Lijun Li, Bowen Dong, Ruohui Wang, Xuhao Hu, Wangmeng Zuo, Dahua Lin, Yu Qiao, Jing Shao. Findings of the Association for Computational Linguistics ACL 2024. 2024.

In this study, we aimed to clinically and genetically characterize LVNC patients and investigate the prevalence of variants in known and novel LVNC disease genes. Left ventricular non-compaction cardiomyopathy (LVNC) is an increasingly recognized cause of heart failure, arrhythmia, thromboembolism, and sudden cardiac death. We sought here to dissect its genetic causes, phenotypic presentation and outcome. In our registry with follow-up of in the median 61 months, we analysed 95 LVNC patients (68 unrelated index patients and 27 affected relatives; definite familial LVNC = 23.5%) by cardiac phenotyping, molecular biomarkers and exome sequencing. Cardiovascular events were significantly more frequent in LVNC patients compared with an age-matched group of patients with non-ischaemic dilated cardiomyopathy (hazard ratio = 2.481, P = 0.002). Stringent genetic classification according to ACMG guidelines revealed that TTN, LMNA, and MYBPC3 are the most prevalent disease genes (13 patients are carrying a pathogenic truncating TTN variant, odds ratio = 40.7, Confidence interval = 21.6–76.6, P < 0.0001, percent spliced in 76–100%). We also identified novel candidate genes for LVNC. For RBM20, we were able to perform detailed familial, molecular and functional studies. We show that the novel variant p.R634L in the RS domain of RBM20 co-segregates with LVNC, leading to titin mis-splicing as revealed by RNA sequencing of heart tissue in mutation carriers, protein analysis, and functional splice-reporter assays. Our data demonstrate that the clinical course of symptomatic LVNC can be severe. The identified pathogenic variants and distribution of disease genes—a titin-related pathomechanism is found in every fourth patient—should be considered in genetic counselling of patients. Pathogenic variants in the nuclear proteins Lamin A/C and RBM20 were associated with worse outcome.

Convolutional neural networks have gained a remarkable success in computer vision. However, most usable network architectures are hand-crafted and usually require expertise and elaborate design. In this paper, we provide a block-wise network generation pipeline called BlockQNN which automatically builds high-performance networks using the Q-Learning paradigm with epsilon-greedy exploration strategy. The optimal network block is constructed by the learning agent which is trained to choose component layers sequentially. We stack the block to construct the whole auto-generated network. To accelerate the generation process, we also propose a distributed asynchronous framework and an early stop strategy. The block-wise generation brings unique advantages: (1) it yields state-of-the-art results in comparison to the hand-crafted networks on image classification, particularly, the best network generated by BlockQNN achieves 2.35% top-1 error rate on CIFAR-10. (2) it offers tremendous reduction of the search space in designing networks, spending only 3 days with 32 GPUs. A faster version can yield a comparable result with only 1 GPU in 20 hours. (3) it has strong generalizability in that the network built on CIFAR also performs well on the larger-scale dataset. The best network achieves very competitive accuracy of 82.0% top-1 and 96.0% top-5 on ImageNet.