Mismatch repair protein deficiency and its implications on distant metastasis in colorectal cancer: A comprehensive analysis.

BACKGROUND: While previous studies have indicated variability in distant metastatic potential among different mismatch repair (MMR) states in colorectal cancer (CRC), their findings remain inconclusive, especially considering potential differences across various ethnic backgrounds. Furthermore, the gene regulatory networks and the underlying mechanisms responsible for these variances in metastatic potential across MMR states have yet to be elucidated. METHODS: We collected 2058 consecutive primary CRC samples from the South West of China and assessed the expression of MMR proteins (MLH1, MSH2, MSH6, and PMS2) using immunohistochemistry. To explore the inconsistencies between different MMR statuses and recurrence, we performed a meta-analysis. To delve deeper, we employed Weighted Gene Co-expression Network Analysis (WGCNA), ClueGo, and iRegulon, pinpointing gene expression networks and key regulatory molecules linked to metastasis and recurrence in CRC. Lastly, both univariate and multivariate Cox regression analyses were applied to determine the impact of core regulatory molecules on metastasis. RESULTS: Of the samples, 8.2% displayed deficient MMR (dMMR), with losses of MLH1 and PSM2 observed in 40.8% and 63.9%, respectively. A unique 24.3% isolated loss of PMS2 without concurrent metastasis was identified, a result that diverges from established literature. Additionally, our meta-analysis further solidifies the reduced recurrence likelihood in dMMR CRC samples compared to proficient MMR (pMMR). Two gene expression networks tied to distant metastasis and recurrence were identified, with a majority of metastasis-related genes located on chromosomes 8 and 18. An IRF1 positive feedback loop was discerned in the metastasis-related network, and IRF1 was identified as a predictive marker for both recurrence-free and distant metastasis-free survival across multiple datasets. CONCLUSION: Geographical and ethnic factors might influence peculiarities in MMR protein loss. Our findings also highlight new gene expression networks and crucial regulatory molecules in CRC metastasis, enhancing our comprehension of the mechanisms driving distant metastasis.

Garlic consumption and colorectal cancer risk in US adults: a large prospective cohort study.

Objective: To clarify the inconsistent findings of epidemiological studies on the association between dietary garlic consumption and colorectal cancer (CRC) incidence, by prospectively assessing the association in a large US population. Methods: Data of 58,508 participants (aged 55-74) from the Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial were analyzed. Dietary data were collected using a validated questionnaire. Multivariable Cox regression analysis determined hazard ratio (HR) and 95% confidence interval (CI). Restricted cubic spline regression was used to investigate the non-linear relationship, and subgroup analysis was conducted to examine potential effect modifiers. Results: During a median follow-up of 12.05 years, 782 CRC cases were documented, including 456 proximal colon cancer cases, 322 distal CRC cases, and 4 CRC cases with an unknown site. Moderate dietary garlic consumption was significantly associated with a reduced risk of overall CRC (HRquintile 3vs. 1: 0.70, 95% CI: 0.54 to 0.91, p = 0.007, P for trend: 0.434), exhibiting a U-shaped dose-response pattern, and also with overall CRC in males in the stratified Cox regression model (Model 2: HRquintile 3vs. 1: 0.57, 95% CI: 0.40 to 0.81, p = 0.002), but not in females. The protective association was more pronounced in men, Caucasian, and those with lower alcohol consumption. Notably, these protective effects were observed for overall distal CRC (HRquintile 3vs. 1: 0.62, 95% CI: 0.42 to 0.93, p = 0.021; and HRquintile 4vs. 1: 0.63, 95% CI: 0.43 to 0.92, p = 0.018, P for trend: 0.208); and for distal CRC in males (HRquintile 3vs. 1: 0.40, 95% CI: 0.22 to 0.71, p = 0.002, P for trend: 0.696), but not for proximal CRC. Conclusion: Moderate consumption of dietary garlic is associated with a decreased CRC risk in the US population, with variations based on CRC anatomic subsites. Further in-depth prospective studies are needed to validate these findings in different populations and to explore subsites-specific associations.

The impact of immunoglobulin G N-glycosylation level on COVID-19 outcome: evidence from a Mendelian randomization study.

Background: The coronavirus disease 2019 (COVID-19) pandemic has exerted a profound influence on humans. Increasing evidence shows that immune response is crucial in influencing the risk of infection and disease severity. Observational studies suggest an association between COVID-19 and immunoglobulin G (IgG) N-glycosylation traits, but the causal relevance of these traits in COVID-19 susceptibility and severity remains controversial. Methods: We conducted a two-sample Mendelian randomization (MR) analysis to explore the causal association between 77 IgG N-glycosylation traits and COVID-19 susceptibility, hospitalization, and severity using summary-level data from genome-wide association studies (GWAS) and applying multiple methods including inverse-variance weighting (IVW), MR Egger, and weighted median. We also used Cochran's Q statistic and leave-one-out analysis to detect heterogeneity across each single nucleotide polymorphism (SNP). Additionally, we used the MR-Egger intercept test, MR-PRESSO global test, and PhenoScanner tool to detect and remove SNPs with horizontal pleiotropy and to ensure the reliability of our results. Results: We found significant causal associations between genetically predicted IgG N-glycosylation traits and COVID-19 susceptibility, hospitalization, and severity. Specifically, we observed reduced risk of COVID-19 with the genetically predicted increased IgG N-glycan trait IGP45 (OR = 0.95, 95% CI = 0.92-0.98; FDR = 0.019). IGP22 and IGP30 were associated with a higher risk of COVID-19 hospitalization and severity. Two (IGP2 and IGP77) and five (IGP10, IGP14, IGP34, IGP36, and IGP50) IgG N-glycosylation traits were causally associated with a decreased risk of COVID-19 hospitalization and severity, respectively. Sensitivity analyses did not identify any horizontal pleiotropy. Conclusions: Our study provides evidence that genetically elevated IgG N-glycosylation traits may have a causal effect on diverse COVID-19 outcomes. Our findings have potential implications for developing targeted interventions to improve COVID-19 outcomes by modulating IgG N-glycosylation levels.

Associations between colorectal cancer risk and dietary intake of tomato, tomato products, and lycopene: evidence from a prospective study of 101,680 US adults.

Background: Previous epidemiological studies have yielded inconsistent results regarding the effects of dietary tomato, tomato products, and lycopene on the incidence of colorectal cancer (CRC), possibly due to variations in sample sizes and study designs. Methods: The current study used multivariable Cox regression, subgroup analyses, and restricted cubic spline functions to investigate correlations between CRC incidence and mortality and raw tomato, tomato salsa, tomato juice, tomato catsup, and lycopene intake, as well as effect modifiers and nonlinear dose-response relationships in 101,680 US adults from the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial. Results: During follow-up 1100 CRC cases and 443 CRC-specific deaths occurred. After adjustment for confounding variables, high consumption of tomato salsa was significantly associated with a reduced risk of CRC incidence (hazard ratio comparing the highest category with the lowest category 0.8, 95% confidence interval 0.65-0.99, p for trend = 0.039), but not with a reduced risk of CRC mortality. Raw tomatoes, tomato juice, tomato catsup, and lycopene consumption were not significantly associated with CRC incidence or CRC mortality. No potential effect modifiers or nonlinear associations were detected, indicating the robustness of the results. Conclusion: In the general US population a higher intake of tomato salsa is associated with a lower CRC incidence, suggesting that tomato salsa consumption has beneficial effects in terms of cancer prevention, but caution is warranted when interpreting these findings. Further prospective studies are needed to evaluate its potential effects in other populations.

Clinical Value of PET.CT Based on Big Data in Colorectal and Peritoneal Metastatic Cancer.

This study focuses on the evaluation of the clinical utility of PET-CT imaging in peritoneal metastases and colorectal cancer. One hundred patients with colorectal peritoneal metastases, who underwent whole-body PET-CT imaging from January 2015 to December 2019, were selected as the experimental group, and 20 healthy individuals were selected as the control group. The SUVmax of the two groups of patients was 5.73 ± 3.84 and 2.70 ± 2.32, respectively, and the difference was statistically significant. The SUVmax AUC was 0.720, and the AUC of serum AFP, CEA, CA125, and CA199 were 0.596, 0.677, 0.642, and 0.696, respectively. Conclusion. 100 patients with colorectal and peritoneal metastatic cancer underwent PET/CT examination. The follow-up or other imaging examinations confirmed the diagnosis. Analysis of the ROC curve in this study found that with a peritoneal SUVmax> 3.2 as the diagnostic index for colorectal peritoneal metastatic cancer, the sum of sensitivity and specificity reached the maximum.

Association of Dietary Carrot/Carotene Intakes With Colorectal Cancer Incidence and Mortality in the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial.

Background: The evidence of dietary carrot/carotene intake's effect on the association with colorectal cancer (CRC) risk is conflicted. We sought to examine the association of carrot/carotene intake with CRC incidence and mortality in the Prostate, Lung, Colorectal, and Ovarian Cancer (PLCO) Screening cohort. Methods: In all, 101,680 participants were enrolled between November 1993 and July 2001 from the PLCO cohort. We employed the multivariable Cox regression analyses to estimate the hazard ratios and 95% confidence interval. Subgroup analyses and interaction tests were performed to examine the potential effect modifiers. We further applied the generalized additive model to explore the non-linear trend of the exposure to cancer-related outcomes. Results: A total of 1,100 CRC cases and 443 cancer-related deaths were documented. We noted that the 4th quintile of dietary carrot intakes was associated with a 21% lower risk of CRC incidence, compared with the lowest quintile group (full-adjusted HRquintile4vs.quintile1 = 0.79, 95%CI = 0.65-0.97, p for trend = 0.05), while the adjusted-HR was 0.95 (95%CI = 0.89-1.02) with per SD increment of carrot intakes, and no statistically significant associations were detected between dietary α-, and ß-carotene intake and CRC incidence. There were no statistically significant associations observed between carrot/carotene intakes and CRC mortality. Furthermore, there were no non-linear dose-response relationships between dietary carrot, α-, and ß-carotene intake and CRC incidence and mortality (all p nonlinearity > 0.05). Of note, smoking status as a modifier on the association of dietary carrot intakes with CRC incidence but not mortality was observed. Conclusions: In summary, this large U.S. prospective cohort study indicated that a moderate consumption of carrots was associated with a lower CRC incidence, which suggested that a certain dose-range of carrots consumed might contribute to a potential cancer-prevention effect, not the more the better.

A retrospective study based on SEER database: not all high-risk factors are equal for stage II colon cancer.

Background: For stage II colon cancer, understanding of high-risk factors (HRFs) that affect the overall survival (OS) and the benefit of chemotherapy is limited. Meanwhile, no stable predictor can effectively predict OS of stage II colon cancer to date. Our study is aimed to identify HRFs associated with OS of stage II colon cancer, to quantify the risk conferred by each HRF, and to evaluate OS benefit gained by chemotherapy. Meanwhile, we attempt to establish a nomogram model for stage II colon cancer. Methods: The clinical variables of patients with stage II colon cancer between 2000 and 2018 were retrieved from the Surveillance, Epidemiology, and End Results (SEER) database. Univariate and multivariate analysis were performed to filtered out all the HRFs. We calculated the hazard ratios (HR) and evaluated the survival benefit of adjuvant chemotherapy for each HRF and combinations of HRFs. Then, a nomogram model based on all HRFs was established and verified. Results: A total of 39,103 patients with stage II colon cancer were included. T4b tumors were the highest risk for reduced OS [HR =2.821; 95% confidence interval (CI): 1.949-4.082], mucin-producing tumors (HR =2.412; 95% CI: 1.326-4.388) the second, and lymph node (LN) examined less than 12 (HR =2.200; 95% CI: 1.786-2.710) the third. T4 tumors (HR =0.790; 95% CI: 0.542-1.151), poorly/undifferentiated tumors (HR =0.468; 95% CI: 0.237-0.924), and some combinations of HRFs containing either could benefit from adjuvant chemotherapy. Meanwhile, we established an effective nomogram model based on the identified HRFs. Conclusions: The study has identified several novel HRFs for stage II colon cancer. Adjuvant chemotherapy has considerable OS benefit for stage II colon cancers with some specific HRFs, and treatment plans need to be individualized. Type and number of HRFs should be taken into consideration when recommending adjuvant chemotherapy. Our new nomogram model has better predictive ability and stability than the tumor-node-metastasis (TNM) stage system of American Joint Committee on Cancer (AJCC) staging system.

Status epilepticus with focal neurologic deficits: a rare presentation of Neurosyphilis.

Neurosyphilis is a late complication of primary syphilis and occurs with a multitude of vague symptoms. In this study, we report a patient with neurosyphilis who presented with status epilepticus, hemiplegia, and aphasia, which may be easily misdiagnosed. After performing the reactive serum test, including the toluidine red unheated serum test and the Treponema pallidum particle agglutination assay test, and cerebrospinal fluid analysis, as well as the brain Magnetic Resonance Imaging (MRI) results, we consider it general paresis of the insane, also known as dementia paralytica. The patient was started on a 14-day course with high-dose intravenous penicillin. After this treatment, the patient made significant recovery with improved cognitive function, evidenced by his Mini-mental State Examination score of 21. However, before this treatment, he could not cooperate with this exam. General paresis of the insane typically has a progressive course and normally presents 10 to 30 years after the initial infection. The manifestations of this patient and his suspicious history of transient ischemic attacks may mislead to the diagnosis of Todd's paresis or stroke. The prevalence of syphilis has been rising again in recent years. To date, there is no gold standard for the diagnosis of neurosyphilis. Early diagnosis is of great importance, as penicillin therapy is highly effective.

Strategy to Decrease the Angle Measurement Error Introduced by the Use of Circular Grating in Dynamic Torque Calibration.

A circular grating angle encoder is a key component in the dynamic torque calibration system. To improve the accuracy of an angle measurement, in this paper, the source of the angle measurement error of the circular grating is analyzed; an eccentricity error model and an inclination error model are proposed, respectively; further, these two models are combined to establish a total error model. Through the simulation study with the models, the conditions, in which the eccentricity error or inclination error can be ignored, are discussed. The calibration and compensation methods of the angle measurement error are given, and a progressive error compensation function which integrates the first harmonic fitting and the second harmonic fitting is obtained. An experiment is performed to verify the proposed calibration and compensation methods. The peak-to-peak value of the compensated angle measurement error of the single reading head can be reduced by about 93.76%, which approximates to the error of the mean value of the double reading heads. The experimental results show that the error calibration and compensation method based on the proposed error model can effectively compensate the angle measurement error of the circular grating with a single reading head, and obtain a high-precision measurement angle.

Balanced Distribution Adaptation for Metal Oxide Semiconductor Gas Sensor Array Drift Compensation.

Drift compensation is an important issue for metal oxide semiconductor (MOS) gas sensor arrays. General machine learning methods require constant calibration and a large amount of label gas data. At the same time, recalibration will cause a lot of costs, and label gas is difficult to obtain in practice. In this paper, a novel drift compensation method based on balanced distribution adaptation (BDA) is proposed. First, the BDA drift compensation method can adjust the conditional distribution and marginal distribution between the two domains through the weight balance factor, thereby more effectively reducing the mismatch between the two domains. When the BDA method performs classification tasks through machine learning, no labeled data is required in the target domain. Then, the particle swarm optimization algorithm is used to improve the accuracy of drift compensation. Individuals in the population are initialized randomly, and their fitness values are calculated. Iterative optimization of the population individuals is conducted until the optimal weight balance factor parameters are calculated. Finally, the BDA method is experimentally verified on the public gas sensor drift data set. Experimental results showed that the BDA method was significantly better than the existing joint distribution adaptation (JDA) method and other standard drift compensation methods such as K-Nearest Neighbor (KNN). In the two setting groups, the recognition accuracy was 4.54% and 1.62% ahead of the JDA method, and 12.23% and 15.83% ahead of the KNN method.