Expression of the mismatch repair gene hMLH1 is enhanced in non-small cell lung cancer with EGFR mutations

Mismatch repair (MMR) plays a pivotal role in keeping the genome stable. MMR dysfunction can lead to carcinogenesis by gene mutation accumulation. HMSH2 and hMLH1 are two key components of MMR. High or low expression of them often mark the status of MMR function. Mutations (EGFR, KRAS, etc) are common in non-small cell lung cancer (NSCLC). However, it is not clear what role MMR plays in NSCLC gene mutations. The expression of MMR proteins hMSH2 and hMLH1, and the proliferation markers PCNA and Ki67 were measured by immunohistochemistry in 181 NSCLCs. EGFR and KRAS mutations were identified by high resolution melting analysis. Stronger hMLH1 expression correlated to a higher frequency of EGFR mutations in exon 19 and 21 (p<0.0005). Overexpression of hMLH1 and the adenocarcinoma subtype were both independent factors that related to EGFR mutations in NSCLCs (p=0.013 and p<0.0005). The expression of hMLH1, hMSH2 and PCNA increased, while Ki67 expression significantly decreased (p=0.030) in NSCLCs with EGFR mutations. Overexpression of hMLH1 could be a new molecular marker to predict the response to EGFR-TKIs in NSCLCs. Furthermore, EGFR mutations might be an early event of NSCLC that occur before MMR dysfunction.This work was supported by the National Nature Science Funds in China (Fund No. 81071805; URL: http://isisn.nsfc.gov.cn/egrantweb/), and Dalian Merricon Gene Diagnosis Technology Co., Ltd. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript

Prevalence of gaming disorder in East Asia: A comprehensive meta-analysis

Background and aims: Asian countries are deemed to be high prevalence areas for gaming disorder (GD). This meta-analysis is the first to synthesize the overall prevalence of GD in East Asia and investigate characteristics that influence prevalence estimates. Methods: Systematic and independent searches were conducted across PubMed, Web of Science, Embase, PsycINFO, and the Cochrane Library since their inception to January 27, 2021. The Agency for Healthcare Research and Quality scale was used for quality assessment. A random effect model was used to calculate the overall GD prevalence and 95% confidence intervals (CIs). Results: In total, 22 articles (26 studies) comprising 51,525 participants were included in this meta-analysis. The overall pooled prevalence of GD in East Asia was 12%, 95% CI (10%–15%); this figure was adjusted to 6%, 95% CI (3%–9%) for a representative sample. Higher prevalence was observed in males than in females (16% vs. 8%, respectively, P < 0.05). Subgroup and meta-regression analyses revealed that studies among gamers or those without random sampling reported significantly higher prevalence rates. There were no significant differences between countries/regions, sample size, quality score, proportion of males, and scale used. Discussion and conclusions: The prevalence of GD in East Asia is higher than that in other world regions. Future studies should extend such epidemiological research to other regions to calculate the accurate prevalence of GD to benefit the local identification, prevention, policy formulation, and treatment efforts. Considering its negative effects, effective preventive and treatment measures for GD in East Asia need greater attention

Hyperconnectivity of the lateral amygdala in long-term methamphetamine abstainers negatively correlated with withdrawal duration

Introduction: Several studies have reported structural and functional abnormalities of the amygdala caused by methamphetamine addiction. However, it is unknown whether abnormalities in amygdala function persist in long-term methamphetamine abstainers.Methods: In this study, 38 long-term male methamphetamine abstainers (&gt;12 months) and 40 demographically matched male healthy controls (HCs) were recruited. Considering the heterogeneous nature of the amygdala structure and function, we chose 4 amygdala subregions (i.e., left lateral, left medial, right lateral, and right medial) as regions of interest (ROI) and compared the ROI-based resting-state functional connectivity (FC) at the whole-brain voxel-wise between the two groups. We explored the relationship between the detected abnormal connectivity, methamphetamine use factors, and the duration of withdrawal using correlation analyses. We also examined the effect of methamphetamine use factors, months of withdrawal, and sociodemographic data on detected abnormal connectivity through multiple linear regressions.Results: Compared with HCs, long-term methamphetamine abstainers showed significant hyperconnectivity between the left lateral amygdala and a continuous area extending to the left inferior/middle occipital gyrus and left middle/superior temporal gyrus. Abnormal connections negatively correlated with methamphetamine withdrawal time (r = −0.85, p &lt; 0.001). The linear regression model further demonstrated that the months of withdrawal could identify the abnormal connectivity (βadj = −0.86, 95%CI: −1.06 to −0.65, p &lt; 0.001).Discussion: The use of methamphetamine can impair the neural sensory system, including the visual and auditory systems, but this abnormal connectivity can gradually recover after prolonged withdrawal of methamphetamine. From a neuroimaging perspective, our results suggest that withdrawal is an effective treatment for methamphetamine

efficient loop-extended model checking of data structure methods

Many methods in data structures contain a loop structure on a collection type. These loops result in a large number of test cases and are one of the main obstacles to systematically test these methods. To deal with the loops in methods, in this paper, we propose a novel loop-extended model checking approach, abbreviated as LEMC, to efficiently test whether methods satisfy their own invariant. Our main idea is to combine dynamic symbolic execution with static analysis techniques. Specifically, a concrete execution of the method under test is initially done to collect dynamic execution information, which is used to statically identify the loop-extended similar paths of the concrete execution path. LEMC statically checks and prunes all the states which follow these loop-extended similar paths. The experiments on several case studies show that LEMC can dramatically reduce as many as 90% of the search space and achieve much better performance, compared with the existing approaches such as the Glass Box model checker and Korat.Many methods in data structures contain a loop structure on a collection type. These loops result in a large number of test cases and are one of the main obstacles to systematically test these methods. To deal with the loops in methods, in this paper, we propose a novel loop-extended model checking approach, abbreviated as LEMC, to efficiently test whether methods satisfy their own invariant. Our main idea is to combine dynamic symbolic execution with static analysis techniques. Specifically, a concrete execution of the method under test is initially done to collect dynamic execution information, which is used to statically identify the loop-extended similar paths of the concrete execution path. LEMC statically checks and prunes all the states which follow these loop-extended similar paths. The experiments on several case studies show that LEMC can dramatically reduce as many as 90% of the search space and achieve much better performance, compared with the existing approaches such as the Glass Box model checker and Korat

Mechanical and Tribological Behaviors of U75VG Rail Flash&minus;Butt Welded Joint

Flash&minus;butt welded rail is widely used in railway transportation; however, the welded joint is vulnerable after a long time of service, and its damage mechanism is controversial. Here, tensile and reciprocating friction tests were carried out to analyze the mechanical and tribological behaviors between the welded joint and the base metal of a U75VG rail. The results show that flash&minus;butt welding promotes the pearlite to transform into ferrite, leading to a relatively low hardness value but high plasticity. In addition, the yielding and strength of the all&minus;weld&minus;metal specimen are 385 MPa and 1090 MPa, respectively, which are about 24.51% and 7.63% lower than that of the base metal specimen. It is worth noting that the elongation of the all&minus;weld&minus;metal specimen is 57.1% higher than that of the base metal specimen, and more dimples and tearing ridges can be detected on the fracture morphology of the all&minus;weld&minus;metal specimen, while the fracture morphology of the base metal specimen is filled with shallow dimples and cleavage planes. Moreover, the weld metal has a relatively higher COF (coefficient of friction), and its fluctuation amplitude is 1.25 times higher than that of the base metal, which is due to the rougher worn surface. Furthermore, the introduction of flash&minus;butt welding changes the wear mechanism of the U75VG rail from adhesive wear and oxidation to fatigue wear and slight oxidation, and ultimately leads to more serious damage