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To reduce the risk of relapse after allogeneic hematopoietic stem cell transplantation (allo-HSCT), there have been continuing efforts to optimize the conditioning regimens. This study aimed to analyze the risk factors associated with the relapse of relapsed/refractory (R/R), high-risk acute myeloid leukemia (AML), and high-risk myelodysplastic syndrome (MDS) post-transplant and the efficacy of a new conditioning regimen involving decitabine and cladribine. Clinical data of 125 patients with R/R AML, high-risk AML, and high-risk MDS who underwent allo-HSCT were collected. In addition, 35 patients with R/R AML, high-risk AML, and high-risk MDS received treatment with a new conditioning regimen including decitabine and cladribine. Cox regression analysis was used to identify risk factors associated with OS, RFS, and relapse. Among 125 patients who underwent allo-HSCT, CR before allo-HSCT and matched sibling donors were independent protective factors for OS. DNMT3A abnormality was an independent risk factor for both relapse and RFS. Among 35 patients who received a new conditioning regimen containing decitabine and cladribine, only six patients relapsed and 1-year cumulative incidence of relapse was 11.7%. Moreover, this new regimen showed efficient MRD clearance early after allo-HSCT. The combined decitabine- and cladribine-based conditioning regimen showed a low relapse rate and a high survival without an increased incidence of GVHD or adverse effects and thus has potential for use in allo-HSCT for R/R AML, high-risk AML, and high-risk MDS.

Prefabricated buildings are assembled from factory prefabricated parts, components, and materials transported to the construction site. Its construction process is often called “building blocks”, and the focus is on “prefabrication” and “assembly”. This paper aims to study how to analyze and study the intelligent construction of prefabricated buildings based on the P-ISOMAP algorithm, and describe the information visualization. This paper presents the problem of information visualization, which is based on the P-ISOMAP algorithm and BIM technology. Therefore, the concepts and related algorithms of the two are expounded, and the case design and analysis of the information visualization of the intelligent construction of prefabricated buildings are carried out. The experimental results show that in the questionnaire survey, 87.61% hope to visualize architectural-related information, 82.30% of structural information, and 91.15% of model display, all of which are very high. The information visualization of intelligent construction meets the needs of the masses. In addition to guiding the assembly of prefabricated components, informatization is also convenient for manufacturing and quality management. According to the data generated by real-time monitoring during the construction process, the construction period and the construction material plan are controlled. In the completion stage, these data can be directly exported to complete the completion report for completion acceptance.

Background Esophageal squamous cell cancer (ESCC) patients with the potentially resectable disease most would experience relapse after surgery. Immunotherapy has been reported to improve the prognosis of advanced esophageal cancer and may be a new strategy to prevent this urgent condition's recurrence. We first evaluated the efficacy and safety of neoadjuvant chemotherapy combined with immunotherapy in patients with resectable ESCC. Methods All patients with resectable locally advanced ESCC (clinical stage III-IVB). Received at least 1 cycle of neoadjuvant chemotherapy combined with immunotherapy (NACI), and the interval between each cycle and the operation should be at least 3 weeks. All patients were treated with standard surgery. The tumor imaginations were obtained at baseline and within a week before surgery. The efficacy endpoint was the rate of major pathologic response (MPR, 10% viable tumor cells). Expression of immunohistochemical-related molecules was investigated in surgical samples. Results A total of 38 patients with ESCC were included (36 males, median age 61 years), and most of them used Pembrolizumab (55.26%) and Camrelizumab (31.58%). We analyzed 19 patients and found that 13 patients (68.42%) achieved radiological partial response (PR) by CT images. R0 resection was performed in 35 patients (92.11%), and 10 patients (26.32%) developed postoperative complications. Through postoperative pathology, we found 13 (34.21%) patients had complete pathologic response (cPR), and 16 (42.11%) patients achieved MPR. We also found that none of the factors had a statistically significant impact on MPR. Still, the regression rate of Sum of lesion diameter (SLD) was significantly positively correlated with the pathological remission rate (P=0.012, r=0.565). Conclusions The rate of MPR in ESCC patients reached 42.11%. The use of the NACI regimen did not increase the occurrence of complications in neoadjuvant treatment and operation, and the SLD regression rate has a certain guiding significance for the effect of immunotherapy.

Background The selective Janus-activated kinase inhibitor ruxolitinib (rux) is now widely used to treat myelofibrosis and polycythemia vera due to its remarkable effect of reducing splenomegaly and improving constitutional symptoms. With opportunistic infections secondary to rux constantly reported; however, an increasing number of studies have begun to investigate the mechanism and underlying immunosuppressive effect of rux. Case presentation We report two cases of tuberculosis (TB) in primary myelofibrosis patients during rux therapy. The first patient received rux soon after diagnosis, and tracheobronchial TB (TBTB) and bronchoesophageal fistula were found after 4 months. After discontinuation of rux, antituberculosis therapy (ATT) was introduced. The second patient initiated rux due to progressive splenomegaly after 7.5 years of interferon therapy and was diagnosed with disseminated TB after 2 months. He received ATT as well. His rux was maintained due to the high burden of systematic symptoms and splenomegaly. Both myelofibrosis and TB were well controlled in these patients. Conclusion This is the first case report that describes rux-related TBTB accompanied by a bronchoesophageal fistula. Through a review of the literature, we provide supporting evidence to the finding that intrinsic disorders of myeloproliferative neoplasms and rux-induced immunologic deregulation together lead to TB. We highlight the importance of screening for latent TB infection and timely chemoprophylaxis before rux therapy. Once TB is diagnosed during treatment, rux is recommended to be stopped and active ATT should begin quickly.

Background Intratumoral heterogeneity is a crucial factor to the outcome of patients and resistance to therapies, in which structural variants play an indispensable but undiscovered role. Methods We performed an integrated analysis of optical mapping and whole-genome sequencing on a primary tumor (PT) and matched metastases including lymph node metastasis (LNM) and tumor thrombus in the pulmonary vein (TPV). Single nucleotide variants, indels and structural variants were analyzed to reveal intratumoral genetic heterogeneity among tumor cells in different sites. Results Our results demonstrated there were less nonsynonymous somatic variants shared with PT in LNM than in TPV, while there were more structural variants shared with PT in LNM than in TPV. More private variants and its affected genes associated with tumorigenesis and progression were identified in TPV than in LNM. It should be noticed that optical mapping detected an average of 77.1% (74.5-78.5%) large structural variants (>5,000 bp) not detected by whole-genome sequencing and identified several structural variants private to metastases. Conclusions Our study does demonstrate structural variants, especially large structural variants play a crucial role in intratumoral genetic heterogeneity and optical mapping could make up for the deficiency of whole-genome sequencing to identify structural variants.

EGFR mutations occur most frequently in patients with lung adenocarcinoma in East Asia. However, the prognostic and therapeutic impact of co-mutational status of EGFR and tumor suppressor genes is not fully understood. This study aims to provide a deeper understanding of lung adenocarcinoma patients with co-mutation of EGFR and tumor suppressor genes. From November 2009 to May 2016, 675 patients with lung adenocarcinoma who underwent complete surgery were included in this study. Samples were collected and pathologically examined. Whole-exome sequencing was performed on 197 samples, while direct sequencing of major driver genes, including EGFR, KRAS, ERBB2 and BRAF and Ion-torrent targeted sequencing of tumor suppressor genes, including TP53, KEAP1, MGA, NF1, RB1, SMARCA4 and STK11, were performed on 478 samples. Tumor mutational burden was calculated and survival analyses were performed. The frequency of EGFR and TP53 mutation was 409 (60.6%) and 215 (31.9%), respectively. Co-mutation of EGFR and TP53 occured in 151 patients (22.4%), while co-mutation of EGFR and at least one tumor suppressor gene occured in 184 patients (27.3%). Compared with patients with only EGFR mutations, patients with co-mutations of EGFR and TP53 had a higher tumor mutational burden (p = 0.007) and worse recurrence-free survival (p = 0.010), while patients with co-mutations of EGFR and at least one tumor suppressor gene had a higher tumor mutational burden (p = 0.007), worse recurrence-free survival (p = 0.016) and worse overall survival (p = 0.018). Lung adenocarcinoma patients harboring EGFR and co-mutational tumor suppressor genes should be regarded as a unique subgroup.

The optimal extent of lymph node dissection (LND) remains controversial. We aimed to investigate whether the addition of station 4L lymph node dissection (S4L-LND) was beneficial for non-small cell lung cancer (NSCLC).Data on 1040 left-sided NSCLC patients undergoing rigorous systematic LND were retrospectively reviewed. Multivariate logistic regression analysis determined risk factors of station 4L (S4L) nodal involvement to facilitate risk stratified analysis of the significance of S4L-LND. Propensity score matching (PSM) was conducted to reduce disparities of baseline characteristics between S4L-LND group and no-S4L-LND group. Recurrence-free survival (RFS), overall survival (OS), and postoperative complications were compared.S4L-LND was performed in 586 (56.3%) patients. The S4L nodal involvement rate was 15.5% (91/586). Aortopulmonary zone nodes involvement (P 0.001), N1 nodes involvement (P 0.001), and advanced T stage (P = 0.015) were independent risk factors of S4L nodal involvement. Patients with ≥ 2 risk factors of S4L nodal involvement were classified as high risk group, and the others were classified as low risk group. Among patients with negative aortopulmonary zone nodes and inferior mediastinal nodes (n = 425), only 28 (6.6%) patients had S4L involvement. After PSM, a total of 416 pairs were well matched. There was no significant survival difference between S4L-LND group and no-S4L-LND group (OS, P = 0.247; RFS, P = 0.569). When stratified by risk subgroup, S4L-LND group did not demonstrate superior survival than no-S4L-LND group in the high risk group (OS, P = 0.273; RFS, P = 0.754) or the low risk group (OS, P = 0.558; RFS, P = 0.319). S4L-LND group demonstrated significantly greater risk of postoperative complications than no-S4L-LND group (9.6% vs. 5.8%; P = 0.037).S4L involvement was not rare and usually occurred with multiple nodal stations involvement. Routine dissection of aortopulmonary zone and inferior mediastinal nodes was sufficient to ensure staging accuracy. The addition of S4L-LND did not improve survival, but might increase the risk of postoperative complications.

Background Repeat pulmonary resection is widely accepted in clinical practice. This study aimed to compare sublobar resection (segmentectomy or wedge resection) with lobectomy in the treatment of patients who underwent a second pulmonary resection. Methods This study retrospectively included patients who underwent lobectomy or sublobar resection for second pulmonary resection. 1:1 propensity score matching (PSM) was performed to balance selection bias. Clinicopathological features, perioperative and survival outcomes of lobectomy and sublobar resection were compared. Results A total of 308 patients who underwent second pulmonary resection were identified: 71 (23.1%) who underwent lobectomy and 237 (76.9%) who underwent sublobar resection. After PSM, 58 patients for each group were selected with well‐balanced clinicopathological characteristics. In patients who underwent sublobar resection, significantly shorter chest tube duration (days) (median, 4 vs. 2, p, Lobectomy does not show advantages in perioperative and survival outcomes for second pulmonary resection compared with sublobar resection. For high‐risk patients unable to tolerate lobectomy, sublobar resection might be an alternative treatment option.

BackgroundLung adenocarcinoma (LUAD) is a highly malignant and heterogeneous tumor that involves various oncogenic genetic alterations. Epigenetic processes play important roles in lung cancer development. However, the variation in enhancer and super-enhancer landscapes of LUAD patients remains largely unknown. To provide an in-depth understanding of the epigenomic heterogeneity of LUAD, we investigate the H3K27ac histone modification profiles of tumors and adjacent normal lung tissues from 42 LUAD patients and explore the role of epigenetic alterations in LUAD progression.ResultsA high intertumoral epigenetic heterogeneity is observed across the LUAD H3K27ac profiles. We quantitatively model the intertumoral variability of H3K27ac levels at proximal gene promoters and distal enhancers and propose a new epigenetic classification of LUAD patients. Our classification defines two LUAD subgroups which are highly related to histological subtypes. Group II patients have significantly worse prognosis than group I, which is further confirmed in the public TCGA-LUAD cohort. Differential RNA-seq analysis between group I and group II groups reveals that those genes upregulated in group II group tend to promote cell proliferation and induce cell de-differentiation. We construct the gene co-expression networks and identify group-specific core regulators. Most of these core regulators are linked with group-specific regulatory elements, such as super-enhancers. We further show that CLU is regulated by 3 group I-specific core regulators and works as a novel tumor suppressor in LUAD.ConclusionsOur study systematically characterizes the epigenetic alterations during LUAD progression and provides a new classification model that is helpful for predicting patient prognosis.

In this paper, we propose a single multi-task learning framework to perform End-to-End (E2E) speech recognition (ASR) and accent recognition (AR) simultaneously. The proposed framework is not only more compact but can also yield comparable or even better results than standalone systems. Specifically, we found that the overall performance is predominantly determined by the ASR task, and the E2E-based ASR pretraining is essential to achieve improved performance, particularly for the AR task. Additionally, we conduct several analyses of the proposed method. First, though the objective loss for the AR task is much smaller compared with its counterpart of ASR task, a smaller weighting factor with the AR task in the joint objective function is necessary to yield better results for each task. Second, we found that sharing only a few layers of the encoder yields better AR results than sharing the overall encoder. Experimentally, the proposed method produces WER results close to the best standalone E2E ASR ones, while it achieves 7.7% and 4.2% relative improvement over standalone and single-task-based joint recognition methods on test set for accent recognition respectively.

Additional file 1: Supplementary figures. All figures explain the content of this study but were not listed as figures in the article.

Eptapirone free base, F11440,4-methyl-2-(4-(4-(pyrimidin-2-yl)piperazin-1-yl)butyl)-1,2,4-triazine-3,5(2H,4H)-dione, represents a potent and selective 5-HT1A receptor agonist with high efficacy and the potential to regulate anxiety disorders. Herein, we report a method to retro-synthesize eptapirone free base. The compound consists of heterocyclic aromatic portion and aliphatic portion, and the synthetic route consisted of a total of nine steps with an overall yield of 8.8% starting from the commercially available materials. The key steps in the synthetic method involved: (1) using sodium hydroxide and ethylene glycol as solvent resulted in a better cyclization and yield (61.6%) of 1,2,4-triazine-3,5(2H,4H)-dione; (2) an acceptable yield (63.1%) of 4-tert-butyl(pyrimidin-2-yl)piperazine-1-carboxylate was obtained under an optimized conditions of using triethylamine as a base, ethanol as a solvent, and a reaction temperature of 50 °C for 16 h with non-metal catalysis and less byproducts; (3) the reaction step of eptapirone could get a better yield (49.6%) with an optimized condition of potassium carbonate as a base, acetonitrile as a solvent, NaI as a catalyst, and a reaction temperature of 50 °C for 12 h by nucleophilic substitution reaction. The main advantages of this route were an acceptable product purity, the commercial availability of all starting materials and the absence of high temperature, high pressure and noble metal catalysts, which could result in more feasible commercial applications.

Background Young patients with non-small cell lung cancer (NSCLC) represent a distinct subgroup of patients with this disease. This study aimed to construct nomograms to predict the overall survival (OS) and cancer-specific survival (CSS) of young patients with NSCLC. Methods NSCLC patients under 50 years old diagnosed between 2010 and 2016 were selected from the Surveillance, Epidemiology, and End Results (SEER) database and randomly divided into training (n=1,357) and validation (n=678) cohorts at a ratio of 2:1. Independent prognostic factors for OS or CSS were identified through the log-rank test, Cox proportional hazards models or competing risk model and further integrated to construct nomograms. The predictive capability of the nomogram was assessed by Harrell's concordance index (C-index), the calibration curve and risk group stratification. Results A total of 2,035 patients were enrolled. In the training cohort, insurance, marital status, histological type, grade, T stage, N stage and surgery were identified as independent prognostic for OS and CSS. The C-index value were 0.759 [95% confidence interval (CI): 0.731-0.787] for OS and 0.810 (95% CI: 0.803-0.818) for BCSS in the training cohort and 0.751 (95% CI: 0.711-0.790) for OS and 0.807 (95% CI: 0.795-0.819) for CSS in the validation cohort. The calibration curves showed optimal agreement between the predicted and actual survival both in internal and external validation. In addition, patients in the validation cohort within different risk groups exhibited significantly different survival even in each TNM stage. Conclusions Nomograms were developed and validated to predict OS and CSS of young patients with NSCLC in our study. A prospective study with more potential prognostic factors and the latest TNM classification is required to ameliorate this model.

Previous proteomic analysis (label-free) of plasma exosomes revealed that the expression of FGG and FGB was significantly higher in the malignant pulmonary nodules group, compared to the benign pulmonary nodules group. The present study was performed to evaluate the role of plasma exosomal proteins FGB and FGG in the diagnosis of benign and malignant pulmonary nodules. We examined the expression levels of FGB and FGG in plasma exosomes from 63 patients before surgery. Postoperative pathological diagnosis confirmed that 43 cases were malignant and 20 cases were benign. The ROC curve was used to describe the sensitivity, specificity, area under the curve (AUC) of the biomarker and the corresponding 95% confidence interval. We confirmed that the expression levels of FGB and FGG were higher in the plasma exosomes of malignant group than in the benign group. The sensitivity and AUC of FGB combined with FGG detection to determine the nature of pulmonary nodules are superior to single FGB or FGG detection. FGB and FGG might represent novel and sensitive biomarker to distinguish benign from malignant pulmonary nodules.

As the most abundant noncoding RNA in cells, tRNA plays an important role in tumorigenesis and development. The report of tRNA on the pathogenesis of lung adenocarcinoma is rare. It is of great clinical significance to explore the relationship between tRNA expression and prognosis of lung adenocarcinoma. The expression level of tRNAs in lung adenocarcinoma tissues and paracarcinoma tissues was detected using a tRNA RT-qPCR array. A total of 104 lung adenocarcinomas were included in the analysis of the correlation between candidate tRNAs expression and prognosis. A tRNA-based prognostic model was constructed and validated using Cox proportional hazards regression. A nomogram was built to help clinicians develop treatment strategies. We screened a series of differentially expressed tRNAs between lung adenocarcinoma tissues and paracarcinoma tissues. Among these tRNAs, tRNAAsn ATT , tRNAIle AAT , tRNALeu TAA , mt-tRNATrp TCA , mt-tRNALeu TAA , tRNAPro AGG , tRNALys CTT -1 and tRNALeu AAG were associated with the clinicopathological characteristics of lung adenocarcinoma. tRNALys CTT -1 , mt-tRNASer GCT and tRNATyr ATA were associated with cancer-specific survival. We constructed a prognostic model for lung adenocarcinoma using specific tRNA expression levels as reference factors. Multivariate analyses showed that tRNA-based prognostic score was a significant and important prognostic factor. The prognostic model based on the tRNAs expression signatures can help predict the prognosis of patients with lung adenocarcinoma.

Additional file 1. Additional figures and tables.