Genome-wide identification of phasiRNAs in Arabidopsis thaliana, and insights into biogenesis, temperature sensitivity, and organ specificity.

The knowledge of biogenesis and target regulation of the phased small interfering RNAs (phasiRNAs) needs continuous update, since the phasiRNA loci are dynamically evolved in plants. Here, hundreds of phasiRNA loci of Arabidopsis thaliana were identified in distinct tissues and under different temperature. In flowers, most of the 24-nt loci are RNA-dependent RNA polymerase 2 (RDR2)-dependent, while the 21-nt loci are RDR6-dependent. Among the RDR-dependent loci, a significant portion is Dicer-like 1-dependent, indicating the involvement of microRNAs in their expression. Besides, two TAS candidates were discovered. Some interesting features of the phasiRNA loci were observed, such as the strong strand bias of phasiRNA generation, and the capacity of one locus for producing phasiRNAs by different increments. Both organ specificity and temperature sensitivity were observed for phasiRNA expression. In leaves, the TAS genes are highly activated under low temperature. Several trans-acting siRNA-target pairs are also temperature-sensitive. In many cases, the phasiRNA expression patterns correlate well with those of the processing signals. Analysis of the rRNA-depleted degradome uncovered several phasiRNA loci to be RNA polymerase II-independent. Our results should advance the understanding on phasiRNA biogenesis and regulation in plants.

CRISPR-mediated MECOM depletion retards tumor growth by reducing cancer stem cell properties in lung squamous cell carcinoma.

Targeted therapy for lung squamous cell carcinoma (LUSC) remains a challenge due to the lack of robust targets. Here, we identified MECOM as a candidate of therapeutic target for LUSC by screening 38 genes that were commonly amplified in three pairs of primary tumors and patient-derived xenografts (PDXs) using a clustered regularly interspaced short palindromic repeats (CRISPR)-mediated approach. High MECOM expression levels were associated with poor prognosis. Forced expression of MECOM in LUSC cell lines promoted cancer stem cell (CSC) properties, and its knockout inhibited CSC phenotypes. Furthermore, systemic delivery of CRISPR-mediated MECOM depletion cassette using adenovirus with an adaptor, which is composed of a single-chain fragment variable (scFv) against epithelial cell adhesion molecules (EpCAM) fused to the ectodomain of coxsackievirus and adenovirus receptor, and a protector, which consists of the scFv connected to the hexon symmetry of the adenovirus, could specifically target subcutaneous and orthotopic LUSC and retard tumor growth. This study could provide a novel therapeutic strategy for LUSC with high efficacy and specificity.

Comprehensive genomic analysis of primary malignant melanoma of the esophagus reveals similar genetic patterns compared with epithelium-associated melanomas.

Primary malignant melanoma of the esophagus (PMME) is an exceedingly rare disease with a poor prognosis. The etiology of PMME remains largely unknown and genetic characteristics are yet to be clarified, essential for identifying potential therapeutic targets and defining treatment guidelines. Here, we performed whole-exome sequencing on 47 formalin-fixed paraffin-embedded specimens from 18 patients with PMME, including 23 tumor samples, 6 metastatic lymph nodes, and 18 tumor-adjacent normal tissues. The genomic features of PMME were comprehensively characterized, and comparative genomic analysis was further performed between these specimens and 398 skin cutaneous melanomas (SKCM), 67 non-esophagus mucosal melanomas (NEMM), and 79 uveal melanomas (UVM). In the PMME cohort, recurrently mutated driver genes, such as MUC16, RANBP2, NRAS, TP53, PTPRT, NF1, MUC4, KMT2C, and BRAF, were identified. All RANBP2 mutations were putatively deleterious, and most affected samples had multipoint mutations. Furthermore, RANBP2 showed parallel evolution by multiregional analysis. Whole-genome doubling was an early truncal event that occurred before most driver mutations, except for in TP53. An ultraviolet radiation-related mutational signature, SBS38, was identified as specific to epithelial melanomas and could predict inferior survival outcomes in both PMME and SKCM patients. Comparing the mutational and copy number landscapes between PMME and other subtypes of melanoma revealed that PMME has a similar genomic pattern and biological characteristics to SKCM. In summary, we comprehensively defined the key genomic aberrations and mutational processes driving PMME and suggested for the first time that PMME may share similar genomic patterns with SKCM; therefore, patients with rare melanomas, such as PMME, may benefit from the current treatment used for common cutaneous melanoma.

Percentage of Newly Proposed High-Grade Patterns Is Associated with Prognosis of Pathological T1-2N0M0 Lung Adenocarcinoma.

OBJECTIVE: To evaluate the prognostic value of the percentage of high-grade patterns (micropapillary, solid, and complex glands) in early-stage lung adenocarcinoma (LUAD). METHODS: A total of 1049 patients undergoing radical surgery with pathological T1-2N0M0 LUAD were screened retrospectively, and 191 patients were involved in the final analysis. Disease-free survival (DFS) was evaluated using the Kaplan-Meier curve and Cox regression analysis. The optimal cut-off value was determined using maximally selected rank statistics. RESULTS: The entire cohort was divided into quartile groups based on the percentage of high-grade patterns: Group 1 (≤ 30%), Group 2 (31-55%), Group 3 (56-85%), and Group 4 (≥ 86%). There were significant differences in smoking history (P = 0.041), EGFR mutations (P < 0.001), and ALK rearrangement (P = 0.010) between the four groups, but no significant differences in other clinicopathological features. Kaplan-Meier analysis showed that a higher percentage of high-grade patterns predicted worse DFS (P = 0.001), and multivariate analysis indicated that the percentage of high-grade patterns was an independent predictor (Group 2 vs. Group 1, HR = 2.136, P = 0.228; Group 3 vs. Group 1, HR = 3.355, P = 0.035; Group 4 vs. Group 1, HR = 5.147, P = 0.003, respectively). A cut-off value of 20% (P = 0.048) and 50% (P <0.001) for high-grade patterns were tested, and both revealed a significant difference in distinguishing DFS between subgroups. CONCLUSIONS: The percentage of high-grade patterns is associated with the prognosis of early-stage invasive LUAD. A higher percentage indicates a worse prognosis.

An ensemble learning with active sampling to predict the prognosis of postoperative non-small cell lung cancer patients.

BACKGROUND: Lung cancer is the leading cause of cancer death worldwide. Prognostic prediction plays a vital role in the decision-making process for postoperative non-small cell lung cancer (NSCLC) patients. However, the high imbalance ratio of prognostic data limits the development of effective prognostic prediction models. METHODS: In this study, we present a novel approach, namely ensemble learning with active sampling (ELAS), to tackle the imbalanced data problem in NSCLC prognostic prediction. ELAS first applies an active sampling mechanism to query the most informative samples to update the base classifier to give it a new perspective. This training process is repeated until no enough samples are queried. Next, an internal validation set is employed to evaluate the base classifiers, and the ones with the best performances are integrated as the ensemble model. Besides, we set up multiple initial training data seeds and internal validation sets to ensure the stability and generalization of the model. RESULTS: We verified the effectiveness of the ELAS on a real clinical dataset containing 1848 postoperative NSCLC patients. Experimental results showed that the ELAS achieved the best averaged 0.736 AUROC value and 0.453 AUPRC value for 6 prognostic tasks and obtained significant improvements in comparison with the SVM, AdaBoost, Bagging, SMOTE and TomekLinks. CONCLUSIONS: We conclude that the ELAS can effectively alleviate the imbalanced data problem in NSCLC prognostic prediction and demonstrates good potential for future postoperative NSCLC prognostic prediction.

LINC00365 inhibited lung adenocarcinoma progression and glycolysis via sponging miR-429/KCTD12 axis.

This study researched the function of long non-coding RNA LINC00365 in lung adenocarcinoma (LAD) progression. LINC00365, miR-429, and KCTD12 expression in the LAD clinical tissues and cells were detcetd by qRT-PCR and Western blot. LINC00365, miR-429, and KCTD12 effects on H1975 cells malignant phenotype were detected by cell counting kit-8 assay, clone formation experiment, Transwell experiment, and glycolysis. Dual luciferase reporter gene assay and RNA pull-down assay were implemented. LINC00365 effect on H1975 cells in vivo growth was detected. LINC00365 was low expressed in the LAD patients and cells, associating with poor outcome. LINC00365 up-regulation attenuated H1975 cells proliferation, migration, invasion, glycolysis and in vivo growth. LINC00365 inhibited KCTD12 expression by sponging miR-429. miR-429 up-regulation and KCTD12 down-regulation partial reversed LINC00365 inhibition on H1975 cells malignant phenotype. Thus, LINC00365 inhibited LAD progression and glycolysis via targeting miR-429/KCTD12 axis. LINC00365 might be a potential candidate for LAD target treatment clinically.

New Organoselenium (NSAIDs-Selenourea and Isoselenocyanate) Derivatives as Potential Antiproliferative Agents: Synthesis, Biological Evaluation and in Silico Calculations.

In this study, we report on the synthesis of new organoselenium derivatives, including nonsteroidal anti-inflammatory drugs (NSAIDs) scaffolds and Se functionalities (isoselenocyanate and selenourea), which were evaluated against four types of cancer cell line: SW480 (human colon adenocarcinoma cells), HeLa (human cervical cancer cells), A549 (human lung carcinoma cells), MCF-7 (human breast adenocarcinoma cells). Among these compounds, most of the investigated compounds reduced the viability of different cancer cell lines. The most promising compound 6b showed IC50 values under 10 µM against the four cancer cell lines, particularly to HeLa and MCF-7, with IC50 values of 2.3 and 2.5 µM, respectively. Furthermore, two compounds, 6b and 6f, were selected to investigate their ability to induce apoptosis in MCF-7 cells via modulation of the expression of anti-apoptotic Bcl-2 protein, pro-inflammatory cytokines (IL-2) and proapoptotic caspase-3 protein. The redox properties of the NSAIDs-Se derivatives were conducted by 2, 2-didiphenyl-1-picrylhydrazyl (DPPH), bleomycin-dependent DNA damage and glutathione peroxidase (GPx)-like assays. Finally, a molecular docking study revealed that an interaction with the active site of thioredoxin reductase 1 (TrxR1) predicted the antiproliferative activity of the synthesized candidates. Overall, these results could serve as a promising launch point for further designs of NSAIDs-Se derivatives as potential antiproliferative agents.

Validation of the 8th Edition Nodal Staging and Proposal of New Nodal Categories for Future Editions of the TNM Classification of Non-Small Cell Lung Cancer.

BACKGROUND: The International Association for the Study of Lung Cancer (IASLC) N classifications, which depend on the location and involvement of the lymph nodes, provide accurate prognoses. This study validated the efficiency of classifications using a single-institution dataset and proposed a modified system based on 5-level N1 node dissection. METHODS: From January 2005 to December 2014, 1851 patients with completely resected non-small cell lung cancer were reviewed. According to the IASLC recommendations, N1 is further subdivided into N1a (single) and N1b (multiple), N2 is divided into N2a1 (single station without N1), N2a2 (single station with N1), and N2b (multiple station). Additionally, we evaluated dividing N0 into N0a (with level 13/14 examination) and N0b (without level 13/14 examination), and N1 into N1a* (only level 13/14 positive) and N1b* (level 10-12 positive). Overall survival was also compared. RESULTS: Multivariate analysis showed that the N classifications recommended by the IASLC and those proposed and evaluated by this study could both significantly predict the prognoses of patients (p < 0.001, respectively). There was no significant difference in survival between N1b and N1a (hazard ratio [HR] 1.049, p = 0.83) and N2a1 and N1b (HR 1.314, p = 0.261); however, there were significant differences between N0a and N0b (HR 1.778, p < 0.001) and N1a* and N1b* (HR 2.014, p = 0.019). The survival curve of N1a* overlapped N0b (HR 0.997, p = 0.991), and N2a1 overlapped N1b* (HR 0.842, p = 0.444). CONCLUSION: More detailed nodal information is required to facilitate future revisions of N staging.

A novel deep learning approach to extract Chinese clinical entities for lung cancer screening and staging.

BACKGROUND: Computed tomography (CT) reports record a large volume of valuable information about patients' conditions and the interpretations of radiology images from radiologists, which can be used for clinical decision-making and further academic study. However, the free-text nature of clinical reports is a critical barrier to use this data more effectively. In this study, we investigate a novel deep learning method to extract entities from Chinese CT reports for lung cancer screening and TNM staging. METHODS: The proposed approach presents a new named entity recognition algorithm, namely the BERT-based-BiLSTM-Transformer network (BERT-BTN) with pre-training, to extract clinical entities for lung cancer screening and staging. Specifically, instead of traditional word embedding methods, BERT is applied to learn the deep semantic representations of characters. Following the long short-term memory layer, a Transformer layer is added to capture the global dependencies between characters. Besides, pre-training technique is employed to alleviate the problem of insufficient labeled data. RESULTS: We verify the effectiveness of the proposed approach on a clinical dataset containing 359 CT reports collected from the Department of Thoracic Surgery II of Peking University Cancer Hospital. The experimental results show that the proposed approach achieves an 85.96% macro-F1 score under exact match scheme, which improves the performance by 1.38%, 1.84%, 3.81%,4.29%,5.12%,5.29% and 8.84% compared to BERT-BTN, BERT-LSTM, BERT-fine-tune, BERT-Transformer, FastText-BTN, FastText-BiLSTM and FastText-Transformer, respectively. CONCLUSIONS: In this study, we developed a novel deep learning method, i.e., BERT-BTN with pre-training, to extract the clinical entities from Chinese CT reports. The experimental results indicate that the proposed approach can efficiently recognize various clinical entities about lung cancer screening and staging, which shows the potential for further clinical decision-making and academic research.

Impact of Early Oral Feeding on Anastomotic Leakage Rate After Esophagectomy: A Systematic Review and Meta-analysis.

BACKGROUND: Esophageal cancer occupies a vital position in fatal cancer-related disease, with esophagectomy procedures helping to improve patient survival. The timing when oral intake should be resumed after esophagectomy and whether early oral feeding (EOF) or delayed oral feeding (DOF) should be the optimal regimen are controversial. METHODS: Databases (PubMed, Embase, Cochrane library) were searched. All records were screened by two authors through full-text reading. Data on the anastomotic leakage rate were extracted and synthesized in meta-analyses. Postoperative pneumonia rate and length of hospital stay were also assessed. RESULTS: Seven studies from 49 records were included after full-text reading; 1595 patients were totally included in the analysis. No significant difference was observed between the EOF and DOF groups (odds ratio [OR] 1.68; 95% confidence interval [CI] 0.70-4.03; p = 0.2495; I2 = 70%). Higher anastomotic leakage rate was observed in EOF compared with DOF (OR 2.89; 95% CI 1.56-5.34; p = 0.0007; I2 = 10%) in the open subgroup. No significant difference was observed in the MIE (OR 0.48; 95% CI 0.22-1.02; p = 0.0564; I2 = 0%). Patients performed similarly in pneumonia (OR 1.12; 95% CI 0.57-2.21; p = 0.745; I2 = 34%). In cervical subgroup, anastomosis leakage may be less in DOF (OR 2.42 95% CI 1.26-4.64; p = 0.0651; I2 = 58%), while in thoracic subgroup, there is no obvious difference (OR 0.86 95% CI 0.46-1.61; p = 0.01; I2 = 84.9%). CONCLUSIONS: Anastomotic leakage related to the timing of oral feeding after open esophagectomy, which is more favorable to the DOF regimen. However, timing of oral feeding did not impair anastomotic healing in patients undergoing MIE.

Synthesis and Potential Anticancer Activity of Some Novel Selenocyanates and Diselenides.

In the present study, twenty-four selenocyanate and diselenide compounds were synthesized and characterized, and their anticancer activities against the human cancer cell lines Caco2, BGC-823, MCF-7 and PC-3 were determined. Interestingly, most of the new compounds were active in reducing the viability of different cancer cell lines. Two compounds exhibited higher promising activities than other derivatives. The most active compound showed the least IC50 values against the four cancer cell lines, particularly to PC-3 with IC50 values below 5 µm. Two compounds were selected to monitor the expression levels of Bcl-2, IL-2 and caspase-3 molecular biomarkers. Interestingly, the two compounds downregulated the Bcl-2 expression levels and upregulated the expression of IL-2 and caspase-3 in PC-3 cells compared to untreated cells. Moreover, most of the synthesized organoselenides exhibited good Gpx-like activities comparable to ebselen. These results appear that introduction of selenocyanate (-SeCN) or diselenides (-Se-Se-) moiety to some carboxy derivatives could serve as a promising launch point for the further design of this type of organic selenium anticancer agent.

Adjuvant chemotherapy may improve outcome of patients with non-small-cell lung cancer with metastasis of intrapulmonary lymph nodes after systematic dissection of N1 nodes.

OBJECTIVE: Survival benefit of adjuvant chemotherapy (AC) of patients with intrapulmonary lymph node (IPLN) metastasis (level 12-14) needs investigation. We evaluated the impact of AC on patients whose metastatic nodes were limited to intrapulmonary levels after systematic dissection of N1 nodes. METHODS: First, 155 consective cases of lung cancer confirmed as pathologic N1 were collected and evaluated. Patients received systematic dissection of N2 and N1 nodes. For patients with IPLN metastasis, survival outcomes were compared between those receiving AC and those not receiving AC. RESULTS: In this group, 112 cases (72.3%) had IPLN metastasis and 55 cases (35.5%) had N1 involvement limited to level 13-14 without further disease spread to higher levels. Patients with IPLN involvement had a better prognosis than that of patients with hilar-interlobar involvement. For the intrapulmonary N1 group (level 12-14-positive, level 10-11-negative or unknown, n=112), no survival benefit was found between the AC group and non-AC group [5-year overall survival (OS): 54.6±1.6vs. 50.4±2.4 months, P=0.177]. However, 76 of 112 cases for whom harvesting of level-10 and level-11 nodes was done did not show cancer involvement in pathology reports (level 12-14-positive, level 10-11 both negative), oncologic outcome was better for patients receiving AC than those not receiving AC in this subgroup (5-year OS: 57.3±1.5vs. 47.1±3.2 months, P=0.002). CONCLUSIONS: Oncologic outcome may be improved by AC for patients with involvement of N1 nodes limited to intrapulmonary levels after complete examination of N1 nodes.

Is radical mediastinal lymphadenectomy necessary for elderly patients with clinical N-negative non-small-cell lung cancer? A single center matched-pair study.

BACKGROUND: The extent of lymph node dissection during surgery in elderly non-small-cell lung cancer patients remains controversial. We evaluated a cohort of elderly patients with clinical N0 disease who underwent lobectomy to determine if radical mediastinal lymphadenectomy (RML) is justified for the special group. PATIENTS AND METHODS: A single-center database of patients over 70 y old from 2001-2011 was used to conduct a matched-pair analysis. The patients undergoing RML were matched 1:1 with those not (non-radical mediastinal lymphadenectomy group) by age, gender, American Society of Anesthesia score, histology, and clinical T status to assess their postoperative and long-term outcomes. RESULTS: A total of 136 patients could be matched (68 RML and 68 non-radical mediastinal lymphadenectomy). No statistical difference was observed in postoperative mortality and overall morbidity rate between the matched groups (0 versus 1, P > 0.99 and 43 versus 35, P = 0.17). Patients undergoing RML experienced more major morbidities, but no significant difference was achieved (15 versus 7, P = 0.06). No significantly more N-positive diseases were discovered in RML group (N1 and N2 involvement disease: 16 versus 16, P > 0.99 and 10 versus 4, P = 0.09, respectively). RML was associated with a significantly longer cancer-related and disease-free survival (P = 0.02 and P = 0.02). Whereas for clinical IA diseases, significant differences were observed neither in cancer-related nor in disease-free survival (P = 0.67 and P = 0.61). CONCLUSIONS: The performance of RML seemed to result in a tendency of higher major morbidity rate in elderly patients, but to contribute a favorable impact on long-term survival. However, for clinical IA patients the survival benefits were not obtained.

Efficient preparation of (R)-2-chloromandelic acid via a recycle process of resolution.

Efficient preparation of (R)-2-chloromandelic acid based on a recycle process of resolution is described. In the process, the desired was obtained by coordination-mediated resolution with D-O,O'-di-(p-toluoyl)-tartaric acid in the presence of Ca(2+) . Meanwhile, the undesired could be racemized in the presence of sodium hydroxide and the product was suitable for further resolution. A carbanion mechanism for the racemization of is proposed.

Does an extended mediastinal lymphadenectomy improve outcome after R0 resection in lung cancer?

OBJECTIVE: This retrospective study was conducted to investigate the impact of more extended mediastinal lymphadenectomy on the outcome of lung cancer patients treated with R0 resection. METHODS: During the investigation period, 325 lung cancer cases were enlisted and 278 cases entered the analysis. The patients were divided into Control group (n=116) and Research group (n=162) according to the different extents of mediastinal lymph node clearance at different time periods. Three major parameters were retrospectively assessed to compare the quality of surgical care: extent of lymph node clearance, resection volume, and postoperative recovery process and common complications. Comparison of the outcome between two groups was carried out. RESULTS: Research group showed a significant quality improvement of lymphadenectomy, such as more mediastinal node stations investigated (more than 3 N2 stations investigated: Research group, 90.7% vs. Control group, 55.2%; P=0.001) and more nodes collection (total nodes 26.1±10.0 vs. 19.1±8.3, P=0.000; N2 nodes 15.5±7.2 vs. 9.8±5.6, P=0.000). However, overall survival (OS) and disease-free survival (DFS) were not significantly different either between two groups (5-year OS: Control group, 56.4±4.6% vs. Research group, 62.6±4.3%; P=0.271) or between subgroups from stage I to IIIa. TNM stage and histology were significant factors associated with OS and DFS in multivariate analysis; extent of mediastinal lymphadenectomy was not associated with OS or DFS. CONCLUSIONS: More radical mediastinal lymphadenectomy may not lead to an improved oncological outcome for lung cancer treated with R0 resection.

Quantitative MRI on MR-Linacs: Towards Biological Image-Guided Adaptive Radiotherapy.

Recognizing the potential of quantitative imaging biomarkers (QIBs) in radiotherapy, many studies have investigated the prognostic value of quantitative MRI (qMRI). With the introduction of MRI-guided radiotherapy systems, the practical challenges of repeated imaging have been substantially reduced. Since patients are treated inside an MRI scanner, acquisition of qMRI can be done during each fraction with limited or no prolongation of the fraction duration. In this review paper, we identify the steps that need been taken to move from MR as an imaging technique to a useful biomarker for MRI-guided radiotherapy (MRgRT).

Beneficial implications of adjuvant chemotherapy for stage IB lung adenocarcinoma exhibiting elevated SUVmax in FDG-PET/CT: a retrospective study from a single center.

Background: Controversy surrounds the efficacy of adjuvant chemotherapy (ACT) in the treatment of stage I lung adenocarcinoma (LUAD). The objective of this study was to examine the impact of the maximum standardized uptake value (SUVmax) as measured by 18F-fluorodeoxyglucose positron emission tomography/computed tomography (FDG-PET/CT) on the efficacy of ACT in patients diagnosed with stage I LUAD. Methods: We scrutinized the medical records of 928 consecutive patients who underwent complete surgical resection for pathological stage I LUAD at our institution. The ideal cut-off value for primary tumor SUVmax in terms of disease-free survival (DFS) and overall survival (OS) was determined using the X-tile software. The Kaplan-Meier method and Cox regression analysis were used for survival analysis. Results: Based on the SUVmax algorithm, the ideal cutoff values were determined to be 4.9 for DFS and 5.0 for OS. We selected 5.0 as the threshold because OS is the more widely accepted predictive endpoint. In a multivariate Cox regression analysis, SUVmax ≥ 5.0, problematic IB stage, and sublobectomy were identified as independent risk factors for poor DFS and OS. It is noteworthy that patients who were administered ACT had significantly longer DFS and OS than what was observed in the subgroup of patients with pathological stage IB LUAD and SUVmax ≥ 5.0 (p < 0.035 and p ≤ 0.046, respectively). However, there was no observed survival advantage for patients in stages IA or IB who had an SUVmax < 5.0. Conclusion: The preoperative SUVmax of tumors served as an indicator of the impact of ACT in the context of completely resected pathological stage I LUAD. Notably, patients within the Stage IB category exhibiting elevated SUVmax levels emerged as a subgroup experiencing substantial benefits from postoperative ACT.

Genome-Scale Multimodal Analysis of Cell-Free DNA Whole-Methylome Sequencing for Noninvasive Esophageal Cancer Detection.

PURPOSE: Simultaneous profiling of cell-free DNA (cfDNA) methylation and fragmentation features to improve the performance of cfDNA-based cancer detection is technically challenging. We developed a method to comprehensively analyze multimodal cfDNA genomic features for more sensitive esophageal squamous cell carcinoma (ESCC) detection. MATERIALS AND METHODS: Enzymatic conversion-mediated whole-methylome sequencing was applied to plasma cfDNA samples extracted from 168 patients with ESCC and 251 noncancer controls. ESCC characteristic cfDNA methylation, fragmentation, and copy number signatures were analyzed both across the genome and at accessible cis-regulatory DNA elements. To distinguish ESCC from noncancer samples, a first-layer classifier was developed for each feature type, the prediction results of which were incorporated to construct the second-layer ensemble model. RESULTS: ESCC plasma genome displayed global hypomethylation, altered fragmentation size, and chromosomal copy number alteration. Methylation and fragmentation changes at cancer tissue-specific accessible cis-regulatory DNA elements were also observed in ESCC plasma. By integrating multimodal genomic features for ESCC detection, the ensemble model showed improved performance over individual modalities. In the training cohort with a specificity of 99.2%, the detection sensitivity was 81.0% for all stages and 70.0% for stage 0-II. Consistent performance was observed in the test cohort with a specificity of 98.4%, an all-stage sensitivity of 79.8%, and a stage 0-II sensitivity of 69.0%. The performance of the classifier was associated with the disease stage, irrespective of clinical covariates. CONCLUSION: This study comprehensively profiles the epigenomic landscape of ESCC plasma and provides a novel noninvasive and sensitive ESCC detection approach with genome-scale multimodal analysis.

Efficacy of a smartphone application assisting home-based rehabilitation and symptom management for patients with lung cancer undergoing video-assisted thoracoscopic lobectomy: a prospective, single-blinded, randomised control trial (POPPER study).

BACKGROUND: Video-assisted thoracoscopic (VATS) lobectomy can affect patients' pulmonary function and quality of life significantly. No optimal protocol combining patient-reported outcome-based symptom management and post-discharge rehabilitation programme has yet been established. This study aimed to assess the efficacy of a novel smartphone app designed for home-based symptom management and rehabilitation. METHODS: The app was developed based on three modules: a symptom reporting system with alerts, aerobic and respiratory training exercises, and educational material. Four core symptoms were selected based on a questionnaire survey of 201 patients and three rounds of Delphi voting by 30 experts. We screened 265 patients and randomly assigned 136 equally to the app group and usual care group. The primary outcome was pulmonary function recovery at 30 days postoperatively. Secondary outcomes included symptom burden and interference with daily living (both rated using the MD Anderson Symptom Inventory for Lung Cancer), aerobic exercise intensity, emergency department visits, app-related safety, and satisfaction with the app. FINDINGS: Of the 136 participants, 56.6% were women and their mean age was 61 years. The pulmonary function recovery ratio 1 month after surgery in the app group was significantly higher than that in the usual care group (79.32% vs. 75.73%; P=0.040). The app group also recorded significantly lower symptom burden and interference with daily living scores and higher aerobic exercise intensity after surgery than the usual care group. Thirty-two alerts were triggered in the app group. The highest pulmonary function recovery ratio and aerobic exercise intensity were recorded in those patients who triggered alerts in both groups. INTERPRETATION: Using a smartphone app is an effective approach to accelerate home-based rehabilitation after VATS lobectomy. The symptom alert mechanism of this app could optimise recovery outcomes, possibly driven by patients' increased self-awareness.