Detection of COVID-19 features in lung ultrasound images using deep neural networks.

BACKGROUND: Deep neural networks (DNNs) to detect COVID-19 features in lung ultrasound B-mode images have primarily relied on either in vivo or simulated images as training data. However, in vivo images suffer from limited access to required manual labeling of thousands of training image examples, and simulated images can suffer from poor generalizability to in vivo images due to domain differences. We address these limitations and identify the best training strategy. METHODS: We investigated in vivo COVID-19 feature detection with DNNs trained on our carefully simulated datasets (40,000 images), publicly available in vivo datasets (174 images), in vivo datasets curated by our team (958 images), and a combination of simulated and internal or external in vivo datasets. Seven DNN training strategies were tested on in vivo B-mode images from COVID-19 patients. RESULTS: Here, we show that Dice similarity coefficients (DSCs) between ground truth and DNN predictions are maximized when simulated data are mixed with external in vivo data and tested on internal in vivo data (i.e., 0.482 ± 0.211), compared with using only simulated B-mode image training data (i.e., 0.464 ± 0.230) or only external in vivo B-mode training data (i.e., 0.407 ± 0.177). Additional maximization is achieved when a separate subset of the internal in vivo B-mode images are included in the training dataset, with the greatest maximization of DSC (and minimization of required training time, or epochs) obtained after mixing simulated data with internal and external in vivo data during training, then testing on the held-out subset of the internal in vivo dataset (i.e., 0.735 ± 0.187). CONCLUSIONS: DNNs trained with simulated and in vivo data are promising alternatives to training with only real or only simulated data when segmenting in vivo COVID-19 lung ultrasound features.

Computational tools are often used to aid detection of COVID-19 from lung ultrasound images. However, this type of detection method can be prone to misdiagnosis if the computational tool is not properly trained and validated to detect image features associated with COVID-19 positive lungs. Here, we devise and test seven different strategies that include real patient data and simulated patient data to train the computational tool on how to correctly diagnose image features with high accuracy. Simulated data were created with software that models ultrasound physics and acoustic wave propagation. We find that incorporating simulated data in the training process improves training efficiency and detection accuracy, indicating that a properly curated simulated dataset can be used when real patient data are limited.

Solid chip-based detection of trace morphine in solutions via portable surface-enhanced Raman spectroscopy.

The accurate, sensitive and portable detection of morphine is important to handle judicial cases, but remains to be a great challenge. In this work, a flexible route is presented for the accurate identification and efficient detection of trace morphine in solutions based on surface-enhanced Raman spectroscopy (SERS) and a solid substrate/chip. A gold-coated jagged silicon nanoarray (Au-JSiNA) is designed and prepared via Si-based polystyrene colloidal template-reactive ion etching and sputtering deposition of Au. Such Au-JSiNA has three-dimensional nanostructure with good structural uniformity, high SERS activity and hydrophobic surface. Adopting this Au-JSiNA as SERS chip, trace morphine in solutions could be detected and identified in both dropping and soaking ways, and the limit of detection is below 10-4 mg/mL. Importantly, such chip is especially suitable for the detection of trace morphine in aqueous solutions and even domestic sewage. The good SERS performance is attributed to the high-density nanotips and nanogaps on this chip as well as its hydrophobic surface. Additionally, the appropriate surface modification of this Au-JSiNA chip with 3-mercapto-1-propanol or 3-mercaptopropionic acid/1-(3-dimethylaminopropyl)-3-ethylcarbodiimide can further increase its SERS performances to morphine. This work provides a facile route and practical solid chip for SERS detection of trace morphine in solutions, which is significant to develop the portable and reliable instruments for on-site analysis of drugs in solutions.

Tetra-Nuclear Cluster-Based Lanthanide Metal-Organic Frameworks as White Phosphor, Information Encryption, Self-Calibrating Thermometers, and Fe2+ Sensors.

The application of one kind of metal-organic framework (MOF) material used in multiple fields is one of the most interesting research topics. In this work, four new tetra-nuclear cluster-based lanthanide metal-organic frameworks (LnMOFs) [Ln2(BTDB)3(DMA)(phen)]n (Ln = Tb TbMOF, Eu EuMOF, Gd GdMOF, Tb1.830Eu0.170 Tb,EuMOF, 3,5-bis(trifluoromethyl)-4',4″-dicarboxytriphenylamine = H2BTDB, 1,10-phenanthroline = phen) are obtained based on the ligand of H2BTDB that is synthesized in our laboratory, and the precise single-crystal structure of H2BTDB is obtained for the first time. The white phosphor was obtained by facilely hybridizing two components of the orange-yellow emission phosphor of Tb,EuMOF and the blue luminescence material of triphenylamine according to the trichromatic theory. At the same time, TbMOF, EuMOF, Tb,EuMOF, and the white phosphor can be used for information encryption, demonstrating their potential application in the field of anti-counterfeiting. Tb,EuMOF is also a multi-mode and self-calibrating thermometer within a broad temperature range of 110-300 K. Further studies show that EuMOF is a rapid response sensor for Fe2+, with a very low limit of detection of 2.0 nM, which is much lower than the national standards for Fe2+ (GB 5749-2005, 5.357 µM). It can achieve strong anti-interference detection of Fe2+ in actual samples of tap water and lake water. In addition, EuMOF can also be made into an easy-to-use sensing device of test paper for real-time and visual sensing of Fe2+.

HIF2α-induced upregulation of RNASET2 promotes triglyceride synthesis and enhances cell migration in clear cell renal cell carcinoma.

Clear cell renal cell carcinoma (ccRCC), the most common malignant subtype of renal cell carcinoma, is characterized by the accumulation of lipid droplets in the cytoplasm. RNASET2 is a protein coding gene with a low expression level in ovarian cancers, but it is overexpressed in poorly differentiated neuroendocrine carcinomas. There is a correlation between RNASET2 upregulation and triglyceride expression levels in human serum but is unknown whether such an association is a factor contributing to lipid accumulation in ccRCC. Herein, we show that RNASET2 expression levels in ccRCC tissues and cell lines are significantly higher than those in both normal adjacent tissues and renal tubular epithelial cells. Furthermore, its upregulation is associated with increases in ccRCC malignancy and declines in patient survival. We also show that an association exists between increases in both cytoplasmic lipid accumulation and HIF-2α transcription factor upregulation, and increases in both RNASET2 and triglyceride expression levels in ccRCC tissues. In addition, DGAT1 and DGAT2, two key enzymes involved in triglyceride synthesis, are highly expressed in ccRCC tissues. By contrast, RNASET2 knockdown inhibited their expression levels and lowered lipid droplet accumulation, as well as suppressing in vitro cell proliferation, cell invasion, and migration. In conclusion, our data suggest HIF2α upregulates RNASET2 transcription in ccRCC cells, which promotes both the synthesis of triglycerides and ccRCC migration. As such, RNASET2 may have the potential as a biomarker or target for the diagnosis and treatment of ccRCC.

Framework Nucleic Acids as Blood-Retinal-Barrier-Penetrable Nanocarrier for Periocular Administration.

Designing an ocular drugs delivery system that can permeate the outer blood-retinal barrier (oBRB) is crucial for the microinvasive or noninvasive treatment of ocular fundus diseases. However, due to the lack of a nanocarrier that can maintain structure and composition at the oBRB, only intravitreal injection at the eyeball can deliver therapeutics directly to the ocular fundus via paracellular and intercellular routes, despite the intraocular operations risks. Here, we demonstrated tetrahedral framework nucleic acids (tFNAs) can penetrate the oBRB and deliver therapeutic nucleic acids to the retina of the rat eye in vivo following subconjunctival injection. We also discovered that tFNAs were transported via a paracellular route across the intercellular tight junctions at the oBRB. The histology analysis for ocular layers indicated that individual and aptamer/doxorubicin-loaded tFNAs penetrated all layers of the posterior segment of the eyeball to reach the innermost retina and persisted for over 3 days with minimal systemic biodistribution. We expect that the programmability and penetrability of tFNAs will provide a promising method for drug delivery across oBRB and long-term sustenance at the target site via periocular administration to various tissues.

The effect of antioxidant dietary supplements and diet-derived circulating antioxidants on vitiligo outcome: evidence from genetic association and comprehensive Mendelian randomization.

Background: Previous studies have indicated that antioxidant diets may have a positive impact on vitiligo by interfering with oxidative stress mechanisms. However, there has been a lack of research utilizing the Mendelian randomization (MR) method to analyze the relationship between antioxidant diet intake and vitiligo. Methods: In this study, we employed both univariate Mendelian randomization (UVMR) and multivariate Mendelian randomization (MVMR) approaches. The specific antioxidant dietary supplements (such as coffee intake, green tea intake, herbal tea intake, standard tea intake, and average weekly red wine intake) as well as diet-derived circulating antioxidants, including Vit. C (ascorbate), Vit. E (α-tocopherol), Vit. E (γ-tocopherol), Carotene, Vit. A (retinol), Zinc, and Selenium (N = 2,603-428,860) were significantly associated with independent single-nucleotide polymorphisms (SNPs). We obtained pooled statistics on vitiligo from a meta-analysis of three genome-wide association studies (GWASs) of European ancestry, including 4,680 cases and 39,586 controls. Inverse variance weighted (IVW) was employed as the primary analytical method, and sensitivity analysis was conducted to assess the robustness of the main findings. Results: Genetically, coffee intake [odds ratio (OR) = 0.17, 95% confidence interval (CI) 0.07-0.37, p = 1.57 × 10-5], average weekly red wine intake (OR = 0.28, 95% CI 0.08-1.00, p = 0.049), and standard tea intake (OR = 0.99, 95% CI 0.98-0.99, p = 5.66 × 10-7) were identified as protective factors against vitiligo. However, no causal effect between the intake of other antioxidant diets and vitiligo was found. Moreover, no instances of pleiotropy or heterogeneity were observed in this study. Conclusion: Our study indicates that coffee, standard tea, and red wine consumption can potentially reduce the risk of vitiligo. However, there is insufficient evidence to support that other antioxidant diets have a significant effect on vitiligo.

Rapid and sensitive SERS detection of opioids in solutions based on the solid chip Au-coated Si nano-cone array.

Rapid and flexible detection or accurate recognition of trace drugs is of great importance in cracking down on drug crimes, but it remains to be expected. Here, a solid chip is presented for the efficient detection and recognition of trace opioids (typically morphine) in aqueous solutions based on surface-enhanced Raman spectroscopy (SERS). Firstly, a Au-coated Si nano-cone array (Au-SNCA) is designed and fabricated via Si-based organic colloidal template etching and Au deposition. This Au-SNCA shows three-dimensional nanostructure with high densities of nanotips and deep nanogaps as well as high structural consistency, which exhibits strong SERS activity to morphine and outstanding stability. Then, such Au-SNCA is used as solid SERS chip to detect morphine in aqueous solutions. It has been demonstrated that using such solid chip, trace morphine in solutions could be recognized and detected within 1 min, and the detection limit is 10-5 mg/mL (∼10 ppb), showing rapid and sensitive detection, which is much better than the previous reports. Meanwhile, the Au-SNCA chip also can be utilized to detect trace morphine in tap water and reservoir water, the recoveries range from 90.4% to 102.4%. Such excellent SERS performance of this Au-SNCA chip is attributed to its special structure which enhances not only local electromagnetic field but also molecular adsorption. The experimental results about the effects of immersion time and concentration show that the adsorption behavior of morphine molecules on such Au-SNCA chip can be explained by the pseudo-second-order kinetic model and Freundlich adsorption mode. Moreover, the Au-SNCA chip is also suitable for the identification of morphine homologues and the broad-spectrum detection of various common drugs. This study presents a practical solid chip and a simple approach for the efficient SERS detection and recognition of trace drugs in solutions. This is of significance to on-site detect drugs in forensic science.

Study of the separation ability differences of three covalent organic frameworks as coated materials in capillary electrochromatography.

Covalent organic frameworks (COFs) have great potential applications in chromatographic separation. So it is crucial to understand the relationship between the separation ability of COFs and their structures. Here we report a strategy to evaluate the separation ability of three 2D COFs and explore the relationship between separation ability and their molecular structures. The three 2D COFs (COF-LZU1, COF-42 and COF-LZU8) have one same building unit 1,3,5-triformylbenzene, while varied from the conjugated linking units and functional side-chains. They were used to construct coated capillary column for capillary electrochromatographic separation of same groups of phthalates. They exhibited different separation efficiencies. COF-42 and COF-LZU8 coated capillary columns provided good signal resolutions and high column efficiencies with high theoretical plate numbers. It is demonstrated that COFs with hydrazone unit and longer side-chains provided higher selectivity and resolutions for the phthalates separation. Molecular simulations and DFT calculations were further proceeded to explore the deep reason why the three COFs coated CEC displayed different separation ability based on the host-guest interactions on molecular level. This work highlights a new opportunity to select or design functional COFs and improve their efficiency in chromatographic separation based on host-guest chemistry.

A Review of Deep Learning Applications in Lung Ultrasound Imaging of COVID-19 Patients.

The massive and continuous spread of COVID-19 has motivated researchers around the world to intensely explore, understand, and develop new techniques for diagnosis and treatment. Although lung ultrasound imaging is a less established approach when compared to other medical imaging modalities such as X-ray and CT, multiple studies have demonstrated its promise to diagnose COVID-19 patients. At the same time, many deep learning models have been built to improve the diagnostic efficiency of medical imaging. The integration of these initially parallel efforts has led multiple researchers to report deep learning applications in medical imaging of COVID-19 patients, most of which demonstrate the outstanding potential of deep learning to aid in the diagnosis of COVID-19. This invited review is focused on deep learning applications in lung ultrasound imaging of COVID-19 and provides a comprehensive overview of ultrasound systems utilized for data acquisition, associated datasets, deep learning models, and comparative performance.

Epigenetic Control of Autophagy Related Genes Transcription in Pulpitis via JMJD3.

Autophagy is an intracellular self-cannibalization process delivering cytoplasmic components to lysosomes for digestion. Autophagy has been reported to be involved in pulpitis, but the regulation of autophagy during pulpitis progression is largely unknown. To figure out the epigenetic regulation of autophagy during pulpitis, we screened several groups of histone methyltransferases and demethylases in response to TNFα treatment. It was found JMJD3, a histone demethylase reducing di- and tri-methylation of H3K27, regulated the expression of several key autophagy genes via demethylation of H3K27me3 at the gene promoters. Our study highlighted the epigenetic regulation of autophagy genes during pulpitis, which will potentially provide a novel therapeutic strategy.

Functional photoacoustic/ultrasound imaging for the assessment of breast intraductal lesions: preliminary clinical findings.

This study aimed to identify features of breast intraductal lesions in photoacoustic/ultrasound (PA/US) imaging and compare PA/US with color Doppler flow/ultrasound (CDFI/US) in the evaluation of breast intraductal lesions. In the nine patients with 10 breast intraductal lesions and 8 patients with 8 benign lesions, total vessel scores evaluated from PA/US are significantly greater than those from CDFI/US (p=0.005). PA internal vessel scores and oxygen saturation (SO2) score are significantly increased in breast intraductal lesions than in benign lesions (p=0.016, p=0.006). With a cutoff PA score (sum of PA internal vessel score and SO2 score) of 2.5, we obtained a sensitivity of 90% and a specificity of 87.5% in differentiation of two groups. PA/US upgraded 40% of breast intraductal lesions, and downgraded 50% of benign lesions from the Breast Imaging Reporting and Data System grading results based on CDFI/US. PA/US functional imaging has the potential in differentiating breast intraductal lesions.

Exploring the diagnostic value of photoacoustic imaging for breast cancer: the identification of regional photoacoustic signal differences of breast tumors.

We examined 14 benign and 26 malignant breast nodules by a handheld dual-modal PA/US imaging system and analyzed the data using the quantitative and semi-quantitative method. The PA signal spatial density and PA scores of different regions of the benign and malignant nodules were compared, and the diagnostic performances of two diagnostic methods based on PA parameters were evaluated. For both quantitative and semi-quantitative results, significant differences in the distributions of PA signals in different regions of benign and malignant breast lesions were identified. The PA parameters showed good performance in diagnosing breast cancer, indicating the potential of PAI in clinical utilization.

The Involvement of Histone Methylation in the Osteogenic Differentiation of Mesenchymal Stem Cells.

Bone is a hard but dynamic organ that is constantly remodeled throughout the life process. The dynamic balance between bone resorption and bone formation is very important. Mesenchymal stem cells (MSCs) have self-renewal and pluripotent differentiation; therefore, their roles as the promising tool for the treatment of osteoporosis and other diseases have become the focus in regenerative medicine in recent years. Over the past years, histone methylation has been recognized as a major player in the regulation of osteogenic differentiation of MSC. In this review, we highlight the recent research progress of histone methylation modification and its possible involvement in MSC osteogenesis.

Exosome-Derived Noncoding RNAs as a Promising Treatment of Bone Regeneration.

The reconstruction of large bone defects remains a crucial challenge in orthopedic surgery. The current treatments including autologous and allogenic bone grafting and bioactive materials have their respective drawbacks. While mesenchymal stem cell (MSC) therapy may address these limitations, growing researches have demonstrated that the effectiveness of MSC therapy depends on paracrine factors, particularly exosomes. This aroused great focus on the exosome-based cell-free therapy in the treatment of bone defects. Exosomes can transfer various cargoes, and noncoding RNAs are the most widely studied cargo through which exosomes exert their ability of osteoinduction. Here, we review the research status of the exosome-derived noncoding RNAs in bone regeneration, the potential application of exosomes, and the existing challenges.

Analysis of volatile components in inkjet printouts by GC-MS: A classification method.

Considering the high use of inkjet printing in forgery cases, the classification of inkjet printing is particularly important in questioned document examination. In this work, a universal GC-MS method has been developed to analyze various ink components extracted from inkjet printouts. The results indicated that several components detected and identified across 195 inks could be used to distinguish printer manufacturers. A trend of decreasing solvent concentration over time was observed through the continuous monitoring of 7 samples. The results shown that this method is useful for forensic classification purposes, and can be useful regardless effects of storage environment, paper or printer. Furthermore, the application of this method in the analysis of counterfeit banknotes illustrated its feasibility and applicability.

A three-dimensional modeling method for quantitative photoacoustic breast imaging with handheld probe.

By providing complementary functional information, photoacoustic (PA) breast imaging based on the handheld ultrasound (US) probe has demonstrated promising potential for breast cancer diagnosis. However, the quantitative PA imaging primarily relies on the knowledge of the optical fluence distribution in the three-dimensional (3D) heterogeneous breast tissue. Previous studies based on the handheld system generally provided two-dimensional (2D) B-scan results, which contains limited anatomical information of the tissue and the lesion. This study proposed a method to perform 3D modeling of the photon transportation for dual-modality PA/US system based on the local 3D breast anatomical information by scanning US probe. Then the calculated optical fluence distribution can be used for PA imaging. Our phantom and clinical pilot study results demonstrated that this method has potential to improve the accuracy of the quantitative PA breast imaging, and it can also be used in other clinical implementations.

A Multiple Primary Malignancy Patient With FANCA Gene Mutation: A Case Report and Literature Review.

Background: Multiple primary malignancies (MPMs) refer to two or more primary malignant tumors in the same individual, the prevalence of which ranges from 0. 734 to 11.7%. The risk factors for MPMs vary and include both genetic and environmental causes. FANCA gene mutation might be a predisposition to the development of a second primary cancer. Here, we report a case in which a patient with a FANCA mutation developed thyroid papillary carcinoma and gastric adenocarcinoma. Case Presentation: A 48-year-old woman was diagnosed with thyroid cancer underwent resection in 2006. In 2008, the patient developed gastric adenocarcinoma and underwent radical gastrectomy. Gastric cancer was completely remitted after radiochemotherapy, but metastasis developed, and she received immunotherapy. The patient died on October 27, 2019. Peripheral blood gene detection showed germline FANCA mutation. Conclusions: Gene detection is of great importance in cancer patients, especially in those with MPMs. FANCA mutation is a predisposition to tumorigenesis that can increase the risk of developing MPMs. Patients with heterozygous FANCA gene mutations have poorer outcomes.

Quantitative analysis of breast tumours aided by three-dimensional photoacoustic/ultrasound functional imaging.

In this pilot study, we explored a quantitative method to analyse characteristics of breast tumours using 3D volumetric data obtained from a three-dimensional (3D) photoacoustic/ultrasound (PA/US) functional imaging system. Imaging results from 24 Asian patients with maximum tumour diameters less than 2 cm, including 8 benign tumours, 16 T1 stage invasive breast cancers (IBCs), and 22 normal breasts, were analysed. We found that the volumetric mean oxygenation saturation (SO2) in tumour regions of T1 stage IBCs was 7.7% lower than that of benign tumours (P = 0.016) and 3.9% lower than that of healthy breasts (P = 0.010). The volumetric mean SO2 in tumour surrounding regions of T1 stage IBCs was 4.9% lower than that of benign tumours (P = 0.009). For differentiating T1 stage IBCs and benign tumours, with a cut-off SO2 value of 78.2% inside tumours, we obtained a sensitivity of 100%, a specificity of 62.5%, and an AUC of 0.81; with a cut-off SO2 value of 77.9% in regions surrounding tumours, we obtained a sensitivity of 100%, a specificity of 75% and an AUC of 0.84. Our preliminary results demonstrate that 3D PA/US functional imaging has the potential to provide valuable quantitative physiological information that may be useful for the detection and evaluation of breast tumours.

Ultrafast ultrasound imaging of surface acoustic waves induced by laser excitation compared with acoustic radiation force.

Two generation mechanisms-optical perturbation and acoustic radiation force (ARF)-were investigated where high frame rate ultrasound imaging was used to track the propagation of induced SAWs. We compared ARF-induced SAWs with laser-induced SAWs generated by laser beam irradiation of the uniformly absorbing tissue-like viscoelastic phantom, where light was preferentially absorbed at the surface. We also compared the frequency content of SAWs generated by ARF versus pulsed laser light, using the same duration of excitation. Differences in the SAW bandwidth were expected because, in general, laser light can be focused into a smaller area. Finally, we compared wave generation and propagation when the wave's origin was below the surface. We also investigated the relationship between shear wave amplitude and optical fluence. The investigation reported here can potentially extend the applications of laser-induced SAW generation and imaging in life sciences and other applications.