Search

Orthotospoviruses, the plant-infecting bunyaviruses, cause serious diseases in agronomic crops and pose major threats to global food security. The family of Tospoviridae contains more than 30 members that are classified into two geographic groups, American-type and Euro/Asian-type orthotospovirus. However, the genetic interaction between different species and the possibility, during mixed infections, for transcomplementation of gene functions by orthotospoviruses from different geographic groups remains underexplored. In this study, minireplicon-based reverse genetics (RG) systems have been established for Impatiens necrotic spot virus (INSV) (an American-type orthotospovirus) and for Calla lily chlorotic spot virus and Tomato zonate spot virus (CCSV and TZSV) (two representative Euro/Asian orthotospoviruses). Together with the earlier established RG system for Tomato spotted wilt virus (TSWV), a type species of the Orthotospovirus American-clade, viral replicase/movement proteins were exchanged and analyzed on interspecies transcomplementation. Whereas the homologous RNA-dependent RNA polymerase (RdRp) and nucleocapsid (N) protein supported the replication of orthotospoviruses from both geographic groups, heterologous combinations of RdRp from one group and N from the other group were unable to support the replication of viruses from both groups. Furthermore, the NSm movement protein (MP), from both geographic groups of orthotospoviruses, was able to transcomplement heterologous orthotospoviruses or a positive-strand Cucumber mosaic virus (CMV) in their movement, albeit with varying efficiency. MP from Rice stripe tenuivirus (RSV), a plant-infecting bunyavirus that is distinct from orthotospoviruses, or MP from CMV also moves orthotospoviruses. Our findings gain insights into the genetic interaction/reassortant potentials for the segmented plant orthotospoviruses. IMPORTANCE Orthotospoviruses are agriculturally important negative-strand RNA viruses and cause severe yield-losses on many crops worldwide. Whereas the emergence of new animal-infecting bunyaviruses is frequently associated with genetic reassortants, this issue remains underexposed with the plant-infecting orthotospovirus. With the development of reverse genetics systems for orthotospoviruses from different geographic regions, the interspecies/intergroup replication/movement complementation between American- and Euro/Asian-type orthotospoviruses were investigated. Genomic RNAs from American orthotospoviruses can be replicated by the RdRp and N from those of Euro/Asia-group orthotospoviruses, and vice versa. However, their genomic RNAs cannot be replicated by a heterologous combination of RdRp from one geographic group and N from another geographic group. Cell-to-cell movement of viral entity is supported by NSm from both geographic groups, with highest efficiency by NSm from viruses belonging to the same group. Our findings provide important insights into the genetic interaction and exchange ability of viral gene functions between different species of orthotospovirus.

We investigate the effectiveness of convex relaxation and nonconvex optimization in solving bilinear systems of equations under two different designs (i.e. a sort of random Fourier design and Gaussian design). Despite the wide applicability, the theoretical understanding about these two paradigms remains largely inadequate in the presence of random noise. The current paper makes two contributions by demonstrating that: (1) a two-stage nonconvex algorithm attains minimax-optimal accuracy within a logarithmic number of iterations, and (2) convex relaxation also achieves minimax-optimal statistical accuracy vis-à-vis random noise. Both results significantly improve upon the state-of-the-art theoretical guarantees.

Background: Marked changes in hemodynamics have been suggested to be a potential contributing factor to portal vein thrombosis (PVT) development. This study investigated the effect of portal hemodynamics based on the anatomical structure of the portal venous system on PVT development., Methods: The morphological features of portal venous system in patients with PVT and those without PVT subgroups were compared. In addition, idealized PV models were established to numerically evaluate the effect of the variation in the angulation of superior mesenteric vein (SMV) and splenic vein (SV) on the hemodynamics of portal venous system., Results: The angle α (angulation of SMV and SV) in patients with PVT was lower than that in patients without PVT (p < 0.0001), which was the only independent risk factor (odds ratio (OR), 0.90 (95% CI 0.84-0.95); p < 0.0001) for the presence of PVT. With the change in angle α, the flow pattern of blood flow changed greatly, especially the helical flow. When α = 80°, helical flow only appeared at the local PV near the intersection of SMV and SV. When α = 120°, most regions were occupied by the helical flow. In addition, the h 2 gradually increased with increasing α, when α = 80°, h 2  = 12.6 m/s 2 ; when α = 120°, h 2  = 29.3 m/s 2 ., Conclusions: The angulation of SV and SMV was closely associated with PVT development. Helical flow changed following the varying angulation of SV and SMV. Therefore, angulation of SV and SMV may help to identify high-risk cohorts for future PVT development earlier., (© 2022. The Author(s).)

An electrocardiography system records electrical activities of the heart, and it is used to assist doctors in the diagnosis of cardiac arrhythmia such as atrial fibrillation. This study presents a fast, automated deep-learning algorithm that predicts atrial fibrillation with excellent performance (F-1 score 88.2% and accuracy 97.3%). Our approach involves the pre-processing of ECG signals, followed by an alternative representation of the signals using a spectrogram, which is then fed to a fine-tuned EfficientNet B0, a pre-trained convolution neural network model, for the classification task. Using the transfer learning approach and with fine-tuning of the EfficientNet, we optimize the model to achieve highly efficient and effective classification of the atrial fibrillation.

Background and Aims: It is important and challenging to evaluate the survival of cirrhotic patients undergoing transjugular intrahepatic portosystemic shunt (TIPS). We aimed to validate the Freiburg index of post-TIPS survival (FIPS) score and classic scores for predicting mortality in Chinese patients after TIPS creation., Methods: A total of 709 consecutive patients with cirrhosis from December 2011 to July 2018 who underwent TIPS placement were retrospectively reviewed. The prognostic value of the FIPS score, the model for end-stage liver disease (MELD) score, Child-Pugh score and Chronic Liver Failure Consortium Acute Decompensation score was validated with the receiver operating characteristic (ROC) curve and DeLong et al. test., Results: The MELD-Na score was superior to the FIPS score in predicting 1-month mortality [AUROC, 0.727 (0.692-0.759) vs. 0.588 (0.551-0.625); P = 0.048]. The MELD and MELD-Na scores were significant superior to the FIPS score in predicting 3-month mortality [AUROC, 0.730 (0.696-0.762) vs. 0.598 (0.561-0.634); P = 0.044 and 0.740 (0.706-0.772) vs. 0.598 (0.561-0.634); P = 0.028]. Subgroup analyses revealed that Child-Pugh score was better than FIPS score in predicting 3-month mortality [AUROC, 0.797 (0.745-0.843) vs. 0.578 (0.517-0.637); P = 0.049] in nonviral cirrhosis group., Conclusion: Classic scores still had good risk stratification and predictive ability of post-TIPS mortality. The FIPS score was not superior to the classic scores in the current Chinese cohort. The MELD and MELD-Na scores were significantly superior to the FIPS score in predicting 3-month mortality., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Facilitative playback-based subjective measures offer a more reliable evaluation of the vocal fold vibration than those derived from direct inspection of video playback. One of the measures is a Nyquist plot, which presents the analyzed cycle-to-cycle vibratory information in a graphical form. While the potential is evident, the information of the features of the Nyquist plot, which the evaluation is based on, is still incomplete. The current identified features and their vibratory behaviors may be inadequate to guarantee accurate interpretation of the findings. The present study aims to address this issue by examining the features of the Nyquist plot and their vibratory behaviors. A total of 56 young normophonic speakers, that is, 20 males and 36 females were recruited as the participants. Each of them underwent laryngeal high-speed videoendoscopy to record the images of the vocal fold vibration, which were then analyzed to generate the Nyquist plots. The features were identified by inspecting the properties of the plot points forming the Nyquist plots. For each identified feature, its vibratory behaviors were examined. The results revealed four features: rim contour depicting the longitudinal phase difference; left edge shape signifying the glottal configuration, phase closure, and closed phase duration; rim width and rim pattern visualizing the regularity of glottal areas and the regularity of the intracycle variations, respectively. The findings present a more complete reference of the features and their vibratory behaviors that is pertinent for the Nyquist plot interpretation., (Copyright © 2020 The Voice Foundation. Published by Elsevier Inc. All rights reserved.)

Objectives: To investigate the usefulness of the criteria with liver stiffness (LS) measured by two-dimensional shear wave elastography (2D-SWE) and platelet count (PLT) for ruling out high-risk varices in patients with compensated advanced chronic liver disease (cACLD)., Methods: A total of 661 patients with cACLD had successfully undergone 2D-SWE and endoscopy screening. We analyzed risk factors for the presence of high-risk varices and compared proportions of patients who were spared endoscopy when used the predicting criteria with LS (ranged from 16 to 25 kPa) and PLT (ranged from 80 × 10 9 /L to 150 × 10 9 /L)., Results: PLT, albumin, LS were found to be independent predictors of high-risk varices. The LS values for ruling out and ruling in high-risk varices were 14.0 kPa and 24.8 kPa, respectively. When the Baveno VI criteria LS < 20 kPa and PLT > 150 × 10 9 /L were used, the high-risk varices miss rate was 2.1%, while the saved endoscopy rate only was 19.2%. The new criteria that LS < 16 kPa and PLT > 100 × 10 9 /L saved 30.4-34.6% endoscopy with 0-3.2% high-risk varices miss rate in the subgroup analysis stratified according to the types of underlying liver disease., Conclusions: The Baveno VI criteria can be applied to LS measurement by 2D-SWE. The new criteria that LS < 16 kPa and PLT > 100 × 10 9 /L could be a potential model to spare more endoscopy screening with < 5% high-risk varices miss rate., Key Points: • LS measured by 2D-SWE is reliable predictive factor for predicting all-size varices and high-risk varices in patients with compensated advanced chronic liver disease. • LS measured by 2D-SWE < 16 kPa and PLT > 100 × 10 9 /L, which can spare more endoscopy than Baveno VI criteria with < 5% high-risk varices miss rate. • The Baveno VI criteria can be applied to LS measurement by 2D-SWE., (© 2021. European Society of Radiology.)

Background: Serum cytokines-reflecting systemic inflammation has been associated with the risk of decompensation and mortality in patients with cirrhosis. However, the role of systemic inflammation in patients with cirrhosis undergoing transjugular intrahepatic portosystemic shunt procedure remains unknown., Patients and Methods: Patients with cirrhosis who received transjugular intrahepatic portosystemic shunt between June 2015 and September 2017 were included. Portal and hepatic venous blood samples were obtained intraoperatively; serum cytokine levels (IL-10, IL-17A, IL-1RA, IL-8, and CXCL10) were measured in 105 patients. Associations with survival and other outcomes during long-term follow-up (median: 1,564 days) were assessed using logistic regression., Results: IL-17A and CXCL10 levels were higher in the portal than in the hepatic veins, whereas IL-1RA levels were higher in the hepatic than in the portal veins. However, IL-8 or IL-10 levels between hepatic and portal veins showed no differences. Multivariate analysis demonstrated that Child-Pugh scores ( P = 0.017, HR: 1.484, 95% CI: 1.072-2.055) and IL-8 level in hepatic veins ( P < 0.001, HR: 1.043, 95% CI: 1.019-1.068) were independent predictors for mortality during long-term follow-up, with an optimal cut-off of 5.87 pg/ml for IL-8 in hepatic veins. Patients with hepatic IL-8 levels < 5.87 pg/ml had significantly higher cumulative survival rates (98.4 vs. 72.9% at 1 year, 98.4 vs. 65.3% at 2 years, 96.7 vs. 60.3% at 3 years, 94.2 vs. 60.3% at 4 years; P < 0.0001)., Conclusions: IL-8 levels in hepatic veins may reflect liver cirrhosis severity. Elevated IL-8 levels suggest shorter survival in patients receiving TIPS., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Liu, Wang, Yang, Yan, Xiang, Yang and Luo.)

Ideally, an analysis method for laryngeal high-speed videoendoscopy (LHSV) based on the glottal area waveforms (GAW) requires images of a complete view of the glottis to ensure findings that are representatives of the vibratory behaviors of the whole vocal folds. However, in practice, the preferred images may not be obtained at all times. Often, the only available images that a clinician has to work with consist of a partial view of the glottis. This study aims to examine the effects of using images of a partial view of the glottis (ie, posterior-middle, anterior-middle, or middle) on the LHSV-based measures (ie, fundamental frequency (F0 GAW) , frequency perturbation (jitter GAW) , amplitude perturbation (shimmer GAW) , open quotient (OQ GAW) , and Nyquist plot). The participants consisted of 9 young normophonic females. The procedures involved LHSV recording of the vibration of the vocal folds. The images of the complete view of the glottis were analyzed to obtain the LHSV-based measures. The same images were used to simulate the images of partial views of the glottis by changing the outline of the region of interest to include only either the posterior-middle, anterior-middle, or middle parts of the glottis. The LHSV-based measures from the images of the partial views were then compared to those with the complete view . The results showed that all LHSV-based measures from the images of the posterior-middle view were similar to those of the complete view. However, only the F0 GAW , jitter GAW , and shimmer GAW from the images of the anterior-middle and middle views were similar to those of the complete view. Lower OQ GAW and different Nyquist plots than those of the complete view were generated by the images of the anterior-middle and middle views. In conclusion, all LHSV-based measures from the images of the posterior-middle view of the glottis, and only the F0 GAW , jitter GAW, and shimmer GAW from the images of the anterior-middle and middle views of the glottis reflect the vibratory behaviors of the whole vocal folds. The same conclusion could not be applied to the OQ GAW and Nyquist plots of the images of the anterior-middle and middle views of the glottis. A possible effect of the presence or absence of a posterior glottal gap on the findings warrants further confirmation., (Copyright © 2020 The Voice Foundation. All rights reserved.)

Objectives: To investigate the diagnostic performance of liver stiffness (LS) measured by 2D-SWE for predicting esophageal varices (EV) and high-risk varices (HRV) in patients with hepatitis B virus (HBV)-related compensated advanced chronic liver disease (cACLD)., Methods: In total, 268 patients with HBV-related cACLD who underwent 2D-SWE and esophagogastroduodenoscopy (EGD) were retrospectively evaluated. The new criteria for ruling out HRV were tested in the training cohort with 175 patients and validated in the validation cohort with 93 patients., Results: The AUROCs of LS for predicting EV and HRV were 0.90(0.86-0.95) and 0.93(0.89-0.96) respectively. LS (OR, 1.64 (95% CI: 1.31-2.07); P < 0.0001), PLT (OR, 0.94 (95% CI: 0.91-0.97); P < 0.0001) and albumin (OR, 0.75 (95% CI: 0.62-0.90); P = 0.02) were independent factors for the presence of HRV. The Baveno VI criteria of LS < 20 kPa and PLT > 150 × 10 9 /L saved 15.1%-17.1% EGD screening with 0-4.3% HRV miss rate. LS < 16 kPa and PLT > 60 × 10 9 /L spared 51.4%-52.7% EGD screening with 3.8%-4.3% HRV miss rate., Conclusion: Baveno VI criteria is suitable for 2D-SWE to rule out HRV. LS < 16 kPa and PLT > 60 × 10 9 /L could be a reliable model for ruling out HRV in patients with HBV-related cACLD.

The curse of dimensionality is a widely known issue in reinforcement learning (RL). In the tabular setting where the state space S and the action space A are both finite, to obtain a nearly optimal policy with sampling access to a generative model, the minimax optimal sample complexity scales linearly with | S | × | A | , which can be prohibitively large when S or A is large. This paper considers a Markov decision process (MDP) that admits a set of state-action features, which can linearly express (or approximate) its probability transition kernel. We show that a model-based approach (resp. Q-learning) provably learns an ε -optimal policy (resp. Q-function) with high probability as soon as the sample size exceeds the order of K ( 1 - γ ) 3 ε 2 ( resp . K ( 1 - γ ) 4 ε 2 ) , up to some logarithmic factor. Here K is the feature dimension and γ ∈ (0, 1) is the discount factor of the MDP. Both sample complexity bounds are provably tight, and our result for the model-based approach matches the minimax lower bound. Our results show that for arbitrarily large-scale MDP, both the model-based approach and Q-learning are sample-efficient when K is relatively small, and hence the title of this paper.

Background: A large portion of patients with compensated advanced chronic liver disease (cACLD) do not have varices or only have low risk varices., Aims: To create and validate an easy-to-use risk scoring system to identify high-risk varices (HRV) and spare esophagogastroduodenoscopy (EGD) in patients with hepatitis B virus (HBV)-related cACLD., Methods: In total, 334 patients with HBV-related cACLD who had undergone routine laboratory tests and ultrasound examination were enrolled. Multivariate logistic regression analysis was used to determine which variables were the independent risk factors for the presence of HRV, so as to establish the scoring system for screening HRV. The criteria were tested in a training cohort with 221 patients and validated in a validation cohort with 113 patients., Results: In the training cohort, the prevalence of HRV was 29.5%. Albumin (ALB) [OR 0.83; 95% confidence index (CI) 0.77-0.90; P < 0.0001], platelet count (PLT) (OR 0.96, 95% CI 0.96-0.99; P < 0.0001) and portal vein diameter (OR 1.40; 95% CI 1.15-1.71; P = 0.001) were independent risk factors for the presence of HRV. The negative predictive value was > 95%, when albumin-platelet-portal vein diameter varices scores (APP score) were < 0.24. One hundred twenty-five of 221 (56.6%) patients met an APP score < 0.24 with a 4.8% HRV miss rate. In the validation cohort, 59 of 113 (51.3%) patients met the APP score < 0.24 with a 1.7% HRV miss rate., Conclusions: APP score is a potential model for safely screening HRV and sparing EGDs in patients with HBV-related cACLD., (© 2021. The Author(s).)

Background and Aims: The optimal treatment for gastric varices (GVs) is a topic that remains open for study. This study compared the efficacy and safety of endoscopic cyanoacrylate injection and balloon-occluded retrograde transvenous obliteration (BRTO) to prevent rebleeding in patients with cirrhosis and GVs after primary hemostasis., Approach and Results: Patients with cirrhosis and history of bleeding from gastroesophageal varices type 2 or isolated gastric varices type 1 were randomized to cyanoacrylate injection (n = 32) or BRTO treatment (n = 32). Primary outcomes were gastric variceal rebleeding or all-cause rebleeding. Patient characteristics were well balanced between two groups. Mean follow-up time was 27.1 ± 12.0 months in a cyanoacrylate injection group and 27.6 ± 14.3 months in a BRTO group. Probability of gastric variceal rebleeding was higher in the cyanoacrylate injection group than in the BRTO group (P = 0.024). Probability of remaining free of all-cause rebleeding at 1 and 2 years for cyanoacrylate injection versus BRTO was 77% versus 96.3% and 65.2% versus 92.6% (P = 0.004). Survival rates, frequency of complications, and worsening of esophageal varices were similar in both groups. BRTO resulted in fewer hospitalizations, inpatient stays, and lower medical costs., Conclusions: BRTO is more effective than cyanoacrylate injection in preventing rebleeding from GVs, with similar frequencies of complications and mortalities., (© 2021 by the American Association for the Study of Liver Diseases.)

This paper delivers improved theoretical guarantees for the convex programming approach in low-rank matrix estimation, in the presence of (1) random noise, (2) gross sparse outliers, and (3) missing data. This problem, often dubbed as robust principal component analysis (robust PCA) , finds applications in various domains. Despite the wide applicability of convex relaxation, the available statistical support (particularly the stability analysis vis-à-vis random noise) remains highly suboptimal, which we strengthen in this paper. When the unknown matrix is well-conditioned, incoherent, and of constant rank, we demonstrate that a principled convex program achieves near-optimal statistical accuracy, in terms of both the Euclidean loss and the ℓ ∞ loss. All of this happens even when nearly a constant fraction of observations are corrupted by outliers with arbitrary magnitudes. The key analysis idea lies in bridging the convex program in use and an auxiliary nonconvex optimization algorithm, and hence the title of this paper.

Objectives : The presence of varices affects the survival of patients with primary biliary cholangitis (PBC). The aim of this study is to assess the criteria based on liver stiffness (LS) measured by two-dimensional shear wave elastography (2D-SWE) and platelet count (PLT), and recently published noninvasive models for triaging PBC patients. Methods : 231 patients with PBC who underwent EGD and 2D-SWE examination were enrolled. Areas under the receiver-operating characteristic curve (AUROC) were used to assess the performance of 2D-SWE for predicting all-size varices and high-risk varices. All-size varices and high-risk varices miss rate < 10% and <5%, respectively, were acceptable for screening varices. Results : The AUROCs of LS for predicting all-size varices and high-risk varices were 0.87 (95%CI: 0.82-0.91) and 0.84 (95%CI: 0.74-0.86), respectively. LS <25 kPa and PLT >110 × 10 9 /L spared 46.3% EGD screening, with 3.7% high-risk varices miss rate and 8.4% all-size varices miss rate. One hundred and sixteen (50.2%) patients met the Newcastle varices in PBC score (cutoff, 0.5), with 4.3% high-risk varices miss rate and 11.2% all-size varices miss rate. Conclusion : The criteria based on LS and PLT are useful for triaging PBC patients. LS <25 kPa and PLT >110 × 10 9 /L could be the optimal criteria for screening varices.

Background: COVID-19 is a global pandemic. The prevention of SARS-CoV-2 infection and the rehabilitation of survivors are currently the most urgent tasks. However, after patients with COVID-19 are discharged from the hospital, how long the antibodies persist, whether the lung lesions can be completely absorbed, and whether cardiopulmonary abnormalities exist remain unclear. Methods: A total of 56 COVID-19 survivors were followed up for 12 months, with examinations including serum virus-specific antibodies, chest CT, and cardiopulmonary exercise testing. Results: The IgG titer of the COVID-19 survivors decreased gradually, especially in the first 6 months after discharge. At 6 and 12 months after discharge, the IgG titer decreased by 68.9 and 86.0%, respectively. The IgG titer in patients with severe disease was higher than that in patients with non-severe disease at each time point, but the difference did not reach statistical significance. Among the patients, 11.8% were IgG negative up to 12 months after discharge. Chest CT scans showed that at 3 and 10 months after discharge, the lung opacity had decreased by 91.9 and 95.5%, respectively, as compared with that at admission. 10 months after discharge, 12.5% of the patients had an opacity percentage >1%, and 18.8% of patients had pulmonary fibrosis (38.5% in the severe group and 5.3% in the non-severe group, P < 0.001). Cardiopulmonary exercise testing showed that 22.9% of patients had FEV1/FVC%Pred <92%, 17.1% of patients had FEV1%Pred <80%, 20.0% of patients had a VO 2 AT <14 mlO 2 /kg/min, and 22.9% of patients had a VE/VCO 2 slope >30%. Conclusions: IgG antibodies in most patients with COVID-19 can last for at least 12 months after discharge. The IgG titers decreased significantly in the first 6 months and remained stable in the following 6 months. The lung lesions of most patients with COVID-19 can be absorbed without sequelae, and a few patients in severe condition are more likely to develop pulmonary fibrosis. Approximately one-fifth of the patients had cardiopulmonary dysfunction 6 months after discharge., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Xiao, Yang, Liu, Pang, Du, Liu, Liu, Jing, Chen, Deng, Zhou, Du, Yin, Yan, Mou and She.)

Despite its clear advantages, laryngeal high-speed videoendoscopy (LHSV) has not yet been accepted as a routine imaging tool for the evaluation of vocal fold vibration due to the unavailability of methods to effectively analyze the huge number of images from the LHSV recording. Recently, a promising LHSV-based analysis method has been introduced. The ability of this analysis method in studying the vocal fold vibratory behaviors had been substantially demonstrated. However, some practical aspects of its clinical applications still require further attention. Most fundamental is that the criteria for the measurement input ie, a segment of interest (SOI), which has not been fully defined. Particularly, the length of the SOI and the location along the sample, where it needs to be selected require further confirmation. Meanwhile, the analysis using any options of a well-delineated glottal area demands verification. Without clear criteria for the SOI, it is difficult to demonstrate the relevance of this analysis method in clinical voice assessment. Therefore, the aim of the present study is to establish the criteria for the SOI, which involved the investigations on the length of the SOI and the location along the sample, where it needs to be selected, as well as the use of any options of a well-delineated glottal area for analysis. The participants in the present study consisted of 36 young normophonic females. The methods involved LHSV recording of the images of the vibrating vocal folds. The captured images were then analyzed using the method. The LHSV-based measures from the analyses were compared according to the specified procedures of each investigation. Results indicated that 2000 frames should be used as the SOI length. The SOI could be selected at any location along the sample as long as well-delineated glottal areas were observed. With the current findings, a more conclusive measurement protocol is available to ensure reliable LHSV-based measures. The findings further support this analysis method for clinical application, which in turn promote LHSV as a reliable laryngeal imaging tool in clinical setting., (Copyright © 2019 The Voice Foundation. All rights reserved.)

Aims: This study aimed to determine the effects of sodium-glucose cotransporter-2 inhibitor (SGLT2i) in heart failure with reduced ejection fraction (HFrEF), compare the effect of SGLT2i with angiotensin receptor neprilysin inhibitor (ARNI), and find whether combination of SGLT2i and ARNI is better than monotherapy., Methods and Results: Embase, Medline, and Cochrane Central Registry of Controlled Trials were searched for randomized controlled trials evaluating SGLT2i or ARNI in HFrEF. And a total of six trials were included. SGLT2i was found to significantly reduce the risk of cardiovascular death or hospitalization for heart failure by 27% [hazard ratio (HR) 0.73, 95% confidence interval (CI) 0.67-0.80], hospitalization for heart failure by 31% (HR 0.69, 95% CI 0.62-0.77), cardiovascular death by 16% (HR 0.84, 95% CI 0.74-0.95), and all-cause death by 16% (HR 0.84, 95% CI 0.75-0.94) in HFrEF only with a statistically higher risk of genital infection (risk ratio (RR) 2.78, 95% CI 1.46-5.29). The reduction in cardiovascular death or hospitalization for heart failure was of similar magnitude in patients with or without diabetes mellitus (HR 0.71, 95% CI 0.64-0.80 vs. HR 0.75, 95% CI 0.65-0.87) using SGLT2i. Indirect treatment comparison showed that SGLT2i and ARNI had similar effects on primary outcome (HR 0.93, 95% CI 0.82-1.06). And combination of SGLT2i and ARNI achieved a better prognosis performance (HR 0.68, 95% CI 0.53-0.89) compared with ARNI monotherapy., Conclusions: SGLT2i could safely reduce cardiovascular death or hospitalization for heart failure in HFrEF regardless of diabetes mellitus status. SGLT2i and ARNI demonstrate similar effects, while combination of SGLT2i and ARNI results in a better cardiovascular protective effect., (© 2021 The Authors. ESC Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.)

Background: Two-dimensional shear-wave elastography (2D-SWE) is an ultrasound-based technique used to stage liver fibrosis by measuring liver stiffness (LS). The diagnostic performance of 2D-SWE for assessing liver fibrosis in patients with primary biliary cholangitis (PBC) has not been reported before., Aims: To investigate the diagnostic performance of 2D-SWE for staging liver fibrosis in patients with PBC by using histologic analysis as a reference standard., Methods: Patients with PBC who underwent liver biopsy and 2D-SWE were retrospectively collected. Liver fibrosis was staged according to the Scheuer scoring system. Areas under receiver operating characteristic curve (AUROC) was constructed to assess the accuracy of 2D-SWE and serum fibrosis models for staging liver fibrosis., Results: The diagnostic performance characteristics were determined for 157 patients with PBC. The AUROCs of LS measured by 2D-SWE for significant fibrosis, severe fibrosis, and cirrhosis were 0.88, 0.97 and 0.99, respectively. The cutoff values of LS measured by 2D-SWE in discriminating significant fibrosis, severe fibrosis, and cirrhosis were 10.7 kPa, 12.2 kPa and 14.1 kPa, respectively. The diagnostic accuracy of 2D-SWE for staging liver fibrosis was 73.9%., Conclusions: 2D-SWE is an efficient noninvasive method for the assessment of liver fibrosis in patients with PBC., (Copyright © 2020 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.)

Sinusoidal obstruction syndrome (SOS) is a rare liver disorder due to hepatic vascular injury. Its rapid and accurate diagnosis is crucial for patient survival. SOS is often established clinically, based on Baltimore, modified Seattle, or European Society for Blood and Marrow Transplantation (EBMT) criteria. Unfortunately, such criteria are not highly specificity and fail to provide a timely, reliable differential diagnosis. The use of noninvasive imaging techniques, such as ultrasound (US), computed tomography (CT), magnetic resonance imaging (MRI), and fluorodeoxyglucose positron emission tomography/computed tomography (FDG-PET/CT), has recently grown in this setting, some key imaging features offering diagnostic improvement. This review provides a synopsis of current noninvasive imaging techniques used for this purpose, summarizing accurate and reliable diagnostic features of SOS.

Background: Increased epicardial adipose tissue (EAT) has been proposed as a risk factor for non-alcoholic fatty liver disease (NAFLD). The aim of this study was to investigate the association of EAT with NAFLD., Methods: The PubMed, EMBASE, and Cochrane databases were systematically reviewed by two independent investigators to identify relevant studies assessing the association of EAT thickness (EAT-t) and volume (EAT-v) with NAFLD. Comparisons between NAFLD subjects and controls were performed with meta-analysis and trial sequential analysis (TSA)., Results: A total of thirteen case-control studies (n = 2260 patients) were included in the final analysis. The EAT was significantly increased in NAFLD patients compared with the controls (EAT, SMD: 0.73, 95% CI 0.51-0.94, p < 0.001; TSA-adjusted 95% CI 0.07-0.18; p < 0.001). When comparing the subgroups of NAFLD, the EAT-t in the severe-hepatic steatosis subgroup was thicker than that in the moderate subgroup (SMD: 1.43, 95% CI 0.15-2.71, p = 0.029). This study indicated that the EAT-t in the F3-4 fibrosis subgroup was thicker than that in the F0-2 fibrosis subgroup (SMD: 0.72, 95% CI 0.30-1.14, p = 0.001). The proportion of hypertension (OR = 1.64, 95% CI = 1.24-2.18, p = 0.001) and atherosclerotic cardiovascular disease (ASCVD) (OR = 1.66, 95% CI = 1.21-2.28, p = 0.002) was higher in the high-EAT-t group compared with the low-EAT-t group in NAFLD patients., Conclusions: The EAT was increased in the NAFLD subjects compared to the controls. The increase in the EAT was associated with the severity of steatosis, fibrosis and cardiovascular disease in patients with NAFLD. These findings provide new information regarding the development and progression of NAFLD.

The assessment of vascular permeability of malignant tumor plays an important role in the diagnosis and treatment of cancer. Dynamic contrast-enhanced magnetic resonance image (DCE-MRI) using Gd-encapsulated carbonaceous dots and Gd-DTPA-BMA as contrast agents was performed in 4T1 mouse breast cancer and HCC827 human non-small-cell lung cancer (NSNLC) xenograft models. Histopathological parameters of tumor vascularity microvessel density (MVD), microvessel area (MVA), endothelial area (EA) and α-SMA CD31 Co-expression (α-SMA/CD31%) were compared with the DCE-MRI parameters. Results demonstrated that DCE-MRI with the new nanoparticle Gd@C-dots can noninvasively evaluate vascular permeability. K trans measured by DCE-MRI with Gd@C-dots is an accurate parameter for the characterization of tumor permeability. EA is a reliable microvessel parameter to evaluate vessel permeability., (Copyright © 2019 Elsevier Inc. All rights reserved.)

The specialized light organ of the ponyfish supports the growth of the bioluminescent symbiont Photobacterium leiognathi. The bioluminescence of P. leiognathi is generated within a heteromeric protein complex composed of the bacterial luciferase and a 20-kDa lumazine binding protein (LUMP), which serves as a Förster resonance energy transfer (FRET) acceptor protein, emitting a cyan-colored fluorescence with an unusually long excited state lifetime of 13.6 ns. The long fluorescence lifetime and small mass of LUMP are exploited for the design of highly optimized encoded sensors for quantitative fluorescence anisotropy (FA) measurements of protein hydrodynamics. In particular, large differences in the FA values of the free and target-bound states of LUMP fusions appended with capture sequences of up to 20 kDa are used in quantitative FA imaging and analysis of target proteins. For example, a fusion protein composed of LUMP and a 5-kDa G protein binding domain is used as an FA sensor to quantify the binding of the GTP-bound cell division control protein 42 homolog (Cdc42) (21 kDa) in solution and within Escherichia coli. Additionally, the long fluorescence lifetime and the surface-bound fluorescent cofactor 6,7-dimethyl-8- (1'-dimethyl-ribityl) lumazine in LUMP are utilized in the design of highly optimized FRET probes that use Venus as an acceptor probe. The efficiency of FRET in a zero-length LUMP-Venus fusion is 62% compared to ∼ 31% in a related CFP-Venus fusion. The improved FRET efficiency obtained by using LUMP as a donor probe is used in the design of a FRET-optimized genetically encoded LUMP-Venus substrate for thrombin.

We present the design, synthesis and characterization of new functionalized fluorescent optical switches for rapid, all-visible light-mediated manipulation of fluorescence signals from labelled structures within living cells, and as probes for high-contrast optical lock-in detection (OLID) imaging microscopy. A triazole-substituted BIPS (TzBIPS) is identified from a rational synthetic design strategy that undergoes robust, rapid and reversible, visible light-driven transitions between a colorless spiro- (SP) and a far-red absorbing merocyanine (MC) state within living cells. The excited MC-state of TzBIPS may also decay to the MC-ground state emitting near infra-red fluorescence, which is used as a sensitive and quantitative read-out of the state of the optical switch in living cells. The SP to MC transition for a membrane-targeted TzBIPS probe (C₁₂-TzBIPS) is triggered at 405 nm at an energy level compatible with studies in living cells, while the action spectrum of the reverse transition (MC to SP) has a maximum at 650 nm. The SP to MC transition is complete within the 790 ns pixel dwell time of the confocal microscope, while a single cycle of optical switching between the SP and MC states in a region of interest is complete within 8 ms (125 Hz) within living cells, the fastest rate attained for any optical switch probe in a biological sample. This property can be exploited for real-time correction of background signals in living cells. A reactive form of TzBIPS is linked to secondary antibodies and used, in conjunction with an enhanced scope-based analysis of the modulated MC-fluorescence in immuno-stained cells, for high-contrast immunofluorescence microscopic analysis of the actin cytoskeleton.

Optical switch probes undergo rapid and reversible transitions between two distinct states, one of which may fluoresce. This class of probe is used in various super-resolution imaging techniques and in the high-contrast imaging technique of optical lock-in detection (OLID) microscopy. Here, we introduce optimized optical switches for studies in living cells under standard conditions of cell culture. In particular, a highly fluorescent cyanine probe (Cy or Cy3) is directly or indirectly linked to naphthoxazine (NISO), a highly efficient optical switch that undergoes robust, 405/532 nm-driven transitions between a colourless spiro (SP) state and a colourful merocyanine (MC) state. The intensity of Cy fluorescence in these Cy/Cy3-NISO probes is reversibly modulated between a low and high value in SP and MC states, respectively, as a result of Förster resonance energy transfer. Cy/Cy3-NISO probes are targeted to specific proteins in living cells where defined waveforms of Cy3 fluorescence are generated by optical switching of the SP and MC states. Finally, we introduce a new imaging technique (called OLID-immunofluorescence microscopy) that combines optical modulation of Cy3 fluorescence from Cy3/NISO co-labelled antibodies within fixed cells and OLID analysis to significantly improve image contrast in samples having high background or rare antigens.

Objectives/hypothesis: A high proportion of the geriatric population suffers from presbylaryngis and presbyphonia; however, our knowledge of vibratory patterns in this population is almost nonexistent. In this study, we investigate the vocal fold vibratory patterns of healthy elderly females to determine which features or combination of them could best describe the geriatric voices., Study Design: Cross-sectional study with 20 elderly healthy females with no history of voice problems., Methods: Hilbert transformed glottal area waveforms (GAWs) from serial high-speed digital imaging of sustained phonation are used to provide quantitative measures of glottal vibratory characteristics and perturbations; open quotient, jitter, and shimmer. Nyquist plots provide interpretable patterns to portray the vibratory characteristics as clear, pressed, breathy, and atypical patterns., Results: The GAW from most elderly speakers (50%) showed vibratory characteristics associated with a more pressed voice and higher glottal perturbation values: their Nyquist plot patterns show wide scatterings around the rim of the plot reflecting a much-reduced ability in sustaining vibratory oscillation; these were distinct differences from previously reported data on younger speakers. Qualitative examination revealed more anteriorly placed glottal gaps in the geriatric females., Conclusion: These findings have important implications in understanding voice production in the geriatric population and in helping to establish normal perturbation references among female speakers across age., (Copyright © 2012 The Voice Foundation. All rights reserved.)

The purpose of the study was to investigate relationships between vocal fold vibrations and voice quality. Laryngeal images obtained from high-speed digital imaging (HSDI) were examined for their open-closed timing characteristics and perturbation values. A customized software delineated the glottal edges and used the Hilbert transform-based method of analysis to provide objective quantification of glottal perturbation. Overlay tracings of the transformed glottal cycles provided visual patterns on the overall vibratory dynamics. In this paper, we described the use of this method in looking at vibratory characteristics of a group of young female speakers (N=23). We found that, females with no voice complaints and who had been perceived to have normal voices were not a homogeneous group in terms of their glottal vibratory patterns during phonation. Their vibratory patterns showed characteristics similar to exemplar voices targeted to be clear (50%), pressed (27%), breathy (15%), or a mixed quality (8%). Perturbation range in terms of cycle-to-cycle frequency and amplitude was small and did not discriminate patterns. All these patterns yielded perceptually normal voices suggesting that in normal young speakers, the level of perturbation may be more important to the judgment than the actual pattern of closure., (Copyright © 2012 The Voice Foundation. All rights reserved.)

A major challenge in cell biology is to elucidate molecular mechanisms that underlie the spatio-temporal control of cellular processes. These studies require microscope imaging techniques and associated optical probes that provide high-contrast and high-resolution images of specific proteins and their complexes. Auto-fluorescence however, can severely compromise image contrast and represents a fundamental limitation for imaging proteins within living cells. We have previously shown that optical switch probes and optical lock-in detection (OLID) image microscopy improve image contrast in high background environments. Here, we present the design, synthesis, and characterization of amino-reactive and cell permeable optical switches that integrate the highly fluorescent fluorophore, tetramethylrhodamine (TMR) and spironaphthoxazine (NISO), a highly efficient optical switch. The NISO moiety in TMR-NISO undergoes rapid and reversible, excited-state driven transitions between a colorless spiro (SP)-state and a colored merocyanine (MC)-state in response to irradiation with 365 and >530nm light. In the MC-state, the TMR (donor) emission is almost completely extinguished by Förster resonance energy transfer (FRET) to the MC probe (acceptor), whereas in the colorless SP-state, the quantum yield for TMR fluorescence is maximal. Irradiation of TMR-NISO with a defined sequence of 365 and 546nm manipulates the levels of SP and MC with concomitant modulation of FRET efficiency and the TMR fluorescence signal. High fidelity optical switching of TMR fluorescence is shown for TMR-NISO probes in vitro and for membrane permeable TMR-NISO within living cells., (Copyright © 2010 Elsevier Ltd. All rights reserved.)

Background: Conventional fiberoptic laryngoscope may cause discomfort to the patient and in some cases it can lead to side effects that include perforation, infection and hemorrhage. Virtual laryngoscopy (VL) can overcome this problem and further it may lower the risk of operation failures. Very few virtual endoscope (VE) based investigations of the larynx have been described in the literature., Material/methods: CT data sets from a healthy subject were used for the VL studies. An algorithm of preprocessing and region-growing for 3-D image segmentation is developed. An octree based approach is applied in our VL system which facilitates a rapid construction of iso-surfaces. Some locating techniques are used for fast rendering and navigation (fly-through)., Results: Our VL visualization system provides for real time and efficient 'fly-through' navigation. The virtual camera can be arranged so that it moves along the airway in either direction. Snap shots were taken during fly-throughs. The system can automatically adjust the direction of the virtual camera and prevent collisions of the camera and the wall of the airway., Conclusions: A virtual laryngoscope (VL) system using OpenGL (Open Graphics Library) platform for interactive rendering and 3D visualization of the laryngeal framework and upper airway is established. OpenGL is supported on major operating systems and works with every major windowing system. The VL system runs on regular PC workstations and was successfully tested and evaluated using CT data from a normal subject.

One of the limitations on imaging fluorescent proteins within living cells is that they are usually present in small numbers and need to be detected over a large background. We have developed the means to isolate specific fluorescence signals from background by using lock-in detection of the modulated fluorescence of a class of optical probe termed "optical switches." This optical lock-in detection (OLID) approach involves modulating the fluorescence emission of the probe through deterministic, optical control of its fluorescent and nonfluorescent states, and subsequently applying a lock-in detection method to isolate the modulated signal of interest from nonmodulated background signals. Cross-correlation analysis provides a measure of correlation between the total fluorescence emission within single pixels of an image detected over several cycles of optical switching and a reference waveform detected within the same image over the same switching cycles. This approach to imaging provides a means to selectively detect the emission from optical switch probes among a larger population of conventional fluorescent probes and is compatible with conventional microscopes. OLID using nitrospirobenzopyran-based probes and the genetically encoded Dronpa fluorescent protein are shown to generate high-contrast images of specific structures and proteins in labeled cells in cultured and explanted neurons and in live Xenopus embryos and zebrafish larvae.

We present a comprehensive, functional analysis of clinical voice data derived from both high-speed digital imaging (HSDI) of the larynx and simultaneously acquired acoustic recordings. The goals of this study are to: (1) correlate dynamic characteristics of the vocal folds derived from direct laryngeal imaging with indirectly acquired acoustic measurements; (2) define the advantages of using a combined imaging/acoustic approach for the analysis of voice condition; and (3) identify new quantitative measures to evaluate the regularity of the vocal fold vibration and the complexity of the vocal output -- these measures will be key to successful diagnosis of vocal abnormalities. Image- and acoustic-based analyses are performed using an analytic phase plot approach previously introduced by our group (referred to as 'Nyquist' plot). Fast Fourier Transform (FFT) spectral analyses are performed on the same data for a comparison. Clinical HSDI and acoustic recordings from subjects having normal and specific voice pathologies, including muscular tension dysphonia (MTD) and recurrent respiratory papillomatosis (RRP) were analyzed using the Nyquist plot approach. The results of these analyses show that a combined imaging/acoustic analysis approach provides better characterization of the vibratory behavior of the vocal folds as it correlates with vocal output and pathology.

This work shows that optical switching between the spiro (SP) and merocyanine (MC) states of different photochromes specifically labeled to G-actin can be used to rapidly and reversibly modulate specific dipolar interactions within the conjugate. Members of a common spirobenzopyran photochrome and a related spironaphthoxazine that differ only in the locations of their alkylating groups were selectively labeled to Cys-374 on G-actin. The nature of MC and SP interactions within G-actin was investigated by using optical spectroscopy. The average absorption energy of the highly polarized MC is sensitive to interactions with polar groups on solvents and G-actin; the average absorption energy of the corresponding SP state was found to be relatively constant, consistent with its lower dipole moment compared with MC (5 and 20 D, respectively). Alternate excitation of spirobenzopyran G-actin conjugates with 365 and 546 nm leads to rapid transitions from the SP to MC states and MC to SP states, respectively; optical switching within spirobenzopyran-G-actin occurs with high fidelity and the recovery of specific dipolar interactions between the protein and the MC and SP states. The difference in the free energy for specific dipolar interactions between different MC states within G-actin (6 kcal/mol) is similar to that found for complexes of G-actin and its regulatory proteins. We propose, therefore, that optical switching between SP and MC within an appropriately labeled conjugate could be used to inhibit a functional interaction with a ligand in the MC, but not the SP, state.

High-speed laryngeal imaging (HSLI) is emerging as a new clinical tool for the assessment of voice disorders. The analysis of high temporal resolution images of the vibrating vocal folds may provide new information on the mechanism of voice production and how altered vibratory properties relate to voice pathologies. An essential procedure in the HSLI data processing is tracing the vocal fold edges, an operation referred to as glottal edge detection. In this paper, we present an adaptive image segmentation method which facilitates fast and effective glottal edge detection operating on a frame-by-frame basis. The glottal area waveform traced from this process is then analyzed using an analytic signal approach we previously developed. In this approach, the analytic phase trace plot, or refereed to as Nyquist plot, is used to show patterns of the vocal fold vibration that correlate with voice quality and health condition. Several examples of clinical voice recordings are used to evaluate and test the effectiveness of our approach.

In this paper, we present a real-time approach for effective and automatic manipulation and navigation in a virtual laryngeal environment. Efficient algorithms are developed for 1), automatic segmentation, and 2) volume data organization and 3), surface rendering. Finally a virtual laryngoscope is built for the visualization of laryngeal systems and this visualization system is tested using CT volume data acquired from two normal subjects.

In this paper, a segmentation scheme that combines thresholding, morphological operation and region growing is proposed for tracing the vocal fold opening region from the high-speed laryngeal image sequences. Specifically, the proposed scheme contains three steps: 1), histogram based global thresholding; 2), morphological operation on the segmented binary output from step 1; 3), region growing process to refine the segmentation. The glottal area waveform, which is the glottis area as a function of time, is obtained on a frame by frame basis from the segmented region of the vocal fold opening, or glottis. Representative clinical image recordings from subjects with normal and pathological voices are processed to validate our approach.

Biophotonics techniques, especially those involving fluorescence, are widely used in proteomics to characterize the in vitro interactions between proteins in high-throughput mode. On the other hand, fluorescence-based imaging studies often show that protein activity is regulated through large protein complexes that transiently form at specific sites in the cell. One could therefore argue that a systematic functional analysis of the human proteome requires technologies that are capable of time and spatially resolved, multiplexed analysis of protein interactions within cells.

This study characterizes the interactions between kabiramide C (KabC) and related macrolides and actin and establishes the mechanisms that underlie their inhibition of actin filament dynamics and cytotoxicity. The G-actin-KabC complex is formed through a two-step binding reaction and is extremely stable and long-lived. Competition-binding studies show that KabC binds to the same site on G-actin as Gelsolin domain 1 and CapG. KabC also binds to protomers within F-actin and results in the severing and capping of the (+) end; these studies suggest that free KabC and related macrolides act as biomimetics of Gelsolin. The G-actin-KabC complex binds to the (+) end of a growing filament, where it functions as a novel, unregulated, (+)-end capper and is largely responsible for the inhibition of motility and cytokinesis in approximately 10 -100 nM KabC-treated cells. KabC and related macrolides are useful probes to study the regulation of the actin filament (+) end and may lead to new therapies to treat diseases of the actin cytoskeleton.