Genomic basis for RNA alterations in cancer.

Transcript alterations often result from somatic changes in cancer genomes1. Various forms of RNA alterations have been described in cancer, including overexpression2, altered splicing3 and gene fusions4; however, it is difficult to attribute these to underlying genomic changes owing to heterogeneity among patients and tumour types, and the relatively small cohorts of patients for whom samples have been analysed by both transcriptome and whole-genome sequencing. Here we present, to our knowledge, the most comprehensive catalogue of cancer-associated gene alterations to date, obtained by characterizing tumour transcriptomes from 1,188 donors of the Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium of the International Cancer Genome Consortium (ICGC) and The Cancer Genome Atlas (TCGA)5. Using matched whole-genome sequencing data, we associated several categories of RNA alterations with germline and somatic DNA alterations, and identified probable genetic mechanisms. Somatic copy-number alterations were the major drivers of variations in total gene and allele-specific expression. We identified 649 associations of somatic single-nucleotide variants with gene expression in cis, of which 68.4% involved associations with flanking non-coding regions of the gene. We found 1,900 splicing alterations associated with somatic mutations, including the formation of exons within introns in proximity to Alu elements. In addition, 82% of gene fusions were associated with structural variants, including 75 of a new class, termed 'bridged' fusions, in which a third genomic location bridges two genes. We observed transcriptomic alteration signatures that differ between cancer types and have associations with variations in DNA mutational signatures. This compendium of RNA alterations in the genomic context provides a rich resource for identifying genes and mechanisms that are functionally implicated in cancer.

Mechanism of gambogic acid repressing invasion and metastasis of colorectal cancer by regulating macrophage polarization via tumor cell-derived extracellular vesicle-shuttled miR-21.

Colorectal cancer (CRC) is a major cause of mortality and morbidity. Gambogic acid (GA) is a promising antitumor drug for treating CRC. We aimed to elucidate its mechanism in CRC invasion/metastasis via tumor cell-derived extracellular vesicle (EV)-carried miR-21. Nude mice peritoneal carcinomatosis (PC) model was subjected to GA treatment liver collection, followed by observation/counting of metastatic liver tissues/liver metastatic nodules by hematoxylin and eosin staining. miR-21 expression in metastatic liver tissues/CD68 + CD86, CD68 + CD206 cell percentages and M2 macrophage marker CD206 level in tumor tissues/interleukin (IL)-12 and IL-10 levels were determined by reverse transcription-quantitative polymerase chain reaction (RT-qPCR)/flow cytometry/enzyme-linked immunosorbent assay. HT-29 cells were treated with GA/miR-21 mimics/negative control for 48 h. miR-21 expression/cell proliferation/migration/invasion/apoptosis were assessed by RT-qPCR/cell counting kit-8/scratch assay/transwell assay/flow cytometry. EVs were extracted from HT-29 cells and identified by transmission electron microscope/nanoparticle tracking analysis/Western blot. IL-4/IL-13-induced macrophages/PC nude mice were treated with GA and EVs, with the internalization of EVs by macrophages assessed through the uptake test. After intraperitoneal injection of GA, PC nude mice exhibited decreased tumor cell density/irregular cell number/liver metastatic nodule number/miR-21 expression, and CRC cells manifested reduced CD68 + CD206 cells/IL-10/miR-21/proliferation/migration/invasion and increased CD68 + CD86 cells/IL-12/apoptosis, while these trends were opposite after miR-21 overexpression, implying that GA curbed CRC/cell invasion/metastasis and macrophage polarization by diminishing miR-21 levels. miR-21 was encapsulated in HT-29 cell-derived EVs. M2 polarization elevated CD206 cells/IL-10, which were decreased by simultaneous GA treatment. EVs could be uptaken by macrophages. CRC cell-EV-miR-21 annulled the suppression effects of GA on macrophage M2 polarization. GA suppressed macrophage M2 polarization by lessening tumor cell derived-EV-shuttled miR-21, thereby weakening CRC invasion/metastasis.

Is Pathologic Complete Response a Good Predictor for the Long-Term, Clinical Outcome in Patients with Gastric Cancer After Neoadjuvant Chemotherapy? A Retrospective, Multi-institution Study in China.

BACKGROUND: Many studies have used pathologic complete response (pCR) after neoadjuvant chemotherapy (NAC) as the primary endpoint for the short-term efficacy in gastric cancer, but whether it is a good indicator for overall survival is poorly understood. METHODS: This study reviewed a multi-institution database of patients who underwent radical gastrectomy and achieved pCR after NAC. Cox regression models were used to identify clinicopathologic predictors of overall survival (OS) and disease-free survival (DFS). Survival curves were calculated by using the Kaplan-Meier method and compared by means of the log-rank test. RESULTS: OS and DFS in patients with pCR were significantly higher than in those with non-pCR (both P < 0.001). Multivariable analysis confirmed pCR was an independent prognostic factor for OS and DFS (P = 0.009 and P = 0.002 for OS and DFS, respectively). However, the survival benefit for pCR was present only for ypN0 tumors (P = 0.004 and P = 0.001 for OS and DFS, respectively), and OS (P = 0.292) and DFS (P = 0.285) among patients with ypN+ gastric cancer could not be stratified by pCR. CONCLUSIONS: In our study, pCR is an independent prognostic factor for OS and DFS, but the survival benefit for pCR is present only for ypN0 tumors but not ypN+ tumors.

Hybrid source translation scanning mode for interior tomography.

Interior tomography is a promising technique that can be used to image large objects with high acquisition efficiency. However, it suffers from truncation artifacts and attenuation value bias due to the contribution from the parts of the object outside the ROI, which compromises its ability of quantitative evaluation in material or biological studies. In this paper, we present a hybrid source translation scanning mode for interior tomography, called hySTCT-where the projections inside the ROI and outside the ROI are finely sampled and coarsely sampled respectively to mitigate truncation artifacts and value bias within the ROI. Inspired by our previous work-virtual projection-based filtered backprojection (V-FBP) algorithm, we develop two reconstruction methods-interpolation V-FBP (iV-FBP) and two-step V-FBP (tV-FBP)-based on the linearity property of the inverse Radon transform for hySTCT reconstruction. The experiments demonstrate that the proposed strategy can effectively suppress truncated artifacts and improve the reconstruction accuracy within the ROI.

Does resection after neoadjuvant chemotherapy of docetaxel, oxaliplatin, and S-1 (DOS regimen) benefit for gastric cancer patients with single non-curable factor? a multicenter, prospective cohort study (Neo-REGATTA).

BACKGROUND: The Neo-REGATTA study evaluated the effectiveness and safety of Docetaxel, oxaliplatin, and S-1 (DOS regimen) followed by radical resection vs. chemotherapy in advanced gastric adenocarcinoma patients with single non-curable factor. METHODS: This cohort study prospectively enrolled advanced gastric adenocarcinoma patients with single non-curable factor between November 2017 and June 2021. Patients without progression after four cycles of DOS were divided into resection group and chemotherapy group. The outcomes included overall survival (OS), progression-free survival (PFS) and safety. Effectiveness analysis was also performed by propensity score matching (PSM). RESULTS: A total of 73 patients were enrolled and 13 patients were withdrawn due to disease progression after 4 cycles of DOS. Afterwards, 35 and 25 participants were in the resection and chemotherapy groups, respectively. After a median follow-up time of 30.0 months, the median PFS and OS were 9.0 months, and 18.0 months for the chemotherapy group, but not reached in the resection group. After PSM, 19 matched participants were in each group, and the median PFS and OS were longer in resection group than that in chemotherapy group. The most common grade 3 or 4 adverse events both in the resection group and chemotherapy groups were neutropenia (5.7%, 8.0%) and leukopenia (5.7%, 8.0%). CONCLUSIONS: Radical resection might provide survival benefit compared with continuous chemotherapy alone in advanced gastric adenocarcinoma patients who had a disease control after DOS, with a good safety profile. TRIAL REGISTRATION: The study protocol was registered on ClinicalTrial.gov (NCT03001726, 23/12/2016).

Palladium/Norbornene Cooperative-Catalyzed Cascade Decarboxylative Cyclization of 4-Iodoisoquinolin-1(2H)-ones with o-Bromobenzoic Acids: Access to Diverse Fused Phenanthridinones and Hepta[1,2-c]isoquinolinones.

A novel three-component Pd/norbornene cooperative catalysis cascade decarboxylative [2+2+2]/[2+2+3]cyclization of 4-iodoisoquinolin-1(2H)-ones and o-bromobenzoic acids or 8-bromo-1-naphthoic acid has been developed. The method affords a range of fused phenanthridinones and hepta[1,2-c]isoquinolinones and displays unique regioselectivity and broad substrate scope. Palladium/norbornene (Pd/NBE)-catalyzed C-H activation and subsequent decarboxylative coupling reactions were involved, and NBE acts as a building block for the construction of rigid nonplanar molecular architectures.

Visible light-induced radical cascade acylmethylation/cyclization of 2-(allyloxy)arylaldehydes with α-bromo ketones: access to cyclic 1,5-dicarbonyl-containing chroman-4-one skeletons.

A novel photocatalytic protocol for effective and efficient synthesis of cyclic 1,5-diketones containing chroman-4-one skeletons in moderate to good yields via radical cascade acylmethylation/cyclization of 2-(allyloxy)arylaldehydes with α-bromo ketones has been described. This reaction features a broad substrate scope, good functional group tolerance, and metal- and oxidant-free conditions. An acylmethyl radical-triggered cascade cyclization was involved.

GEPIA2021: integrating multiple deconvolution-based analysis into GEPIA.

In 2017, we released GEPIA (Gene Expression Profiling Interactive Analysis) webserver to facilitate the widely used analyses based on the bulk gene expression datasets in the TCGA and the GTEx projects, providing the biologists and clinicians with a handy tool to perform comprehensive and complex data mining tasks. Recently, the deconvolution tools have led to revolutionary trends to resolve bulk RNA datasets at cell type-level resolution, interrogating the characteristics of different cell types in cancer and controlled cohorts became an important strategy to investigate the biological questions. Thus, we present GEPIA2021, a standalone extension of GEPIA, allowing users to perform multiple interactive analysis based on the deconvolution results, including cell type-level proportion comparison, correlation analysis, differential expression, and survival analysis. With GEPIA2021, experimental biologists could easily explore the large TCGA and GTEx datasets and validate their hypotheses in an enhanced resolution. GEPIA2021 is publicly accessible at http://gepia2021.cancer-pku.cn/.

Epidemiology and Association Rules Analysis for Pulmonary Tuberculosis Cases with Extrapulmonary Tuberculosis from Age and Gender Perspective: A Large-Scale Retrospective Multicenter Observational Study in China.

Background: Tuberculosis (TB), a multisystemic disease with protean presentation, remains a major global health problem. Although concurrent pulmonary tuberculosis (PTB) and extrapulmonary tuberculosis (EPTB) cases are commonly observed clinically, knowledge regarding concurrent PTB-EPTB is limited. Here, a large-scale multicenter observational study conducted in China aimed to study the epidemiology of concurrent PTB-EPTB cases by diagnostically defining TB types and then implementing association rules analysis. Methods: The retrospective study was conducted at 21 hospitals in 15 provinces in China and included all inpatients with confirmed TB diagnoses admitted from Jan 2011 to Dec 2017. Association rules analysis was conducted for cases with concurrent PTB and various types of EPTB using the Apriori algorithm. Results: Evaluation of 438,979TB inpatients indicated PTB was the most commonly diagnosed (82.05%) followed by tuberculous pleurisy (23.62%). Concurrent PTB-EPTB was found in 129,422 cases (29.48%) of which tuberculous pleurisy was the most common concurrent EPTB type observed. The multivariable logistic regression models demonstrated that odds ratios of concurrent PTB-EPTB cases varied by gender and age group. For PTB cases with concurrent EPTB, the strongest association was found between PTB and concurrent bronchial tuberculosis (lift = 1.09). For EPTB cases with concurrent PTB, the strongest association was found between pharyngeal/laryngeal tuberculosis and concurrent PTB (lift = 1.11). Confidence and lift values of concurrent PTB-EPTB cases varied with gender and age. Conclusions: Numerous concurrent PTB-EPTB case types were observed, with confidence and lift values varying with gender and age. Clinicians should screen for concurrent PTB-EPTB in order to improve treatment outcomes.

A Heart Image Segmentation Method Based on Position Attention Mechanism and Inverted Pyramid.

In the realm of modern medicine, medical imaging stands as an irreplaceable pillar for accurate diagnostics. The significance of precise segmentation in medical images cannot be overstated, especially considering the variability introduced by different practitioners. With the escalating volume of medical imaging data, the demand for automated and efficient segmentation methods has become imperative. This study introduces an innovative approach to heart image segmentation, embedding a multi-scale feature and attention mechanism within an inverted pyramid framework. Recognizing the intricacies of extracting contextual information from low-resolution medical images, our method adopts an inverted pyramid architecture. Through training with multi-scale images and integrating prediction outcomes, we enhance the network's contextual understanding. Acknowledging the consistent patterns in the relative positions of organs, we introduce an attention module enriched with positional encoding information. This module empowers the network to capture essential positional cues, thereby elevating segmentation accuracy. Our research resides at the intersection of medical imaging and sensor technology, emphasizing the foundational role of sensors in medical image analysis. The integration of sensor-generated data showcases the symbiotic relationship between sensor technology and advanced machine learning techniques. Evaluation on two heart datasets substantiates the superior performance of our approach. Metrics such as the Dice coefficient, Jaccard coefficient, recall, and F-measure demonstrate the method's efficacy compared to state-of-the-art techniques. In conclusion, our proposed heart image segmentation method addresses the challenges posed by diverse medical images, offering a promising solution for efficiently processing 2D/3D sensor data in contemporary medical imaging.

A Salient Object Detection Method Based on Boundary Enhancement.

Visual saliency refers to the human's ability to quickly focus on important parts of their visual field, which is a crucial aspect of image processing, particularly in fields like medical imaging and robotics. Understanding and simulating this mechanism is crucial for solving complex visual problems. In this paper, we propose a salient object detection method based on boundary enhancement, which is applicable to both 2D and 3D sensors data. To address the problem of large-scale variation of salient objects, our method introduces a multi-level feature aggregation module that enhances the expressive ability of fixed-resolution features by utilizing adjacent features to complement each other. Additionally, we propose a multi-scale information extraction module to capture local contextual information at different scales for back-propagated level-by-level features, which allows for better measurement of the composition of the feature map after back-fusion. To tackle the low confidence issue of boundary pixels, we also introduce a boundary extraction module to extract the boundary information of salient regions. This information is then fused with salient target information to further refine the saliency prediction results. During the training process, our method uses a mixed loss function to constrain the model training from two levels: pixels and images. The experimental results demonstrate that our salient target detection method based on boundary enhancement shows good detection effects on targets of different scales, multi-targets, linear targets, and targets in complex scenes. We compare our method with the best method in four conventional datasets and achieve an average improvement of 6.2% on the mean absolute error (MAE) indicators. Overall, our approach shows promise for improving the accuracy and efficiency of salient object detection in a variety of settings, including those involving 2D/3D semantic analysis and reconstruction/inpainting of image/video/point cloud data.

[Discussion on the Authenticity Verification Method in the Verification of Medical Device Registration Quality Management System].

Authenticity verification is a very important aspect of medical device registration quality management system verification of medical device. How to verify the authenticity of samples is a problem worth discussing. This study analyzes the methods of authenticity verification from the aspects of product retention sample, registration inspection report, traceability of records, hardware facilities and equipment. In order to provide reference for relevant supervisors and inspectors in the verification of registration quality management system.

Multi source translation based projection completion for interior region of interest tomography with CBCT.

Interior tomography by rotary computed tomography (RCT) is an effective method to improve the detection efficiency and achieve high-resolution imaging for the region of interest (ROI) within a large-scale object. However, because only the X-rays through the ROI can be received by detector, the projection data is inevitably truncated, resulting in truncation artifacts in the reconstructed image. When the ROI is totally within the object, the solution of the problem is not unique, which is named interior problem. Fortunately, projection completion (PC) is an effective technique to solve the interior problem. In this study, we proposed a multi source translation CT based PC method (mSTCT-PC) to cope with the interior problem. Firstly, mSTCT-PC employs multi-source translation to sparsely obtain the global projection which covered the whole object. Secondly, the sparse global projection is utilized to fill up the truncated projection of ROI. The global projection and truncated projection are obtained under the same geometric parameters. Therefore, it omits the registration of projection. To verify the feasibility of this method, simulation and practical experiments were implemented. Compared with the results of ROI reconstructed by filtered back-projection (FBP), simultaneous iterative reconstruction technique-total variation (SIRT-TV) and the multi-resolution based method (mR-PC), the proposed mSTCT-PC is good at mitigating truncation artifacts, preserving details and improving the accuracy of ROI images.

Tumor-derived LIF promotes chemoresistance via activating tumor-associated macrophages in gastric cancers.

Chemotherapy is the preferred clinical treatment for advanced stage gastric cancer (GC) patients, of which efficacy could be markedly impaired due to the development of chemoresistance. Alternatively activated or M2-type tumor associated macrophages (TAMs) are recruited under chemotherapy and are highly implicated in the chemoresistance development, but underlying molecular mechanism for TAM activation is largely unknown. Here, we present that tumor-derived Leukemia inhibitory factor (LIF) induced by chemo drugs represses the chemo sensitivity of gastric tumor cells in a TAM-dependent manner. Mechanistically, cisplatin-induced HIF1α signaling activation directly drive the transcription of LIF, which promotes the resistance of gastric tumors to chemo drug. Further study revealed that tumor cell-derived LIF stimulates macrophages into tumor-supporting M2-type phenotype via activating STAT3 signaling pathway. Therapeutically, blocking LIF efficiently elevates chemo sensitivity of tumor cells and further represses the growth rates of tumors under chemotherapy. Therefore, our study reveals a novel insight in understanding the cross talking between tumor cells and immune cells and provides new therapeutic targets for gastric cancer.

Perioperative Safety Evaluation of Gastrointestinal Surgery in Patients With Prosthetic Valves.

BACKGROUND: In patients with prosthetic valves, the perioperative outcomes, as well as the risk factors, following gastrointestinal surgery remain to be defined.  Methods: From January 2010 to March 2018, the clinical data of 69 cases with prosthetic valves after gastrointestinal surgery retrospectively were collected. Univariate and multivariate analysis were applied to identify the risk factors associated with significant bleeding events and non-hemorrhagic complications. RESULTS: Among 69 cases, 9 patients (13.0%) presented major bleeding events, and 21 patients (30.4%) presented non-hemorrhagic complications. Major bleeding events were significantly higher in patients with simple aortic valve replacement (AVR) than in other types of prosthetic valves (27.6% vs. 2.5%, P = 0.003), and there was no significant difference in the incidence of non-hemorrhagic complications. Simple AVR was the significant risk factor for major bleeding events (P = 0.043). Significant risk factors for non-hemorrhagic complications were operative duration ≥ 160 minutes (P = 0.021), duration from heart valve replacement to gastrointestinal surgery ≥ 84 months (P = 0.039), and simple AVR (P = 0.047). CONCLUSION: The patients with simple AVR had a much higher bleeding risk following gastrointestinal surgery.

Antifreeze Proteins: Novel Applications and Navigation towards Their Clinical Application in Cryobanking.

Antifreeze proteins (AFPs) or thermal hysteresis (TH) proteins are biomolecular gifts of nature to sustain life in extremely cold environments. This family of peptides, glycopeptides and proteins produced by diverse organisms including bacteria, yeast, insects and fish act by non-colligatively depressing the freezing temperature of the water below its melting point in a process termed thermal hysteresis which is then responsible for ice crystal equilibrium and inhibition of ice recrystallisation; the major cause of cell dehydration, membrane rupture and subsequent cryodamage. Scientists on the other hand have been exploring various substances as cryoprotectants. Some of the cryoprotectants in use include trehalose, dimethyl sulfoxide (DMSO), ethylene glycol (EG), sucrose, propylene glycol (PG) and glycerol but their extensive application is limited mostly by toxicity, thus fueling the quest for better cryoprotectants. Hence, extracting or synthesizing antifreeze protein and testing their cryoprotective activity has become a popular topic among researchers. Research concerning AFPs encompasses lots of effort ranging from understanding their sources and mechanism of action, extraction and purification/synthesis to structural elucidation with the aim of achieving better outcomes in cryopreservation. This review explores the potential clinical application of AFPs in the cryopreservation of different cells, tissues and organs. Here, we discuss novel approaches, identify research gaps and propose future research directions in the application of AFPs based on recent studies with the aim of achieving successful clinical and commercial use of AFPs in the future.

[A multicenter retrospective study on the efficacy of different anti-reflux reconstruction methods after proximal gastrectomy for gastric cancer].

Objective: To examine the clinical efficacy of 3 anti-reflux methods of digestive tract reconstruction after proximal gastrectomy for gastric cancer. Methods: The clinical data and follow-up data of gastric cancer patients who underwent anti-reflux reconstruction after proximal gastrectomy in 11 medical centers of China from September 2016 to August 2021 were retrospectively collected, including 273 males and 65 females, aging of (63±10) years (range: 28 to 91 years). Among them, 159 cases were performed with gastric tube anastomosis (GTA), 107 cases with double tract reconstruction (DTR), and 72 cases with double-flap technique (DFT), respectively. The duration of operation, length of postoperative hospital stay and early postoperative complications (referring to Clavien-Dindo classification) of different anti-reflux reconstruction methods were assessed. Body mass index, hemoglobin and albumin were used to reflect postoperative nutritional status. Reflux esophagitis was graded according to Los Angeles criteria based on the routinely gastroscopy within 12 months after surgery. The postoperative quality of life (QoL) was evaluated by Visick score system. The ANOVA analysis, Kruskal-Wallis rank sum test, χ2 test and Fisher's exact test were used for comparison between multiple groups, and further comparison among groups were performed with LSD, Tamhane's test or Bonferroni corrected χ2 test. The mixed effect model was used to compare the trends of Body mass index, hemoglobin and albumin over time among different groups. Results: The operation time of DFT was significantly longer than that of GTA and DTR ((352±63) minutes vs. (221±66) minutes, (352±63) minutes vs. (234±61) minutes, both P<0.01). The incidence of early complications with Clavien-Dindo grade Ⅱ to Ⅴ in GTA, DFT and DTR groups was 17.0% (27/159), 9.7% (7/72) and 10.3% (11/107), respectively, without significant difference among these three groups (χ2=3.51, P=0.173). Body mass index decreased more significantly in GTA than DFT group at 6 and 12 months after surgery (mean difference=1.721 kg/m2, P<0.01; mean difference=2.429 kg/m2, P<0.01). body mass index decreased significantly in DTR compared with DFT at 12 months after surgery (mean difference=1.319 kg/m2, P=0.027). There was no significant difference in hemoglobin or albumin fluctuation between different reconstruction methods perioperative. The incidence of reflux esophagitis one year after surgery in DTR group was 12.9% (4/31), which was lower than that in DFT (45.9% (17/37), χ2=8.63, P=0.003). Follow-up of postoperative quality of life showed the incidence of Visick grade 2 to 4 in DFT group was lower than that in GTA group (10.4% (7/67) vs. 34.6% (27/78), χ2=11.70, P=0.018), while there was no significant difference between DFT and DTR group (10.4% (7/67) vs. 22.2% (8/36, P>0.05). Conclusions: Compared with GTA and DTR, DFT is more time-consuming, but there is no significant difference in early complications among three methods. DFT reconstruction is more conducive to maintain postoperative nutritional status and improve QoL, especially compared with GTA. The risk of reflux esophagitis after DTR reconstruction is lower than that of DFT.

Tertiary lymphoid structure patterns predicted anti-PD1 therapeutic responses in gastric cancer.

Objective: Recent studies have highlighted the distinct value of tertiary lymphoid structure (TLS) for immunotherapeutic response prediction. However, it remains unclear whether TLS could play such roles in gastric cancer (GC). Methods: In this study, tumor tissue slices from 292 GC patients from Zhongshan Hospital were firstly reviewed to explore the correlation between TLS and clinical characteristics. Subsequently, we curated 38 reported genes that may function as triggers of TLS and performed consensus molecular subtyping in public RNA-seq datasets to determine TLS patterns in GC. Based on the differentially expressed genes acquired from two TLS patterns, we quantified TLS-related genes on the principal component analysis (PCA) algorithm to develop TLS score. A Zhongshan immunotherapy cohort including 13 patients who received programmed cell death 1 (PD1) blockade therapy was established to conduct RNA sequencing analysis and multiplex immunohistochemistry (mIHC) tests using formalin-fixed and paraffin-embedded (FFPE) tissues. The corresponding TLS score and immune cell counts were further compared based on therapeutic response variations. Results: Mature TLS was revealed as an independent prognostic factor in 292 GC patients. Patients with higher TLS score was characterized by prolonged survival time and superior response to immunotherapy. TLS score was correlated with immunotherapy-related characters, such as microsatellite instability (MSI) and tumor mutation burden (TMB). In addition, RNA-seq data analysis in the Zhongshan immunotherapy cohort indicated that a higher TLS score was correlated with a superior response to PD1 blockade therapy. mIHC tests also revealed that PD1+CD8+ T cell counts were significantly increased in the high-TLS score group. Conclusions: This study highlighted that TLS was significantly associated with immune landscape diversity and complexity. Quantitatively evaluating TLS patterns of individual tumor will strengthen our understanding of TME characteristics and promote more effective immunotherapy strategies.

X-ray source translation based computed tomography (STCT).

Micro computed tomography (µCT) allows the noninvasive visualization and 3D reconstruction of internal structures of objects with high resolution. However, the current commercial µCT system relatively rotates the source-detector or objects to collect projections, referred as RCT in this paper, and has difficulties in imaging large objects with high resolutions because fabrication of large-area, inexpensive flat-panel detectors remains a challenge. In this paper, we proposed a source translation based CT (STCT) for imaging large objects with high resolution to get rid of the limitation of the detector size, where the field of view is primarily determined by the source translation distance. To compensate for the deficiency of incomplete data in STCT, we introduced multi-scanning STCT (mSTCT), from which the projections theoretically meet the conditions required for accurate reconstructions. Theoretical and numerical studies showed that mSTCT has the ability to accurately image large objects without any visible artifacts. Numerical simulations also indicated that mSTCT has a potential capability to precisely image the region of interest (ROI) inside objects, which remains a challenge in RCT due to truncated projections. In addition, an experimental platform for mSTCT has been established, from which the 2D and 3D reconstructed results demonstrated its feasibility for µCT applications. Moreover, STCT also has a great potential for security inspection and product screening by using two perpendicular STCTs, with advantages of low-cost equipment and high-speed examination.