Prognostic Significance of Preoperative and Postoperative Evaluation of Combined Tumor Markers for Patients With Colon Cancer.

BACKGROUND: The combined value of the tumor markers carcinoembryonic antigen (CEA) and carbohydrate antigen 19-9 (CA19-9) in patients with colon cancer (CC) is unclear. This study aimed to investigate the role of composite tumor markers in the prognosis of CC. METHODS: Patients who underwent curative resection of colon adenocarcinoma were enrolled. The tumor marker status before and after the operation was used to divide the patients into groups according to the number of tumor markers with abnormal expression, and recurrence-free survival (RFS) and overall survival (OS) of different groups were compared. The impact of changes in composite tumor markers in the perioperative period on outcomes was further explored. RESULTS: Ultimately, 531 patients were enrolled in the study. As the number of preoperative and postoperative elevated tumor markers increased, both RFS and OS rates became lower (both P<0.05). Further analysis revealed that the number of elevated tumor markers after resection can significantly affect the outcomes (both P<0.05). In patients with abnormal preoperative tumor markers, normalization of markers after surgery was a protective factor for prognosis (both P<0.05), and patients with postoperative elevated levels of both tumor markers had a 5.5-fold and 6-fold increase in the risk of recurrence and death. In addition, patients with elevated markers after surgery had a high risk of recurrence within 5 years after colectomy. CONCLUSIONS: Postoperative tumor markers had a better ability to differentiate postoperative outcomes in patients with CC than preoperative tumor markers. Patients whose tumor markers normalized after surgery had a better prognosis.

Fibrosis signature of anastomotic margins for predicting anastomotic stenosis in rectal cancer with neoadjuvant chemoradiotherapy and sphincter-preserving surgery.

Background: Radiation-induced colorectal fibrosis (RICF) is a common pathological alteration among patients with rectal cancer undergoing neoadjuvant chemoradiotherapy (nCRT). Anastomotic stenosis (AS) causes symptoms and negatively impacts patients' quality of life and long-term survival. In this study, we aimed to evaluate the fibrosis signature of RICF and develop a nomogram to predict the risk of AS in patients with rectal cancer undergoing nCRT. Methods: Overall, 335 pairs of proximal and distal margins were collected and randomly assigned at a 7:3 ratio to the training and testing cohorts. The RICF score was established to evaluate the fibrosis signature in the anastomotic margins. A nomogram based on the RICF score for AS was developed and evaluated by using the area under the curve, decision curve analysis, and the DeLong test. Results: The training cohort included 235 patients (161 males [68.51%]; mean age, 59.61 years) with an occurrence rate of AS of 17.4%, whereas the testing cohort included 100 patients (72 males [72.00%]; mean age, 57.17 years) with an occurrence rate of AS of 11%. The RICF total score of proximal and distal margins was significantly associated with AS (odds ratio, 3.064; 95% confidence interval [CI], 2.200-4.268; P < 0.001). Multivariable analysis revealed that the RICF total score, neoadjuvant radiotherapy, and surgical approach were independent predictors for AS. The nomogram demonstrated good discrimination in the training cohort (area under the receiver-operating characteristic curve, 0.876; 95% CI, 0.816-0.937), with a sensitivity of 68.3% (95% CI, 51.9%-81.9%) and a specificity of 85.5% (95% CI, 78.7%-89.3%). Similar results were observed in the testing cohort. Conclusions: This study results suggest that the RICF total score of anastomotic margins is an independent predictor for AS. The prediction model developed based on the RICF total score may be useful for individualized AS risk prediction in patients with rectal cancer undergoing nCRT and sphincter-preserving surgery.

The transplant rejection response involves neutrophil and macrophage adhesion-mediated trogocytosis and is regulated by NFATc3.

The anti-foreign tissue (transplant rejection) response, mediated by the immune system, has been the biggest obstacle to successful organ transplantation. There are still many enigmas regarding this process and some aspects of the underlying mechanisms driving the immune response against foreign tissues remain poorly understood. Here, we found that a large number of neutrophils and macrophages were attached to the graft during skin transplantation. Furthermore, both types of cells could autonomously adhere to and damage neonatal rat cardiomyocyte mass (NRCM) in vitro. We have demonstrated that Complement C3 and the receptor CR3 participated in neutrophils/macrophages-mediated adhesion and damage this foreign tissue (NRCM or skin grafts). We have provided direct evidence that the damage to these tissues occurs by a process referred to as trogocytosis, a damage mode that has never previously been reported to directly destroy grafts. We further demonstrated that this process can be regulated by NFAT, in particular, NFATc3. This study not only enriches an understanding of host-donor interaction in transplant rejection, but also provides new avenues for exploring the development of novel immunosuppressive drugs which prevent rejection during transplant therapy.

The PERK Branch of the Unfolded Protein Response Safeguards Protein Homeostasis and Mesendoderm Specification of Human Pluripotent Stem Cells.

Cardiac development involves large-scale rearrangements of the proteome. How the developing cardiac cells maintain the integrity of the proteome during the rapid lineage transition remains unclear. Here it is shown that proteotoxic stress visualized by the misfolded and/or aggregated proteins appears during early cardiac differentiation of human pluripotent stem cells and is resolved by activation of the PERK branch of unfolded protein response (UPR). PERK depletion increases misfolded and/or aggregated protein accumulation, leading to pluripotency exit defect and impaired mesendoderm specification of human pluripotent stem cells. Mechanistically, it is found that PERK safeguards mesendoderm specification through its conserved downstream effector ATF4, which subsequently activates a novel transcriptional target WARS1, to cope with the differentiation-induced proteotoxic stress. The results indicate that protein quality control represents a previously unrecognized core component of the cardiogenic regulatory network. Broadly, these findings provide a framework for understanding how UPR is integrated into the developmental program by activating the PERK-ATF4-WARS1 axis.

Pathways of lymph node metastasis and prognosis after right hemicolectomy for cecal cancer: results from a retrospective single center.

BACKGROUND: The recommended operation for cecum cancer (CC) is right hemicolectomy (RH) in some Western countries while the principle of D3 lymphadenectomy in Japan recommends resecting approximately 10 cm from the tumor edge. Therefore, the optimal surgical approach for cecum cancer (CC) remains controversial. We conducted this retrospective study to explore the pattern of lymph node metastasis and better surgical procedures for CC. METHODS: A total of 224 cecum cancer patients from January 1, 2014, to December 31, 2021, were retrospectively included in the final study. The pattern of lymph node metastasis (LNM) was investigated. RESULTS: A total of 113 (50.4%, 113/224) patients had pathologically confirmed LNM. The most frequent metastatic site was no. 201 lymph node (46%, 103/224), while 20 (8.9%, 20/224) patients had LNM in no. 202 lymph node, and 8 (3.6%, 8/224) patients had LNM in no. 203 lymph node. Only 1 (0.4%, 1/224) patient had LNM in no. 221 lymph node, four (1.8, 4/224%) patients had LNM in no. 223 lymph node, and no patients had LNM in no. 222 lymph node. LNM in no. 223 lymph node was significantly associated with a poor prognosis. Multivariate analysis indicated that LNM in no. 223 lymph node (HR = 4.59, 95% CI 1.18-17.86, P = 0.028) was the only independent risk factor associated with worse disease-free survival (DFS). CONCLUSIONS: The LNM in no. 223 lymph node for cecum cancer was rare. Therefore, standard right hemicolectomy excision is too extensive for most CC cases.

Co-effects of m6A and chromatin accessibility dynamics in the regulation of cardiomyocyte differentiation.

BACKGROUND: Cardiomyocyte growth and differentiation rely on precise gene expression regulation, with epigenetic modifications emerging as key players in this intricate process. Among these modifications, N6-methyladenosine (m6A) stands out as one of the most prevalent modifications on mRNA, exerting influence over mRNA metabolism and gene expression. However, the specific function of m6A in cardiomyocyte differentiation remains poorly understood. RESULTS: We investigated the relationship between m6A modification and cardiomyocyte differentiation by conducting a comprehensive profiling of m6A dynamics during the transition from pluripotent stem cells to cardiomyocytes. Our findings reveal that while the overall m6A modification level remains relatively stable, the m6A levels of individual genes undergo significant changes throughout cardiomyocyte differentiation. We discovered the correlation between alterations in chromatin accessibility and the binding capabilities of m6A writers, erasers, and readers. The changes in chromatin accessibility influence the recruitment and activity of m6A regulatory proteins, thereby impacting the levels of m6A modification on specific mRNA transcripts. CONCLUSION: Our data demonstrate that the coordinated dynamics of m6A modification and chromatin accessibility are prominent during the cardiomyocyte differentiation.

Orientational Distribution Learning With Hierarchical Spatial Attention for Open Set Recognition.

Open set recognition (OSR) aims to correctly recognize the known classes and reject the unknown classes for increasing the reliability of the recognition system. The distance-based loss is often employed in deep neural networks-based OSR methods to constrain the latent representation of known classes. However, the optimization is usually conducted using the nondirectional euclidean distance in a single feature space without considering the potential impact of spatial distribution. To address this problem, we propose orientational distribution learning (ODL) with hierarchical spatial attention for OSR. In ODL, the spatial distribution of feature representation is optimized orientationally to increase the discriminability of decision boundaries for open set recognition. Then, a hierarchical spatial attention mechanism is proposed to assist ODL to capture the global distribution dependencies in the feature space based on spatial relationships. Moreover, a composite feature space is constructed to integrate the features from different layers and different mapping approaches, and it can well enrich the representation information. Finally, a decision-level fusion method is developed to combine the composite feature space and the naive feature space for producing a more comprehensive classification result. The effectiveness of ODL has been demonstrated on various benchmark datasets, and ODL achieves state-of-the-art performance.

Cysteine-Based Redox-Responsive Nanoparticles for Fibroblast-Targeted Drug Delivery in the Treatment of Myocardial Infarction.

Upon myocardial infarction (MI), activated cardiac fibroblasts (CFs) begin to remodel the myocardium, leading to cardiac fibrosis and even heart failure. No therapeutic approaches are currently available to prevent the development of MI-induced pathological fibrosis. Most pharmacological trials fail from poor local drug activity and side effects caused by systemic toxicity, largely due to the lack of a heart-targeted drug delivery system that is selective for activated CFs. Here, we developed a reduced glutathione (GSH)-responsive nanoparticle platform capable of targeted delivering of drugs to activated CFs within the infarct area of a post-MI heart. Compared with systemic drug administration, CF-targeted delivery of PF543, a sphingosine kinase 1 inhibitor identified in a high-throughput antifibrotic drug screening, had higher therapeutic efficacy and lower systemic toxicity in a MI mouse model. Our results provide a CF-targeted strategy to deliver therapeutic agents for pharmacological intervention of cardiac fibrosis.

Cross-Domain Pattern Classification With Distribution Adaptation Based on Evidence Theory.

In pattern classification, there may not exist labeled patterns in the target domain to train a classifier. Domain adaptation (DA) techniques can transfer the knowledge from the source domain with massive labeled patterns to the target domain for learning a classification model. In practice, some objects in the target domain are easily classified by this classification model, and these objects usually can provide more or less useful information for classifying the other objects in the target domain. So a new method called distribution adaptation based on evidence theory (DAET) is proposed to improve the classification accuracy by combining the complementary information derived from both the source and target domains. In DAET, the objects that are easy to classify are first selected as easy-target objects, and the other objects are regarded as hard-target objects. For each hard-target object, we can obtain one classification result with the assistance of massive labeled patterns in the source domain, and another classification result can be acquired based on the easy-target objects with confidently predicted (pseudo) labels. However, the weights of these classification results may vary because the reliabilities of the used information sources are different. The weights are estimated by mean difference reflecting the information source quality. Then, we discount the classification results with the corresponding weights under the framework of the evidence theory, which is expert at dealing with uncertain information. These discounted classification results are combined by an evidential combination rule for making the final class decision. The effectiveness of DAET for cross-domain pattern classification is evaluated with respect to some advanced DA methods, and the experiment results show DAET can significantly improve the classification accuracy.

Pressure-Induced Emission from All-Inorganic Two-Dimensional Vacancy-Ordered Lead-Free Metal Halide Perovskite Nanocrystals.

Although seeking an effective strategy for further improving their optical properties is a great challenge, two-dimensional (2D) halide perovskites have attracted a significant amount of attention because of their performance. In this regard, the pressure-induced emission accompanied by a remarkable pressure-enhanced emission is achieved without a phase transition in 2D vacancy-ordered perovskite Cs3Bi2Cl9 nanocrystals (NCs). Note that the initial Cs3Bi2Cl9 NCs possess extremely strong electron-phonon coupling, leading to the easy annihilation of trapped excitons by the phonon. Upon compression, pressure could effectively suppress phonon-assisted nonradiative decay and give rise to an intriguing emission from "0" to "1". Both the weakened electron-phonon coupling and the relaxed halide octahedral distortion benefiting from the vacancy-ordered structure contributed to the subsequent enhanced emission. This work not only elucidates the underlying photophysical mechanism but also identifies pressure engineering as a robust means for improving their potential applications in environmentally friendly solid-state lighting at extremes.

Pathological and Molecular Characterization of a Duck Plague Outbreak in Southern China in 2021.

Duck plague (DP) is a highly contagious viral disease in ducks caused by the duck plague virus (DPV). The DPV, a member of Herpesviridae, poses a severe threat to the waterfowl farming industry worldwide. In this study, we reported a recent outbreak of DPV in domestic laying ducks at 310 days of age from southern China in December 2021. The gross lesion, histopathologic examination, molecular detection, and genetic characterization studies of DPV are described here. As a result, gross lesions such as an enlarged congestive spleen and liver were observed. Liver with vacuolar degeneration and small vacuoles and spleen with hemosiderosis were remarkable microscopic findings. Our results suggested that the liver had the highest viral load, followed by the trachea, pancreas, kidney, brain, spleen, and heart. In addition, DPV was successfully isolated in chicken embryo fibroblast cell culture and designated as DP-GD-305-21. The UL2, UL12, UL41, UL47, and LORF11 genes of DP-GD-305-21 shared a high nucleotide homology with the Chinese virulent (CHv) strain and the Chinese variant (CV) strain. In conclusion, this study reports the isolation and molecular characterization of DPV from a recent outbreak in southern China. Our results contributed to the understanding of the pathological and molecular characterization of currently circulating DPV in China.

A New Progressive Multisource Domain Adaptation Network With Weighted Decision Fusion.

Multisource unsupervised domain adaptation (MUDA) is an important and challenging topic for target classification with the assistance of labeled data in source domains. When we have several labeled source domains, it is difficult to map all source domains and target domain into a common feature space for classifying the targets well. In this article, a new progressive multisource domain adaptation network (PMSDAN) is proposed to further improve the classification performance. PMSDAN mainly consists of two steps for distribution alignment. First, the multiple source domains are integrated as one auxiliary domain to match the distribution with the target domain. By doing this, we can generally reduce the distribution discrepancy between each source and target domains, as well as the discrepancy between different source domains. It can efficiently explore useful knowledge from the integrated source domain. Second, to mine assistance knowledge from each source domain as much as possible, the distribution of the target domain is separately aligned with that of each source domain. A weighted fusion method is employed to combine the multiple classification results for making the final decision. In the optimization of domain adaption, weighted hybrid maximum mean discrepancy (WHMMD) is proposed, and it considers both the interclass and intraclass discrepancies. The effectiveness of the proposed PMSDAN is demonstrated in the experiments comparing with some state-of-the-art methods.

Reprogramming of fibroblasts into expandable cardiovascular progenitor cells via small molecules in xeno-free conditions.

A major hurdle in cardiac cell therapy is the lack of a bona fide autologous stem-cell type that can be expanded long-term and has authentic cardiovascular differentiation potential. Here we report that a proliferative cell population with robust cardiovascular differentiation potential can be generated from mouse or human fibroblasts via a combination of six small molecules. These chemically induced cardiovascular progenitor cells (ciCPCs) self-renew long-term in fully chemically defined and xeno-free conditions, with faithful preservation of the CPC phenotype and of cardiovascular differentiation capacity in vitro and in vivo. Transplantation of ciCPCs into infarcted mouse hearts improved animal survival and cardiac function up to 13 weeks post-infarction. Mechanistically, activated fibroblasts revert to a plastic state permissive to cardiogenic signals, enabling their reprogramming into ciCPCs. Expanded autologous cardiovascular cells may find uses in drug discovery, disease modelling and cardiac cell therapy.

Combined laparoscopic lymphoadenectomy of lateral pelvic and inguinal nodal metastases using indocyanine green fluorescence imaging guidance in low rectal cancer after preoperative chemoradiotherapy: a case report.

BACKGROUND: Intraoperative near-infrared fluorescence (NIR) imaging with indocyanine green (ICG) can demonstrate real-time lymphatic drainage and thus improve the accuracy and completeness of lymphadenectomy in colorectal cancer surgery. However, it has not been utilized in the inguinal lymphadenectomy in rectal cancer. This study aimed to describe a case of combined laparoscopic lymphadenectomy of left lateral pelvic and inguinal nodal metastases using NIR imaging with ICG imaging guidance for a rectal cancer patient with left lateral pelvic and inguinal lymph node metastases. CASE PRESENTATION: A 26-year-old man presented rectal cancer located 7 cm from the anal verge and enlarged lymph nodes in the left inguinal area. Pretreatment workup revealed rectal cancer with left lateral pelvic and inguinal lymph node metastases. The patient received preoperative chemoradiotherapy (pCRT), including radiation (total dose of 50.4 Gy in 28 fractions) to the whole pelvis and bilateral inguinal regions together with eight cycles of FOLFOX (oxaliplatin, fluoropyrimidine, and leucovorin) and three cycles of bevacizumab targeted chemotherapy. After pCRT, both colonoscopy and MR scan revealed a significant response of the primary tumor to pCRT, while MR scan revealed enlarged left lateral pelvic and inguinal lymph nodes. After four months from the completion of radiation (2 months after the last course of bevacizumab targeted therapy), the patient underwent laparoscopic-assisted ultra-low anterior resection and lymphadenectomy of left lateral pelvic and inguinal nodal metastases using ICG-NIR fluorescence imaging. The combined procedure was performed successfully without perioperative complication. Total operative time was 480 min and estimated blood loss 50 mL. Totally 34 lymph nodes were retrieved. CONCLUSIONS: This is the first report of the safety and feasibility of ICG-NIR fluorescence imaging-guided laparoscopic lymphadenectomy of left lateral pelvic and inguinal nodal metastases in managing low rectal cancer with lateral pelvic and inguinal LNs metastases.

Influencing factors of resource utilisation in haemodialysis patients-Based on socioecological pyramid model.

AIMS AND OBJECTIVES: To describe the current situation and analyse influencing factors of resource utilisation in maintenance haemodialysis patients. BACKGROUND: The self-management level of patients undergoing maintenance haemodialysis in China is low. The applicability of the Chronic Illness Resources Survey in Chinese maintenance haemodialysis patients has been validated, and this survey can be used to assess the utilisation of self-management support resources among haemodialysis patients. Determining the influencing factors of resource utilisation can help improve the self-management behaviour of haemodialysis patients and control the progression of the disease. DESIGN: A descriptive study design was chosen. METHODS: A convenience sample of 314 patients undergoing haemodialysis was recruited from dialysis centres in three hospitals in western Xinjiang from June 2018-April 2019. SPSS19.0 software was used to describe the current situation of resource utilisation. Moreover, t test, analysis of variance and multivariate linear regression were applied to explore the influencing factors of patients' resource utilisation. Standards for observational studies STROBE Statement checklist-v4 were chosen on reporting the study process. RESULTS: The average score of the total resource utilisation was 2.95 ± 0.51. The average item score of seven dimensions from high to low was 3.46 for medical staff, 3.32 for personal, 3.22 for family and friends, 3.16 for work-related, 3.12 for media policy, 2.55 for neighbourhood/community and 2.23 for organisation. Multiple linear regression showed that there have six main factors, which explained 65.4% of the variance of haemodialysis patients' resource utilisation. CONCLUSIONS: The personal, family and friends, work and media and policy subscales were rated the highest, with support from neighbourhood/community and organisation rated the lowest. In general, participants perceived moderate levels of support. Government and healthcare team should pay more attention on haemodialysis patients who had low level of education, poor economic conditions and poor mental condition. RELEVANCE TO CLINICAL PRACTICE: ESRD has caused a burden on healthcare expenditure and has become a critical public health problem worldwide. Self-management is particularly important for dialysis patients which have attracted extensive interest. In the future research, we can use this questionnaire to evaluate the related resources of disease management of dialysis patients, encourage patients to make full use of the resources around them and focus on those patients with low education and monthly income level and bad mental state.

A New Belief-Based Bidirectional Transfer Classification Method.

In pattern classification, we may have a few labeled data points in the target domain, but a number of labeled samples are available in another related domain (called the source domain). Transfer learning can solve such classification problems via the knowledge transfer from source to target domains. The source and target domains can be represented by heterogeneous features. There may exist uncertainty in domain transformation, and such uncertainty is not good for classification. The effective management of uncertainty is important for improving classification accuracy. So, a new belief-based bidirectional transfer classification (BDTC) method is proposed. In BDTC, the intraclass transformation matrix is estimated at first for mapping the patterns from source to target domains, and this matrix can be learned using the labeled patterns of the same class represented by heterogeneous domains (features). The labeled patterns in the source domain are transferred to the target domain by the corresponding transformation matrix. Then, we learn a classifier using all the labeled patterns in the target domain to classify the objects. In order to take full advantage of the complementary knowledge of different domains, we transfer the query patterns from target to source domains using the K-NN technique and do the classification task in the source domain. Thus, two pieces of classification results can be obtained for each query pattern in the source and target domains, but the classification results may have different reliabilities/weights. A weighted combination rule is developed to combine the two classification results based on the belief functions theory, which is an expert at dealing with uncertain information. We can efficiently reduce the uncertainty of transfer classification via the combination strategy. Experiments on some domain adaptation benchmarks show that our method can effectively improve classification accuracy compared with other related methods.

Individualized conditional survival nomograms for patients with locally advanced rectal cancer treated with neoadjuvant chemoradiotherapy and radical surgery.

BACKGROUND: Conditional survival (CS) considers the time already survived after surgery when estimating the survival probability, which may provide further useful prognostic information. OBJECTIVE: To evaluate CS in patients with locally advanced rectal cancer (LARC) treated with neoadjuvant chemoradiotherapy (nCRT) and to create CS nomograms predicting the conditional probability of survival after proctectomy. METHODS: Consecutive patients with LARC who received nCRT followed by radical resection between 2011 and 2016 were identified. CS was defined as the probability of surviving y years after already surviving for x years. The formula used for CS was CS(x|y) = S(x + y)/S(x), where S(x) represents the survival at x years. Nomograms were constructed to predict the 5-year conditional overall survival (cOS) and conditional recurrence-free survival (cRFS). RESULTS: A total of 785 patients were included. The median follow-up time was 65.5 months. The probability of achieving 5-year survival after surgery for cancer increases with additional survival time. Maximum tumor diameter, distance from the anal verge, preoperative CA19-9 level, ypTNM stage and perineural invasion were independent predictors of OS, while maximum tumor diameter, distance from the anal verge, ypTNM stage and perineural invasion were independent risk factors for RFS. The nomograms predicted 5-year cOS and cRFS using these predictors and the time already survived. The online calculator can be accessed at http://www.rectalcancer.top/webcalculator. CONCLUSION: The proposed nomograms predict survival in patients after surgery, taking the time already survived into account.

Harvesting Cool Daylight in Hybrid Organic-Inorganic Halides Microtubules through the Reservation of Pressure-Induced Emission.

Pressure-induced emission (PIE) is extensively studied in halide perovskites or derivative hybrid halides. However, owing to the soft inorganic lattice of these materials, the intense emission is barely retained under ambient conditions, thus largely limiting their practical applications in optoelectronics at atmospheric pressure. Here, remarkably enhanced emission in microtubules of the 0D hybrid halide (C5 H7 N2 )2 ZnBr4 ((4AMP)2 ZnBr4 ) is successfully achieved by means of pressure treatment at room temperature. Notably, the emission, which is over ten times more intense than the emission in the initial state, is retained under ambient conditions upon the complete release of pressure. Furthermore, the pressure processing enables the tuning of "sky blue light" before compression to "cool daylight" with a remarkable quantum yield of 88.52% after decompression, which is of considerable interest for applications in next-generation lighting and displays. The irreversible electronic structural transition, induced by the steric hindrance with respect to complexly configurational organic molecules [4AMP], is highly responsible for the eventual retention of PIE and tuning of the color temperature. The findings represent a significant step toward the capture of PIE under ambient conditions, thus facilitating its potential solid-state lighting applications.

Human pluripotent stem cell-based cardiovascular disease modeling and drug discovery.

Heart diseases are prevalent worldwide and account for the highest mortality than any other illness. Although investment in drug discovery and development has increased, the amount of drug approvals has seen a progressive decline. Moreover, adverse side effects to the heart have become the most common reasons for preclinical project cessation, partly due to the lack of suitable humanized preclinical models. Human pluripotent stem cells (hPSCs) have emerged as a powerful non-animal platform to model heart disease, to screen for novel drugs, and to test drug cardiotoxicity in a high-throughput and cost-effective manner. Here, we review and discuss recent breakthroughs in the development of cardiovascular modeling and their current and future applications of hPSC-based drug discovery and testing.

Combination of Transferable Classification With Multisource Domain Adaptation Based on Evidential Reasoning.

In applications of domain adaptation, there may exist multiple source domains, which can provide more or less complementary knowledge for pattern classification in the target domain. In order to improve the classification accuracy, a decision-level combination method is proposed for the multisource domain adaptation based on evidential reasoning. The classification results obtained from different source domains usually have different reliabilities/weights, which are calculated according to domain consistency. Therefore, the multiple classification results are discounted by the corresponding weights under belief functions framework, and then, Dempster's rule is employed to combine these discounted results. In order to reduce errors, a neighborhood-based cautious decision-making rule is developed to make the class decision depending on the combination result. The object is assigned to a singleton class if its neighborhoods can be (almost) correctly classified. Otherwise, it is cautiously committed to the disjunction of several possible classes. By doing this, we can well characterize the partial imprecision of classification and reduce the error risk as well. A unified utility value is defined here to reflect the benefit of such classification. This cautious decision-making rule can achieve the maximum unified utility value because partial imprecision is considered better than an error. Several real data sets are used to test the performance of the proposed method, and the experimental results show that our new method can efficiently improve the classification accuracy with respect to other related combination methods.