MUC1 in lung adenocarcinoma: cross-sectional genetic and serological study

[Background]Mucin 1 (MUC1) contributes to the growth and metastasis of various cancers, including lung cancer, and MUC1 gene length polymorphisms are associated with susceptibility to lung cancer and its prognosis. In contrast, the association between rs4072037, a single nucleotide polymorphism in MUC1, and lung cancer has not been well studied. [Methods]In the present study, we determined the rs4072037 genotype and measured serum KL-6 levels to evaluate the association between lung adenocarcinoma (ADC) and rs4072037 or serum KL-6 levels. DNA samples were available for 172 patients and these were included in the genomic analyses. In addition, 304 patients were included in the serum analyses. Furthermore, 276 healthy volunteers were included in both genomic and serum analyses. [Results]The rs4072037 genotype was not associated with susceptibility to lung ADC or its prognosis. Interestingly, serum KL-6 levels significantly differed according to rs4072037 genotype in those with T1 or T2 (P < 0.001), N0 or N1 (P = 0.002) and M0 (P < 0.001), but not in those with T3 or T4 (P = 0.882), N2 or N3 (P = 0.616) and M1a or M1b (P = 0.501). Serum KL-6 levels were significantly associated with the presence of lung ADC, as well as with its progression and prognosis, indicating the crucial involvement of KL-6/MUC1 in the development of lung cancer and its progression. [Conclusion]Based on these findings, we conclude that rs4072037 does not have a significant impact on the pathogenesis or prognosis of lung ADC, whereas serum KL-6 levels, which might reflecting the molecular length of MUC1, are significantly associated with lung ADC.This work was partly supported by Grants-in-Aid for Scientific Research from the Ministry of Education, Culture, Sports, Science and Technology of Japan. The funders had no role in study design, collection, analysis and interpretation of data and in writing the manuscript

CNVs in Three Psychiatric Disorders

BACKGROUND: We aimed to determine the similarities and differences in the roles of genic and regulatory copy number variations (CNVs) in bipolar disorder (BD), schizophrenia (SCZ), and autism spectrum disorder (ASD). METHODS: Based on high-resolution CNV data from 8708 Japanese samples, we performed to our knowledge the largest cross-disorder analysis of genic and regulatory CNVs in BD, SCZ, and ASD. RESULTS: In genic CNVs, we found an increased burden of smaller (500 kb) exonic CNVs in SCZ/ASD. Pathogenic CNVs linked to neurodevelopmental disorders were significantly associated with the risk for each disorder, but BD and SCZ/ASD differed in terms of the effect size (smaller in BD) and subtype distribution of CNVs linked to neurodevelopmental disorders. We identified 3 synaptic genes (DLG2, PCDH15, and ASTN2) as risk factors for BD. Whereas gene set analysis showed that BD-associated pathways were restricted to chromatin biology, SCZ and ASD involved more extensive and similar pathways. Nevertheless, a correlation analysis of gene set results indicated weak but significant pathway similarities between BD and SCZ or ASD (r = 0.25–0.31). In SCZ and ASD, but not BD, CNVs were significantly enriched in enhancers and promoters in brain tissue. CONCLUSIONS: BD and SCZ/ASD differ in terms of CNV burden, characteristics of CNVs linked to neurodevelopmental disorders, and regulatory CNVs. On the other hand, they have shared molecular mechanisms, including chromatin biology. The BD risk genes identified here could provide insight into the pathogenesis of BD

Microstructure evolution depended on welding tip geometry on AZ31B alloy joints applied ultrasonic spot welding

Our study systematically evaluated the microstructure evolution which depended on the shape of the welding tip. And then, it was revealed that the different microstructure was generated in the slope and flat regions of the welding tip. In the slope region corresponded to the end of the joints, the wavy behavior due to the intense plastic deformation was observed, and the grain refinement occurred near the weld interface in the slope region at the welding conditions. It was associated that the expansion of the weld diameter was led by the enhancement of the plastic deformation in the slope region, and the weld strength increased. On the other hand, as the welding process progresses, the grain growth occurred in both the slope and flat regions. It was revealed that the {1012} deformation twin and the twin growth were the main deformation mechanism in the process which the grains became coarse during the high strain rate processing such as the ultrasonic spot welding

Interface Characterization of Ultrasonic Spot-Welded Mg Alloy Interlayered with Cu Coating

The effect of Cu coating metallic interlayer on the weldability, joint strength, and interfacial microstructure during high-power ultrasonic spot welding (HP-USW) of AZ31B Mg alloy has been studied. Interlayered samples exhibited good weldability and they resulted in strong sound joints with nearly the same strength as joints without interlayer, with the distinction of lower energy being required. The Cu interlayer affected the thermal and vibrational properties of the interface, as the maximum interface temperature decreased and approached better uniformity across the weld nugget. The base metal grain structure changed to equiaxed larger grains after ultrasonic welding and a chain of parent metal small grains were observed around the interface. A binary intermetallic compound product of Mg-Cu, which was rich in Mg, has been found around the interface that was diffused toward base metal. According to the electron probe micro-analyzer (EPMA) results, alongside temperature measurements and hardness data, the formation of Mg2Cu is suggested in this region. At the interface centerline, a narrow region was identified that was composed of Mg, Cu, and Al. Complementary transmission electron microscopy analysis estimated that Al-containing reaction product is a ternary alloy of the MgCuxAly type. The dispersion of fine grain intermetallic compounds as discrete particles inside Mg substrate in both interfacial regions formed a composite like structure that could participate in joint strengthening

Impact of Extracorporeal Membrane Oxygenation in an Infant Treated with Vancomycin: A Case Report

Vancomycin is a glycopeptide antibiotic used for prophylaxis and treatment of infections caused by methicillin-resistant Staphylococcus aureus. Although major organ sizes and functions mature during infancy, pharmacokinetic studies, especially those focused on infants, are limited. Changes in extracorporeal membrane oxygenation-related drug disposition largely contribute to changes in pharmacokinetics. Here, pharmacokinetic profiles of vancomycin in an infant receiving extracorporeal membrane oxygenation therapy are presented. A two-month-old Japanese infant with moderately decreased renal function was started on 12.0 mg/kg vancomycin every 8 h from day X for prophylaxis of pneumonia during extracorporeal membrane oxygenation therapy. As the trough concentration of vancomycin observed on day X+3 was 27.1 &mu;g/mL, vancomycin was then discontinued. The trough concentration decreased to 18.6 &mu;g/mL 24 h after discontinuation, and 9.0 mg/kg vancomycin every 12 h was restarted from day X+5. On day X+6, the trough concentration increased to 36.1 &mu;g/mL, and vancomycin therapy was again discontinued. On day X+7, the trough concentration decreased to 22.4 &mu;g/mL. The pharmacokinetic profiles of vancomycin based on first-order conditional estimation in this infant were as follows: plasma clearance = 0.053 L/kg/hour, distribution volume = 2.19 L/kg, and half-life = 29.5 h. This research reported the prolonged half-life of vancomycin during extracorporeal membrane oxygenation in infants with moderately decreased renal function

Absolute lymphocyte count and neutrophil-to-lymphocyte ratio as predictors of CDK 4/6 inhibitor efficacy in advanced breast cancer

Cyclin-dependent kinase 4 and 6 inhibitors (CDK4/6i) are the standard agents for treating patients with estrogen receptor-positive and human epidermal growth factor receptor 2-negative advanced breast cancer (ER + HER2 - ABC). However, markers predicting the outcomes of CDK4/6i treatment have yet to be identified. This study was a single-center retrospective cohort study. We retrospectively evaluated 101 patients with ER + HER2 - ABC receiving CDK4/6i in combination with endocrine therapy at Fukuyama City Hospital between November 2017 and July 2021. We investigated the clinical outcomes and the safety of CDK4/6i treatment, and the absolute lymphocyte count (ALC) and neutrophil-to-lymphocyte ratio (NLR) as predictive markers for CDK4/6i. We defined the cut-off values as 1000/mu L for ALC and 3 for NLR, and divided into "low" and "high" groups, respectively. We evaluated 43 and 58 patients who received abemaciclib and palbociclib, respectively. Patients with high ALC and low NLR had significantly longer overall survival than those with low ALC and high NLR (high vs. low; ALC: HR 0.29; 95% CI 0.12-0.70; NLR: HR 2.94; 95% CI 1.21-7.13). There was no significant difference in efficacy between abemaciclib and palbociclib and both had good safety profiles. We demonstrated that ALC and NLR might predict the outcomes of CDK4/6i treatment in patients with ER + HER2 - ABC