
Int J Infect Dis ; 122: 622-627, 2022 Sep.
Article in English | MEDLINE | ID: mdl-35842216

ABSTRACT

OBJECTIVES: Here, we retrospectively described the diagnosis and treatment of 32 cases diagnosed with Chlamydia psittaci pneumonia during the COVID-19 pandemic. METHODS: Clinical information was collected from all the patients. Reverse transcription-PCR and ELISAs were conducted for the detection of COVID-19 using nasal swabs and bronchoalveolar lavage fluid (BALF) samples. Metagenomic next-generation sequencing (mNGS) was performed for the identification of causative pathogens using BALF, peripheral blood and sputum samples. End-point PCR was performed to confirm the mNGS results. RESULTS: All 32 patients showed atypical pneumonia and had infection-like symptoms that were similar to COVID-19. Results of reverse transcription-PCR and ELISAs ruled out COVID-19 infection. mNGS identified C. psittaci as the suspected pathogen in these patients within 48 hours, which was validated by PCR, except for three blood samples. The sequence reads that covered fragments of C. psittaci genome were detected more often in BALF than in sputum or blood samples. All patients received doxycycline-based treatment regimens and showed favorable outcomes. CONCLUSION: This retrospective study, with the highest number of C. psittaci pneumonia enrolled cases in China so far, suggests that human psittacosis may be underdiagnosed and misdiagnosed clinically, especially in the midst of the COVID-19 pandemic.


Subject(s)
COVID-19 , Chlamydophila psittaci , Influenza, Human , Mycoses , Pneumonia, Mycoplasma , Pneumonia , Psittacosis , COVID-19/diagnosis , Chlamydophila psittaci/genetics , Humans , Pandemics , Psittacosis/diagnosis , Psittacosis/drug therapy , Psittacosis/epidemiology , Retrospective Studies
8.
Article in English | MEDLINE | ID: mdl-35457788

ABSTRACT

Protected areas constitute a global strategic resource for enhancing the effectiveness of ecological protection, which can alleviate the impact of unsustainable human production and living activities on the ecological environment. However, the spatiotemporal evolution of ecological protection effectiveness needs to be quantitatively revealed. The net primary productivity (NPP) of plants is an important measure of the effectiveness of ecological protection efforts. The main purpose of this study is to use the relative change in the annual average NPP to evaluate the ecological protection effectiveness of protected areas. We compared the historical changes in the annual average NPP of protected areas in Sichuan Province from 2000 to 2019. We added the spatial coordinates to the impact factor system and adopted propensity score matching (PSM) in a quasi-natural experimental method to determine the experimental group and the control group. The ecological protection effectiveness of the protected areas in the study area in 2000, 2005, 2010, 2015, and 2019 was measured and classified into three types of changes in protection effectiveness, namely effective, ineffective, or fluctuating. According to the administrative level, type, and spatial distribution, we determined the number and type of changes in the protection effectiveness of different protected areas. The results show that the annual average NPP of the protected areas in Sichuan Province generally fluctuated. The annual average NPP increased in 95.47% of the total protected area and decreased in 4.53%. The overall protection effectiveness of protected areas was positive and significant and gradually improved. Effective protected areas at the national, provincial, and county levels accounted for 40.27% of the total number of protected areas, and the other 14.77% of effective protected area was managed at other administrative levels. Among the different types of protected areas, the proportion of effective protected areas was highest in wild animal protected areas, followed by forest ecology protected areas, wild plant protected areas, and wetland ecology protected areas. The results of this study can provide an important reference for the verification and improvement of the ecological protection effectiveness of various protected areas.


Subject(s)
Ecosystem , Forests , China , Plants , Propensity Score , Wetlands
9.
Infect Drug Resist ; 14: 2965-2968, 2021.
Article in English | MEDLINE | ID: mdl-34349532

ABSTRACT

Nontuberculous mycobacteria infections present mostly pulmonary characteristics. However, the incidence of skin and soft tissue infections caused by nontuberculous mycobacteria has increased in part due to the increased popularity of cosmetic and plastic surgery. Here, we report a case of Mycobacterium agri infection. The patient underwent a one-year course of anti-infection therapy. To the best of our knowledge, this is the first report of a previously healthy patient presenting a skin and soft tissue infection caused by Mycobacterium agri. Clinical personnel should be aware of possible causes of persistent skin and soft tissue infection after cosmetic and plastic surgery.

10.
Medicine (Baltimore) ; 100(24): e25937, 2021 Jun 18.
Article in English | MEDLINE | ID: mdl-34128842

ABSTRACT

ABSTRACT: The aim of this study was to investigate the correlation between single-nucleotide polymorphisms (SNPs) in the 3 primer of untranslated region (3'UTR) of the Pentraxin 3 (PTX3) gene and the risk of essential hypertension (EHT).PTX3 genotypes, rs2614, rs111451363, and rs73158510 locus, were found in 260 patients with EHT and 260 healthy controls. Quantitative real-time polymerase chain reaction was used to detect plasma hsa-miR-4766-5p levels. Enzyme-linked immunosorbent assay was used to detect plasma PTX3 levels. The dual-luciferase reporter assay was used to identify the binding site of hsa-miR-4766-5p to the PTX3.PTX3 rs2614 locus T allele was a high risk factor for EHT (odds ratio [OR] = 2.76, 95% confidence interval [CI]: 1.86-4.09, P < .01). Sex and diabetes history affected the correlation between PTX3 gene rs2614 locus SNP and EHT risk. The CCG haplotype was a protective factor for EHT (OR = 0.40, 95% CI: 0.28-0.57, P < .01), whereas the TCG haplotype was a risk factor for EHT (OR = 2.35, 95% CI: 1.51-3.66, P < .01). The plasma PTX3 level of patients with EHT was significantly higher than that of the control group, and the difference was statistically significant (P < .01). The area under the curve for EHT diagnosis in plasma PTX3 levels was 0.62 (95% CI: 0.57-0.66, P < .01). The plasma hsa-miR-4766-5p level in patients with EHT was significantly lower than that in the control group (P < .01). The area under the curve for the diagnosis of EHT according to the plasma hsa-miR-4766-5p level was 0.88 (95% CI: 0.85-0.91, P < .01). Plasma PTX3 levels were significantly negatively correlated with hsa-miR-4766-5p levels in patients with EHT and the control group (r = -0.87, -0.85, P < .01, P < .01). The PTX3 gene rs2614 locus C allele was the target gene of hsa-miR-4766-5p.The PTX3 rs2614 locus SNP is significantly associated with EHT risk.


Subject(s)
3' Untranslated Regions/genetics , C-Reactive Protein/genetics , Essential Hypertension/genetics , Genetic Predisposition to Disease/genetics , Polymorphism, Single Nucleotide/genetics , Serum Amyloid P-Component/genetics , Adult , Aged , Aged, 80 and over , Alleles , Area Under Curve , Binding Sites , Case-Control Studies , Female , Genotype , Haplotypes , Humans , Male , MicroRNAs/blood , Middle Aged , Risk Factors
11.
Medicine (Baltimore) ; 100(24): e26279, 2021 Jun 18.
Article in English | MEDLINE | ID: mdl-34128861

ABSTRACT

ABSTRACT: Early determination of coronavirus disease 2019 (COVID-19) pneumonia from numerous suspected cases is critical for the early isolation and treatment of patients.The purpose of the study was to develop and validate a rapid screening model to predict early COVID-19 pneumonia from suspected cases using a random forest algorithm in China.A total of 914 initially suspected COVID-19 pneumonia in multiple centers were prospectively included. The computer-assisted embedding method was used to screen the variables. The random forest algorithm was adopted to build a rapid screening model based on the training set. The screening model was evaluated by the confusion matrix and receiver operating characteristic (ROC) analysis in the validation.The rapid screening model was set up based on 4 epidemiological features, 3 clinical manifestations, decreased white blood cell count and lymphocytes, and imaging changes on chest X-ray or computed tomography. The area under the ROC curve was 0.956, and the model had a sensitivity of 83.82% and a specificity of 89.57%. The confusion matrix revealed that the prospective screening model had an accuracy of 87.0% for predicting early COVID-19 pneumonia.Here, we developed and validated a rapid screening model that could predict early COVID-19 pneumonia with high sensitivity and specificity. The use of this model to screen for COVID-19 pneumonia have epidemiological and clinical significance.


Subject(s)
Algorithms , COVID-19 Testing/methods , COVID-19/diagnosis , Mass Screening/methods , SARS-CoV-2/isolation & purification , Adult , China , Female , Humans , Male , Middle Aged , Prospective Studies , ROC Curve , Sensitivity and Specificity
12.
Nano Lett ; 21(12): 5254-5261, 2021 06 23.
Article in English | MEDLINE | ID: mdl-34105964

ABSTRACT

Uneven lithium plating/stripping is an essential issue that inhibits stable cycling of a lithium metal anode and thus hinders its practical applications. The investigation of this process is challenging because it is difficult to observe lithium in an operating device. Here, we demonstrate that the microscopic lithium plating behavior can be observed in situ in a close-to-practical cell setup using X-ray computed tomography. The results reveal the formation of porous structure and its progressive evolution in space over the charging process with a large current. The elaborated analysis indicates that the microstructure of deposited lithium makes a significant impact on the subsequent lithium plating, and the impact of structural inhomogeneity, further exaggerated by the large-current charging, can lead to severely uneven lithium plating and eventually cell failure. Therefore, a codesign strategy involving delicate controls of microstructure and electrochemical conditions could be a necessity for the next-generation battery with lithium metal anode.


Subject(s)
Lithium , Tomography, X-Ray Computed , Electric Power Supplies , Ions , Metals
13.
ACS Appl Mater Interfaces ; 13(16): 18743-18749, 2021 Apr 28.
Article in English | MEDLINE | ID: mdl-33871956

ABSTRACT

All-solid-state batteries (ASSBs) are expected to address the battery safety issues fundamentally by replacing the flammable electrolyte with solid electrolytes (SEs). However, recent studies report that the thermal runaway happened for NASICON-type SEs when they contact with Li metal at high temperature and indicate that the ASSBs may not be totally safe. Here, the thermal stability of a NASICON-type Li1.4Al0.4Ti1.6(PO4)3 (LATP) SE pellet against metallic lithium is quantified in a quasi-practical situation. Accelerated thermal runaway of the LATP pellet compared to LATP powder is observed when they contact with lithium. Combining electrochemical impedance spectroscopy and X-ray computed tomography analysis, lithium penetration into the pellet at high temperature has been observed. The penetrated lithium without surface impurities and the high reactivity of LATP at defect sites (atomic structural defects, cracks, voids, etc.) lead to higher interfacial reactivity and earlier thermal runaway. By adding LiPO2F2 to modify those defect sites of the LATP pellet and impede the lithium/SE interfacial reactions, the thermal runaway can be remarkably delayed. This work elucidates the thermal runaway behaviors of Li/LATP pellets in a quasi-practical environment, provides new information about safety issues of ASSBs, and inspires future investigations into this urgent-needed area.

14.
Mol Med Rep ; 23(6)2021 06.
Article in English | MEDLINE | ID: mdl-33786614

ABSTRACT

Cervical cancer is a common public health issue with high morbidity worldwide. Paeonol (Pae) has been recognized as a traditional Chinese medicine used for the treatment of various cancer types. However, whether Pae could exert a protective effect on cervical cancer remains to be investigated. The aim of the present study was to explore the role of Pae in cervical cancer cells and identify the potential mechanism. Cell Counting Kit­8 and colony­formation assays were conducted to test the proliferation of HeLa cells. Additionally, wound healing and transwell assays were used to detect the migratory and invasive abilities of cells. The plasmid that overexpressed 5­lipoxygenase (5­LO) or control vector was constructed and transfected into the cells. Subsequently, flow cytometry was used to monitor the apoptotic rate of cells. The expression levels of apoptosis­associated proteins and 5­LO were detected using western blot analysis. Reverse transcription­quantitative PCR analysis detected the expression of 5­LO. Pae inhibited the proliferation, invasion and migration of HeLa cells, promoted cell apoptosis and downregulated the expression of 5­LO. Overexpression of 5­LO, however, attenuated these effects. Thus, Pae could inhibit the proliferation, migration and invasion, as well as promote apoptosis of HeLa cells by regulating the expression of 5­LO.


Subject(s)
Acetophenones/pharmacology , Antineoplastic Agents/pharmacology , Apoptosis/drug effects , Arachidonate 5-Lipoxygenase/metabolism , Cell Movement/drug effects , Arachidonate 5-Lipoxygenase/genetics , Cell Proliferation/drug effects , HeLa Cells , Humans
15.
Sensors (Basel) ; 20(10)2020 May 20.
Article in English | MEDLINE | ID: mdl-32443739

ABSTRACT

In this paper, we propose a deep convolutional neural network for camera based wildfire detection. We train the neural network via transfer learning and use window based analysis strategy to increase the fire detection rate. To achieve computational efficiency, we calculate frequency response of the kernels in convolutional and dense layers and eliminate those filters with low energy impulse response. Moreover, to reduce the storage for edge devices, we compare the convolutional kernels in Fourier domain and discard similar filters using the cosine similarity measure in the frequency domain. We test the performance of the neural network with a variety of wildfire video clips and the pruned system performs as good as the regular network in daytime wild fire detection, and it also works well on some night wild fire video clips.

16.
Eur Respir J ; 54(2)2019 08.
Article in English | MEDLINE | ID: mdl-31273041

ABSTRACT

Sarcoidosis is an unpredictable granulomatous disease in which African Americans disproportionately experience aggressive phenotypes. Mitochondrial DNA (mtDNA) released by cells in response to various stressors contributes to tissue remodelling and inflammation. While extracellular mtDNA has emerged as a biomarker in multiple diseases, its relevance to sarcoidosis remains unknown. We aimed to define an association between extracellular mtDNA and clinical features of sarcoidosis.Extracellular mtDNA concentrations were measured using quantitative PCR for the human MT-ATP6 gene in bronchoalveolar (BAL) and plasma samples from healthy controls and patients with sarcoidosis from The Yale Lung Repository; associations between MT-ATP6 concentrations and Scadding stage, extrapulmonary disease and demographics were sought. Results were validated in the Genomic Research in Alpha-1 Antitrypsin Deficiency and Sarcoidosis cohort.Relative to controls, MT-ATP6 concentrations in sarcoidosis subjects were robustly elevated in the BAL fluid and plasma, particularly in the plasma of patients with extrapulmonary disease. Relative to Caucasians, African Americans displayed excessive MT-ATP6 concentrations in the BAL fluid and plasma, for which the latter compartment correlated with significantly higher odds of extrapulmonary disease.Enrichments in extracellular mtDNA in sarcoidosis are associated with extrapulmonary disease and African American descent. Further study into the mechanistic basis of these clinical findings may lead to novel pathophysiologic and therapeutic insights.


Subject(s)
DNA, Mitochondrial/blood , Sarcoidosis, Pulmonary/blood , Adult , Aged , Biomarkers/blood , Bronchoalveolar Lavage , Bronchoalveolar Lavage Fluid , Case-Control Studies , Female , HEK293 Cells , HMGB1 Protein/metabolism , Humans , Lung/physiopathology , Male , Middle Aged , Mitochondrial Proton-Translocating ATPases/blood , Phenotype , Sarcoidosis, Pulmonary/physiopathology , Toll-Like Receptor 9/metabolism
18.
Respirology ; 23(8): 771-779, 2018 08.
Article in English | MEDLINE | ID: mdl-29611244

ABSTRACT

BACKGROUND AND OBJECTIVE: Molecular biomarkers are needed to refine prognostication and phenotyping of pulmonary hypertension (PH) patients. S100A12 is an emerging biomarker of various inflammatory diseases. This study aims to determine the prognostic value of S100A12 in PH. METHODS: Exploratory microarray analysis performed on peripheral blood mononuclear cells (PBMC) collected from idiopathic pulmonary fibrosis (IPF) patients suggested an association between S100A12 and both PH and mortality. So the current study was designed to evaluate for an association between S100A12 in peripheral blood collected from two well-phenotyped PH cohorts in two other centres to derive and validate an association between S100A12 protein serum concentrations and mortality. RESULTS: The majority of the patients in the discovery and validation cohorts were either World Health Organization (WHO) group 1 (pulmonary arterial hypertension (PAH)) or 3 (lung disease-associated) PH. In the discovery PH cohort, S100A12 was significantly increased in patients with PH (n = 51) compared to controls (n = 22) (29.8 vs 15.7 ng/mL, P < 0.001) and negatively correlated with cardiac output (r = -0.58, P < 0.001) in PH patients. When S100A12 data were pooled from both cohorts, PAH and non-PAH PH patients had higher S100A12 compared to healthy external controls (32.6, 30.9, 15.7 ng/mL; P < 0.001). S100A12 was associated with an increased risk in overall mortality in PH patients in both the discovery (n = 51; P = 0.008) and validation (n = 40; P < 0.001) cohorts. CONCLUSION: S100A12 levels are increased in PH patients and are associated with increased mortality.


Subject(s)
Cardiac Output , Hypertension, Pulmonary/blood , Hypertension, Pulmonary/mortality , S100A12 Protein/blood , Adult , Aged , Biomarkers/blood , Case-Control Studies , Cohort Studies , Female , Humans , Hypertension, Pulmonary/physiopathology , Leukocytes, Mononuclear , Lung/physiopathology , Male , Middle Aged , Prognosis
19.
Am J Respir Crit Care Med ; 196(12): 1571-1581, 2017 12 15.
Article in English | MEDLINE | ID: mdl-28783377

ABSTRACT

RATIONALE: Idiopathic pulmonary fibrosis (IPF) involves the accumulation of α-smooth muscle actin-expressing myofibroblasts arising from interactions with soluble mediators such as transforming growth factor-ß1 (TGF-ß1) and mechanical influences such as local tissue stiffness. Whereas IPF fibroblasts are enriched for aerobic glycolysis and innate immune receptor activation, innate immune ligands related to mitochondrial injury, such as extracellular mitochondrial DNA (mtDNA), have not been identified in IPF. OBJECTIVES: We aimed to define an association between mtDNA and fibroblast responses in IPF. METHODS: We evaluated the response of normal human lung fibroblasts (NHLFs) to stimulation with mtDNA and determined whether the glycolytic reprogramming that occurs in response to TGF-ß1 stimulation and direct contact with stiff substrates, and spontaneously in IPF fibroblasts, is associated with excessive levels of mtDNA. We measured mtDNA concentrations in bronchoalveolar lavage (BAL) from subjects with and without IPF, as well as in plasma samples from two longitudinal IPF cohorts and demographically matched control subjects. MEASUREMENTS AND MAIN RESULTS: Exposure to mtDNA augments α-smooth muscle actin expression in NHLFs. The metabolic changes in NHLFs that are induced by interactions with TGF-ß1 or stiff hydrogels are accompanied by the accumulation of extracellular mtDNA. These findings replicate the spontaneous phenotype of IPF fibroblasts. mtDNA concentrations are increased in IPF BAL and plasma, and in the latter compartment, they display robust associations with disease progression and reduced event-free survival. CONCLUSIONS: These findings demonstrate a previously unrecognized and highly novel connection between metabolic reprogramming, mtDNA, fibroblast activation, and clinical outcomes that provides new insight into IPF.


Subject(s)
DNA, Mitochondrial/metabolism , Fibroblasts/metabolism , Idiopathic Pulmonary Fibrosis/metabolism , Idiopathic Pulmonary Fibrosis/mortality , Aged , Disease-Free Survival , Female , Humans , Male
20.
Am J Case Rep ; 18: 157-159, 2017 Feb 13.
Article in English | MEDLINE | ID: mdl-28190872

ABSTRACT

BACKGROUND Laryngeal sarcoidosis is a rare extrapulmonary manifestation of sarcoidosis, accounting for 0.33-2.1% of cases. A life-threatening complication of laryngeal sarcoidosis is upper airway obstruction. In this report we describe our experience in the acute and chronic care of a patient who required an emergent tracheostomy, with the aim to provide further insight into this difficult to manage disease. CASE REPORT A 37-year-old African American female with a 10-year history of stage 1 sarcoidosis presented with severe dyspnea. Laryngeal sarcoidosis was diagnosed three years previously, and she remained stable on low-dose prednisone until six months prior to admission, at which time she self-discontinued her prednisone for the homeopathic treatment Nopalea cactus juice. Her physical examination was concerning for impending respiratory failure as she presented with inspiratory stridor and hoarseness. Laryngoscopy showed a retroflexed epiglottis obstructing the glottis with edematous arytenoids and aryepiglottic folds. Otolaryngology performed an emergent tracheostomy to secure her airway and obtained epiglottic biopsies, which were consistent with sarcoidosis. She was eventually discharged home on prednisone 60 mg daily. Following months of corticosteroids, a laryngoscopy showed the epiglottis continuing to obstruct the glottis. The addition of methotrexate to a tapered dosage of prednisone 10 mg daily was unsuccessful, and she remains on prednisone 20 mg daily for disease control. CONCLUSIONS Laryngeal sarcoidosis, a rare extrapulmonary manifestation of sarcoidosis, uncommonly presents as the life-threatening complication of complete upper airway obstruction. As such, laryngeal sarcoidosis is associated with significant morbidity and mortality, requiring a high index of suspicion for timely diagnosis and treatment.


Subject(s)
Airway Obstruction/etiology , Airway Obstruction/surgery , Laryngeal Diseases/complications , Laryngeal Diseases/surgery , Sarcoidosis/complications , Sarcoidosis/surgery , Tracheostomy , Adult , Emergencies , Female , Glucocorticoids/therapeutic use , Humans , Laryngeal Diseases/drug therapy , Laryngoscopy , Prednisone/therapeutic use , Sarcoidosis/diagnosis , Sarcoidosis/drug therapy , Tracheostomy/methods , Treatment Outcome
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