Parse and Recall: Towards Accurate Lung Nodule Malignancy Prediction like Radiologists

Lung cancer is a leading cause of death worldwide and early screening is critical for improving survival outcomes. In clinical practice, the contextual structure of nodules and the accumulated experience of radiologists are the two core elements related to the accuracy of identification of benign and malignant nodules. Contextual information provides comprehensive information about nodules such as location, shape, and peripheral vessels, and experienced radiologists can search for clues from previous cases as a reference to enrich the basis of decision-making. In this paper, we propose a radiologist-inspired method to simulate the diagnostic process of radiologists, which is composed of context parsing and prototype recalling modules. The context parsing module first segments the context structure of nodules and then aggregates contextual information for a more comprehensive understanding of the nodule. The prototype recalling module utilizes prototype-based learning to condense previously learned cases as prototypes for comparative analysis, which is updated online in a momentum way during training. Building on the two modules, our method leverages both the intrinsic characteristics of the nodules and the external knowledge accumulated from other nodules to achieve a sound diagnosis. To meet the needs of both low-dose and noncontrast screening, we collect a large-scale dataset of 12,852 and 4,029 nodules from low-dose and noncontrast CTs respectively, each with pathology- or follow-up-confirmed labels. Experiments on several datasets demonstrate that our method achieves advanced screening performance on both low-dose and noncontrast scenarios.Comment: MICCAI 202

Clinicopathological Features and Prognostic Factors of Colorectal Neuroendocrine Neoplasms

Background. Limited research is available regarding colorectal NENs and the prognostic factors remain controversial. Materials and Methods. A total of 68 patients with colorectal NENs were studied retrospectively. Clinical characteristics and prognosis between colonic and rectal NENs were compared. The Cox regression models were used to evaluate the predictive capacity. Results. Of the 68 colorectal NENs patients, 43 (63.2%) had rectal NENs, and 25 (36.8%) had colonic NENs. Compared with rectal NENs, colonic NENs more frequently exhibited larger tumor size (P<0.0001) and distant metastasis (P<0.0001). Colonic NENs had a worse prognosis (P=0.027), with 5-year overall survival rates of 66.7% versus 88.1%. NET, NEC, and MANEC were noted in 61.8%, 23.5%, and 14.7% of patients, respectively. Multivariate analyses revealed that tumor location was not an independent prognostic factor (P=0.081), but tumor size (P=0.037) and pathological classification (P=0.012) were independent prognostic factors. Conclusion. Significant differences exist between colonic and rectal NENs. Multivariate analysis indicated that tumor size and pathological classification were associated with prognosis. Tumor location was not an independent factor. The worse outcome of colonic NENs observed in clinical practice might be due not only to the biological differences, but also to larger tumor size in colonic NENs caused by the delayed diagnosis

Endowing improved osteogenic activities with collagen membrane by incorporating biocompatible iron oxide nanoparticles

Introduction: Collagen-based scaffolds, renowned for their exceptional biocompatibility, have garnered attention as promising scaffolds for advancing bone tissue regeneration. Nevertheless, these scaffolds possess inherent limitations, such as notably compromised osteo-conductivity and osteo-inductivity.Methods: Our study focused on enhancing the mechanical properties and osteogenic bioactivities of bovine-derived collagen membranes (CMs) from the Achilles tendon by incorporating FDA-approved iron oxide nanoparticles (IONPs), termed as IONP-CM. Three types of IONP-CMs (IONP-CM-0.5, IONP-CM-1, and IONPCM-1.5) were constructed by altering the amounts of feeding IONPs.Results: Surface topography analysis demonstrated comparable characteristics between the IONP-CM and neat CM, with the former exhibiting augmented mechanical properties. In vitro evaluations revealed the remarkable biocompatibility of IONP-CMs toward mouse calvarial pre-osteoblast MC3T3-E1 cells, concurrently stimulating osteogenic differentiation. Mechanistic investigations unveiled that the osteogenic differentiation induced by IONP-CMs stemmed from the activation of the Wnt/β-catenin signaling pathway. Furthermore, in vivo bone regeneration assessment was performed by implanting IONP-CMs into the radial defect in rabbits. Results derived from micro-computed tomography and histological analyses unequivocally substantiated the capacity of IONP-CMs to expedite bone repair processes.Discussion: IONP-CMs emerged as scaffolds boasting exceptional biocompatibility and enhanced osteogenic properties, positioning them as promising candidates for facilitating bone tissue regeneration

Repulsive guidance molecule B inhibits metastasis and is associated with decreased mortality in non-small cell lung cancer

Repulsive guidance molecules (RGMs) are co-receptors of bone morphogenetic proteins (BMPs) and programmed death ligand 2 (PD-L2), and might be involved in lung and other cancers. We evaluated repulsive guidance molecule B (RGMB) expression in 165 non-small cell lung cancer (NSCLC) tumors and 22 normal lung tissue samples, and validated the results in an independent series of 131 samples. RGMB was downregulated in NSCLC (P ≤ 0.001), possibly through promoter hypermethylation. Reduced RGMB expression was observed in advanced-stage tumors (P = 0.017) and in tumors with vascular invasion (P < 0.01), and was significantly associated with poor overall survival (39 vs. 62 months, P < 0.001) and with disease-associated patient mortality (P = 0.015). RGMB knockdown promoted cell adhesion, invasion and migration, in both NSCLC cell lines and an in vivo mouse model, which enhanced metastatic potential. Conversely, RGMB overexpression and secretion suppressed cancer progression. The tumor-suppressing effect of RGMB was exerted through inhibition of the Smad1/5/8 pathway. Our results demonstrate that RGMB is an important inhibitor of NSCLC metastasis and that low RGMB expression is a novel predictor or a poor prognosis

5-Fluorouracil targets thymidylate synthase in the selective suppression of TH17 cell differentiation

While it is well established that treatment of cancer patients with 5-Fluorouracil (5-FU) can result in immune suppression, the exact function of 5-FU in the modulation of immune cells has not been fully established. We found that low dose 5-FU selectively suppresses TH17 and TH1 cell differentiation without apparent effect on Treg, TH2, and significantly suppresses thymidylate synthase (TS) expression in TH17 and TH1 cells but has a lesser effect in tumor cells and macrophages. Interestingly, the basal expression of TS varies significantly between T helper phenotypes and knockdown of TS significantly impairs TH17 and TH1 cell differentiation without affecting the differentiation of either Treg or TH2 cells. Finally, low dose 5-FU is effective in ameliorating colitis development by suppressing TH17 and TH1 cell development in a T cell transfer colitis model. Taken together, the results highlight the importance of the anti-inflammatory functions of low dose 5-FU by selectively suppressing TH17 and TH1 immune responses

Efficacy of early prone or lateral positioning in patients with severe COVID-19: a single-center prospective cohort

Abstract Background Position intervention has been shown to improve oxygenation, but its role in non-invasively ventilated patients with severe COVID-19 has not been assessed. The objective of this study was to investigate the efficacy of early position intervention on non-invasively ventilated patients with severe COVID-19. Methods This was a single-center, prospective observational study in consecutive patients with severe COVID-19 managed in a provisional ICU at Renmin Hospital of Wuhan University from 31 January to 15 February 2020. Patients with chest CT showing exudation or consolidation in bilateral peripheral and posterior parts of the lungs were included. Early position intervention (prone or lateral) was commenced for &amp;gt; 4 hours daily for 10 days in these patients, while others received standard care. Results The baseline parameters were comparable between the position intervention group (n = 17) and the standard care group (n = 35). Position intervention was well-tolerated and increased cumulative adjusted mean difference of SpO2/FiO2 (409, 95% CI 86 to 733) and ROX index (26, 95% CI 9 to 43) with decreased Borg scale (−9, 95% CI −15 to −3) during the first 7 days. It also facilitated absorption of lung lesions and reduced the proportion of patients with high National Early Warning Score 2 (≥ 7) on days 7 and 14, with a trend toward faster clinical improvement. Virus shedding and length of hospital stay were comparable between the two groups. Conclusions This study provides the first evidence for improved oxygenation and lung lesion absorption using early position intervention in non-invasively ventilated patients with severe COVID-19, and warrants further randomized trials. </jats:sec

Multiobjective Joint Optimization of Production Scheduling and Maintenance Planning in the Flexible Job-Shop Problem

In order to solve the joint optimization of production scheduling and maintenance planning problem in the flexible job-shop, a multiobjective joint optimization model considering the maximum completion time and maintenance costs per unit time is established based on the concept of flexible job-shop and preventive maintenance. A weighted sum method is adopted to eliminate the index dimension. In addition, a double-coded genetic algorithm is designed according to the problem characteristics. The best result under the circumstances of joint decision-making is obtained through multiple simulation experiments, which proves the validity of the algorithm. We can prove the superiority of joint optimization model by comparing the result of joint decision-making project with the result of independent decision-making project under fixed preventive maintenance period. This study will enrich and expand the theoretical framework and analytical methods of this problem; it provides a scientific decision analysis method for enterprise to make production plan and maintenance plan