Study of prevalence and risk factors of chemotherapy-induced mucositis in gastrointestinal cancer using machine learning models

ObjectiveChemotherapy-induced mucositis (CIM) significantly impacts clinical outcomes and diminishes the quality of life in patients with gastrointestinal cancer. This study aims to prospectively determine the incidence, severity, and underlying risk factors associated with CIM in this patient population.MethodsTo achieve this objective, we introduce a novel Machine Learning-based Toxicity Prediction Model (ML-TPM) designed to analyze the risk factors contributing to CIM development in gastrointestinal cancer patients. Within the winter season spanning from December 15th, 2018 to January 14th, 2019, we conducted in-person interviews with patients undergoing chemotherapy for gastrointestinal cancer. These interviews encompassed comprehensive questionnaires pertaining to patient demographics, CIM incidence, severity, and any supplementary prophylactic measures employed.ResultsThe study encompassed a cohort of 447 participating patients who provided complete questionnaire responses (100%). Of these, 328 patients (73.4%) reported experiencing CIM during the course of their treatment. Notably, CIM-induced complications led to treatment discontinuation in 14 patients (3%). The most frequently encountered CIM symptoms were diarrhea (41.6%), followed by nausea (37.8%), vomiting (25.1%), abdominal pain (21%), gastritis (10.5%), and oral pain (10.3%). Supplementary prophylaxis was administered to approximately 62% of the patients. The analysis revealed significant correlations between the overall incidence of CIM and gender (p=0.015), number of chemotherapy cycles exceeding one (p=0.039), utilization of platinum-based regimens (p=0.039), and administration of irinotecan (p=0.003). Specifically, the incidence of diarrhea exhibited positive correlations with prior surgical history (p=0.037), irinotecan treatment (p=0.021), and probiotics usage (p=0.035). Conversely, diarrhea incidence demonstrated an adverse correlation with platinum-based treatment (p=0.026).ConclusionIn conclusion, this study demonstrates the successful implementation of the ML-TPM model for automating toxicity prediction with accuracy comparable to conventional physical analyses. Our findings provide valuable insights into the identification of CIM risk factors among gastrointestinal cancer patients undergoing chemotherapy. Furthermore, the results underscore the potential of machine learning in enhancing our understanding of chemotherapy-induced mucositis and advancing personalized patient care strategies

Hyponatremia in Children With Bacterial Meningitis

Background: Hyponatremia has frequently been described as a common complication associated with bacterial meningitis, though its frequency and clinical course in children with bacterial meningitis are unclear. The present study aimed to investigate the frequency, clinical characteristics, and prognosis associated with pediatric hyponatremia due to bacterial meningitis.Methods: We performed a retrospective review of children with bacterial meningitis provided with standard care. One hundred seventy-five children were included. We documented all participants' symptoms and signs, laboratory and microbiological data, radiological findings, and complications that occurred during their hospital admission. Disease severity was determined using the maximum Pediatric Cerebral Performance Category (PCPC) and minimum Glasgow Coma Scale (GCS). Residual deficits were assessed using PCPC at discharge.Results: Hyponatremia (<135 mmol/L) was seen in 116 (66.4%) of the patients assessed and was classified as mild (130–135 mmol/L) in 77, moderate (125–129 mmol/L) in 26, and severe (<125 mmol/L) in 13. Hyponatremia was associated with a shorter duration of symptoms before admission, higher CSF white cell counts, and a longer duration of hospitalization. Moderate and severe hyponatremia were associated with an increase in convulsions, impaired consciousness, altered CSF protein levels, higher maximum PCPC scores, and lower minimum GCS scores. Severe hyponatremia was further associated with the development of systemic complications including shock, multiple organ dysfunction syndrome, respiratory failure requiring mechanical ventilation, and an increase in poor outcome (PCPC ≥ 2). Hyponatremia was not associated with the development of neurologic complications. Logistic regression analyses revealed that convulsions (OR 12.09, 95% CI 2.63–56.84) and blood glucose levels > 6.1 mmol/L (OR 8.28, 95% CI 1.65–41.60) predicted severe hyponatremia.Conclusion: Hyponatremia occurred in 66.4% of the assessed pediatric bacterial meningitis patients. Moderate and severe hyponatremia affected the severity of pediatric bacterial meningitis. Only severe hyponatremia affected the short-term prognosis of patients with pediatric bacterial meningitis. We recommend that patients with pediatric bacterial meningitis who exhibit convulsions and increased blood glucose levels should be checked for severe hyponatremia. Further studies are needed to evaluate the effectiveness of treatment of hyponatremia

Psoriasin promotes invasion, aggregation and survival of pancreatic cancer cells; association with disease progression

Psoriasin (S100A7) is an 11-kDa small calcium binding protein initially isolated from psoriatic skin lesions. It belongs to the S100 family of proteins which play an important role in a range of cell functions including proliferation, differentiation, migration and apoptosis. Aberrant Psoriasin expression has been implicated in a range of cancers and is often associated with poor prognosis. This study examined the role of Psoriasin on pancreatic cancer cell functions and the implication in progression of the disease. Expression of Psoriasin was determined in a cohort of pancreatic tissues comprised of 126 pancreatic tumours and 114 adjacent non-tumour pancreatic tissues. Knockdown and overexpression of Psoriasin in pancreatic cancer cells was performed using specifically constructed plasmids, which either had anti-Psoriasin ribozyme transgene or the full length human Psoriasin coding sequence. Psoriasin knockdown and overexpression was verified using conventional RT-PCR and qPCR. The effect of manipulating Psoriasin expression on pancreatic cancer cell functions was assessed using several in vitro cell function assays. Local invasive pancreatic cancers extended beyond the pancreas expressed higher levels of Psoriasin transcripts compared with the cancers confined to the pancreas. Primary tumours with distant metastases exhibited a reduced expression of Psoriasin. Psoriasin overexpression cell lines exhibited significantly increased growth and migration compared to control cells. In addition, Psoriasin overexpression resulted in increased pancreatic cancer cell invasion which was associated with upregulation of matrix metalloproteinase-2 (MMP-2) and MMP-9. Overexpression of Psoriasin also promoted aggregation and survival of pancreatic cancer cells when they lost anchorage. Taken together, higher expression of Psoriasin was associated with local invasion in pancreatic cancers. Psoriasin expression is associated with pancreatic cancer cell growth, migration, cell-matrix adhesion, and invasion via regulation of MMPs. As such, the proposed implications of Psoriasin in invasion, disease progression and as a potential therapeutic target warrant further investigation

Reduced kinase D‑interacting substrate of 220 kDa (Kidins220) in pancreatic cancer promotes EGFR/ERK signalling and disease progression

Kidins220 is a transmembrane scaffold protein involved in several types of cancer. The aim of the present study was to examine the role of Kidins220 in tumorigenesis and disease progression of pancreatic cancer. The relevant signalling pathways including EGFR, EMT, and MMP were also investigated. The expression of Kidins220 was examined at the transcript and protein level. The Kidins220 knockdown cell model was established and its influence on cellular functions was determined. Involvement of Kidins220 in tumorigenesis and metastasis was examined in CD1 mice, respectively. The results showed that, reduced Kidin220 expression was associated with tumorigenesis, metastasis, and overall survival of pancreatic cancer. Knockdown of Kidins220 promoted proliferation, colony formation and tumorigenic capacity of pancreatic cancer cells in vitro and in vivo, respectively. Kidins220 regulated pancreatic cancer cell migration through the EGFR/AKT/ERK signalling pathway. Furthermore, enhanced EMT was observed in the pancreatic cancer cell lines with the knockdown of Kidins220, underlying EGFR regulation. Kidins220 also affected cell invasion via MMP1. A reduced expression of Kidins220 was observed in pancreatic cancer, which is associated with disease progression, distant metastasis and poor prognosis. The loss of Kidins220 in pancreatic cancer may contribute to disease progression through the upregulation of EGFR and downstream signalling

牛乳蛋白質の発癌性ヘテロサイクリックアミンに対する結合性

牛乳中の各種蛋白質、即ち whole casein, αs-casein, β-casein, κ-casein, β-lactoglobulin A, β-lactoglobulin B, α-lactalbumin, lactoferrin, lactoperoxidase を分離精製し、これらの蛋白質が発癌性ヘテロサイクリックアミンである 3-amino-1, 4-dimethyl-5Hpyrido[4, 3-b]indole (Trp-P-1) と給合するか否かについて実験を行った。さらに我々自身で分離調製した蛋白質と比較検討する為にSigma社製のα-casein, β-casein, κ-casein, β-lactoglobulin A, β-lactoglobulin B, α-lactalbumin, lactoferrin, lactoperoxidase ついても同様の実験を行った。凍結乾燥した蛋白質2mg, Trp-P1 20μgを0.4mlのpH7.4, 50mM燐酸バッファーに溶解し、37℃で10分間振盪し反応させる。つづいて、日本ミリポアリミテッド製のUFC3LGC00を用いて反応液中の非結合型 Trp-P-1 を限外濾過により分離し、この Trp-P-1 を HPLC 法により測定する。HPLC は日立 L-6000ポンプ・L-4000UV 検出機に GL-Science 製 Inertsil ODS-2(4.6×150mm)カラムを使用し、acetonitrile-H2O-triethylamine 50:50:0.05 で展開した。254nmに於ける吸収を SIC System Instruments 製Labchart 12で記録する。Whole casein:54.04%, αs-casein:40.02%, β-casein:56.24%, κ-casein:33.75% で反応液中の Trp-P-1 を比較的に高い割合で結合した。Sigma 社製の α-Casein:59.46%, β-casein:40.43%, κ-casein:23.75% で類似の傾向を示した。β-Lactoglobulin A:23.61%, β-lactoglobulin B:17.87%, β-lactoglobulin A・Sigma:15.78%, β-lactoglebulin B・sigma:3.65% であった。Lactoperoxidase:15.20%, lactoperoxidase・Sigma:6.41%, lactoferrin-a:22.53%, lacteferrin-b:6.92% であったが、α-lactalbumain, α-lactalbumin・Sigma, lacteferrin・Sigma は Trp-P-1 と結合しなかった。The binding ability of bovine milk proteins with mutagenic heterocyclic amine was investigated. Binding was determined with 2 mg of protein and 20 g of 3-amino-1, 4-dimethyl-5H-pyrido[4, 3-b]indole (Trp-P-1) in 0.4 ml of pH 7.4, 50 mM phosphate buffer, at 37°C, in a shaker for 10 min. The unbound Trp-P-1 in protein-free ultrafiltrate was prepared using Ultrafree UFC3LGC00 and was analyzed by HPLC method. The binding of whole casein, αs-casein, β-casein and κ-casein were 54,03, 40.02, 56.24 and 33.75%, respectively. β-Lactoglobulin A, β-lactoglobulin B, lactoperoxidase, lactoferrin-a and lactoferrin-b were 23.61, 17.87, 15.20, 22.53 and 6.92% respectively. However, α-lactalbumin could not bind Trp-P-1 in this experiment. The binding of these milk proteins which were prepared by ourselves were compared with purchased proteins. They showed similar tendency to our proteins

Innovations to Attribute Reduction of Covering Decision System Based on Conditional Information Entropy

Traditional rough set theory is mainly used to reduce attributes and extract rules in databases in which attributes are characterised by partitions, which the covering rough set theory, a generalisation of traditional rough set theory, covers. In this article, we posit a method to reduce the attributes of covering decision systems, which are databases incarnated in the form of covers. First, we define different covering decision systems and their attributes’ reductions. Further, we describe the necessity and sufficiency for reductions. Thereafter, we construct a discernible matrix to design algorithms that compute all the reductions of covering decision systems. Finally, the above methods are illustrated using a practical example and the obtained results are contrasted with other results

Optimal parameters for laccase-mediated destaining of Coomassie Brilliant Blue R-250-stained polyacrylamide gels

The data presented in this article are related to the research article entitled “Destaining of Coomassie Brilliant Blue R-250-stained polyacrylamide gels with fungal laccase” [1]. Laccase is a class of multicopper oxidases that can catalyze oxidation of recalcitrant dyestuffs. This article describes optimal parameters for destaining of polyacrylamide gels, stained with Coomassie Brilliant Blue R-250, with laccase from basidiomycete Cerrena sp. strain HYB07. Effects of laccase activity, mediator type and concentration, temperature and time on destaining of polyacrylamide gels were evaluated with respect to gel background intensity and protein band signals, and the optimal destaining effects were obtained with 15 U mL−1 laccase and 2 μM ABTS at 37 °C after 2 h. Keywords: Laccase, Destaining, Polyacrylamide gel, Coomassie Brilliant Blue R-25

Exogenous Alanine Reverses the Bacterial Resistance to Zhongshengmycin with the Promotion of the P Cycle in <i>Xanthomonas oryzae</i>

Microbial antibiotic resistance has become a worldwide concern, as it weakens the efficiency of the control of pathogenic microbes in both the fields of medicine and plant protection. A better understanding of antibiotic resistance mechanisms is helpful for the development of efficient approaches to settle this issue. In the present study, GC-MS-based metabolomic analysis was applied to explore the mechanisms of Zhongshengmycin (ZSM) resistance in Xanthomonas oryzae (Xoo), a bacterium that causes serious disease in rice. Our results show that the decline in the pyruvate cycle (the P cycle) was a feature for ZSM resistance in the metabolome of ZSM-resistant strain (Xoo-ZSM), which was further demonstrated as the expression level of genes involved in the P cycle and two enzyme activities were reduced. On the other hand, alanine was considered a crucial metabolite as it was significantly decreased in Xoo-ZSM. Exogenous alanine promoted the P cycle and enhanced the ZSM-mediated killing efficiency in Xoo-ZSM. Our study highlights that the depressed P cycle is a feature in Xoo-ZSM for the first time. Additionally, exogenous alanine is a candidate enhancer and can be applied with ZSM to improve the antibiotic-mediated killing efficiency in the control of infection caused by Xoo