Identification of fibrosis in hypertrophic cardiomyopathy: a radiomic study on cardiac magnetic resonance cine imaging.

OBJECTIVES: Hypertrophic cardiomyopathy (HCM) often requires repeated enhanced cardiac magnetic resonance (CMR) imaging to detect fibrosis. We aimed to develop a practical model based on cine imaging to help identify patients with high risk of fibrosis and screen out patients without fibrosis to avoid unnecessary injection of contrast. METHODS: A total of 273 patients with HCM were divided into training and test sets at a ratio of 7:3. Logistic regression analysis was used to find predictive image features to construct CMR model. Radiomic features were derived from the maximal wall thickness (MWT) slice and entire left ventricular (LV) myocardium. Extreme gradient boosting was used to build radiomic models. Integrated models were established by fusing image features and radiomic models. The model performance was validated in the test set and assessed by ROC and calibration curve and decision curve analysis (DCA). RESULTS: We established five prediction models, including CMR, R1 (based on the MWT slice), R2 (based on the entire LV myocardium), and two integrated models (ICMR+R1 and ICMR+R2). In the test set, ICMR+R2 model had an excellent AUC value (0.898), diagnostic accuracy (89.02%), sensitivity (92.54%), and F1 score (93.23%) in identifying patients with positive late gadolinium enhancement. The calibration plots and DCA indicated that ICMR+R2 model was well-calibrated and presented a better net benefit than other models. CONCLUSIONS: A predictive model that fused image and radiomic features from the entire LV myocardium had good diagnostic performance, robustness, and clinical utility. KEY POINTS: • Hypertrophic cardiomyopathy is prone to fibrosis, requiring patients to undergo repeated enhanced cardiac magnetic resonance imaging to detect fibrosis over their lifetime follow-up. • A predictive model based on the entire left ventricular myocardium outperformed a model based on a slice of the maximal wall thickness. • A predictive model that fused image and radiomic features from the entire left ventricular myocardium had excellent diagnostic performance, robustness, and clinical utility.

Correlation analysis of epicardial adipose tissue and ventricular myocardial strain in Chinese amateur marathoners using cardiac magnetic resonance.

BACKGROUND: The volume of epicardial adipose tissue (EAT) is associated with an increased incidence of cardiovascular disease (CVD); however, only a few studies have examined its effect on the myocardial function of endurance in athletes. The association between the EAT and the variation of myocardial function is still unclear in amateur marathoners. Consequently, by using some sedentary individuals as the control, this study aims to evaluate the correlation between the EAT volume and the myocardial strain in the left and right ventricles of Chinese amateur marathoners by cardiac magnetic resonance (CMR). METHODS: A total of 30 amateur marathoners were included as the exercise group and 20 sedentary people as a control group. All participants received the cardiac magnetic resonance (CMR) to measure the left and right ventricular end-diastolic volume, end-systolic volume and volume index, stroke volume and index, cardiac output index, ejection fraction and myocardial mass, the EAT volume, global radial, circumferential, and longi-tudinal strains, and the strain rates of left and right ventricular myocardium. RESULTS: There was a significant difference in the EAT volume (EATV) index between the exercise group and the control group (26.82±11.76ml/m2 vs 37.82±17.15ml/m2, P = 0.01). Results from the multivariate linear regression analysis showed that BMI (standardized ß = 0.458; P < 0.001) had an independent positive correlation with the EATV index. The EATV index was negatively correlated with the left ventricular global radial strain (GRS) (r = -0.505; P = 0.004) in the exercise group, while it is negatively correlated with right ventricular GRS (r = -0.492; P = 0.027) and positively correlated with global longitudinal strain (GLS) (r = 0.601; P = 0.005) in the control group. In the exercise group, the multivariate linear regression analysis showed that the EATV index (standardized ß = -0.429; P = 0.021) was an independent determinant of the left ventricular GRS, and being a male (standardized ß = 0.396; P = 0.029) was an independent determinant of the right ventricular GLS. CONCLUSION: The EATV index is independently correlated with the left ventricular GRS in the amateur Chinese marathoners, also, the amateur marathon reduces the EATV index and increases the left ventricular myocardial mass, which consequently reduces the adverse effects on myocardial function.

Review of lipoic acid: From a clinical therapeutic agent to various emerging biomaterials.

Lipoic acid (LA), an endogenous small molecule in organisms, has been extensively used for the highly efficient clinical treatment of malignant diseases, which include diabetes, Alzheimer's disease, and cancer over the past seven decades. Tremendous progresses have been made on the use of LA in nanomedicine for the development of various biomaterials because of its unique biological properties and highly adaptable structure since the first discovery. However, there are few reviews thus far, to our knowledge, summarizing this hot subject of research of LA and its derived biomaterials. For this purpose, we present herein the first comprehensive summary on the design and development of LA and its derived materials for biomedical applications. This review first discusses the therapeutic use of LA followed by the description of synthesis and preclinical study of LA-derived-small molecules. The applications of various LA and poly (lipoic acid) (PLA)-derived-biomaterials are next summarized in detail with an emphasis on the use of LA for the design of biomaterials and the diverse properties. This review describes the development of LA from a clinical therapeutic agent to a building unit of various biomaterials field, which will promote the further discovery of new therapeutic uses of LA as therapeutic agents and facile development of LA-based derivates with greater performance for biomedical applications.

Neural Basis of the Implicit Learning of Complex Artificial Grammar with Nonadjacent Dependencies.

The capacity for the implicit learning/processing of complex grammar with nonadjacent dependencies is an important feature of human language learning. In this fMRI study, using an implicit AGL paradigm, we explored the neural basis of the implicit learning of the nonadjacent dependency rule, disentangling from sequence-based chunk knowledge (i.e., local sequential regularities or substring) by focusing on the low chunk strength items (which were naturally less similar to training strings), based on tracking neural responses during training and test phases. After listening to and memorizing a series of strings of 10 syllables generated from nonadjacent artificial grammar in the training phase, participants implicitly acquired the knowledge of grammar and chunks. Regarding grammaticality, Broca's area was specifically related to low chunk strength grammatical strings relative to nongrammatical strings in the test phase. This region showed decreased activity with time in the training phase, and a lesser decrease in activity was associated with higher performance in grammar learning. Furthermore, Broca's area showed significantly higher strength of functional connectivity with the left superior temporal gyrus in the low chunk strength grammatical string compared with nongrammatical strings, and this functional connectivity increased with the training time. For the chunks, the performance of accurate discrimination of high chunk strength from low chunk strength nongrammatical strings was predicted by hippocampal activity in the training phase. Converging evidence from the training and test phases showed that Broca's area and its functional connectivity with the left superior temporal gyrus were engaged in the implicit learning/processing of the nonadjacent dependency rule, separating the effects of chunks.

Prolonged blood circulation outperforms active targeting for nanocarriers-mediated enhanced hepatocellular carcinoma therapy in vivo.

Successful hepatocellular carcinoma (HCC) therapy in vivo remains a significant challenge due to the down-regulated expression of the receptors on the surface of tumor cells for compromised active targeting efficiency and cellular uptake of nanoparticles (NPs)-based drug delivery systems (DDSs) and "accelerated blood clearance" and premature unpackaging of NPs in vivo induced by the poly(ethylene glycol)ylation (PEGylation). Inspired by the repeatedly highlighted prolonged blood circulation property of RBCm-camouflaged NPs, we hypothesis that the prolonged blood circulation property resulting from RBCm coating outperforms the active targeting mechanisms of various targeting ligands for enhanced HCC therapy in vivo. Clarification of this hypothesis is therefore of great significance and urgency to break the afore mentioned bottlenecks that hamper the efficient HCC treatment in vivo. For this purpose, we reported in this study the first identification of a determining factor of nanocarriers for enhanced HCC therapy in vivo by the use of the previously fabricated pectin-doxorubicin nanoparticles (PDC-NPs) as a typical example, i.e., the natural RBCm was used as a stealth coating of PDC-NPs for the fabrication of biomimetic DDSs, PDC@RBC-NPs via hypotonic dialysis and mechanical co-extrusion methods. Comprehensive in vitro and in vivo evaluation and comparison of the properties and performance of PDC@RBC-NPs and PDC-NPs were performed in terms of colloidal stability, biosafety, drug release profiles, macrophage escape, anti-HCC effect. The resulting PDC@RBC-NPs outperformed PDC-NPs for HCC therapy in vitro and in vivo. Notably, PDC@RBC-NPs-treated BALB/c nude mice showed a significantly smaller final average tumor volume of 613 mm3 after 16 days than the PDC-NPs-treated group with an average value of 957 mm3. Therefore, the PDC@RBC-NPs developed herein showed great potential for clinical transformations due to the facile preparation and superior therapeutic efficiency against HCC. Most importantly, prolonged blood circulation was identified as a determining factor of nanocarriers instead of active targeting for enhanced HCC therapy in vivo, which could be used to direct the future design and development of advanced DDSs with greater therapeutic efficiency for HCC.

Punishment cost affects third-parties' behavioral and neural responses to unfairness.

Third-party punishment plays a crucial role in fairness norm enforcement. The present study investigated how punishment cost would affect third-parties' behavioral and neural responses to unfairness using a modified Third-Party Dictator Game and functional magnetic resonance imaging (fMRI). Participants acted as third-parties and decided how many monetary units (MUs) to invest to punish norm violations in two punishment cost contexts. Participants' every MU investment reduced dictators' payoff by 6 MUs in the low punishment cost context and 3 MUs in the high one. Participants' invested MUs reflected the cost they would like to pay to punish dictators while dictators' reduced MUs represented the amount of punishment they received. Behavioral results showed participants' fairness ratings were not affected by punishment cost. However, punishment amount decreased in the high punishment cost context where participants invested more MUs and spent more time for decision-making. Neurally, left anterior insula (AI) and bilateral dorsolateral prefrontal cortex (dlPFC) showed stronger responses to unfair relative to fair allocations in both contexts. Moreover, dorsal anterior cingulate cortex (dACC) was more active during unfair allocations in the high punishment cost context than in the low one and the difference of dACC activity between these two conditions was positively correlated with the difference of reaction times. Overall, the present study demonstrated that punishment cost would not affect people's fairness perception but increase the conflicts between norm enforcement and self-interest. The decision for punishment was the outcome of integrating fairness and economic considerations.

Classification and Quantification of Emphysema Using a Multi-Scale Residual Network.

Automated tissue classification is an essential step for quantitative analysis and treatment of emphysema. Although many studies have been conducted in this area, there still remain two major challenges. First, different emphysematous tissue appears in different scales, which we call "inter-class variations." Second, the intensities of CT images acquired from different patients, scanners or scanning protocols may vary, which we call "intra-class variations". In this paper, we present a novel multi-scale residual network with two channels of raw CT image and its differential excitation component. We incorporate multi-scale information into our networks to address the challenge of inter-class variations. In addition to the conventional raw CT image, we use its differential excitation component as a pair of inputs to handle intra-class variations. Experimental results show that our approach has superior performance over the state-of-the- art methods, achieving a classification accuracy of 93.74% on our original emphysema database. Based on the classification results, we also perform the quantitative analysis of emphysema in 50 subjects by correlating the quantitative results (the area percentage of each class) with pulmonary functions. We show that centrilobular emphysema (CLE) and panlobular emphysema (PLE) have strong correlation with the pulmonary functions and the sum of CLE and PLE can be used as a new and accurate measure of emphysema severity instead of the conventional measure (sum of all subtypes of emphysema). The correlations between the new measure and various pulmonary functions are up to |r| = 0.922 (r is correlation coefficient).

Does maintaining bindings in visual working memory require more attention than maintaining features?

Whether more attention is required for maintaining bindings than maintaining features in visual working memory (VWM) remains an open question. If maintaining bindings in VWM does not require more attention than maintaining features, is it related to the stability of binding representations? In this study, we explored whether maintaining bindings requires more attention than maintaining features for similar and dissimilar objects by inserting a feature report task into the maintenance phase of VWM in Experiments 1 and 2. We also investigated whether the effect of similarity on the attentional requirement for maintaining bindings and features is due to the stability of VWM representations by inserting a suffix during the maintenance phase of VWM in Experiment 3. The results showed that when object-based attention was consumed, bindings were more impaired than features for dissimilar objects but not for similar objects. We also found that the bindings of similar objects were less interfered by the suffix than those of dissimilar objects. Our findings suggest that maintaining bindings does not require more attention than maintaining features when the binding representations are stable in VWM and similarity improves the stability of binding representations.

Cross-cultural differences in implicit learning of chunks versus symmetries.

Three experiments explore whether knowledge of grammars defining global versus local regularities has an advantage in implicit acquisition and whether this advantage is affected by cultural differences. Participants were asked to listen to and memorize a number of strings of 10 syllables instantiating an inversion (i.e. a global pattern); after the training phase, they were required to judge whether new strings were well formed. In Experiment 1, Western people implicitly acquired the inversion rule defined over the Chinese tones in a similar way as Chinese participants when alternative structures (specifically, chunking and repetition structures) were controlled. In Experiments 2 and 3, we directly pitted knowledge of the inversion (global) against chunk (local) knowledge, and found that Chinese participants had a striking global advantage in implicit learning, which was greater than that of Western participants. Taken together, we show for the first time cross-cultural differences in the type of regularities implicitly acquired.

Tonal Symmetry Induces Fluency and Sense of Well-Formedness.

Fluency influences grammaticality judgments of visually presented strings in artificial grammar learning (AGL). Of many potential sources that engender fluency, symmetry is considered to be an important factor. However, symmetry may function differently for visual and auditory stimuli, which present computationally different problems. Thus, the current study aimed to examine whether objectively manipulating fluency by speeding up perception (i.e., manipulating the inter-stimulus interval, ISI, between each syllable of a string) influenced judgments of tonal strings; and thus how symmetry-based fluency might influence judgments. In Experiment 1, with only a test phase, participants were required to give their preference ratings of tonal strings as a measurement of fluency. In experiment 2, participants were instructed to make grammaticality judgments after being incidentally trained on tonal symmetry. Results of Experiment 1 showed that tonal strings with shorter ISI were liked more than those with longer ISI while such difference was not found between symmetric and asymmetric strings without training. Additionally, Experiment 2 found both main effects of symmetry and ISI as well as an interaction. In particular, only asymmetric strings were more likely to be judged as grammatical when they were presented at a shorter ISI. Taken together, participants were sensitive to the fluency induced by the manipulation of ISI and sensitive to symmetry only after training. In sum, we conclude that objective speed influenced grammaticality judgments, implicit learning of tonal symmetry resulted in enhanced fluency, and that fluency may serve as a basis for grammaticality judgments.

Modulation of financial deprivation on deception and its neural correlates.

Deception is a universal phenomenon in human society and plays an important role in everyday life. Previous studies have revealed that people might have an internalized moral norm of keeping honest and the deceptive behavior was reliably correlated with activation in executive brain regions of prefrontal cortices to over-ride intuitive honest responses. Using functional magnetic resonance imaging, this study sought to investigate how financial position modulated the neural responses during deceptive decision. Twenty-one participants were scanned when they played a series of adapted Dictator Game with different partners after a ball-guess game. Specifically, participants gained or lost money in the ball-guess game, and had opportunities to get more financial gains through cheating in the following adapted Dictator Game. Behavioral results indicated that participants did not cheat to the full extent; instead they were more likely to lie after losing money compared with gaining money. At the neural level, weaker activities in the dorsolateral prefrontal cortices were observed when participants lied after losing money than gaining money. Together, our data indicated that, people really had an internalized norm of keeping honest, but it would be lenient when people feel financial deprivation. And suppressing the truthful response originating from moral norm of keeping honest was associated with increased level of activation in the dorsolateral prefrontal cortices, but this association became weaker when people were under financial deprivation.

Fluency Expresses Implicit Knowledge of Tonal Symmetry.

The purposes of the present study were twofold. First, we sought to establish whether tonal symmetry produces processing fluency. Second, we sought to explore whether symmetry and chunk strength express themselves differently in fluency, as an indication of different mechanisms being involved for sub- and supra-finite state processing. Across two experiments, participants were asked to listen to and memorize artificial poetry showing a mirror symmetry (an inversion, i.e., a type of cross serial dependency); after this training phase, people completed a four-choice RT task in which they were presented with new artificial poetry. Participants were required to identify the stimulus displayed. We found that symmetry sped up responding to the second half of strings, indicating a fluency effect. Furthermore, there was a dissociation between fluency effects arising from symmetry vs. chunk strength, with stronger fluency effects for symmetry rather than chunks in the second half of strings. Taken together, we conjecture a divide between finite state and supra-finite state mechanisms in learning grammatical sequences.

Perceived reputation of others modulates empathic neural responses.

Empathy enables us to understand and share the emotional and affective states of another person and plays a key role in social behaviors. The current study investigated whether and how empathic neural responses to pain were modulated by the perceived reputation of others. Action histories reflecting individuals' past cooperation or betrayal actions in the repeated prisoner's dilemma game were introduced as an index of reputation. We assessed brain activity with functional magnetic resonance imaging while the participants observed individuals with a good or bad reputation receiving or not receiving pain. The results indicated that the participants exhibited reduced empathic responses in AI and dACC to the individual who had a bad reputation relative to the one who had a good reputation, suggesting that their empathy for pain was modulated by the perceived reputation of others.

The neural basis of implicit learning of task-irrelevant Chinese tonal sequence.

The present study sought to investigate the neural basis of implicit learning of task-irrelevant perceptual sequence. A novel SRT task, the serial syllable identification task (SSI task), was used in which the participants were asked to recognize which one of two Chinese syllables was presented. The tones of the syllables were irrelevant to the task but followed an underlying structured sequence. Participants were scanned while they performed the SSI task. Results showed that, at the behavioral level, faster RTs for the sequential material indicated that task-irrelevant sequence knowledge could be learned. In the subsequent prediction test of knowledge of the tonal cues using subjective measures, we found that the knowledge was obtained unconsciously. At the neural level, the left caudate, bilateral hippocampus and bilateral superior parietal lobule were engaged during the sequence condition relative to the random condition. Further analyses revealed that greater learning-related activation (relative to random) in the right caudate nucleus, bilateral hippocampus and left superior parietal lobule were found during the second half of the training phase compared with the first half. When people reported that they were guessing, the magnitude of the right hippocampus and left superior parietal lobule activations was positively related to the accuracy of prediction test, which was significantly better than chance. Together, the present results indicated that the caudate, hippocampus and superior parietal lobule played critical roles in the implicit perceptual sequence learning even when the perceptual features were task irrelevant.