Neoadjuvant camrelizumab plus apatinib for locally advanced microsatellite instability-high or mismatch repair-deficient colorectal cancer (NEOCAP): a single-arm, open-label, phase 2 study.

BACKGROUND: PD-1 blockade is highly efficacious for mismatch repair-deficient colorectal cancer in both metastatic and neoadjuvant settings. We aimed to explore the activity and safety of neoadjuvant therapy with PD-1 blockade plus an angiogenesis inhibitor and the feasibility of organ preservation in patients with locally advanced mismatch repair-deficient colorectal cancer. METHODS: We initiated a single-arm, open-label, phase 2 trial (NEOCAP) at Sun Yat-sen University Cancer Center and the Provincial Hospital of Traditional Chinese Medicine, Guangzhou, China. Patients aged 18-75 years with untreated mismatch repair-deficient or microsatellite instability-high or POLE/POLD1-mutated locally advanced colorectal cancer (cT3 or N+ for rectal cancer, and T3 with invasion ≥5mm or T4, with or without N+ for colon cancer) and an Eastern Cooperative Oncology Group performance score of 0-1 were enrolled and given 200 mg camrelizumab intravenously on day 1 and 250 mg apatinib orally from day 1-14, every 3 weeks for 3 months followed by surgery or 6 months if patients did not have surgery. Patients who had a clinical complete response did not undergo surgery and proceeded with a watch-and-wait approach. The primary endpoint was the proportion of patients with a pathological or clinical complete response. Eligible enrolled patients who received at least one cycle of neoadjuvant treatment and had at least one tumour response assessment following the baseline assessment were included in the activity analysis, and patients who received at least one dose of study drug were included in the safety analysis. The study is registered with ClinicalTrials.gov (NCT04715633) and is ongoing. FINDINGS: Between Sept 29, 2020, and Dec 15, 2022, 53 patients were enrolled; one patient was excluded from the activity analysis because they were found to be mismatch repair-proficient and microsatellite-stable. 23 (44%) patients were female and 29 (56%) were male. The median follow-up was 16·4 (IQR 10·5-23·5) months. 28 (54%; 95% CI 35-68) patients had a clinical complete response and 24 of these patients were managed with a watch-and-wait approach, including 20 patients with colon cancer and multiple primary colorectal cancer. 23 (44%) of 52 patients underwent surgery for the primary tumour, and 14 (61%; 95% CI 39-80) had a pathological complete response. 38 (73%; 95% CI 59-84) of 52 patients had a complete response. Grade 3-5 adverse events occurred in 20 (38%) of 53 patients; the most common were increased aminotransferase (six [11%]), bowel obstruction (four [8%]), and hypertension (four [8%]). Drug-related serious adverse events occurred in six (11%) of 53 patients. One patient died from treatment-related immune-related hepatitis. INTERPRETATION: Neoadjuvant camrelizumab plus apatinib show promising antitumour activity in patients with locally advanced mismatch repair-deficient or microsatellite instability-high colorectal cancer. Immune-related adverse events should be monitored with the utmost vigilance. Organ preservation seems promising not only in patients with rectal cancer, but also in those with colon cancer who have a clinical complete response. Longer follow-up is needed to assess the oncological outcomes of the watch-and-wait approach. FUNDING: The National Natural Science Foundation of China, Guangdong Basic and Applied Basic Research Foundation, and the Cancer Innovative Research Program of Sun Yat-sen University Cancer Center. TRANSLATION: For the Chinese translation of the abstract see Supplementary Materials section.

A new chromosome-scale genome of wild Brassica oleracea provides insights into the domestication of Brassica crops.

The cultivated diploid Brassica oleracea is an important vegetable crop, but the genetic basis of its domestication remains largely unclear in the absence of high-quality reference genomes of wild B. oleracea. Here, we report the first chromosome-level assembly of the wild Brassica oleracea L. W03 genome (total genome size, 630.7 Mb; scaffold N50, 64.6 Mb). Using the newly assembled W03 genome, we constructed a gene-based B. oleracea pangenome and identified 29 744 core genes, 23 306 dispensable genes, and 1896 private genes. We re-sequenced 53 accessions, representing six potential wild B. oleracea progenitor species. The results of the population genomic analysis showed that the wild B. oleracea populations had the highest level of diversity and represents the most closely related population to modern-day horticultural B. oleracea. In addition, the WUSCHEL gene was found to play a decisive role in domestication and to be involved in cauliflower and broccoli curd formation. We also illustrate the loss of disease-resistance genes during selection for domestication. Our results provide new insights into the domestication of B. oleracea and will facilitate the future genetic improvement of Brassica crops.

Research Progress on the Effect of Nitrogen on Rapeseed between Seed Yield and Oil Content and Its Regulation Mechanism.

Rapeseed (Brassica napus L.) is one of the most important oil crops in China. Improving the oil production of rapeseed is an important way to ensure the safety of edible oil in China. Oil production is an important index that reflects the quality of rapeseed and is determined by the oil content and yield. Applying nitrogen is an important way to ensure a strong and stable yield. However, the seed oil content has been shown to be reduced in most rapeseed varieties after nitrogen application. Thus, it is critical to screen elite germplasm resources with stable or improved oil content under high levels of nitrogen, and to investigate the molecular mechanisms of the regulation by nitrogen of oil accumulation. However, few studies on these aspects have been published. In this review, we analyze the effect of nitrogen on the growth and development of rapeseed, including photosynthetic assimilation, substance distribution, and the synthesis of lipids and proteins. In this process, the expression levels of genes related to nitrogen absorption, assimilation, and transport changed after nitrogen application, which enhanced the ability of carbon and nitrogen assimilation and increased biomass, thus leading to a higher yield. After a crop enters the reproductive growth phase, photosynthates in the body are transported to the developing seed for protein and lipid synthesis. However, protein synthesis precedes lipid synthesis, and a large number of photosynthates are consumed during protein synthesis, which weakens lipid synthesis. Moreover, we suggest several research directions, especially for exploring genes involved in lipid and protein accumulation under nitrogen regulation. In this study, we summarize the effects of nitrogen at both the physiological and molecular levels, aiming to reveal the mechanisms of nitrogen regulation in oil accumulation and, thereby, provide a theoretical basis for breeding varieties with a high oil content.

Research Progress in High-Efficiency Utilization of Nitrogen in Rapeseed.

Nitrogen (N) is one of the most important mineral elements for plant growth and development and a key factor for improving crop yield. Rapeseed, Brassica napus, is the largest oil crop in China, producing more than 50% of the domestic vegetable oil. However, high N fertilizer input with low utilization efficiency not only increases the production cost but also causes serious environmental pollution. Therefore, the breeding of rapeseed with high N efficiency is of great strategic significance to ensure the security of grain and oil and the sustainable development of the rapeseed industry. In order to provide reference for genetic improvement of rapeseed N-efficient utilization, in this article, we mainly reviewed the recent research progress of rapeseed N efficiency, including rapeseed N efficiency evaluation, N-efficient germplasm screening, and N-efficient physiological and molecular genetic mechanisms.

Genome-Wide Identification and Functional Characterization of Stress Related Glyoxalase Genes in Brassica napus L.

Rapeseed (Brassica napus L.) is not only one of the most important oil crops in the world, but it is also an important vegetable crop with a high value nutrients and metabolites. However, rapeseed is often severely damaged by adverse stresses, such as low temperature, pathogen infection and so on. Glyoxalase I (GLYI) and glyoxalase II (GLYII) are two enzymes responsible for the detoxification of a cytotoxic metabolite methylglyoxal (MG) into the nontoxic S-D-lactoylglutathione, which plays crucial roles in stress tolerance in plants. Considering the important roles of glyoxalases, the GLY gene families have been analyzed in higher plans, such as rice, soybean and Chinese cabbage; however, little is known about the presence, distribution, localizations and expression of glyoxalase genes in rapeseed, a young allotetraploid. In this study, a total of 35 BnaGLYI and 30 BnaGLYII genes were identified in the B. napus genome and were clustered into six and eight subfamilies, respectively. The classification, chromosomal distribution, gene structure and conserved motif were identified or predicted. BnaGLYI and BnaGLYII proteins were mainly localized in chloroplast and cytoplasm. By using publicly available RNA-seq data and a quantitative real-time PCR analysis (qRT-PCR), the expression profiling of these genes of different tissues was demonstrated in different developmental stages as well as under stresses. The results indicated that their expression profiles varied among different tissues. Some members are highly expressed in specific tissues, BnaGLYI11 and BnaGLYI27 expressed in flowers and germinating seed. At the same time, the two genes were significantly up-regulated under heat, cold and freezing stresses. Notably, a number of BnaGLY genes showed responses to Plasmodiophora brassicae infection. Overexpression of BnGLYI11 gene in Arabidopsis thaliana seedlings confirmed that this gene conferred freezing tolerance. This study provides insight of the BnaGLYI and BnaGLYII gene families in allotetraploid B. napus and their roles in stress resistance, and important information and gene resources for developing stress resistant vegetable and rapeseed oil.

ALKBH5 promotes cadmium-induced transformation of human bronchial epithelial cells by regulating PTEN expression in an m6A-dependent manner.

Cadmium is a carcinogenic heavy metal that poses a severe threat to human beings. The underlying mechanism, however, remains elusive. N6-methyladenosine (m6A) is the most abundant post-transcriptional modification in mRNA that regulates RNA metabolism. Emerging evidence shows that m6A is involved in the pathogenesis of various cancers. In this study, human bronchial epithelial BEAS-2B cells were transformed by exposing to 2 µM of cadmium for 20 weeks to investigate the role of m6A in cadmium carcinogenesis. We found the level of m6A in mRNA was significantly decreased in cadmium-transformed BEAS-2B cells, and this change was regulated by m6A demethylase ALKBH5. ALKBH5 was significantly upregulated in the middle and late stages of cell transformation at week 8, 12, 16 and 20. Knockdown of ALKBH5 in cadmium-transformed cells alleviated cell proliferation, migration, invasion, and anchorage-independent growth, but co-transfection with ALKBH5 siRNA and PTEN siRNA restored the inhibitory effects of ALKBH5 knockdown on those transformation properties. ALKBH5 decreased the m6A level of PTEN mRNA, resulting in its instability and reduction of PTEN protein expression. These results indicate that ALKBH5-mediated demethylation m6A at PTEN mRNA is involved in cadmium-induced cell transformation. Our study provides a new perspective for the involvement of m6A modification in cadmium carcinogenesis.

Circ-SHPRH suppresses cadmium-induced transformation of human bronchial epithelial cells by regulating QKI expression via miR-224-5p.

Circular RNAs (circRNAs) have been demonstrated to play critical roles in the pathogenesis of human cancers and carcinogenesis of several environmental pollutants. Nevertheless, the function of circRNAs in cadmium carcinogenesis is unclear. circ-SHPRH is down-regulated in many cancers including non-small cell lung cancer. In our present study, during cadmium-induced transformation of human bronchial epithelial BEAS-2B cells, epithelial-mesenchymal transition (EMT) was induced. Meanwhile, at the middle and late stages of cell transformation, cadmium down-regulated the expression of circ-SHPRH, as well as QKI, a tumor suppressor protein known to prevent the proliferation and EMT during progression of human cancers, compared with passage-matched control BEAS-2B cells. Overexpression of circ-SHPRH in cadmium-transformed BEAS-2B cells promoted the expression of QKI and significantly inhibited proliferation, EMT, invasion, migration and anchorage-independent growth in soft agar of the cells. Mechanistic studies showed that circ-SHPRH functioned as a sponge of miR-224-5p to regulate QKI expression. Interestingly, QKI and circ-SHPRH could form a positive-feedback loop that perpetuated circ-SHPRH/miR-224-5p/QKI axis. Collectively, our results demonstrated that circ-SHPRH inhibited cadmium-induced transformation of BEAS-2B cells through sponging miR-224-5p to regulate QKI expression under cadmium treatment. Our study uncovered a novel molecular mechanism involved in circRNAs in the development of lung cancer due to cadmium exposure.

Comparison of the cytoplastic genomes by resequencing: insights into the genetic diversity and the phylogeny of the agriculturally important genus Brassica.

BACKGROUND: The genus Brassica mainly comprises three diploid and three recently derived allotetraploid species, most of which are highly important vegetable, oil or ornamental crops cultivated worldwide. Despite being extensively studied, the origination of B. napus and certain detailed interspecific relationships within Brassica genus remains undetermined and somewhere confused. In the current high-throughput sequencing era, a systemic comparative genomic study based on a large population is necessary and would be crucial to resolve these questions. RESULTS: The chloroplast DNA and mitochondrial DNA were synchronously resequenced in a selected set of Brassica materials, which contain 72 accessions and maximally integrated the known Brassica species. The Brassica genomewide cpDNA and mtDNA variations have been identified. Detailed phylogenetic relationships inside and around Brassica genus have been delineated by the cpDNA- and mtDNA- variation derived phylogenies. Different from B. juncea and B. carinata, the natural B. napus contains three major cytoplasmic haplotypes: the cam-type which directly inherited from B. rapa, polima-type which is close to cam-type as a sister, and the mysterious but predominant nap-type. Certain sparse C-genome wild species might have primarily contributed the nap-type cytoplasm and the corresponding C subgenome to B. napus, implied by their con-clustering in both phylogenies. The strictly concurrent inheritance of mtDNA and cpDNA were dramatically disturbed in the B. napus cytoplasmic male sterile lines (e.g., mori and nsa). The genera Raphanus, Sinapis, Eruca, Moricandia show a strong parallel evolutional relationships with Brassica. CONCLUSIONS: The overall variation data and elaborated phylogenetic relationships provide further insights into genetic understanding of Brassica, which can substantially facilitate the development of novel Brassica germplasms.

Surface functionalized red fluorescent dual-metallic Au/Ag nanoclusters for endoplasmic reticulum imaging.

An efficient method is reported to prepare endoplasmic reticulum-targetable dual-metallic gold-silver nanoclusters, denoted as ER-Au/Ag nanoclusters (NCs), by virtue of a rationally designed molecular ligand. The prepared ER-Au/Ag NCs possesses red-emitting fluorescence with a strong emission at 622 nm and a high fluorescence quantum yield of 5.1%, which could avoid the influence of biological auto-fluorescence. Further investigation results showed that ER-Au/Ag NCs exhibited superior photostability, minimal cytotoxicity, and ER-targeting capability. Enabled by these meritorious features, ER-Au/Ag NCs have been successfully employed for long-term bioimaging of ER in living cells.Graphical abstract A sensitive non-enzymatic fluorescent glucose probe-based ZnO nanorod decorated with Au nanoparticles.

Generalized trust predicts young children's willingness to delay gratification.

Young children's willingness to delay gratification by forgoing an immediate reward to obtain a more desirable one in the future predicts a wide range of positive social, cognitive, and health outcomes. Standard accounts of this phenomenon have focused on individual differences in cognitive control skills that allow children to engage in goal-oriented behavior, but recent findings suggest that person-specific trust is also important, with children showing a stronger tendency to delay gratification if they have reason to trust the individual who is promising the future reward. The current research builds on those findings by examining generalized trust, which refers to the extent to which others are generally viewed as trustworthy. A total of 150 3- to 5-year-olds in China were tested. Participants were given the opportunity to obtain one sticker immediately, or wait for 15 min for two stickers. Results showed that participants with high levels of generalized trust waited longer even after controlling for age and level of executive function. These results suggest that trust plays a role in delaying gratification even when children have no information about the individual who is promising the future reward. More broadly, the findings build on recent evidence that there is more to delay of gratification than cognitive capacity, and they suggest that there are individual differences in whether children consider sacrificing for a future outcome to be worth the risk.

[Intracranial involvement in newly diagnosed multiple myeloma with TP53 deletion: Two case reports].

We report two rare cases of multiple myeloma (MM) with dural intracranial disease and TP53 deletion. The two patients presented with skull lytic lesion and dural involvement of myeloma. The association between intracranial involvement in MM and TP53 deletion has not been determined. The two patients received bortezomib-based intensive induction and got good response, just as that reported in literature. MM presenting with dural intracranial disease and TP53 deletion at diagnosis is associated with poor outcome. Multi-drug regime containing bortezomib followed by autologous or allogeneic stem cell transportation would improve the prognosis.

Continuous wound infusion of ropivacaine for the control of pain after thoracolumbar spinal surgery: a randomized clinical trial.

PURPOSE: A prospective randomized clinical trial was carried out to observe the analgesic efficacy of ropivacaine for postoperative pain following thoracolumbar spinal surgery. METHODS: Seventy-one patients with elective posterior thoracolumbar spinal surgery were randomly divided into two groups. Local group received 0.33 % ropivacaine by pump through the wound, and intravenous group received flurbiprofen axetil, pentazocine and palonosetron via intravenous pump. We evaluated the level of pain, the incidence of adverse reactions at 2, 4, 6, 12, 24, 36 and 48 h after operation, and the occurrence of chronic pain 3 months later. RESULTS: There were no significant differences in the pain level between the two groups. However, the incidence of nausea, vomiting and chronic pain was significantly lower in the local group. CONCLUSIONS: Our results showed that local infusion of ropivacaine achieved similar analgesic effects to intravenous delivery of analgesic drugs, but significantly reduced incidence of nausea, vomiting and chronic pain.

Parenthood and the risk of diabetes in men and women: a 7 year prospective study of 0.5 million individuals.

AIMS/HYPOTHESIS: In women, higher parity has been associated with increased risk of diabetes later in life. It is unclear, however, whether this association is mainly due to biological effects of childbearing, or to socioeconomic and lifestyle factors associated with childrearing. We assessed the association between number of children and diabetes risk separately in women and men. METHODS: Between 2004 and 2008, the nationwide China Kadoorie Biobank recruited 0.5 million individuals aged 30-79 (mean 51 years) from ten diverse regions across China. During 7 years of follow-up, 8,840 incident cases of diabetes were recorded among 463,347 participants without prior cardiovascular diseases or diabetes. Multivariable Cox regression yielded sex-specific HRs and 95% CIs for incident diabetes by number of children. RESULTS: Overall, ∼98% of all participants had children. In women, there was a J-shaped association between number of children and risk of diabetes. Compared with women with one child, the adjusted HRs for diabetes were 1.39 (95% CI 1.11, 1.73) for childless women, 1.12 (95% CI 1.07, 1.18) for those with two children, 1.23 (95% CI 1.16, 1.31) for those with three children, and 1.32 (95% CI 1.21, 1.44) for those with four or more children. In men, there was a similar association with risk of diabetes; the corresponding HRs were 1.28 (95% CI 1.02, 1.60), 1.19 (95% CI 1.12, 1.26), 1.32 (95% CI 1.21, 1.44) and 1.41 (95% CI 1.24, 1.60), respectively. In both sexes, the findings were broadly similar in different population subgroups. CONCLUSIONS/INTERPRETATION: The similarity between women and men in the association between number of children and risk of diabetes suggests that parenthood is most likely to affect diabetes risk through factors associated with childrearing rather than via biological effects of childbearing.

Characterization of FAE1 in the zero erucic acid germplasm of Brassica rapa L.

The modification of erucic acid content in seeds is one of the major goals for quality breeding in oil-yielding Brassica species. However, few low erucic acid (LEA) resources are available, and novel LEA genetic resources are being sought. Fatty acid elongase 1 (FAE1) is the key gene that controls erucic acid synthesis. However, the mechanism for erucic acid synthesis in B. rapa lacks systematic study. Here, we isolated zero erucic acid lines from 1981 Chinese landraces of B. rapa and found that the formation of LEA is not attributable to variations in FAE1 coding sequences, as reported for B. napus, but may be attributable to the decrease in FAE1 expression. Moreover, the FAE1 promoter sequences of LEA and high erucic acid materials shared 95% similarity. Twenty-eight bases deletions (containing a 24-base AT-rich region) were identified approximately 1300 bp upstream from the FAE1 start codon in the LEA accessions. The genotype with the deletions co-segregated with the LEA trait in the segregating population. This study isolated an LEA B. rapa resource that can be exploited in Brassica cultivation. The promoter variations might modify the expression level of FAE1, and the results shed light on novel regulation mechanisms for erucic acid synthesis.

Genome-wide investigation of genetic changes during modern breeding of Brassica napus.

KEY MESSAGE: Considerable genome variation had been incorporated within rapeseed breeding programs over past decades. In past decades, there have been substantial changes in phenotypic properties of rapeseed as a result of extensive breeding effort. Uncovering the underlying patterns of allelic variation in the context of genome organisation would provide knowledge to guide future genetic improvement. We assessed genome-wide genetic changes, including population structure, genetic relatedness, the extent of linkage disequilibrium, nucleotide diversity and genetic differentiation based on F ST outlier detection, for a panel of 472 Brassica napus inbred accessions using a 60 k Brassica Infinium® SNP array. We found genetic diversity varied in different sub-groups. Moreover, the genetic diversity increased from 1950 to 1980 and then remained at a similar level in China and Europe. We also found ~6-10 % genomic regions revealed high F ST values. Some QTLs previously associated with important agronomic traits overlapped with these regions. Overall, the B. napus C genome was found to have more high F ST signals than the A genome, and we concluded that the C genome may contribute more valuable alleles to generate elite traits. The results of this study indicate that considerable genome variation had been incorporated within rapeseed breeding programs over past decades. These results also contribute to understanding the impact of rapeseed improvement on available genome variation and the potential for dissecting complex agronomic traits.

Comparison of the heat stress induced variations in DNA methylation between heat-tolerant and heat-sensitive rapeseed seedlings.

DNA methylation is responsive to various biotic and abiotic stresses. Heat stress is a serious threat to crop growth and development worldwide. Heat stress results in an array of morphological, physiological and biochemical changes in plants. The relationship between DNA methylation and heat stress in crops is relatively unknown. We investigated the differences in methylation levels and changes in the cytosine methylation patterns in seedlings of two rapeseed genotypes (heat-sensitive and heat-tolerant) under heat stress. Our results revealed that the methylation levels were different between a heat-tolerant genotype and a heat-sensitive one under control conditions. Under heat treatment, methylation increased more in the heat-sensitive genotype than in the heat-tolerant genotype. More DNA demethylation events occurred in the heat-tolerant genotype, while more DNA methylation occurred in the heat-sensitive genotype. A large and diverse set of genes were affected by heat stress via cytosine methylation changes, suggesting that these genes likely play important roles in the response and adaption to heat stress in Brassica napus L. This study indicated that the changes in DNA methylation differed between heat-tolerant and heat-sensitive genotypes of B. napus in response to heat stress, which further illuminates the molecular mechanisms of the adaption to heat stress in B. napus.

Assessing and broadening genetic diversity of a rapeseed germplasm collection.

Assessing the level of genetic diversity within a germplasm collection contributes to evaluating the potential for its utilization as a gene pool to improve the performance of cultivars. In this study, 45 high-quality simple sequence repeat (SSR) markers were screened and used to estimate the genetic base of a world-wide collection of 248 rapeseed (Brassica napus) inbred lines. For the whole collection, the genetic diversity of A genome was higher than that of C genome. The genetic diversity of C genome for the semi-winter type was the lowest among the different germplasm types. Because B. oleracea is usually used to broaden the genetic diversity of C genome in rapeseed, we evaluated the potential of 25 wild B. oleracea lines. More allelic variations and a higher genetic diversity were observed in B. oleracea than in rapeseed. One B. oleracea line and one oilseed B. rapa line were used to generate a resynthesized Brassica napus line, which was then crossed with six semi-winter rapeseed cultivars to produce 7 F1 hybrids. Not only the allele introgression but also mutations were observed in the hybrids, resulting in significant improvement of the genetic base.

Development and validation of a deep learning signature for predicting lymphovascular invasion and survival outcomes in clinical stage IA lung adenocarcinoma: A multicenter retrospective cohort study.

PURPOSE: The presence of lymphovascular invasion (LVI) influences the management and outcomes of patients with clinical stage IA lung adenocarcinoma. The objective was the development of a deep learning (DL) signature for the prediction of LVI and stratification of prognosis. METHODS: A total of 2077 patients from three centers were retrospectively enrolled and divided into a training set (n = 1515), an internal validation set (n = 381), and an external set (n = 181). A -three-dimensional residual neural network was used to extract the DL signature and three models, namely, the clinical, DL, and combined models, were developed. Diagnostic efficiency was assessed by ROC curves and AUC values. Kaplan-Meier curves and Cox proportional hazards regression analyses were conducted to evaluate links between various factors and disease-free survival. RESULTS: The DL model could effectively predict LVI, shown by AUC values of 0.72 (95 %CI: 0.68-0.76) and 0.63 (0.54-0.73) in the internal and external validation sets, respectively. The incorporation of DL signature and clinical-radiological factors increased the AUC to 0.74 (0.71-0.78) and 0.77 (0.70-0.84) in comparison with the DL and clinical models (AUC of 0.71 [0.68-0.75], 0.71 [0.61-0.81]) in the internal and external validation sets, respectively. Pathologic LVI, LVI predicted by both DL and combined models were associated with unfavorable prognosis (all p < 0.05). CONCLUSION: The effectiveness of the DL signature in the diagnosis of LVI and prognosis prediction in patients with clinical stage IA lung adenocarcinoma was demonstrated. These findings suggest the potential of the model in clinical decision-making.

A CT-based deep learning model: visceral pleural invasion and survival prediction in clinical stage IA lung adenocarcinoma.

Pathologic visceral pleural invasion (VPI) in patients with early-stage lung cancer can result in the upstaging of T1 to T2, in addition to having implications for surgical resection and prognostic outcomes. This study was designed with the goal of establishing and validating a CT-based deep learning (DL) model capable of predicting VPI status and stratifying patients based on their prognostic outcomes. In total, 2077 patients from three centers with pathologically confirmed clinical stage IA lung adenocarcinoma were enrolled. DL signatures were extracted with a 3D residual neural network. DL model was able to effectively predict VPI status. VPI predicted by the DL models, as well as pathologic VPI, was associated with shorter disease-free survival. The established deep learning signature provides a tool capable of aiding the accurate prediction of VPI in patients with clinical stage IA lung adenocarcinoma, thus enabling prognostic stratification.

Ecology and geography of hemorrhagic fever with renal syndrome in Changsha, China.

BACKGROUND: Hemorrhagic fever with renal syndrome (HFRS) is an important public health problem in mainland China. HFRS is particularly endemic in Changsha, the capital city of Hunan Province, with one of the highest incidences in China. The occurrence of HFRS is influenced by environmental factors. However, few studies have examined the relationship between environmental variation (such as land use changes and climate variations), rodents and HFRS occurrence. The purpose of this study is to predict the distribution of HFRS and identify the risk factors and relationship between HFRS occurrence and rodent hosts, combining ecological modeling with the Markov chain Monte Carlo approach. METHODS: Ecological niche models (ENMs) were used to evaluate potential geographic distributions of rodent species by reconstructing details of their ecological niches in ecological dimensions, and projecting the results onto geography. The Genetic Algorithm for Rule-set Production was used to produce ENMs. Data were collected on HFRS cases in Changsha from 2005 to 2009, as well as national land survey data, surveillance data of rodents, meteorological data and normalized difference vegetation index (NDVI). RESULTS: The highest occurrence of HFRS was in districts with strong temperature seasonality, where elevation is below 200 m, mean annual temperature is around 17.5°C, and annual precipitation is below 1600 mm. Cultivated and urban lands in particular are associated with HFRS occurrence. Monthly NDVI values of areas predicted present is lower than areas predicted absent, with high seasonal variation. The number of HFRS cases was correlated with rodent density, and the incidence of HFRS cases in urban and forest areas was mainly associated with the density of Rattus norvegicus and Apodemus agrarius, respectively. CONCLUSIONS: Heterogeneity between different areas shows that HFRS occurrence is affected by the intensity of human activity, climate conditions, and landscape elements. Rodent density and species composition have significant impacts on the number of HFRS cases and their distribution.