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Recurrent spontaneous abortion (RSA) is the most common pregnancy-related complication, affecting 1–5% of pregnancies. Currently, immune imbalance at the maternal–fetal interface is one of the main causes of recurrent abortion. Icariin (ICA) can exert immunomodulatory effects in a variety of autoimmune diseases. Nevertheless, it has not been reported for use in recurrent abortion. In this study, to clarify the effects and mechanisms of ICA for recurrent abortion, female mice CBA/J were randomly divided into Normal group, RSA group and RSA + ICA group. From 0.5 days of pregnancy to 12.5 days, the RSA + ICA group was subjected to orally ICA (50 mg/Kg) daily, and the Normal group and the RSA group were given with an equal volume of distilled water. The results showed the amount of reabsorbed embryo in the RSA group was significantly higher than that in the normal-pregnancy group. However, ICA treatment showed a rescue effect on spontaneous abortion in RSA mice. ICA was able to increase the ratio of the labyrinth to total placental area in abortion-prone model. Further investigation showed that ICA treatment can expand the regulatory T cell (Treg) population in mice prone to abortion, significantly decrease the populations of Th1 cells, and reduce the expression of pro-inflammatory factors. Additionally, ICA treatment was able to decrease the expression of mechanical target of rapamycin (mTOR) in the placenta. ICA may increase Treg cell expansion and reducing pro-inflammatory factors expression via the mTOR pathway, then reducing placental inflammation and improving pregnancy outcomes in abortion-prone mice.

The GE Discovery NM (DNM) 530c/570c are dedicated cardiac SPECT scanners with 19 detector modules designed for stationary imaging. This study aims to incorporate additional projection angular sampling to improve reconstruction quality. A deep learning method is also proposed to generate synthetic dense-view image volumes from few-view counterparts.By moving the detector array, a total of four projection angle sets were acquired and combined for image reconstructions. A deep neural network is proposed to generate synthetic four-angle images with 76 ([Formula: see text]) projections from corresponding one-angle images with 19 projections. Simulated data, pig, physical phantom, and human studies were used for network training and evaluation. Reconstruction results were quantitatively evaluated using representative image metrics. The myocardial perfusion defect size of different subjects was quantified using an FDA-cleared clinical software.Multi-angle reconstructions and network results have higher image resolution, improved uniformity on normal myocardium, more accurate defect quantification, and superior quantitative values on all the testing data. As validated against cardiac catheterization and diagnostic results, deep learning results showed improved image quality with better defect contrast on human studies.Increasing angular sampling can substantially improve image quality on DNM, and deep learning can be implemented to improve reconstruction quality in case of stationary imaging.

We characterize a new chaos lidar system configuration and demonstrate its capability for high-speed 3D imaging. Compared with a homodyned scheme employing single-element avalanche photodetectors (APDs), the proposed scheme utilizes a fiber Bragg grating and quadrant APDs to substantially increase the system throughput, frame rate, and field-of-view. By quantitatively analyzing the signal-to-noise ratio, peak-to-standard deviation of the sidelobe level, precision, and detection probability, we show that the proposed scheme has better detection performance suitable for practical applications. To show the feasibility of the chaos lidar system, while under the constrain of eye-safe regulation, we demonstrate high-speed 3D imaging with indoor and outdoor scenes at a throughput of 100 kHz, a frame rate of 10 Hz, and a FOV of 24.5$$^\circ $$ ∘ $$\times $$ × 11.5$$^\circ $$ ∘ for the first time.

BACKGROUND Attenuation correction can improve the quantitative accuracy of single-photon emission computed tomography (SPECT) images. Existing SPECT-only systems normally can only provide non-attenuation corrected (NC) images which are susceptible to attenuation artifacts. In this work, we developed a post-reconstruction attenuation correction (PRAC) approach facilitated by a deep learning-based attenuation map for myocardial perfusion SPECT imaging. METHODS In the PRAC method, new projection data were estimated via forwardly projecting the scanner-generated NC image. Then an attenuation map, generated from NC image using a pretrained deep learning (DL) convolutional neural network, was incorporated into an offline reconstruction algorithm to obtain the attenuation-corrected images from the forwardly projected projections. We evaluated the PRAC method using 30 subjects with a DL network trained with 40 subjects, using the vendor-generated AC images and CT-based attenuation maps as the ground truth. RESULTS The PRAC methods using DL-generated and CT-based attenuation maps were both highly consistent with the scanner-generated AC image. The globally normalized mean absolute errors were 1.1% ± .6% and .7% ± .4% and the localized absolute percentage errors were 8.9% ± 13.4% and 7.8% ± 11.4% in the left ventricular (LV) blood pool, respectively, and - 1.3% ± 8.0% and - 3.8% ± 4.5% in the LV myocardium for PRAC methods using DL-generated and CT-based attenuation maps, respectively. The summed stress scores after PRAC using both attenuation maps were more consistent with the ground truth than those of the NC images. CONCLUSION We developed a PRAC approach facilitated by deep learning-based attenuation maps for SPECT myocardial perfusion imaging. It may be feasible for this approach to provide AC images for SPECT-only scanner data.

This study aimed to evaluate the protein expression of glutathione peroxidase 4 (GPX4) in resected non-small cell lung cancer (NSCLC). The clinical relevance and prognostic significance of GPX4 expression were analyzed. We reviewed patients with resected NSCLCs at Taipei Veterans General Hospital between September 2002 and January 2018. Available paraffin-embedded specimens were retrieved for immunohistochemistry (IHC) staining to detect GPX4 expression. The cutoff value for defining GPX4 positivity was determined according to the percentage of tumor stained in the microscopic field. The correlation between immune expression, clinicopathologic data, overall survival (OS), and disease-free survival (DFS) were analyzed. A total of 265 NSCLC specimens were retrieved for IHC staining. GPX4 expression positive was in 192 (72.5%) according to a cutoff value of 5%. GPX4 was a significant prognostic factor for OS and DFS on multivariate analysis at both 5% and 25% cutoff values. GPX4 expression was associated with poor OS and DFS, especially in lung adenocarcinoma (p = 0.008, and 0.027, respectively). In conclusions, IHC analysis revealed that GPX4 expression was associated with poor survival outcomes in patients with resected lung adenocarcinoma. Further research is needed to understand the role of GPX4 in tumorigenesis and the underlying mechanism responsible for survival outcomes in patients with resected lung adenocarcinoma.

Immunosenescence is the deterioration of the innate and adaptive immune systems associated with aging and is primarily characterized by a reduction in T cell production and accumulation of atypical subsets. Age-related immunological dysfunction leads to impaired immune protection and persistent low-grade chronic inflammation, resulting in a decreased vaccination response and increased vulnerability to infection, cancer, cardiovascular disease, and autoimmune disease in the elderly. As the elderly constitute a growing proportion of the population with renal disease, immunosenescence is a normal aging process that is prevalent among older people. In addition, immunosenescence seems to be more pronounced in patients with kidney diseases than in healthy controls, as shown by severe chronic inflammation, accumulation of immune cells with the senescent phenotype (CD28− T cells, CD14+CD16+ monocytes), and proinflammatory cytokine production. Immunosenescence inhibits immunological clearance and renal tissue regeneration, thereby increasing the risk of permanent renal damage, infection, and cardiovascular events in patients with kidney disease, lowering the prognosis, and even influencing the efficacy of renal replacement treatment. Biological drugs (senomorphics and senolytics) target the aging immune system and exert renoprotective effects. This review aims to emphasize the features of immunosenescence and its influence on kidney diseases and immunotherapy, highlighting the future directions of kidney disease treatment using senescence-focused techniques.

BackgroundRetinal ganglion cells (RGCs) are important retinal neurons that connect visual receptors to the brain, and lysine-specific demethylase 1 (LSD1) is implicated in the development of RGCs. This study expounded the mechanism of LSD1 in oxygen-glucose deprivation/reoxygenation (OGD/R)-induced pyroptosis of RGCs.MethodsMouse RGCs underwent OGD/R exposure, and then RGC viability was examined using the cell counting kit-8 method. The mRNA levels of Caspase 1, the protein levels of NOD-like receptor family pyrin domain-containing 3 (NLRP3), N-terminal fragment of gasdermin D (GSDMD-N), and cleaved-Caspase1, and the concentrations of interleukin (IL)-1β and IL-18 were respectively examined. Subsequently, LSD1 expression was intervened to explore the underlying effect of LSD1 on OGD/R-induced pyroptosis of RGCs. Afterwards, the enrichments of LSD1 and histone H3 lysine 4 methylation (H3K4me) 1/2 on the microRNA (miR)-21-5p promoter were determined using chromatin-immunoprecipitation assay. And the binding interaction between miR-21-5p and NLRP12 was detected using dual-luciferase and RNA pull-down assays. Finally, the effects of miR-21-5p/NLRP12 on LSD1-mediated pyroptosis of RGCs were verified through functional rescue experiments.ResultsOGD/R treatment increased pyroptosis of RGCs and LSD1 expression. Silencing LSD1 declined levels of Caspase 1 mRNA, NLRP3, GSDMD-N, cleaved-Caspase1, IL-1β, and IL-18 and limited pyroptosis of OGD/R-treated RGCs. Mechanically, LSD1 suppressed miR-21-5p expression via demethylation of H3K4me2 on the miR-21-5p promoter to hamper the binding of miR-21-5p to NLRP12, and thereby increased NLRP12 expression. Silencing miR-21-5p or overexpressing NLRP12 facilitated OGD/R-induced pyroptosis of RGCs.ConclusionLSD1-mediated demethylation of H3K4me2 decreased miR-21-5p expression to increase NLRP12 expression, promoting pyroptosis of OGD/R-treated RGCs.

Early cancer detection by cell-free DNA faces multiple challenges: low fraction of tumor cell-free DNA, molecular heterogeneity of cancer, and sample sizes that are not sufficient to reflect diverse patient populations. Here, we develop a cancer detection approach to address these challenges. It consists of an assay, cfMethyl-Seq, for cost-effective sequencing of the cell-free DNA methylome (with > 12-fold enrichment over whole genome bisulfite sequencing in CpG islands), and a computational method to extract methylation information and diagnose patients. Applying our approach to 408 colon, liver, lung, and stomach cancer patients and controls, at 97.9% specificity we achieve 80.7% and 74.5% sensitivity in detecting all-stage and early-stage cancer, and 89.1% and 85.0% accuracy for locating tissue-of-origin of all-stage and early-stage cancer, respectively. Our approach cost-effectively retains methylome profiles of cancer abnormalities, allowing us to learn new features and expand to other cancer types as training cohorts grow.

Malignant tumors have become the most dangerous disease in recent years. Chemotherapy is the most effective treatment for this disease; however, the problem of drug resistance has become even more common, which leads to the poor prognosis of patients suffering from cancers. Thus, necessary measures should be taken to address these problems at the earliest. Many studies have demonstrated that drug resistance is closely related to the abnormal expressions of long non-coding RNAs (lncRNAs). This review aimed to summarize the molecular mechanisms underlying the association of lncRNAs and the development of drug resistance and to find potential strategies for the clinical diagnosis and treatment of cancer drug resistance. Studies showed that lncRNAs can regulate the expression of genes through chromatin remodeling, transcriptional regulation, and post-transcriptional processing. Furthermore, lncRNAs have been reported to be closely related to the occurrence of malignant tumors. In summary, lncRNAs have gained attention in related fields during recent years. According to previous studies, lncRNAs have a vital role in several different types of cancers owing to their multiple mechanisms of action. Different mechanisms have different functions that could result in different consequences in the same disease. LncRNAs closely participated in cancer drug resistance by regulating miRNA, signaling pathways, proteins, cancer stem cells, pro- and ant-apoptosis, and autophagy. lncRNAs can be used as biomarkers of the possible treatment target in chemotherapy, which could provide solutions to the problem of drug resistance in chemotherapy in the future.

Gene editing is a new genetic engineering technology that uses sequence-specific nucleases to insert, delete, or replace nucleic acid base(s) of the target gene, or introduce exogenous DNA sequences at a specific site in the genome of an organism to achieve the desired modification. Currently, the CRISPR/Cas system is the most widely used genome editing technology because it is relatively simple with high editing efficiency. In this review, we discuss the CRISPR/Cas system’s application and its current limitations in rice breeding. Also, we elaborate on possible improved methods regarding its mechanism and development history.

Attenuation correction (AC) using CT transmission scanning enables the accurate quantitative analysis of dedicated cardiac SPECT. However, AC is challenging for SPECT-only scanners. We developed a deep learning-based approach to generate synthetic AC images from SPECT images without AC. CT-free AC was implemented using our customized Dual Squeeze-and-Excitation Residual Dense Network (DuRDN). 172 anonymized clinical hybrid SPECT/CT stress/rest myocardial perfusion studies were used in training, validation, and testing. Additional body mass index (BMI), gender, and scatter-window information were encoded as channel-wise input to further improve the network performance. Quantitative and qualitative analysis based on image voxels and 17-segment polar map showed the potential of our approach to generate consistent SPECT AC images. Our customized DuRDN showed superior performance to conventional network design such as U-Net. The averaged voxel-wise normalized mean square error (NMSE) between the predicted AC images by DuRDN and the ground-truth AC images was 2.01 ± 1.01%, as compared to 2.23 ± 1.20% by U-Net. Our customized DuRDN facilitates dedicated cardiac SPECT AC without CT scanning. DuRDN can efficiently incorporate additional patient information and may achieve better performance compared to conventional U-Net.

Intramuscular vaccines have greatly reduced hospitalization and death due to severe COVID-19. However, most countries are experiencing a resurgence of infection driven predominantly by the Delta and Omicron variants of SARS-CoV-2. In response, booster dosing of COVID-19 vaccines has been implemented in many countries to address waning immunity and reduced protection against the variants. However, intramuscular boosting fails to elicit mucosal immunity and therefore does not solve the problem of persistent viral carriage and transmission, even in patients protected from severe disease. In this study, two doses of stabilized prefusion SARS-CoV-2 spike (S-2P)-based intramuscular vaccine adjuvanted with Alum/CpG1018, MVC-COV1901, were used as a primary vaccination series, followed by an intranasal booster vaccination with nanoemulsion (NE01)-adjuvanted S-2P vaccine in a hamster model to demonstrate immunogenicity and protection from viral challenge. Here we report that this vaccination regimen resulted not only in the induction of robust immunity and protection against weight loss and lung pathology following challenge with SARS-CoV-2, but also led to increased viral clearance from both upper and lower respiratory tracts. Our findings showed that intramuscular MVC-COV1901 vaccine followed by a booster with intranasal NE01-adjuvanted vaccine promotes protective immunity against both viral infection and disease, suggesting that this immunization protocol may offer a solution in addressing a significant, unmet medical need for both the COVID-19 and future pandemics.

Hypertension is a pathological condition of persistent high blood pressure (BP) of which the underlying neural mechanisms remain obscure. Here, we show that the afferent nerves in perirenal adipose tissue (PRAT) contribute to maintain pathological high BP, without affecting physiological BP. Bilateral PRAT ablation or denervation leads to a long-term reduction of high BP in spontaneous hypertensive rats (SHR), but has no effect on normal BP in control rats. Further, gain- and loss-of-function and neuron transcriptomics studies show that augmented activities and remodeling of L1-L2 dorsal root ganglia neurons are responsible for hypertension in SHR. Moreover, we went on to show that calcitonin gene-related peptide (CGRP) is a key endogenous suppressor of hypertension that is sequestered by pro-hypertensive PRAT in SHRs. Taken together, we identify PRAT afferent nerves as a pro-hypertensive node that sustains high BP via suppressing CGRP, thereby providing a therapeutic target to tackle primary hypertension.

The uniaxial compressive strength (UCS) is an important parameter for rock mass classification and rock engineering designs. This study proposes a novel method for predicting the UCS of rocks using X-ray computed tomography and convolutional neural networks. First, X-ray CT scanning was conducted on five mudstone specimens. The volume data characteristics of the different density compositions in rock specimens were extracted from the CT slices according to the CT thresholds. Then, the function between the cumulative CT value and the peak strength was established. The given CT image data samples of a certain rock correspond to the scope of the predictive UCS. To approve the accuracy of the UCS prediction of rocks, X-ray CT slices pre-processed with the Laplacian of Gaussian (LOG) algorithm were used to enhance the feature sharpness of the compositions in the rocks. Then, a convolutional neural network (CNN) technique based on the stochastic pooling method was applied to the LOG images of the X-ray slices to estimate the UCS of the rocks. This proposed method shows superior performance for the UCS prediction of rocks and could be widely used in the future of artificial intelligence rock engineering.

Periodontal disease is prevalent in patients with chronic kidney disease (CKD) and potentially associated with kidney function decline. However, it is uncertain whether periodontal disease affects the risk of mortality and morbidity in patients with advanced CKD. Taiwan’s National Health Insurance Research Database was used to conduct a nationwide population-based cohort study. Propensity score matching procedures were performed to select people with stage 5 CKD and to compare the long-term risk of mortality, end-stage renal disease, and major adverse cardiovascular events (MACE) between people with and without periodontal disease. Multivariable Cox regression analyses were conducted to calculate the adjusted hazard ratio (aHR) with 95% confidence interval (CI) for the outcome of interest. A total of 8119 subjects with stage 5 CKD were initially included. After matching to demographic and clinical covariates, 1254 subjects with 7099 person-years of follow-up were selected for analyses. Periodontal disease was not associated with long-term risks of all-cause mortality (aHR: 0.77, 95% CI: 0.49–1.22), progression to end-stage renal disease (aHR: 0.91, 95% CI: 0.75–1.10), or MACE (aHR: 1.18, 95% CI: 0.91–1.53). These findings were generally consistent across subgroups of age, sex, comorbid diabetes, uses of systemic antibiotic, and different dental procedures. Periodontal disease is not a predictor for long-term mortality or morbidity in patients with advanced CKD. These results provide important evidence to elucidate the relationship between periodontitis and critical clinical outcomes of advanced CKD.

Deep convolutional neural networks (CNN) for single photon emission computed tomography (SPECT) myocardial perfusion imaging (MPI) has been used to improve the diagnostic accuracy of coronary artery disease (CAD). This study was to design and evaluate a deep learning (DL) approach to automatic diagnosis of myocardial perfusion abnormalities from stress-only MPI. The new DL approach developed for this study was compared to a conventional quantitative perfusion defect size (DS) method. A total of 37,243 patients (51.5% males) undergone stress 99mTc-Tetrofosmin or 99mTc-Sestamibi MPI were selected retrospectively from Yale New Haven Hospital. Patients were dichotomized as studies with normal (75.4%) or abnormal (24.6%) myocardial perfusion based on final diagnoses of clinical nuclear cardiologists. Stress myocardial perfusion defect size was calculated using Yale quantitative analytic software. A deep CNN was trained using the circumferential count profile maps derived from SPECT MPI and was evaluated for the diagnosis of perfusion abnormality with a 5-fold cross-validation approach. In each fold, 27,933, 1862 and 7448 patients were used as training, validation and testing datasets, respectively. The area under the receiver-operating characteristic curve (AUC) was calculated and analyzed for all patients as well as for the eight sub-groups classified based on patient genders, quantitative algorithms, radioactive tracers and SPECT cameras. The AUC value resulted from the DL method was significantly higher than that from the DS method (0.872 ± 0.002 vs. 0.838 ± 0.003, p

Prostate cancer (PCa) is the second most common cause of cancer-related mortality in men. Prostate cancer metastasis usually observed at the last stage is the major cause of prostate cancer-related death. Long non-coding RNAs were reported to be involved in tumorigenesis and progression of prostate cancer. This study aimed to investigate the effects and related mechanisms of AC245100.4 in prostate cancer. Knockdown and overexpression of AC245100.4 was used to detect the effect of AC245100.4 on cell migration. qRT-PCR was used to confirm the downstream target of AC245100.4. RAP-MS was used to find pathways related to AC245100.4. Western blot was performed to detect the expression of p-p38 and p38. We found that AC245100.4 promoted the migration of prostate cancer cells via regulating PAR2. The AC245100.4 or PAR2 knockdown resulted in a decrease in Vimentin but an increase in E-cadherin protein levels, while the AC245100.4 or PAR2 overexpression got the opposite results. Moreover, we discovered that AC245100.4 activated the p38-MAPK via regulating PAR2. In brief, these results have suggested that AC245100.4 and PAR2 served as oncogenic factors in cellular migration in PCa cells.

Acute psychological stressors such as anger can precipitate ventricular arrhythmias, but the mechanism is incompletely understood. Quantification of regional myocardial sympathetic activity with 123I-metaiodobenzylguanidine (123I-mIBG) SPECT imaging in conjunction with perfusion imaging during mental stress may identify a mismatch between perfusion and sympathetic activity that may exacerbate a mismatch between perfusion and sympathetic activity that could create a milieu of increased vulnerability to ventricular arrhythmia. Five men with ischemic cardiomyopathy (ICM), and five age-matched healthy male controls underwent serial 123I-mIBG and 99mTc-Tetrofosmin SPECT/CT imaging during an anger recall mental stress task and dual isotope imaging was repeated approximately 1 week later during rest. Images were reconstructed using an iterative reconstruction algorithm with CT-based attenuation correction. The mismatch of left ventricular myocardial 123I-mIBG and 99mTc-Tetrofosmin was assessed along with radiotracer heterogeneity and the 123I-mIBG heart-to-mediastinal ratios (HMR) were calculated using custom software developed at Yale. The hemodynamic response to mental stress was similar in both groups. The resting-HMR was greater in healthy control subjects (3.67 ± 0.95) than those with ICM (3.18 ± 0.68, P = .04). Anger recall significantly decreased the HMR in ICM patients (2.62 ± 0.3, P = .04), but not in normal subjects. The heterogeneity of 123I-mIBG uptake in the myocardium was significantly increased in ICM patients during mental stress (26% ± 8.23% vs. rest: 19.62% ± 9.56%; P = .01), whereas the 99mTc-Tetrofosmin uptake pattern was unchanged. Mental stress decreased the 123I-mIBG HMR, increased mismatch between sympathetic activity and myocardial perfusion, and increased the heterogeneity of 123I-mIBG uptake in ICM patients, while there was no significant change in myocardial defect size or the heterogeneity of 99mTc-Tetrofosmin perfusion. The changes observed in this proof-of-concept study may provide valuable information about the trigger–substrate interaction and the potential vulnerability for ventricular arrhythmias.

Let $$S(t,F):=\pi ^{-1}\arg L\big (\frac{1}{2}+it,F\big ),$$ where F is a Hecke–Maass cusp form for $$\mathrm {SL}_3({\mathbb {Z}}).$$ We establish an asymptotic formula for the spectral moments of S(t, F), and obtain several other results on S(t, F).

We aimed to develop a dynamic imaging technique for a novel PET superoxide tracer, [18F]DHMT, to allow for absolute quantification of myocardial reactive oxygen species (ROS) production in a large animal model. Six beagle dogs underwent a single baseline dynamic [18F]DHMT PET study, whereas one animal underwent three serial dynamic studies over the course of chronic doxorubicin administration (1 mg·kg−1·week−1 for 15 weeks). During the scans, sequential arterial blood samples were obtained for plasma metabolite correction. The optimal compartment model and graphical analysis method were identified for kinetic modeling. Values for the left ventricular (LV) net influx rate, Ki, were reported for all the studies and compared with the LV standard uptake values (SUVs) and the LV-to-blood pool SUV ratios from the 60 to 90 minute static images. Parametric images were also generated. [18F]DHMT followed irreversible kinetics once oxidized within the myocardium in the presence of superoxide, as evidenced by the fitting generated by the irreversible two-tissue (2Ti) compartment model and the linearity of Patlak analysis. Myocardial Ki values showed a weak correlation with LV SUV (R2 = 0.27), but a strong correlation with LV-to-blood pool SUV ratio (R2 = 0.92). Generation of high-quality parametric images showed superior myocardial to blood contrast compared to static images. A dynamic PET imaging technique for [18F]DHMT was developed with full and simplified kinetic modeling for absolute quantification of myocardial superoxide production in a large animal model.

Attenuation correction using CT transmission scanning increases the accuracy of single-photon emission computed tomography (SPECT) and enables quantitative analysis. Current existing SPECT-only systems normally do not support transmission scanning and therefore scans on these systems are susceptible to attenuation artifacts. Moreover, the use of CT scans also increases radiation dose to patients and significant artifacts can occur due to the misregistration between the SPECT and CT scans as a result of patient motion. The purpose of this study is to develop an approach to estimate attenuation maps directly from SPECT emission data using deep learning methods. Both photopeak window and scatter window SPECT images were used as inputs to better utilize the underlying attenuation information embedded in the emission data. The CT-based attenuation maps were used as labels with which cardiac SPECT/CT images of 65 patients were included for training and testing. We implemented and evaluated deep fully convolutional neural networks using both standard training and training using an adversarial strategy. The synthetic attenuation maps were qualitatively and quantitatively consistent with the CT-based attenuation map. The globally normalized mean absolute error (NMAE) between the synthetic and CT-based attenuation maps were 3.60% ± 0.85% among the 25 testing subjects. The SPECT reconstructed images corrected using the CT-based attenuation map and synthetic attenuation map are highly consistent. The NMAE between the reconstructed SPECT images that were corrected using the synthetic and CT-based attenuation maps was 0.26% ± 0.15%, whereas the localized absolute percentage error was 1.33% ± 3.80% in the left ventricle (LV) myocardium and 1.07% ± 2.58% in the LV blood pool. We developed a deep convolutional neural network to estimate attenuation maps for SPECT directly from the emission data. The proposed method is capable of generating highly reliable attenuation maps to facilitate attenuation correction for SPECT-only scanners for myocardial perfusion imaging.

An important aspect of breast cancer survivorship is finding comfortable undergarments that work for women's post-treatment bodies. Patients who undergo mastectomy, including both those who do and do not receive reconstruction, need bras that can accommodate new breast shape, size, and feel, as well as scarring and skin sensitivity. Our research with breast cancer patients and the literature reveal that ready-to-wear bras are inadequate for the variety of patients' needs, and many women lack support and guidance to make decisions about undergarments after cancer. This commentary describes a major quality-of-life challenge for breast cancer survivors and makes recommendations for future research. Healthcare providers need more guidance and resources to be able to help their patients prepare for this aspect of survivorship. New technologies, such as biomechanical modeling, 3D body scanning, and manufacturing techniques, should be pursued in collaboration with patients, healthcare providers, and clothing designers to ease this burden for breast cancer patients.

To analyze the overall survival (OS) of elderly acute myeloid leukemia (AML) patients treated with oral arsenic-containing Qinghuang Powder (青黄散, QHP) or low-intensity chemotherapy (LIC). Forty-two elderly AML patients treated with intravenous or subcutaneous LIC (1 month for each course, at least 3 courses) or oral QHP (3 months for each course, at least 2 courses) were retrospectively analyzed from January 2015 to December 2017. The main endpoints of analysis were OS and 1-, 2-, 3-year OS rates of patients, respectively. And the adverse reactions induding bone marrow suppression, digestive tract discomfort and myocardia injury were observed. Out of 42 elderly AML patients, 22 received LIC treatment and 20 received QHP treatment, according to patients’ preference. There was no significant difference on OS between LIC and QHP patients (13.0 months vs. 13.5 months, >0.05). There was no significant difference on OS rates between LIC and QHP groups at 1 year (59.1% vs. 70.0%), 2 years (13.6% vs. 15%), and 3 years (4.6% vs. 5.0%, all >0.05). Furthermore, there was no significant difference of OS on prognosis stratification of performance status > 2 (12 months vs. 12 months), age> 75 year-old (12.0 months vs. 12.5 months), hematopoietic stem cell transplant comorbidity index >2 (12 months vs. 13 months), poor cytogenetics (12 months vs. 8 months), and diagnosis of secondary AML (10 months vs. 14 months) between LIC and QHP patients (>0.05). QHP may be an alternative treatment for elderly AML patients refusing LIC therapy.

Background Insulin resistance (IR), evaluation of which is difficult and complex, is closely associated with cardiovascular disease. Recently, various IR surrogates have been proposed and proved to be highly correlated with IR assessed by the gold standard. It remains indistinct whether different IR surrogates perform equivalently on prognostic prediction and stratification following percutaneous coronary intervention (PCI) in non-ST-segment elevation acute coronary syndrome (NSTE-ACS) patients with and without type 2 diabetes mellitus (T2DM). Methods The present study recruited patients who were diagnosed with NSTE-ACS and successfully underwent PCI. IR surrogates evaluated in the current study included triglyceride-glucose (TyG) index, visceral adiposity index, Chinese visceral adiposity index, lipid accumulation product, and triglyceride-to-high density lipoprotein cholesterol ratio, calculations of which were conformed to previous studies. The observational endpoint was defined as the major adverse cardiovascular and cerebrovascular events (MACCE), including cardiac death, non-fatal myocardial infarction, and non-fatal ischemic stroke. Results 2107 patients (60.02 ± 9.03 years, 28.0% female) were ultimately enrolled in the present study. A total of 187 (8.9%) MACCEs were documented during the 24-month follow-up. Despite regarding the lower median as reference [hazard ratio (HR) 3.805, 95% confidence interval (CI) 2.581–5.608, P Conclusion The TyG index, which is most strongly associated with the risk of MACCE, can be served as the most valuable IR surrogate for risk prediction and stratification in NSTE-ACS patients receiving PCI, with and without T2DM.

First principles were used to investigate electronic properties of Au-doped graphene, Ag-doped graphene, and Cu-doped graphene and the effect of adsorption behavior of hydrogen sulfide (H2S) molecule on their electronic properties. Doped graphene exhibits interesting electronic properties. The gap value of Ag-doped graphene is 0.29 eV, whereas Au-doped graphene is 0.48 eV which is the largest one in three doped systems, a clear difference of structure and electronic properties among three doped systems absorbing H2S molecule. The doped atom and the H2S molecule are on the same side of the graphene for Au-doped graphene and Cu-doped graphene, which belong to a kind of bonding orbital hybridization of electron cloud showed from charge difference density plots. However, Ag-doped graphene adsorbed with H2S molecule exhibits a kind of antibonding orbital hybridization. With the analysis in this paper, it is beneficial to research H2S gas sensors.

Two-dimensional (2D) materials are promising for next-generation photo detection because of their exceptional properties such as a strong interaction with light, electronic and optical properties that depend on the number of layers, and the ability to form hybrid structures. However, the intrinsic detection ability of 2D material-based photodetectors is low due to their atomic thickness. Photogating is widely used to improve the responsivity of devices, which usually generates large noise current, resulting in limited detectivity. Here, we report a molybdenum-based phototransistor with MoS2 channel and α-MoO3-x contact electrodes. The device works in a photo-induced barrier-lowering (PIBL) mechanism and its double heterojunctions between the channel and the electrodes can provide positive feedback to each other. As a result, a detectivity of 9.8 × 1016 cm Hz1/2 W−1 has been achieved. The proposed double heterojunction PIBL mechanism adds to the techniques available for the fabrication of 2D material-based phototransistors with an ultrahigh photosensitivity., Here, the authors exploit a photo-induced barrier-lowering mechanism in MoS2/ α-MoO3-x heterojunctions to realize two-dimensional phototransistors with enhanced performance and fast response at low bias voltage.

In stability analysis of discontinuity-controlled slopes, the rationality of results is related to the accuracy of three-dimensional (3D) slope morphology and the reliability of the discontinuity survey. With the advent of remote sensing technologies for engineering geological surveys and slope stability analyses, step-change increases have been made in the quality of data available and geometrical characterization of rock slopes. Although these techniques are frequently employed in the characterization of slope geometry and joint surfaces at present, limited research has been undertaken to effectively process the derived data and improve the quality in the reconstruction of slope geometry imported into 3D discontinuous numerical models. In this paper, an integrated system coupling 3D-DDA and UAV-LS photogrammetry is presented as a tool to evaluate the stability of a blocky rock mass slope. The system includes a UAV-LS module, a modeling module, a block-generation module, and a 3D-DDA calculation module. In the UAV-LS module, the use of UAV-LS system integrated with field mapping and site observations allows the acquisition of detailed outputs (point clouds) on both the slope and discontinuity geometry. An effective combination of commercial software Geomagic and Hyperworks is used in the modeling module to process oceans of 3D point cloud data and construct complex 3D geometrical models based on reverse engineering. In the block-generation module, the three-dimensional discontinuous deformation analysis (3D-DDA) method is then carried out in order to simulate the movement of potentially unstable blocks, within which an independent block-cutting algorithm is used to generate the blocks with arbitrary shapes and the finite structural planes similar to the real cases. The 3D-DDA calculation module uses 3D-DDA calculation algorithm to derive the simulation results. The capability of the proposed system for stability analysis of a jointed slope is demonstrated by a practical example.

The prevalence of cardiovascular diseases (CVD) is increased in subjects with post-traumatic stress disorder (PTSD). Vascular inflammation mediates CVD and may be assessed by(18)F-fluorodeoxyglucose (FDG) positron emission tomography (PET) imaging. In this pilot study, we investigated whether subjects with PTSD have enhanced vascular and systemic inflammation compared to healthy controls, as assessed by FDG PET imaging. METHODS: A prospective group of 16 subjects (9 PTSD and 7 controls, age 34±7) without prior history of CVD underwent FDG PET/CT imaging. The presence of PTSD symptoms at the time of the study was confirmed using PTSD checklist for DSM-5 (PCL5) questionnaire. Blood samples were collected to determine blood glucose, lipid and inflammatory biomarkers (tumor necrosis factor α, interleukin-1β, and interleukin-6) levels. FDG signal in the ascending aorta, amygdala, spleen and bone marrow was quantified. RESULTS: The two groups matched closely with regards to cardiovascular risk factors. The inflammatory biomarkers were all within the normal range. There was no significant difference in FDG signal in the aorta (target to background ratio: 2.40±0.29 and 2.34±0.29 for control and PTSD subjects, difference −0.6, 95% confidence interval of difference −0.38 – 0.26), spleen, bone marrow, or amygdala between control and PTSD subjects. There was no significant correlation between aortic and amygdala FDG signal. However, a significant positive correlation existed between amygdala, splenic, and bone marrow FDG signal. CONCLUSION: This pilot, small study did not reveal any difference in vascular or systemic inflammation as assessed by FDG PET imaging between PTSD and healthy control subjects. Because of the small number of subjects, a modest increase in vascular inflammation, which requires larger scale studies to establish, cannot be excluded. The correlation between FDG signal in amygdala, spleen and bone marrow may reflect a link between amygdala activity and systemic inflammation.

The use of operant chambers for research and teaching in behavior analysis is in decline due to the expense, maintenance, and ethical considerations of such complex mechanical apparati (Venneman and Knowles in Teach Psychol 32(1):66–68, 2005. https://doi.org/10.1207/s15328023top3201_13). Other technologies for testing and demonstrating behavioral principles have emerged in the pursuit of creating free operant paradigms that are accessible and effective for students and economical for institutions. One example is virtual programs that emulate the behavior of organisms such as CyberRat and Sniffy (Graham et al. in Behav Res Methods Instrum Comput 26(2):134–141, 1994. https://doi.org/10.3758/bf03204606; Ray in CyberRat (version 1.0), Brown & Benchmark, Madison, 1996; Behav Philos 39:203–301, 2011). Recently, a new instrument has been developed—the Portable Operant Research and Teaching Lab (PORTL; Rosales-Ruiz and Hunter in Operants 4:34–36, 2016). PORTL is a tabletop apparatus comprised of various objects and tools that enable students to experience and manage free operant situations. In addition to its instructional benefits, PORTL provides a setting for basic research to be completed quickly and ethically with human participants. The purpose of this paper is to outline how to incorporate PORTL into undergraduate behavior analysis courses. Several examples of how PORTL has been incorporated into such courses, including sample exercises, are provided as a model for other course instructors.

The complexity of cancer therapies has vastly expanded in the last decade, along with type and severity of cardiac toxicities associated with these treatments. Prevention of pre-clinical cardiotoxicity may improve cardiovascular outcomes and circumvent the decision to place life-sustaining chemotherapeutic agents on hold, making the early detection of cancer therapeutic related cardiac toxicity with non-invasive imaging essential to the care of these patients. There are several established methods of cardiac imaging in the areas of nuclear cardiology, echocardiography, computed tomography, and cardiac magnetic resonance imaging that are used to assess for cardiovascular toxicity of cancer treatments, with several methods under development. The following review will provide an overview of current and emerging imaging techniques in these areas.

The challenges of developing neuromorphic vision systems inspired by the human eye come not only from how to recreate the flexibility, sophistication, and adaptability of animal systems, but also how to do so with computational efficiency and elegance. Similar to biological systems, these neuromorphic circuits integrate functions of image sensing, memory and processing into the device, and process continuous analog brightness signal in real-time. High-integration, flexibility and ultra-sensitivity are essential for practical artificial vision systems that attempt to emulate biological processing. Here, we present a flexible optoelectronic sensor array of 1024 pixels using a combination of carbon nanotubes and perovskite quantum dots as active materials for an efficient neuromorphic vision system. The device has an extraordinary sensitivity to light with a responsivity of 5.1 × 107 A/W and a specific detectivity of 2 × 1016 Jones, and demonstrates neuromorphic reinforcement learning by training the sensor array with a weak light pulse of 1 μW/cm2., To emulate nature biological processing, highly-integrated ultra-sensitive artificial neuromorphic system is highly desirable. Here, the authors report flexible sensor array of 1024 pixels using combination of carbon nanotubes and perovskite QDs as active matetials, achieving highly responsive device for reinforcement learning.

Late-onset asthma (LOA) is beginning to account for an increasing proportion of asthma patients, which is often underdiagnosed in the elderly. Studies on the possible relations between aging-related genes and LOA contribute to the diagnosis and treatment of LOA. Forkhead Box O3 (FOXO3) and TP53 are two classic aging-related genes. DNA methylation varies greatly with age which may play an important role in the pathogenesis of LOA. We supposed that the differentially methylated sites of FOXO3 and TP53 associated with clinical phenotypes of LOA may be useful biomarkers for the early screening of LOA.The mRNA expression and DNA methylation of FOXO3 and TP53 in peripheral blood of 43 LOA patients (15 mild LOA, 15 moderate LOA and 13 severe LOA) and 60 healthy controls (HCs) were determined. The association of methylated sites with age was assessed by Cox regression to control the potential confounders. Then, the correlation between differentially methylated sites (DMSs; p-value 0.05) and clinical lung function in LOA patients was evaluated. Next, candidate DMSs combining with age were evaluated to predict LOA by receiver operating characteristic (ROC) analysis and principal components analysis (PCA). Finally, HDM-stressed asthma model was constructed, and DNA methylation inhibitor 5-Aza-2'-deoxycytidine (5-AZA) were used to determine the regulation of DNA methylation on the expression of FOXO3 and TP53.Compared with HCs, the mRNA expression and DNA methylation of FOXO3 and TP53 vary significantly in LOA patients. Besides, 8 DMSs from LOA patients were identified. Two of the DMSs, chr6:108882977 (FOXO3) and chr17:7591672 (TP53), were associated with the severity of LOA. The combination of the two DMSs and age could predict LOA with high accuracy (AUC values = 0.924). In HDM-stressed asthma model, DNA demethylation increased the expression of FOXO3 and P53.The mRNA expression of FOXO3 and TP53 varies significantly in peripheral blood of LOA patients, which may be due to the regulation of DNA methylation. FOXO3 and TP53 methylation is a suitable blood biomarker to predict LOA, which may be useful targets for the risk diagnosis and clinical management of LOA.

Background Air pollution exposure and idiopathic pulmonary fibrosis (IPF) cause a poor prognosis after SARS-CoV-2 infection, but the underlying mechanisms are not well explored. Angiotensin-converting enzyme 2 (ACE2) and transmembrane serine protease 2 (TMPRSS2) are the keys to the entry of SARS-CoV-2. We therefore hypothesized that air pollution exposure and IPF may increase the expression of ACE2 and TMPRSS2 in the lung alveolar region. We measured their expression levels in lung tissues of control non-IPF and IPF patients, and used murine animal models to study the deterioration of IPF caused by particulate matter (PM) and the molecular pathways involved in the expression of ACE2 and TMPRSS2. Results In non-IPF patients, cells expressing ACE2 and TMPRSS2 were limited to human alveolar cells. ACE2 and TMPRSS2 were largely upregulated in IPF patients, and were co-expressed by fibroblast specific protein 1 (FSP-1) + lung fibroblasts in human pulmonary fibrotic tissue. In animal models, PM exposure increased the severity of bleomycin-induced pulmonary fibrosis. ACE2 and TMPRSS2 were also expressed in FSP-1+ lung fibroblasts in bleomycin-induced pulmonary fibrosis, and when combined with PM exposure, they were further upregulated. The severity of pulmonary fibrosis and the expression of ACE2 and TMPRSS2 caused by PM exposure were blocked by deletion of KC, a murine homologue of IL-8, or treatment with reparixin, an inhibitor of IL-8 receptors CXCR1/2. Conclusions These data suggested that risk of SARS-CoV-2 infection and COVID-19 disease severity increased by air pollution exposure and underlying IPF. It can be mediated through upregulating ACE2 and TMPRSS2 in pulmonary fibroblasts, and prevented by blocking the IL-8/CXCR1/2 pathway.

Background Domestic cats rarely develop hepatocellular carcinoma. The reason for the low prevalence is unknown. Reductions in hepatocellular ploidy have been associated with hepatic carcinogenesis. Recent work in mice has shown that livers with more polyploid hepatocytes are protected against the development of hepatocellular carcinoma. Hepatocyte ploidy in the domestic cat has not been evaluated. We hypothesized that ploidy would be reduced in peri-tumoral and neoplastic hepatocytes compared to normal feline hepatocytes. Using integrated fluorescence microscopy, we quantified the spectra of ploidy in hepatocellular carcinoma and healthy control tissue from paraffin embedded tissue sections. Results Feline hepatocytes are predominantly mononuclear and the number of nuclei per hepatocyte did not differ significantly between groups. Normal cats have a greater number of tetraploid hepatocytes than cats with hepatocellular carcinoma. Conclusions Total hepatocellular polyploidy in normal cat liver is consistent with values reported in humans, yet cellular ploidy (nuclei per cell) is greater in humans than in cats. Tetraploid cat hepatocytes are predominantly mononuclear.

The introduction of femtosecond laser-assisted cataract surgery is an alternative approach to conventional cataract surgery. Our study aimed to determine the effectiveness of femtosecond laser-assisted capsulotomy in the presence of different ophthalmic viscoelastic devices (OVDs) in the anterior chamber. Fresh porcine eyes (n = 96) underwent LDV Z8-assisted anterior capsulotomy, either in the presence of an OVD (Viscoat, Provisc, Healon, Healon GV or HPMC) or without, using 90% and 150% energies respectively. Following that, the capsule circularity, tag's arc-length, tag-length, tag-area and rupture strength (mN) of the residual capsular bag were evaluated. We found that increasing energy from 90 to 150% across the OVD sub-groups improved the studied capsulotomy parameters. Amongst the 90% energy sub-groups, the circularity and tag-parameters were worse with Viscoat and Healon GV, which have higher refractive index and viscosity compared to the aqueous humour. Using 150% energy, Healon GV showed a significantly worse total arc-length (p = 0.01), total tag-length (p = 0.03) and total tag-area (p = 0.05) compared to the control group. We concluded that; an OVD with a refractive index similar to aqueous humour and lower viscosity, such as Healon or Provisc, as well as a higher energy setting, are recommended, to enhance the efficacy of laser capsulotomy. National Medical Research Council (NMRC) National Research Foundation (NRF) Published version This research was supported by the Singapore National Research Foundation under its Translational and Clinical Research (TCR) programme (NMRC/TCR/1021-SERI/2013), and by Duke-NUS Medical School, Singapore under its Academia Clinical Programme (ACP) (R1396/82/2016).