Less-is-more: selecting transcription factor binding regions informative for motif inference.

Numerous statistical methods have emerged for inferring DNA motifs for transcription factors (TFs) from genomic regions. However, the process of selecting informative regions for motif inference remains understudied. Current approaches select regions with strong ChIP-seq signal for a given TF, assuming that such strong signal primarily results from specific interactions between the TF and its motif. Additionally, these selection approaches do not account for non-target motifs, i.e. motifs of other TFs; they presume the occurrence of these non-target motifs infrequent compared to that of the target motif, and thus assume these have minimal interference with the identification of the target. Leveraging extensive ChIP-seq datasets, we introduced the concept of TF signal 'crowdedness', referred to as C-score, for each genomic region. The C-score helps in highlighting TF signals arising from non-specific interactions. Moreover, by considering the C-score (and adjusting for the length of genomic regions), we can effectively mitigate interference of non-target motifs. Using these tools, we find that in many instances, strong ChIP-seq signal stems mainly from non-specific interactions, and the occurrence of non-target motifs significantly impacts the accurate inference of the target motif. Prioritizing genomic regions with reduced crowdedness and short length markedly improves motif inference. This 'less-is-more' effect suggests that ChIP-seq region selection warrants more attention.

Binding profiles for 954 Drosophila and C. elegans transcription factors reveal tissue specific regulatory relationships.

A catalog of transcription factor (TF) binding sites in the genome is critical for deciphering regulatory relationships. Here we present the culmination of the modERN (model organism Encyclopedia of Regulatory Networks) consortium that systematically assayed TF binding events in vivo in two major model organisms, Drosophila melanogaster (fly) and Caenorhabditis elegans (worm). We describe key features of these datasets, comprising 604 TFs identifying 3.6M sites in the fly and 350 TFs identifying 0.9 M sites in the worm. Applying a machine learning model to these data identifies sets of TFs with a prominent role in promoting target gene expression in specific cell types. TF binding data are available through the ENCODE Data Coordinating Center and at https://epic.gs.washington.edu/modERNresource, which provides access to processed and summary data, as well as widgets to probe cell type-specific TF-target relationships. These data are a rich resource that should fuel investigations into TF function during development.

Correction: Nie et al. Endoplasmic Reticulum Stress Mediated NLRP3 Inflammasome Activation and Pyroptosis in THP-1 Macrophages Infected with Bacillus Calmette-Guérin. Int. J. Mol. Sci. 2023, 24, 11692.

Lei Liu was not included as an author in the original publication [...].

GSK2656157, a PERK Inhibitor, Alleviates Pyroptosis of Macrophages Induced by Mycobacterium Bacillus Calmette-Guerin Infection.

Tuberculosis (TB) is the leading cause of human death worldwide due to Mycobacterium tuberculosis (Mtb) infection. Mtb infection can cause macrophage pyroptosis. PERK, as a signaling pathway protein on the endoplasmic reticulum, plays an important role in infectious diseases. It is not clear whether PERK is involved in the regulation of pyroptosis of macrophages during Mtb infection. In this study, Bacillus Calmette-Guerin (BCG) infection resulted in high expression of pro-caspase-1, caspase-1 p20, GSDMD-N, and p-PERK in the THP-1 macrophage, being downregulated with the pre-treatment of GSK2656157, a PERK inhibitor. In addition, GSK2656157 inhibited the secretion of IL-1ß and IL-18, cell content release, and cell membrane rupture, as well as the decline in cell viability induced by BCG infection. Similarly, GSK2656157 treatment downregulated the expressions of pro-caspase-1, caspase-1 p20, caspase-11, IL-1ß p17, IL-18 p22, GSDMD, GSDMD-N, and p-PERK, as well as reducing fibrous tissue hyperplasia, inflammatory infiltration, and the bacterial load in the lung tissue of C57BL/6J mice infected with BCG. In conclusion, the inhibition of PERK alleviated pyroptosis induced by BCG infection, which has an effect of resisting infection.

S100A4 Promotes BCG-Induced Pyroptosis of Macrophages by Activating the NF-κB/NLRP3 Inflammasome Signaling Pathway.

Pyroptosis is a host immune strategy to defend against Mycobacterium tuberculosis (Mtb) infection. S100A4, a calcium-binding protein that plays an important role in promoting cancer progression as well as the pathophysiological development of various non-tumor diseases, has not been explored in Mtb-infected hosts. In this study, transcriptome analysis of the peripheral blood of patients with pulmonary tuberculosis (PTB) revealed that S100A4 and GSDMD were significantly up-regulated in PTB patients' peripheral blood. Furthermore, there was a positive correlation between the expression of GSDMD and S100A4. KEGG pathway enrichment analysis showed that differentially expressed genes between PTB patients and healthy controls were significantly related to inflammation, such as the NOD-like receptor signaling pathway and NF-κB signaling pathway. To investigate the regulatory effects of S100A4 on macrophage pyroptosis, THP-1 macrophages infected with Bacillus Calmette-Guérin (BCG) were pre-treated with exogenous S100A4, S100A4 inhibitor or si-S100A4. This research study has shown that S100A4 promotes the pyroptosis of THP-1 macrophages caused by BCG infection and activates NLRP3 inflammasome and NF-κB signaling pathways, which can be inhibited by knockdown or inhibition of S100A4. In addition, inhibition of NF-κB or NLRP3 blocks the promotion effect of S100A4 on BCG-induced pyroptosis of THP-1 macrophages. In conclusion, S100A4 activates the NF-κB/NLRP3 inflammasome signaling pathway to promote macrophage pyroptosis induced by Mtb infection. These data provide new insights into how S100A4 affects Mtb-induced macrophage pyroptosis.

Endoplasmic Reticulum Stress Mediated NLRP3 Inflammasome Activation and Pyroptosis in THP-1 Macrophages Infected with Bacillus Calmette-Guérin.

Tuberculosis (TB) is a zoonotic infectious disease caused by Mycobacterium tuberculosis (Mtb). Mtb is a typical intracellular parasite, and macrophages are its main host cells. NLRP3 inflammasome-mediated pyroptosis is a form of programmed cell death implicated in the clearance of pathogenic infections. The bidirectional regulatory effect of endoplasmic reticulum stress (ERS) plays a crucial role in determining cell survival and death. Whether ERS is involved in macrophage pyroptosis with Mtb infection remains unclear. This article aims to explore the regulation of the NLRP3 inflammasome and pyroptosis by ERS in THP-1 macrophages infected with Mycobacterium bovis Bacillus Calmette-Guérin (BCG). The results showed that BCG infection induced THP-1 macrophage ERS, NLRP3 inflammasome activation and pyroptosis, which was inhibited by ERS inhibitor TUDCA. NLRP3 inhibitor MCC950 inhibited THP-1 macrophage NLRP3 inflammasome activation and pyroptosis caused by BCG infection. Compared with specific Caspase-1 inhibitor VX-765, pan-Caspase inhibitor Z-VAD-FMK showed a more significant inhibitory effect on BCG infection-induced pyroptosis of THP-1 macrophages. Taken together, this study demonstrates that ERS mediated NLRP3 inflammasome activation and pyroptosis after BCG infection of THP-1 macrophages, and that BCG infection of THP-1 macrophages induces pyroptosis through canonical and noncanonical pathways.

DNA 5-methylcytosine detection and methylation phasing using PacBio circular consensus sequencing.

Long single-molecular sequencing technologies, such as PacBio circular consensus sequencing (CCS) and nanopore sequencing, are advantageous in detecting DNA 5-methylcytosine in CpGs (5mCpGs), especially in repetitive genomic regions. However, existing methods for detecting 5mCpGs using PacBio CCS are less accurate and robust. Here, we present ccsmeth, a deep-learning method to detect DNA 5mCpGs using CCS reads. We sequence polymerase-chain-reaction treated and M.SssI-methyltransferase treated DNA of one human sample using PacBio CCS for training ccsmeth. Using long (≥10 Kb) CCS reads, ccsmeth achieves 0.90 accuracy and 0.97 Area Under the Curve on 5mCpG detection at single-molecule resolution. At the genome-wide site level, ccsmeth achieves >0.90 correlations with bisulfite sequencing and nanopore sequencing using only 10× reads. Furthermore, we develop a Nextflow pipeline, ccsmethphase, to detect haplotype-aware methylation using CCS reads, and then sequence a Chinese family trio to validate it. ccsmeth and ccsmethphase can be robust and accurate tools for detecting DNA 5-methylcytosines.

[Knockdown of Wnt7a inhibits BCG induced autophagy in mouse alveolar epithelial cells].

Objective To investigate the regulatory effect of wingless gene 7a (Wnt7a) on Bacille Calmette Guerin (BCG) induced autophagy in alveolar epithelial cells. Methods The alveolar epithelial cells of TC-1 mice were treated with interfering Wnt7a lentivirus and BCG alone or together in four groups, namely, small interfering RNA control (si-NC) group, si-NC combined with BCG group, Wnt7a small interfering RNA (si-Wnt7a) group, and si-Wnt7a combined with BCG group. The expressions of Wnt7a, microtubule associated protein 1 light chain 3 (LC3), P62, and autophagy related gene 5 (ATG5) were detected by Western blot analysis, and the distribution of LC3 was detected by immunofluorescence cytochemical staining. Results Compared with those in the si-NC group, Wnt7a, ATG5 and LC3 expressions increased and green fluorescent spots of LC3 significantly increased in the BCG infected TC-1 cells; the expressions of Wnt7a, LC3, P62, and ATG5 and green fluorescent spots of LC3 significantly decreased in the si-Wnt7a combined with BCG group comparing with those in the si-NC combined with BCG group. Conclusion Knocking down Wnt7a inhibits BCG induced autophagy in mouse alveolar epithelial cells.

Human Pluripotent Stem Cell-Mesenchymal Stem Cell-Derived Exosomes Promote Ovarian Granulosa Cell Proliferation and Attenuate Cell Apoptosis Induced by Cyclophosphamide in a POI-like Mouse Model.

Premature ovarian insufficiency (POI) is a complex disease which causes amenorrhea, hypergonadotropism and infertility in patients no more than 40 years old. Recently, several studies have reported that exosomes have the potential to protect ovarian function using a POI-like mouse model induced by chemotherapy drugs. In this study, the therapeutic potential of exosomes derived from human pluripotent stem cell-mesenchymal stem cells (hiMSC exosomes) was evaluated through a cyclophosphamide (CTX)-induced POI-like mouse model. POI-like pathological changes in mice were determined by serum sex-hormones levels and the available number of ovarian follicles. The expression levels of cellular proliferation proteins and apoptosis-related proteins in mouse ovarian granulosa cells were measured using immunofluorescence, immunohistochemistry and Western blotting. Notably, a positive effect on the preservation of ovarian function was evidenced, since the loss of follicles in the POI-like mouse ovaries was slowed. Additionally, hiMSC exosomes not only restored the levels of serum sex hormones, but also significantly promoted the proliferation of granulosa cells and inhibited cell apoptosis. The current study suggests that the administration of hiMSC exosomes in the ovaries can preserve female-mouse fertility.

The EN-TEx resource of multi-tissue personal epigenomes & variant-impact models.

Understanding how genetic variants impact molecular phenotypes is a key goal of functional genomics, currently hindered by reliance on a single haploid reference genome. Here, we present the EN-TEx resource of 1,635 open-access datasets from four donors (∼30 tissues × âˆ¼15 assays). The datasets are mapped to matched, diploid genomes with long-read phasing and structural variants, instantiating a catalog of >1 million allele-specific loci. These loci exhibit coordinated activity along haplotypes and are less conserved than corresponding, non-allele-specific ones. Surprisingly, a deep-learning transformer model can predict the allele-specific activity based only on local nucleotide-sequence context, highlighting the importance of transcription-factor-binding motifs particularly sensitive to variants. Furthermore, combining EN-TEx with existing genome annotations reveals strong associations between allele-specific and GWAS loci. It also enables models for transferring known eQTLs to difficult-to-profile tissues (e.g., from skin to heart). Overall, EN-TEx provides rich data and generalizable models for more accurate personal functional genomics.

To explore the regulatory role of Wnt/P53/Caspase3 signal in mouse ovarian development based on LFQ proteomics.

Early ovarian follicular development is regulated by multiple proteins and signaling pathways, including the Wnt gene. To explore the regulatory mechanism of Wnt signaling on early ovarian follicular development, ovaries from 17.5 days post coitum (17.5 dpc) mice were collected and cultured in vitro for four days in the presence of IWP2 as a Wnt activity inhibitor and KN93 as a CaMKII inhibitor. LFQ proteomics technique was then used to analyze the significant differentially abundant (P-SDA) 93 and 262 proteins in the IWP2 and KN93 groups, respectively. Of these, 63 up-regulated proteins and 30 down-regulated proteins were identified for IWP2, along with 3 significant KEGG pathways (P < 0.05). For the KN93 group, 168 up-regulated proteins and 94 down-regulated ones were P-SDA, with 9 significant KEGG pathways also noted (P < 0.05). In both IWP2 and KN93 groups, key pathways (Wnt signaling pathway, Notch signaling pathway, P53 signaling pathway, TGF-ß signaling pathway, ovarian steroid production) and metabolic regulation (energy metabolism, metal ion metabolism) were found to be related to early ovarian follicular development. Finally, western blotting demonstrated the regulatory role of Wnt/P53/Caspase3 signaling pathway in mouse ovarian development. These results contribute new knowledge to the understanding of regulatory factors of early ovarian follicular development. SIGNIFICANCE: In this study, label-free quantification (LFQ) was used in combination with liquid chromatography-mass spectrometer (LC-MS/MS) to study potential changes in the proteomic profiles of embryonic mice subjected to Wnt inhibitor IWP2 and CaMKIIinhibitor KN93. In addition, bioinformatics and comparative analyses were performed using publicly available proteomics databases to further explore the underlying mechanisms associated with early mouse ovarian growth and development.

Cyproterone Acetate Mediates IRE1α Signaling Pathway to Alleviate Pyroptosis of Ovarian Granulosa Cells Induced by Hyperandrogen.

OBJECTIVE: Hyperandrogenemia (HA) is the main pathophysiological change that takes place in polycystic ovary syndrome (PCOS). Cyproterone acetate (CYA) is a drug commonly used to reduce androgen in patients with PCOS. Long-term and continuous exposure to HA can cause ovarian granulosa cells (GCs), pyroptotic death, and follicular dysfunction in PCOS mice. The aim of this study was to investigate whether CYA could ameliorate the hyperandrogenemia-induced pyroptosis of PCOS ovarian GCs by alleviating the activation of the IRE1α signaling pathway. METHODS: Firstly, thirty PCOS patients with HA as their main clinical manifestation were selected as the study group, and thirty non-PCOS patients were selected as the control group. The GCs and follicular fluid of the patients were collected, and the expression of pyroptosis-related proteins was detected. Secondly, a PCOS mouse model induced by dehydroepiandrosterone (DHEA) was constructed, and the treatment group model was constructed with the subcutaneous injection of cyproterone acetate in PCOS mice. The expression of pyroptosis-related protein in ovarian GCs was detected to explore the alleviating effect of CYA on the pyroptosis of ovarian GCs in PCOS mice. Thirdly, KGN cells-i.e., from the human GC line-were cultured with dihydrotestosterone, CYA, and ERN1 (IRE1α gene) small interfering RNA in vitro to explore whether CYA can alleviate the activation of the IRE1α signaling pathway and ameliorate the hyperandrogenemia-induced pyroptosis of PCOS ovarian GCs. RESULTS: The expression of pyroptosis-related proteins was significantly increased in ovarian GCs of PCOS patients with HA as the main clinical manifestation, and in the PCOS mouse model induced by DHEA. After treatment with CYA, the expression of pyroptosis-related proteins in the ovarian GCs of mice was significantly lower than that in PCOS mice. In vitro experiments showed that CYA could ameliorate KGN cells' pyroptosis by alleviating the activation of the IRE1α signaling pathway. CONCLUSION: This study showed that CYA could ameliorate the activation of the IRE1α signaling pathway in mouse GCs and KGN cells, and also alleviate pyroptosis in ovarian GCs. This study provides a new mechanism and evidential support for CYA in the treatment of PCOS patients.

Construction of a predictive model of abdominal lymph node metastasis in thoracic esophageal squamous cell carcinoma and preliminary analysis of its effect on target for postoperative radiotherapy.

Purpose: To investigate the influencing factors of abdominal lymph node metastasis in thoracic esophageal squamous cell carcinoma (TESCC), and to construct its predictive model, in order to analyze the targets for postoperative radiotherapy. Methods and materials: From January 2008 to December 2014, the clinicopathological data of 479 patients who underwent radical resection for esophageal cancer in the Fourth Hospital of Hebei Medical University were collected and retrospectively analyzed. The influencing factors of postoperative abdominal lymph node metastasis were analyzed, and a predictive model was constructed based on their independent influencing factors. Receiver operating characteristic (ROC) curve was utilized to analyze the predictive value of this model; in the meantime, the postoperative locoregional recurrence (LRR) of this group was analyzed. Results: The postoperative pathology of all patients showed that the lymph node metastasis rate (LNR) was 39.7%, of which the abdominal lymph node metastasis rate was 22.0%. Logistic regression analysis revealed that the patient's lesion location, pN stage, vascular invasion, LND and mediastinal lymph node metastasis were independent risk factors for the positive rate of abdominal lymph nodes after surgery (P = 0.000, 0.000, 0.033, 0.000, 0.000). The probability of abdominal lymph node metastasis was Y = ex/(1 + ex), and X = -5.502 + 1.569 × lesion location + 4.269 × pN stage + 1.890 × vascular invasion + 1.950 × LND-4.248 × mediastinal lymph node metastasis. The area under the ROC curve (AUC) of this model in predicting abdominal lymph node metastasis was 0.962 (95% CI, 0.946-0.977). This mathematical model had a high predictive value for the occurrence of abdominal lymph node metastasis (P = 0.000), and the sensitivity and specificity of prediction were 94.6% and 88.3% respectively. The overall survival rate was significantly higher (X2 = 29.178, P = 0.000), while abdominal lymph node recurrence rate was lower in patients with negative abdominal lymph nodes than in those with negative lymph nodes (1.4%&7.7%, X2 = 12.254, P = 0.000). Conclusion: The lesion location, pN stage, vascular invasion, LND and mediastinal lymph node metastasis are independent influencing factors of abdominal lymph node metastasis in patients with TESCC. The mathematical model constructed by these indicators can accurately predict abdominal lymph node metastasis, which can help clinicians to choose the targets for postoperative radiotherapy.

[Knockdown of receptor tyrosine kinase-like orphan receptor 2 (ROR2) inhibits the autophagy of RAW264.7 mouse macrophages induced by BCG vaccine].

Objective To investigate the regulation of Wnt5a/receptor tyrosine kinase-like orphan receptor 2 (ROR2) signaling pathway on macrophage autophagy induced by Bacille Calmette Guerin (BCG) infection. Methods RAW264.7 cells were infected with BCG at 0, 2, 6, 12 and 24 hours, and the expressions of Wnt5a, ROR2 and autophagy-related protein microtubule-associated protein 1 light chain 3II (LC3II ) were detected by Western blot analysis. After RAW264.7 cells were treated with ROR2 small interfering RNA and BCG infection respectively or together, the protein expressions of autophagy-related genes 5 (ATG5), P62, beclin-1, ATG7 and LC3II in RAW264.7 cells were tested by Western blot analysis. Autophagy flux was detected by mRFP-GFP-LC3 double-label adenovirus assay. Results Compared with the control group, Wnt5a, ROR2 and LC3II had the highest expression in RAW264.7 cells 6 hours after BCG infection. Compared with the non-infected control group, the expressions of autophagy-related proteins ATG5, P62, beclin-1, ATG7 and LC3II showed an increase, along with increased number of autophagosomes and autophagolysosomes in RAW264.7 cells infected with BCG. Compared with BCG infected group, the expressions of the above proteins observed a decrease, and the number of autophagosomes and autophagolysosomes both descended in the co-treatment group with knockdown ROR2 and BCG infection. Conclusion Knockdown of ROR2 can inhibit autophagy in macrophages induced by BCG infection.

[Wnt5a activates JNK to promote the proliferation and autophagy of KGN human granulosa cells].

Objective To investigate the effect of Wnt5a on autophagy in KGN human granulosa cells. Methods KGN human granulosa cells were treated with DMSO (control group), recombinant Wnt5a protein (rWnt5a), Wnt5a inhibitor IWP2 or BOX5, separately. The expression level of Wnt5a protein was detected by Western blot. The co-localization of the Wnt5a protein and the forkhead box L2 (FOXL2), a specific marker of granulosa cells, was observed by immunofluorescence cytochemical staining in rWnt5a group and IWP2 group. The proliferation of KGN cells was detected by CCK-8 assay. The effects of rWnt5a and IWP2 on autophagy of KGN cells and the expressions of c-Jun N-terminal kinase (JNK) and nuclear factor of activated T cells 1 (NFAT1) proteins were detected by Western blot. Results Compared with those in the control group, the expression of Wnt5a protein in the rWnt5a group was increased, cell proliferation was promoted, and the expressions of microtubule-associated proteins 1 light chain 3 (LC3), JNK, and NFAT1 were increased, while the expression of nucleoporin 62 (P62) protein was decreased. In contrast to the rWnt5a group, the expression of Wnt5a protein was decreased, cell proliferation was inhibited, and the expressions of LC3, JNK, and NFAT1 proteins were decreased, while the expression of P62 protein was increased in IWP2 group. Conclusion Wnt5a promotes the proliferation and autophagy of KGN human granulosa cells by activating JNK.

Wnt5a regulates autophagy in Bacille Calmette-Guérin (BCG)-Infected pulmonary epithelial cells.

Autophagy functions as a critical process that can suppress the proliferation of Mycobacterium tuberculosis (Mtb) within infected host cells. Wnt5a is a secreted protein that plays a range of physiological functions, activating several signaling pathways and thereby controlling cellular responses to particular stimuli. The importance of Wnt5a as a regulator of protection against Mtb infection, however, has yet to be fully characterized. Here, changes in murine pulmonary epithelial-like TC-1 cell morphology, autophagy, the Wnt/Ca2+ signaling pathway, and the mTOR autophagy pathway were analyzed following infection with the Mtb model pathogen Bacille Calmette-Guerin (BCG) in order to understand the regulatory role of Wnt5a in this context. These experiments revealed that Wnt5a was upregulated and autophagy was enhanced in TC-1 cells infected with BCG, and Wnt5a overexpression was found to drive BCG-induced autophagy in these cells upon infection, whereas the inhibition or knockdown of Wnt5a yielded the opposite effect. At the mechanistic level, Wnt5a was found to mediate non-canonical Wnt/Ca2+ signaling and thereby inhibit mTOR-dependent pathway activation, promoting autophagic induction within BCG-infected TC-1 cells. These data offer new insight regarding how Wnt5a influences Mtb-induced autophagy within pulmonary epithelial cells, providing a foundation for further research exploring the immunological control of this infection through the modulation of autophagy.

Building integrative functional maps of gene regulation.

Every cell in the human body inherits a copy of the same genetic information. The three billion base pairs of DNA in the human genome, and the roughly 50 000 coding and non-coding genes they contain, must thus encode all the complexity of human development and cell and tissue type diversity. Differences in gene regulation, or the modulation of gene expression, enable individual cells to interpret the genome differently to carry out their specific functions. Here we discuss recent and ongoing efforts to build gene regulatory maps, which aim to characterize the regulatory roles of all sequences in a genome. Many researchers and consortia have identified such regulatory elements using functional assays and evolutionary analyses; we discuss the results, strengths and shortcomings of their approaches. We also discuss new techniques the field can leverage and emerging challenges it will face while striving to build gene regulatory maps of ever-increasing resolution and comprehensiveness.

Patterns of failure and long-term outcome of postoperative radiotherapy on the survival of patients with pathological T3N0M0 esophageal cancer.

Purpose: The prognostic effect of postoperative radiotherapy (PORT) on pathological T3N0M0 (pT3N0M0) esophageal squamous cell carcinoma (ESCC) remains inconclusive. This study aimed to retrospectively investigate patterns of failure and whether PORT after R0 resection improves survival in patients with pT3N0M0 ESCC, compared with surgery alone. Patients and methods: The clinical data of 256 patients with pT3N0M0 ESCC from January 2007 to December 2010 were retrospectively reviewed. The included patients were classified into two groups: the surgery-plus-postoperative radiotherapy group (S + R) and the surgery-alone group (S). Propensity score matching (PSM) was used to create comparable groups that were balanced across several covariates (n = 71 in each group). Statistical analyses were performed using the Kaplan-Meier method and Chi-squared test. Results: In the study cohort, the 5- and 10-year overall survival (OS) rates in the S + R group were 53.4% and 38.4%, and those in the S group were 50.3%, 40.9% (p = 0.810), respectively. The 5- and 10-year disease-free survival (DFS) rates in the S + R group were 47.9% and 32.9%, and those in the S group were 43.2%, 24.0% (p = 0.056), respectively. The results were coincident in the matched samples (p = 0.883, 0.081) after PSM. Subgroup analysis showed that patients with upper thoracic lesions in the S + R group had significantly higher OS than patients in the S group (p = 0.013), in addition, patients with upper and middle thoracic lesions in the S + R group had significantly higher DFS than patients in the S group (p = 0.018, 0.049). The results were also confirmed in the matched samples after PSM. The locoregional recurrence between the two groups were significantly different before and after PSM (p = 0.009, 0.002). The locoregional control rate (LCR) in the S + R group was significantly higher than that in the S group before and after PSM (p = 0.015, 0.008). Conclusion: Postoperative radiotherapy may be associated with a survival benefit for patients with pT3N0M0 upper thoracic ESCC. A multicenter, randomized phase III clinical trial is required to confirm the results of this study.

HA-ResNet: Residual Neural Network With Hidden Attention for ECG Arrhythmia Detection Using Two-Dimensional Signal.

Arrhythmia is an abnormal heart rhythm, a common clinical problem in cardiology. Long-term or severe arrhythmia may lead to stroke and sudden cardiac death. The electrocardiogram (ECG) is the most commonly used tool to diagnose arrhythmia. However, the traditional diagnosis relies on experts for manual interpretation, which is time-consuming and laborious. In recent years, many automatic arrhythmia detection methods have emerged due to advancements in deep learning. These methods can reduce manual intervention and improve diagnostic efficiency. However, extracting useful features from raw ECG signals for arrhythmia detection is still challenging due to the low frequency of ECG signals and noise distribution. In this paper, we propose a novel hidden attention residual network (HA-ResNet) for automated arrhythmia classification. In this model, the one-dimensional ECG signals are first converted into two-dimensional images and fed into an embedding layer to obtain the relevant shallow features in ECG. Then, a hidden attention layer combining Squeeze-and-Excitation (SE) block and Bidirectional Convolutional LSTM (BConvLSTM) is used to further capture the deep Spatio-temporal features. We evaluate our HA-ResNet on two public datasets and achieve F1 scores of 96.0%, 96.7%, and 87.6% on 2 s segments, 5 s segments, and 10 s segments, respectively, which significantly outperform the existing state-of-the-art approaches. The experimental results demonstrate the effectiveness and generalization of our method.

Efficacy and Safety of Simultaneous Integrated Boost Intensity-Modulation Radiation Therapy Combined with Systematic and Standardized Management for Esophageal Cancer.

Objective: To analyze and compare the efficacy and safety of simultaneous integrated boost intensity-modulation radiation therapy (SIB-IMRT) combined with systematic and standardized management for esophageal cancer. Methods: From January 2012 to January 2019, 200 patients with esophageal cancer who received radical chemoradiotherapy in our hospital were treated with lymphatic drainage area radiation prevention combined with systematic and standardized management. According to difference in radiotherapy methods, the patients were divided into local lesion 92 patients treated with simultaneous integrated boost intensity-modulation radiation therapy (SIB-IMRT) combined with systematic standardized management (SIB-IMRT group), and late course boost intensity-modulation radiation therapy (LCB-IMRT) combined with systematic standardized management 108 patients (LCB-IMRT group). The short-term eficacy of the two groups were compared. The dose volume parameters of the organ in danger are evaluated based on the dose volume histogram. The related adverse reactions during chemoradiotherapy were compared between two groups. The local control rate and survival rate were compared between the two groups. Results: The recent total effective rates of rats in the SIB-IMRT group and LCB-IMRT group were 95.65% and 90.74%, respectively, and there was no significant difference between the two groups (p > 0.05). The mean doses to left and right lung, heart and spinal cord in the SIB-IMRT group were significantly lower than that in the LCB-IMRT group (p < 0.05). There was no significant difference in the incidence of adverse reactions such as radiation esophagitis, radiation pneumonitis, radiation tracheitis, gastrointestinal reaction and bone marrow suppression between the SIB-IMRT group and LCB-IMRT groups (p > 0.05). The one-year and three-year overall survival rates in the SIB-IMRT group and LCB-IMRT groups were 82.61%, 42.39% and 77.78%, 34.26%, respectively, and the median survival times were 38 and 29 months, respectively. The local control rates in the SIB-IMRT group and LCB-IMRT group in one and three years were 84.78%, 56.52% and 75.93%, 41.67%, respectively. The 3-year local control rate in the SIB-IMRT group was higher than that in the LCB-IMRT group (p < 0.05), but there was no significant difference in the 1-and 3-year overall survival rates between the two groups (p > 0.05). Conclusion: SIB-IMRT combined with systematic and standardized management in the treatment of esophageal cancer can reduce the amount of some organs at risk and improve the local control rate of the lesion.