IndGOterm: a qualitative method for the identification of individually dysregulated GO terms in cancer.

Individual pathway analysis can dissect heterogeneities among different cancer patients and provide efficient guidelines for individualized therapy. However, the existence of the batch effect brings extensive limitations for the application of many individual methods for pathway analysis. Previously, researchers proposed that methods based on within-sample relative expression ordering (REO) of the genes are notably insensitive to 'batch effects'. In this article, we focus on the Gene Ontology (GO) database and propose an individual qualitative GO term analysis method (IndGOterm) based on the REO of genes. Compared with some current widely used single-sample enrichment analysis methods, such as ssGSEA and GSVA, IndGOterm has a predominance of ignoring the batch effects caused by diverse technologies. Through the survival and drug responses analysis, we found IndGOterm could capture more terms connected to cancer than other single-sample enrichment analysis methods. Furthermore, through the application of IndGOterm, we found some terms that present different dysregulation models that manifest heterogenetic in homologous patients. Collectively, these results attested that IndGOterm could capture useful information from patients and be a useful tool to reveal the intrinsic characteristic of cancer. An open-source R statistical analysis package 'IndGOterm' is available at https://github.com/robert19960424/IndGOterm.

Association between lead and circulating markers of inflammation among traffic enforcers in Metro Manila, Philippines: the MMDA traffic enforcer's health study.

PURPOSE: Several epidemiological studies have linked lead (Pb) exposure to induced oxidative stress and the promotion of inflammatory response. We performed a within-subjects study (repeated measures study) to evaluate the relationship between the concentration of blood lead (B-Pb) and toenail lead (T-Pb) and circulating markers of inflammation. METHODS: We evaluated the associations between B-Pb concentrations and T-Pb concentrations and circulating markers of inflammation, soluble intracellular adhesion molecule-1 (s-ICAM-1), soluble vascular adhesion molecule-1 (s-VCAM-1), and high-sensitivity C-reactive protein (hs-CRP) on 158 traffic enforcers from the Metropolitan Manila Development Authority (MMDA) traffic enforcer's health study. Linear mixed-effects models with random subject-specific intercepts were fitted to estimate the association between B-Pb and T-Pb exposure and circulating markers of inflammation, adjusting for confounding factors. RESULTS: Traffic enforcers were middle-aged men (89.4%) with a mean age (± SD) of 37.1 years ± 8.9 years and had a total of 293 valid markers of inflammation measurements. B-Pb concentration was related to increased hs-CRP levels. A 10% increase in B-Pb was associated with a 5.7% increase in hs-CRP level [95% confidence interval (95% CI): 1.3-10.1]. However, B-Pb was not associated with s-ICAM-1 and s-VCAM-1. Furthermore, no associations were observed between T-Pb and all the circulating markers of inflammation. CONCLUSIONS: Low-level B-Pb may increase hs-CRP among traffic enforcers. Moreover, the study suggests that Pb via the oxidative and inflammation pathways may have an essential role in the development of cardiovascular disease. Furthermore, MMDA and the Department of Labor and Employment can use our study's findings as evidence to conduct routine screening of blood heavy metals, especially Pb, among MMDA and other traffic enforcers as part of their yearly medical examination.

Rapid and Sensitive Detection of Verticillium dahliae from Soil Using LAMP-CRISPR/Cas12a Technology.

Cotton Verticillium wilt is mainly caused by the fungus Verticillium dahliae, which threatens the production of cotton. Its pathogen can survive in the soil for several years in the form of microsclerotia, making it a destructive soil-borne disease. The accurate, sensitive, and rapid detection of V. dahliae from complex soil samples is of great significance for the early warning and management of cotton Verticillium wilt. In this study, we combined the loop-mediated isothermal amplification (LAMP) with CRISPR/Cas12a technology to develop an accurate, sensitive, and rapid detection method for V. dahliae. Initially, LAMP primers and CRISPR RNA (crRNA) were designed based on a specific DNA sequence of V. dahliae, which was validated using several closely related Verticillium spp. The lower detection limit of the LAMP-CRISPR/Cas12a combined with the fluorescent visualization detection system is approximately ~10 fg/µL genomic DNA per reaction. When combined with crude DNA-extraction methods, it is possible to detect as few as two microsclerotia per gram of soil, with the total detection process taking less than 90 min. Furthermore, to improve the method's user and field friendliness, the field detection results were visualized using lateral flow strips (LFS). The LAMP-CRISPR/Cas12a-LFS system has a lower detection limit of ~1 fg/µL genomic DNA of the V. dahliae, and when combined with the field crude DNA-extraction method, it can detect as few as six microsclerotia per gram of soil, with the total detection process taking less than 2 h. In summary, this study expands the application of LAMP-CRISPR/Cas12a nucleic acid detection in V. dahliae and will contribute to the development of field-deployable diagnostic productions.

The Rubber Tree (Heveae brasiliensis) MLO Protein HbMLO12 Promotes Plant Susceptibility to Sustain Infection by a Powdery Mildew Fungus.

Powdery mildew severely affects several important crops and cash plants. Disruption of mildew resistance locus O (MLO) genes elevates resistance against powdery mildew in several plants. However, whether rubber tree (Heveae brasiliensis) MLO proteins are linked to susceptibility remains unknown, owing to technical limitations in the genetic manipulation of this woody plant. A previous study showed that the H. brasiliensis MLO-like protein HbMLO12 demonstrates high amino acid sequence similarity with the known Arabidopsis MLO protein AtMLO12. In this study, we investigated whether HbMLO12 regulates susceptibility to powdery mildew. H. brasiliensis leaves take up exogenously synthesized double-stranded RNAs (dsRNAs), and foliar application of dsRNA homologous to HbMLO12 gene specifically induces HbMLO12 silencing in H. brasiliensis leaf tissues. Notably, HbMLO12 silencing inhibited fungal infection and elevated the immune response during interaction with the rubber tree powdery mildew fungus. Furthermore, the heterologous expression of HbMLO12 suppressed bacterial flg22- and fungal chitin-induced immune responses and enhanced bacterial infection in Arabidopsis. Our study provides evidence that HbMLO12 contributes to susceptibility to powdery mildew. [Formula: see text] Copyright © 2023 The Author(s). This is an open access article distributed under the CC BY-NC-ND 4.0 International license.

Multilevel prioritization of gene regulators associated with consensus molecular subtypes of colorectal cancer.

Consensus molecular subtypes (CMSs) are emerging as critical factor for prognosis and treatment of colorectal cancer. Gene regulators, including chromatin regulator, RNA-binding protein and transcriptional factor, are critical modulators of cancer hallmark, yet little is known regarding the underlying functional mechanism in CMSs. Herein, we identified a core set of 235 functional gene regulators (FGRs) by integrating genome, epigenome, transcriptome and interactome of CMSs. FGRs exhibited significant multi-omics alterations and impacts on cell lines growth, as well as significantly enriched cancer driver genes and pathways. Moreover, common FGRs played different roles in the context of CMSs. In accordance with the immune characteristics of CMSs, we found that the anti-tumor immune pathways were mainly activated by FGRs (e.g. STAT1 and CREBBP) in CMS1, while inhibited by FGRs in CMS2-4. FGRs mediated aberrant expression of ligands, which bind to receptor on immune cells, and modulated tumor immune microenvironment of subtypes. Intriguingly, systematic exploration of datasets using genomic and transcriptome co-similarity reveals the coordinated manner in FGRs act in CMSs to orchestrate their pathways and patients' prognosis. Expression signatures of the FGRs revealed an optimized CMS classifier, which demonstrated 88% concordance with the gold-standard classifier, but avoiding the influence of sample composition. Overall, our integrative analysis identified FGRs to regulate core tumorigenic processes/pathways across CMSs.

An absolute human stemness index associated with oncogenic dedifferentiation.

The progression of cancer is accompanied by the acquisition of stemness features. Many stemness evaluation methods based on transcriptional profiles have been presented to reveal the relationship between stemness and cancer. However, instead of absolute stemness index values-the values with certain range-these methods gave the values without range, which makes them unable to intuitively evaluate the stemness. Besides, these indices were based on the absolute expression values of genes, which were found to be seriously influenced by batch effects and the composition of samples in the dataset. Recently, we have showed that the signatures based on the relative expression orderings (REOs) of gene pairs within a sample were highly robust against these factors, which makes that the REO-based signatures have been stably applied in the evaluations of the continuous scores with certain range. Here, we provided an absolute REO-based stemness index to evaluate the stemness. We found that this stemness index had higher correlation with the culture time of the differentiated stem cells than the previous stemness index. When applied to the cancer and normal tissue samples, the stemness index showed its significant difference between cancers and normal tissues and its ability to reveal the intratumor heterogeneity at stemness level. Importantly, higher stemness index was associated with poorer prognosis and greater oncogenic dedifferentiation reflected by histological grade. All results showed the capability of the REO-based stemness index to assist the assignment of tumor grade and its potential therapeutic and diagnostic implications.

Reference genome and annotation updates lead to contradictory prognostic predictions in gene expression signatures: a case study of resected stage I lung adenocarcinoma.

RNA-sequencing enables accurate and low-cost transcriptome-wide detection. However, expression estimates vary as reference genomes and gene annotations are updated, confounding existing expression-based prognostic signatures. Herein, prognostic 9-gene pair signature (GPS) was applied to 197 patients with stage I lung adenocarcinoma derived from previous and latest data from The Cancer Genome Atlas (TCGA) processed with different reference genomes and annotations. For 9-GPS, 6.6% of patients exhibited discordant risk classifications between the two TCGA versions. Similar results were observed for other prognostic signatures, including IRGPI, 15-gene and ORACLE. We found that conflicting annotations for gene length and overlap were the major cause of their discordant risk classification. Therefore, we constructed a prognostic 40-GPS based on stable genes across GENCODE v20-v30 and validated it using public data of 471 stage I samples (log-rank P < 0.0010). Risk classification was still stable in RNA-sequencing data processed with the newest GENCODE v32 versus GENCODE v20-v30. Specifically, 40-GPS could predict survival for 30 stage I samples with formalin-fixed paraffin-embedded tissues (log-rank P = 0.0177). In conclusion, this method overcomes the vulnerability of existing prognostic signatures due to reference genome and annotation updates. 40-GPS may offer individualized clinical applications due to its prognostic accuracy and classification stability.

Satellite estimation of suspended particle types using a backscattering efficiency-based model in the marginal seas.

The particle composition of suspended matter provides crucial information for a deeper understanding of marine biogeochemical processes and environmental changes. Particulate backscattering efficiency (Qbbe(λ)) is critical to understand particle composition, and a Qbbe(λ)-based model for classifying particle types was proposed. In this study, we evaluated the applicability of the Qbbe(λ)-based model to satellite observations in the shallow marginal Bohai and Yellow Seas. Spatiotemporal variations of the particle types and their potential driving factors were studied. The results showed that the Qbbe(λ) products generated from Moderate Resolution Imaging Spectroradiometer (MODIS) on the satellite Aqua agreed well with the in situ measured values, with determination coefficient, root mean square error, bias, and mean absolute percentage error of 0.76, 0.007, 16.5%, and 31.0%, respectively. This result verifies the satellite applicability of the Qbbe(λ)-based model. Based on long-term MODIS data, we observed evident spatiotemporal variations of the Qbbe(λ), from which distinct particle types were identified. Coastal waters were often dominated by minerals, with high Qbbe(λ) values, though their temporal changes were also observed. In contrast, waters in the offshore regions showed clear changes in particle types, which shifted from organic-dominated with low Qbbe(λ) levels in summer to mineral-dominated with high Qbbe(λ) values in winter. We also observed long-term increasing and decreasing trends in Qbbe(λ) in some regions, indicating a relative increase in the proportions of mineral and organic particles in the past decades, respectively. These spatiotemporal variations of Qbbe(λ) and particle types were probably attributed to sediment re-suspension related to water mixing driven by wind and tidal forcing, and to sediment load associated with river discharge. Overall, the findings of this study may provide valuable proxies for better studying marine biogeochemical processes, material exchanges, and sediment flux.

ICGA combined with EP monitoring in microclipping of cerebral aneurysms.

Cerebral aneurysm is one of the common cerebrovascular diseases in neurosurgery, and rupture of cerebral aneurysm is the most important cause of spontaneous subarachnoid hemorrhage. How to precisely clip the aneurysm has been a topic worth discussing, so the authors explore the value of ICGA combined with electrophysiological monitoring in the microclipping of cerebral aneurysms. Using the method of retrospective analysis of cases, 661 patients with cerebral aneurysms admitted to the Department of Neurosurgery, Zhongnan Hospital of Wuhan University, from 2021.8 to 2022.10 were studied, 390 patients with aneurysm clipping were included, and patients with Hunt-Hess classification ≥ 4 were excluded, and whether to use ICGA combined with EP in microclipping of the ruptured and unruptured aneurysm in pterional approach was investigated at the time of discharge, respectively. The MRS and total hospital days were compared to investigate the value of ICGA combined with EP in the microclipping of cerebral aneurysms. All 390 patients enrolled in the group had successful aneurysm clipping, 178 patients were screened for ruptured aneurysm pterional approach and 120 patients for unruptured aneurysm pterional approach access; the MRS at discharge was significantly lower in the ICGA combined with EP group than in the no-EP group for ruptured aneurysm pterional approach microclipping (p < 0.001), and the mean number of days in hospital was significantly lower (p < 0.01). Patients in the ICGA combined with EP group in microclipping of unruptured aneurysms with pterional approach also had significantly lower MRS at discharge compared with patients in the ICGA alone group (p < 0.001), with no statistically significant difference in the mean number of days in hospital (p = 0.09). In open cerebral aneurysm microclipping, ICGA combined with EP monitoring for both ruptured and unruptured aneurysms can effectively reduce the false-negative rate of ICGA, significantly reduce the incidence of postoperative neurological deficits, and shorten the total hospital stay to some extent. ICGA combined with EP monitoring may be an effective means to reduce the rate of false clipping of the penetrating vessels and to avoid stenosis or occlusion of the aneurysm-carrying artery and is worth promoting in microclipping of cerebral aneurysms except for Hunt-Hess ≥ 4.

TBC1Domain Family Member 25 deficiency aggravates cerebral ischemia-reperfusion injury via TAK1-JNK/p38 pathway.

TBC1Domain Family Member 25 (TBC1D25) is a protein that contains a TBC/RAB-GTPase activating protein (GAP) domain, which was shown to participate in autophagy in previous studies. However, the role of TBC1D25 in cerebral ischemia-reperfusion (I/R) injury remains unknown. In this study, we found that the mRNA and protein expression levels of TBC1D25 decreased in mouse brain after I/R injury and primary cortical neurons treated with oxygen and glucose deprivation/reoxygenation (OGD/R). Then TBC1D25 knockout (KO) mice were applied to demonstrate that TBC1D25 ablation aggravated cerebral I/R-induced neuronal loss and infarct size. In addition, neuronal apoptosis and inflammation were significantly potentiated in the TBC1D25-KO group. In in vitro OGD/R model, TBC1D25 knockdown can attenuate neuronal cell viability and aggravate the process of inflammation and apoptosis. Conversely, over-expression of TBC1D25 in primary neurons ameliorated the aforementioned processes. Mechanistically, RNA-sequencing (RNA-seq) analysis revealed mitogen-activated protein kinase (MAPK) signaling pathway was the most significant pathway that contributed to TBC1D25-mediated brain I/R injury process. Through experimental verification, TBC1D25 deficiency increased the phosphorylation of the transforming growth factor-ß-activated kinase 1 (TAK1)-c-Jun N-terminal kinase (JNK)/p38 axis in neurons during the brain I/R injury. Furthermore, we found that TAK1 blockade abrogated the apoptosis and inflammatory response produced by TBC1D25 knockdown in vitro. In conclusion, this study is the first to demonstrate the functional significance of TBC1D25 in the pathophysiology of brain I/R injury, and the protective mechanism of TBC1D25 is dependent on the TAK1-JNK/p38 pathway.

A putative effector of the rubber-tree powdery mildew fungus has elicitor activity that can trigger plant immunity.

MAIN CONCLUSION: A putative powdery mildew effector can elicit defense responses including reactive oxygen species and callose accumulations in model plants Nicotiana benthamiana and Arabidopsis thaliana and host plant Hevea brasiliensis. Powdery mildew fungi cause severe diseases in many agricultural plants, such as the mildew fungus Erysiphe quercicola infecting the rubber tree (Hevea brasiliensis), causing latex yield losses. However, effectors of E. quercicola were rarely functionally characterized. In this study, we identified a highly specific candidate-secreted effector protein, EqCSEP04187, from E. quercicola. This putative effector is expressed at the late stage but not the early stage during infection. The constitutive expression of EqCSEP04187 in model plants Nicotiana benthamiana and Arabidopsis thaliana elicited defense responses, as did transient expression of EqCSEP04187 in protoplasts of H. brasiliensis. Introducing EqCSEP04187 into another H. brasiliensis-associated fungal pathogen, Colletotrichum gloeosporioides, inhibited H. brasiliensis infection, and infection by E. quercicola was decreased in the A. thaliana eds1 mutant expressing EqCSEP04187. Further analysis suggests that these reductions in infection were the consequences of EqCSEP04187 eliciting defense responses. Our study suggests that this putative effector has elicitor activity that can improve plant resistance.

Cerebral ischemia after treatment of posterior communicating artery aneurysms: clipping versus coiling.

OBJECTION: This study aimed to compare the incidence of cerebral ischemia and outcomes between surgical clipping and endovascular coiling in patients with posterior communicating artery (PCoA) aneurysms. METHODS: Clinical and imaging data of patients with at least one PCoA aneurysm who underwent surgical clipping or endovascular coiling in our institution from January 2017 to December 2019 were analyzed. RESULTS: Three hundred sixty-three aneurysms in 353 patients were included for analysis, 257 in the clipping group, and 106 in the coiling group. The groups did not differ in terms of baseline characteristics. The incidence of postoperative cerebral ischemia (23.35% vs. 11.32%, p = 0.029) was higher in the clipping group. The proportion of patients with a modified Rankin Scale score ≥ 2 was significantly higher in the clipping group at discharge (35.80% vs. 15.09%; p < 0.05) but not six months after discharge (15.56% vs. 8.49%; p > 0.05). In the clipping group, the mean age was significantly higher in patients who developed cerebral ischemia than in those who did not. In the coiling group, modified Fisher grade and incidence of fetal PCoA were significantly higher in patients who developed ischemia. CONCLUSION: The incidence of postoperative cerebral ischemia was higher after PCoA aneurysm clipping than after coiling. The causes and characteristics of postoperative cerebral ischemia after PCoA clipping and coiling are different; therefore, treatment should be selected accordingly.

The prognostic value of hyperglycemia in aneurysmal subarachnoid hemorrhage: a systematic review and meta-analysis.

Recent studies have demonstrated that hyperglycemia may result in a poor prognosis following aneurysmal subarachnoid hemorrhage (aSAH). However, the association between hyperglycemia and the clinical outcome of aSAH has not been clearly established thus far. Therefore, we performed a systematic review and meta-analysis to investigate the association between hyperglycemia and the development of aSAH. We completed a literature search in four databases (PubMed, EMBASE, Cochrane Library, and Web of Science) up to November 1, 2021, including all eligible studies investigating the prognostic value of hyperglycemia in patients with aSAH. We performed a quality assessment of included studies using the Newcastle-Ottawa Quality Assessment Scale. The pooled odds ratios (ORs) with corresponding 95% confidence intervals (CIs) were calculated to assess the association of hyperglycemia in aneurysmal subarachnoid hemorrhage. A total of 35 studies with 11,519 patients were finally included in the meta-analysis. Nineteen studies reported the association between hyperglycemia and poor outcome, 12 studies reported the association between hyperglycemia and all-cause mortality, 7 studies reported the association between hyperglycemia and cerebral vasospasm, and 9 studies reported the association between hyperglycemia and cerebral infarction. The pooled data of these studies suggested that hyperglycemia was significantly associated with poor functional outcomes (odds ratio [OR], 1.29; 95% confidence interval [CI], 1.17-1.42; P < 0.00001; I2 = 83%), all-cause mortality (OR, 1.02; 95% CI, 1.01-1.04; P = 0.0006; I2 = 89%), cerebral vasospasm (OR, 1.02; 95% CI, 1.01-1.02; P = 0.0002; I2 = 35%), and cerebral infarction (OR, 1.16; 95% CI, 1.09-1.23; P < 0.00001; I2 = 10%) in aSAH patients. These findings suggested that assessing for hyperglycemia at admission may help clinicians to identify critically ill patients and complete patient stratification early, which may achieve better management and improve the prognosis of patients with aSAH.

Genomic Basis for Individual Differences in Susceptibility to the Neurotoxic Effects of Diesel Exhaust.

Air pollution is a known environmental health hazard. A major source of air pollution includes diesel exhaust (DE). Initially, research on DE focused on respiratory morbidities; however, more recently, exposures to DE have been associated with neurological developmental disorders and neurodegeneration. In this study, we investigated the effects of sub-chronic inhalation exposure to DE on neuroinflammatory markers in two inbred mouse strains and both sexes, including whole transcriptome examination of the medial prefrontal cortex. We exposed aged male and female C57BL/6J (B6) and DBA/2J (D2) mice to DE, which was cooled and diluted with HEPA-filtered compressed air for 2 h per day, 5 days a week, for 4 weeks. Control animals were exposed to HEPA-filtered air on the same schedule as DE-exposed animals. The prefrontal cortex was harvested and analyzed for proinflammatory cytokine gene expression (Il1ß, Il6, Tnfα) and transcriptome-wide response by RNA-seq. We observed differential cytokine gene expression between strains and sexes in the DE-exposed vs. control-exposed groups for Il1ß, Tnfα, and Il6. For RNA-seq, we identified 150 differentially expressed genes between air and DE treatment related to natural killer cell-mediated cytotoxicity per Kyoto Encyclopedia of Genes and Genomes pathways. Overall, our data show differential strain-related effects of DE on neuroinflammation and neurotoxicity and demonstrate that B6 are more susceptible than D2 to gene expression changes due to DE exposures than D2. These results are important because B6 mice are often used as the default mouse model for DE studies and strain-related effects of DE neurotoxicity warrant expanded studies.

Link synthetic lethality to drug sensitivity of cancer cells.

Synthetic lethal (SL) interactions occur when alterations in two genes lead to cell death but alteration in only one of them is not lethal. SL interactions provide a new strategy for molecular-targeted cancer therapy. Currently, there are few drugs targeting SL interactions that entered into clinical trials. Therefore, it is necessary to investigate the link between SL interactions and drug sensitivity of cancer cells systematically for drug development purpose. We identified SL interactions by integrating the high-throughput data from The Cancer Genome Atlas, small hairpin RNA data and genetic interactions of yeast. By integrating SL interactions from other studies, we tested whether the SL pairs that consist of drug target genes and the genes with genomic alterations are related with drug sensitivity of cancer cells. We found that only 6.26%∼34.61% of SL interactions showed the expected significant drug sensitivity using the pooled cancer cell line data from different tissues, but the proportion increased significantly to approximately 90% using the cancer cell line data for each specific tissue. From an independent pharmacogenomics data of 41 breast cancer cell lines, we found three SL interactions (ABL1-IFI16, ABL1-SLC50A1 and ABL1-SYT11) showed significantly better prognosis for the patients with both genes being altered than the patients with only one gene being altered, which partially supports the SL effect between the gene pairs. Our study not only provides a new way for unraveling the complex mechanisms of drug sensitivity but also suggests numerous potentially important drug targets for cancer therapy.

Prediction Model Combining Clinical and MR Data for Diagnosis of Lymph Node Metastasis in Patients With Rectal Cancer.

BACKGROUND: Determining the status of lymph node (LN) metastasis in rectal cancer patients preoperatively is crucial for the treatment option. However, the diagnostic accuracy of current imaging methods is low. PURPOSE: To develop and test a model for predicting metastatic LNs of rectal cancer patients based on clinical data and MR images to improve the diagnosis of metastatic LNs. STUDY TYPE: Retrospective. SUBJECTS: In all, 341 patients with histologically confirmed rectal cancer were divided into one training set (120 cases) and three validation sets (69, 103, 49 cases). FIELD STRENGTH/SEQUENCE: 3.0T, axial and sagittal T2 -weighted turbo spin echo and diffusion-weighted imaging (b = 0 s/mm2 , 800 s/mm2 ) ASSESSMENT: In the training dataset, univariate logistic regression was used to identify the clinical factors (age, gender, and tumor markers) and MR data that correlated with LN metastasis. Then we developed a prediction model with these factors by multiple logistic regression analysis. The accuracy of the model was verified using three validation sets and compared with the traditional MRI method. STATISTICAL TESTS: Univariate and multivariate logistic regression. The area under the curve (AUC) value was used to quantify the diagnostic accuracy of the model. RESULTS: Eight factors (CEA, CA199, ADCmean, mriT stage, mriN stage, CRM, EMVI, and differentiation degree) were significantly associated with LN metastasis in rectal cancer patients (P<0.1). In the training set (120) and the three validation sets (69, 103, 49), the AUC values of the model were much higher than the diagnosis by MR alone (training set, 0.902 vs. 0.580; first validation set, 0.789 vs. 0.743; second validation set, 0.774 vs. 0.573; third validation set, 0.761 vs. 0.524). DATA CONCLUSION: For the diagnosis of metastatic LNs in rectal cancer patients, our proposed logistic regression model, combining clinical and MR data, demonstrated higher diagnostic efficiency than MRI alone. LEVEL OF EVIDENCE: 4 TECHNICAL EFFICACY STAGE: 2.

Safety and effectiveness of high flow extracranial to intracranial saphenous vein bypass grafting in the treatment of complex intracranial aneurysms: a single-centre long-term retrospective study.

BACKGROUND: To summarize the safety and effectiveness of high flow extracranial to intracranial saphenous vein bypass grafting in the treatment of complex intracranial aneurysms. METHODS: The data of complex intracranial aneurysms patients for high flow extracranial to intracranial saphenous vein bypass grafting from January 2008 to January 2020 were retrospectively collected and analyzed. Eighty-two patients (31 men and 51 women) with 89 aneurysms underwent 82 saphenous vein bypass grafts followed by immediate parent vessel occlusion. The aneurysm was located at the internal carotid artery, middle cerebral artery, and basilar artery in 75, 11, and 3 cases, respectively. RESULTS: The patency rate of bypass grafting was 100, 100, 96.3 and 92.4% on intraoperation, on the first postoperative day, at discharge and 6 months follow-up, respectively. At discharge and 6 months follow-up, 3 and 6 patients had graft occlusions. The main postoperative complications were transient hemiparesis and hemianopsia. 3 patients died due to bypass complications and poor physical condition. CONCLUSIONS: High flow extracranial to intracranial saphenous vein bypass grafting is safe and effective in the treatment of complex intracranial aneurysms and the saphenous vein can meet the requirements of brain blood supply. A high rate of graft patency and adequate cerebral blood flow can be achieved. HIGHLIGHTS: A single-centre long-term retrospective study was conducted to assess the safety and effectiveness of high flow EC-IC saphenous vein bypass grafting in the treatment of complex intracranial aneurysms. The data of 82 patients from January 2008 to January 2020 were retrospectively collected and analysed. We found the patency rate of bypass grafting was 100, 100, 96.3 and 92.4% on intraoperation, on the first postoperative day, at discharge and 6 months follow-up, respectively. At discharge and 6 months follow-up, 3 and 6 patients had graft occlusions. Finally, we conclude that high flow extracranial to intracranial saphenous vein bypass grafting is safe and effective in the treatment of complex intracranial aneurysms and the selected blood supply vessels can meet the requirements of blood supply. As far as we know, this study is one of the maximum number of cases in the treatment of complex intracranial aneurysms with saphenous vein bypass.

Genetic differences in ethanol consumption: effects on iron, copper, and zinc regulation in mouse hippocampus.

One common characteristic of neurodegenerative diseases is dysregulation of iron, usually with observed increases in its concentration in various regions. Heavy alcohol consumption is believed to contribute to such iron dysregulation in the brain with accompanying dementia. To examine this effect and related genetic-based individual differences in an animal model, we subjected female mice from 12 BXD recombinant inbred strains to 16 weeks of alcohol consumption using the drinking in the dark (DID) method. Daily consumption was recorded and at the end of 16 weeks hippocampus tissues harvested. Concentrations of iron, copper and zinc were measured using X-ray fluorescence technology. The results showed that, DID increased iron overall across all strains, ranging from 3 to 68%. Copper and Zinc both decreased, ranging from 0.4-42 and 5-35% respectively. Analysis of variance revealed significant strain by treatment interactions for all three metals. Additionally, in the DID group, we observed strain differences in reduction of hippocampus mass. These findings are particularly interesting to us because high alcohol consumption in humans has been associated with neurodegeneration and dementia related to disruption of iron regulation. The findings of alcohol consumption associated decreases in copper and zinc are novel. The role of copper regulation and neurological function related to alcohol consumption is as yet largely unexplored. The role of zinc is better known as a neuromodulator in the hippocampus and appears to be protective against neurological damage. It would seem then, that the alcohol-related decrease in zinc in the hippocampus would be of concern and warrants further study.

Identifying modifier genes for hypertrophic cardiomyopathy.

BACKGROUND: Hypertrophic cardiomyopathy (HCM) severity greatly varies among patients even with the same HCM gene mutations. This variation is largely regulated by modifier gene(s), which, however, remain largely unknown. The current study is aimed to identify modifier genes using BXD strains, a large murine genetic reference population (GRP) derived from crosses between C57BL/6 J (B6) and D2 DBA/2 J (D2) mice. D2 mice natualy carrythe genetic basis and phenotypes of HCM. METHODS: Myocardial hypertrophy, the major phenotype of HCM, was determined by cardiomyocyte size on cardiac sections in 30 BXD strains, and their parental B6 and D2 strains and morphometric analysis was performed. Quantitative Trait Locus (QTL) mapping for cardiomyocyte sizes was conducted with WebQTL in GeneNetwork. Correlation of cardiomyocyte size and cardiac gene expression in BXDs accessed from GeneNetwork were evaluated. QTL candidate genes associated with cardiomyocyte sizes were prioritized based on the score system. RESULTS: Cardiomyocyte size varied significantly among BXD strains. Interval mapping on cardiomyocyte size data showed a significant QTL on chromosome (Chr) 2 at 66- 73.5 Mb and a suggestive QTL on Chr 5 at 20.9-39.7 Mb. Further score system revealed a high QTL score for Xirp2 in Chr 2. Xirp2 encodes xin actin-binding repeat containing 2, which is highly expressed in cardiac tissue and associate with cardiomyopathy and heart failure. In Chr5 QTL, Nos3, encoding nitric oxide synthase 3, received the highest score, which is significantly correlated with cardiomyocyte size. CONCLUSION: These results indicate that Xirp2 and Nos3 serve as novel candidate modifier genes for myocardial hypertrophy in HCM. These candidate genes will be validated in our future studies.

Qualitative transcriptional signature for predicting pathological response of colorectal cancer to FOLFOX therapy.

FOLFOX (5-fluorouracil, leucovorin and oxaliplatin) is one of the main chemotherapy regimens for colorectal cancer (CRC), but only half of CRC patients respond to this regimen. Using gene expression profiles of 96 metastatic CRC patients treated with FOLFOX, we first selected gene pairs whose within-sample relative expression orderings (REO) were significantly associated with the response to FOLFOX using the exact binomial test. Then, from these gene pairs, we applied an optimization procedure to obtain a subset that achieved the largest F-score in predicting pathological response of CRC to FOLFOX. The REO-based qualitative transcriptional signature, consisting of five gene pairs, was developed in the training dataset consisting of 96 samples with an F-score of 0.90. In an independent test dataset consisting of 25 samples with the response information, an F-score of 0.82 was obtained. In three other independent survival datasets, the predicted responders showed significantly better progression-free survival than the predicted non-responders. In addition, the signature showed a better predictive performance than two published FOLFOX signatures across different datasets and is more suitable for CRC patients treated with FOLFOX than 5-fluorouracil-based signatures. In conclusion, the REO-based qualitative transcriptional signature can accurately identify metastatic CRC patients who may benefit from the FOLFOX regimen.