1,271 research outputs found
Polymorphisms in Apoptosis-Related Genes and TP53 Mutations in Non-Small Cell Lung Cancer
Apoptosis plays an essential role in the elimination of mutated or transformed cells from the body. Therefore, polymorphisms of apoptosis-related genes may lead to an alteration in apoptotic capacity, thereby affecting the occurrence of TP53 mutations in lung cancer. We investigated the relationship between potentially functional polymorphisms of apoptosis-related genes and TP53 mutations in non-small cell lung cancer (NSCLC). Twenty-seven single nucleotide polymorphisms in 20 apoptosis-related genes were genotyped by a sequenome mass spectrometry-based genotyping assay in 173 NSCLCs and the associations with TP53 mutations in the entire coding exons (exons 2-11), including splicing sites of the gene, were analyzed. None of the 27 polymorphisms was significantly associated with the occurrence of TP53 mutations. This suggests that apoptosis-related genes may not play an important role in the occurrence of TP53 mutations in lung cancer
Inflammatory bowel disease–associated intestinal fibrosis
Fibrosis is characterized by a proliferation of fibroblasts and excessive extracellular matrix following chronic inflammation, and this replacement of organ tissue with fibrotic tissue causes a loss of function. Inflammatory bowel disease (IBD) is a chronic inflammation of the gastrointestinal tract, and intestinal fibrosis is common in IBD patients, resulting in several complications that require surgery, such as a stricture or penetration. This review describes the pathogenesis and various factors involved in intestinal fibrosis in IBD, including cytokines, growth factors, epithelial-mesenchymal and endothelial-mesenchymal transitions, and gut microbiota. Furthermore, histopathologic findings and scoring systems used for stenosis in IBD are discussed, and differences in the fibrosis patterns of ulcerative colitis and Crohn’s disease are compared. Biomarkers and therapeutic agents targeting intestinal fibrosis are briefly mentioned at the end
A Functional Polymorphism on Chromosome 15q25 Associated with Survival of Early Stage Non–Small-Cell Lung Cancer
Introduction:The 15q25 region has been associated with lung-cancer risk and might also be associated with the prognosis of lung cancer. This study was conducted to determine the impact of a functional polymorphism in the CHRNA3 gene on chromosome 15q25 in the survival of patients with early-stage non–small-cell lung cancer (NSCLC).Methods:Five hundred and eighty-three consecutive patients with surgically resected NSCLC were enrolled. The rs6495309C > T polymorphism in the promoter of the CHRNA3 gene was investigated. The association between genotype and overall survival (OS) and disease-free survival (DFS) was analyzed.Results:Patients with the rs6495309 CT or TT genotype had a significantly better OS and DFS than the rs6495309 CC genotype (adjusted hazard ratio for OS = 0.56, 95% confidence interval = 0.41–0.75, p = 0.0001; and adjusted hazard ratio for DFS = 0.61, 95% confidence interval = 0.48–0.79, p = 0.0001). An association between the rs6495309C > T polymorphism and survival outcome was demonstrated in smokers and never-smokers, and in squamous-cell carcinomas and adenocarcinomas.Conclusion:The CHRNA3 rs6495309C > T polymorphism may affect survival in patients with early-stage NSCLC. Analysis of the rs6495309C > T polymorphism can help identify patients at high risk of a poor disease outcome
AlphaTuning: Quantization-Aware Parameter-Efficient Adaptation of Large-Scale Pre-Trained Language Models
There are growing interests in adapting large-scale language models using
parameter-efficient fine-tuning methods. However, accelerating the model itself
and achieving better inference efficiency through model compression has not
been thoroughly explored yet. Model compression could provide the benefits of
reducing memory footprints, enabling low-precision computations, and ultimately
achieving cost-effective inference. To combine parameter-efficient adaptation
and model compression, we propose AlphaTuning consisting of post-training
quantization of the pre-trained language model and fine-tuning only some parts
of quantized parameters for a target task. Specifically, AlphaTuning works by
employing binary-coding quantization, which factorizes the full-precision
parameters into binary parameters and a separate set of scaling factors. During
the adaptation phase, the binary values are frozen for all tasks, while the
scaling factors are fine-tuned for the downstream task. We demonstrate that
AlphaTuning, when applied to GPT-2 and OPT, performs competitively with full
fine-tuning on a variety of downstream tasks while achieving >10x compression
ratio under 4-bit quantization and >1,000x reduction in the number of trainable
parameters.Comment: Findings of EMNLP 202
Foreign investors’ trading behaviors around merger and acquisition announcements: Evidence from Korea
© 2019 Elsevier Inc. This study examines foreign investors’ trading behaviors around merger and acquisition (M&A) announcements in the Korean stock market (both KOSPI and KOSDAQ markets). We find evidence that foreign investors are more likely to buy target stocks with larger wealth effects on the KOSPI market. In contrast, our results reveal that both foreign and domestic investors are not able to identify target stocks with larger wealth effects on the KOSDAQ market. Further, we find that in response to M&A announcements, only foreign investors can find target stocks with greater subsequent returns on the KOSDAQ market, but not on the KOSPI market
Curative Effects of Thiacremonone against Acetaminophen-Induced Acute Hepatic Failure via Inhibition of Proinflammatory Cytokines Production and Infiltration of Cytotoxic Immune Cells and Kupffer Cells
High doses of acetaminophen (APAP; N-acetyl-p-aminophenol) cause severe hepatotoxicity after metabolic activation by cytochrome P450 2E1. This study was undertaken to examine the preventive effects of thiacremonone, a compound extracted from garlic, on APAP-induced acute hepatic failure in male C57BL/6J. Mice received with 500 mg/kg APAP after a 7-day pretreatment with thiacremonone (10–50 mg/kg). Thiacremonone inhibited the APAP-induced serum ALT and AST levels in a dose-dependent manner, and markedly reduced the restricted area of necrosis and inflammation by administration of APAP. Thiacremonone also inhibited the APAP-induced depletion of intracellular GSH, induction of nitric oxide, and lipid peroxidation as well as expression of P450 2E1. After APAP injection, the numbers of Kupffer cells, natural killer cells, and cytotoxic T cells were elevated, but the elevated cell numbers in the liver were reduced in thiacremonone pretreated mice. The expression levels of I-309, M-CSF, MIG, MIP-1α, MIP-1β, IL-7, and IL-17 were increased by APAP treatment, which were inhibited in thiacremonone pretreated mice. These data indicate that thiacremonone could be a useful agent for the treatment of drug-induced hepatic failure and that the reduction of cytotoxic immune cells as well as proinflammatory cytokine production may be critical for the prevention of APAP-induced acute liver toxicity
Efficacy of Central Neck Dissection for Clinically Node-Negative Papillary Thyroid Carcinoma: Propensity Scoring Matching
Objectives: The utility of prophylactic central neck dissection (pCND) for papillary thyroid carcinoma (PTC) is still controversial. Although the procedure may reduce locoregional recurrence, it is associated with a high rate of postoperative complications. The aim of this study was to evaluate the role of pCND in patients with PTC.Materials and Methods: From January 1995 to April 2011, the records of 477 patients who underwent total thyroidectomy with or without pCND for clinically node-negative PTC measuring < 4 cm were retrospectively reviewed. Of these, 341 patients had undergone pCND with total thyroidectomy and 136 patients did not undergo pCND. The clinicopathologic characteristics, surgical outcomes, complications, recurrence, and survival were analyzed using propensity score matching, using age, sex, tumor size, extrathyroidal extension, and radioactive iodine ablation as covariates to minimize selection bias.Results: At baseline, there was no significant difference in sex, age, and multiplicity and bilaterality of the cancer between the two groups. However, extrathyroidal extension was more common and tumor size larger in patients who underwent pCND. For the propensity score-matched analysis, two matched groups, each comprising 135 patients, were generated. After propensity score matching, the significant differences observed at baseline between the two groups disappeared. The postoperative complication rate did not differ between the two groups. Recurrence occurred in 4 patients (2.96%) who had undergone pCND and in 2 patients (1.48%) who did not undergo pCND (P = 0.684). The recurrence-free survival curves did not differ between the two groups.Conclusion: The efficacy of pCND in total thyroidectomy for clinically node-negative PTC is limited, and pCND is not recommended for these patients
Role of age and sex in determining antibiotic resistance in febrile urinary tract infections
SummaryObjectivesTo identify the age- and sex-specific antimicrobial susceptibility patterns of Gram-negative bacteria (GNB) in outpatient febrile urinary tract infections (UTIs) in Korea.MethodsA total 2262 consecutive samples collected from patients aged 1–101 years with febrile UTIs, during the period January 2012 to December 2014, were analyzed in this multicentre, retrospective cohort study.ResultsThe sensitivities to cefotaxime and cefoxitin were over 85% for females but under 75% for males. Sex played an important role in the susceptibility of GNB to cefotaxime (p<0.001) and cefoxitin (p<0.001). The sensitivity to ciprofloxacin (age >20 years) was under 75% in both sexes, and was not influenced by sex (p=0.204). Age distributions of the incidences of resistance to cefotaxime, cefoxitin, and ciprofloxacin (age >20 years) were similar to the age distribution of the incidence of GNB, which indicates that the resistance patterns to these drugs were not affected by age (Kolmogorov–Smirnov test, female/male: p=0.927/p=0.509, p=0.193/p=0.911, and p=0.077/p=0.999, respectively).ConclusionsAge is not a considerable factor in determining the antibiotic resistance in febrile UTIs. Ciprofloxacin should be withheld from both sexes until culture results indicate its use. Second- or third-generation cephalosporins such as cefoxitin and cefotaxime can be used empirically only in females
- …