Search

Neonatal jaundice has been suggested as a perinatal risk factor for autism spectrum disorder (ASD). We examined UGT1A1 polymorphisms to assess the potential of neonatal jaundice as a risk factor for ASD in children by using DNA extracted from preserved umbilical cord. In total, 79 children with ASD were genotyped for "UGT1A1*28" (c.-41-40dup), "UGT1A1*6" (c.211 G > A), and "UGT1A1*27" (c.686 C > A). The allele frequency of "UGT1A1*6" (OR = 1.34, p = 0.26) and "UGT1A1*28" (OR = 0.80, p = 0.54) and the prevalence of "UGT1A1*28/*6" diplotypes did not differ significantly from those in the control population. No "UGT1A1*27" allele was detected in the subjects. ASD symptom assessment scores were not associated with "UGT1A1*28/*6/*27" genotypes or "UGT1A1*28/*6" diplotypes. These results suggest that neonatal jaundice is not significantly associated with ASD.

Addressing the lack of English tests that measure critical thinking (CT) abilities of EFL learners, this study aims to develop an English Critical Thinking Test (ECTT) designed to measure the consistency, analysis, and inference CT skills. It is a follow-up to a pilot study to accumulate validity evidence for the use of the ECTT. A total of 262 Japanese EFL learners who were first-year college students took the ECTT, a Japanese Critical Thinking Test (JCTT), and an English proficiency test (EPT). The result of the internal structures of ECTT and JCTT revealed that both CT tests fit two-factor models better than three-factor models, with consistency as one factor and analysis and inference as the other factor. This implies that it is difficult to measure the CT skills' hierarchical nature. However, the model that included the three tests fit the data well and indicated moderately high correlations between the ECTT and EPT (r = 0.64) and between the ECTT and JCTT (r = 0.55). In addition, we confirmed that the skills that test-takers needed most in solving questions in each of the three CT sections (i.e., consistency, analysis, and inference CT skills) of the ECTT were as intended. Based on these findings, the validation of the ECTT has been improved; ECTT can be used for EFL learners at upper secondary and university levels in Japan.

PURPOSE: Human epidermal growth factor receptor 2 (HER2)–targeted therapies have shown promise in treating HER2 -amplified metastatic colorectal cancer (mCRC). Identifying optimal biomarkers for treatment decisions remains challenging. This study explores the potential of artificial intelligence (AI) in predicting treatment responses to trastuzumab plus pertuzumab (TP) in patients with HER2 -amplified mCRC from the phase II TRIUMPH trial. MATERIALS AND METHODS: AI-powered HER2 quantification continuous score (QCS) and tumor microenvironment (TME) analysis were applied to the prescreening cohort (n = 143) and the TRIUMPH cohort (n = 30). AI analyzers determined the proportions of tumor cells (TCs) with HER2 staining intensity and the densities of various cells in TME, examining their associations with clinical outcomes of TP. RESULTS: The AI-powered HER2 QCS for HER2 immunohistochemistry (IHC) achieved an accuracy of 86.7% against pathologist evaluations, with a 100% accuracy for HER2 IHC 3+ patients. Patients with ≥50% of TCs showing HER2 3+ staining intensity (AI-H3-high) exhibited significantly prolonged progression-free survival (PFS; median PFS, 4.4 v 1.4 months; hazard ratio [HR], 0.12 [95% CI, 0.04 to 0.38]) and overall survival (OS; median OS, 16.5 v 4.1 months; HR, 0.13 [95% CI, 0.05 to 0.38]) compared with the AI-H3-low (<50% group). Stratification among patients with AI-H3-high included TME-high (all lymphocyte, fibroblast, and macrophage densities in the cancer stroma above the median) and TME-low (anything below the median), showing a median PFS of 1.3 and 5.6 months for TME-high and TME-low respectively, with an HR of 0.04 (95% CI, 0.01 to 0.19) for AI-H3-high with TME-low compared with AI-H3-low. CONCLUSION: AI-powered HER2 QCS and TME analysis demonstrated potential in enhancing treatment response predictions in patients with HER2 -amplified mCRC undergoing TP therapy. [ABSTRACT FROM AUTHOR]

Simple Summary: There is no evidence on the efficacy of FOLFIRI plus ramucirumab in colorectal cancer refractory to oxaliplatin plus fluoropyrimidine without bevacizumab. No predictive marker has been established for ramucirumab, either. We planned a prospective study of the efficacy and toxicity of FOLFIRI plus ramucirumab refractory to adjuvant oxaliplatin plus fluoropyrimidine, adding an exploratory analysis to estimate the association of biomarkers with ramucirumab's efficacy. A total of 48 patients were enrolled between September 2017 and September 2020. The median progression-free survival was 8.9 months (90% CI: 6.3–11.8), so the primary endpoint was met. The median overall survival and objective response rate were 22.3 months (95% CI: 17.4-NA) and 41.7% (95% CI: 4.9–7.6), respectively. The incidence of adverse events was consistent with that in previous reports. FOLFIRI plus ramucirumab is one of the options for recurrent colorectal cancer refractory to adjuvant oxaliplatin plus fluoropyrimidine. Serum VEGF-D levels may not be a predictive biomarker for ramucirumab. Serum TSP-2 may be a potential prognostic biomarker. Background: FOLFIRI (5-FU + leucovorin + irinotecan) plus ramucirumab is one of the standards in second-line metastatic colorectal cancer (CRC) patients progressing after treatment with oxaliplatin/fluoropyrimidine with bevacizumab, but there is no evidence on its efficacy without prior bevacizumab. Moreover, VEGF-D has not been confirmed as a predictive biomarker for ramucirumab's efficacy, either. Methods: The RAINCLOUD study was a multicenter, single-arm, phase II trial conducted in Japan. Patients with recurrent CRC pretreated with fluoropyrimidine and oxaliplatin without bevacizumab were analyzed. The primary endpoint was progression-free survival (PFS). The secondary endpoints measured were overall survival (OS), overall response rate (ORR), and safety. Results: A total of 48 patients were enrolled from 15 sites between September 2017 and September 2020. Their median age was 63.5 years (25~77), 20.1% had a right-sided tumor, and 68.8% had RAS-mutant cancer. The median PFS was 8.9 months (90% CI: 6.3–11.8), so the primary endpoint was met. Their median OS and ORR were 22.3 months (95% CI: 17.4-NA) and 41.7% (95% CI: 4.9–7.6), respectively. An incidence of grade 3/4 adverse events that reached over 5% applied to neutropenia (44%), leucopenia (10%), and hypertension (8%). In the biomarker analysis, the serum VEGF-D levels post-treatment were higher than those pre-treatment, but the PFS in those with high VEGF-D levels trended towards being worse than that in those with low VEGF-D (7.6M/5.6M (p = 0.095; HR: 0.56)). Instead, those with low TSP-2 had a better PFS than those with high TSP-2 (7.5M/4.3M (p = 0.022; HR: 0.45)). Conclusions: Our data suggested that FOLFIRI plus ramucirumab was effective and tolerable for CRC refractory to fluoropyrimidine and oxaliplatin without anti-angiogenesis. Serum VEGF-D levels may not be predictive but TSP-2 may be a potential prognostic biomarker for ramucirumab's efficacy. [ABSTRACT FROM AUTHOR]

Fatty acid binding protein 4 (FABP4) is highly expressed in adipocytes. Lipolysis, caused by an elevated adrenergic input, has been suggested to contribute to elevated serum FABP4 levels in patients with cardiovascular diseases. However, the relationship between the serum FABP4 and efferent sympathetic nerve activity remains poorly understood. Twenty‐one healthy subjects (average age, 29.1 years; 15 men) performed an isometric handgrip (HG) exercise at 30% of the maximal voluntary contraction until they were fatigued. The beat‐by‐beat heart rate (HR), blood pressure (BP), and muscle sympathetic nerve activity (MSNA) were recorded. Blood samples were collected at rest and at the time of peak fatigue. The MSNA, HR, and systolic BP were significantly increased by the HG exercise (all, p < 0.05). MSNA was obtained from 14 patients. The change in the FABP4 on HG exercise was significantly correlated with the change in MSNA (bursts/100 heartbeats) (R = 0.808, p < 0.001) but not with changes in other parameters, which might, in part, reflect an association of efferent sympathetic drive with FABP4. Meanwhile, resting FABP4 levels were not associated with any parameters including MSNA, in healthy individuals. Future studies on patients with elevated sympathetic activity are warranted to examine the relationship further. [ABSTRACT FROM AUTHOR]

We developed an on-site system for the rapid simultaneous determination of multiple elements that integrates microdroplet technology with a handheld X-ray fluorescence spectrometer. This system combines the concentration of heavy metals in microdroplets through homogeneous liquid–liquid extraction with the widespread application of handheld X-ray fluorescence spectrometry. The focus of our research was the analysis of heavy metals, specifically lead. Under optimal conditions, we achieved a high extraction percentage of 93.3%, and a high volume ratio of 120 times was achieved (from 23.9 to 0.200 mL). Building on these optimal conditions, we explored a mixed solution of copper and lead to facilitate the simultaneous rapid determination of multiple elements. By exposing a 200-μL microdroplet to a focused X-ray beam (9.0 mm in diameter), we confirmed a good proportional relationship for copper and lead concentrations ranging from 0.0837 to 0.126 mg/L. The determination limit (10 σ) was 0.040 mg/L for copper and 0.030 mg/L for lead. This system enables the stable evaluation of heavy metals at low concentrations (ppb level) with a straightforward operation. [ABSTRACT FROM AUTHOR]

Platinum group metal-free (PGM-free) catalysts based on transition metal-nitrogen-carbon nanomaterials have been studied by a combination of ex situ and in situ synchrotron X-ray spectroscopy techniques; high-resolution Transmission Electron Microscope (TEM); Mößbauer spectroscopy combined with electrochemical methods and Density Functional Theory (DFT) modeling/theoretical approaches. The main objective of this study was to correlate the HO₂- generation with the chemical nature and surface availability of active sites in iron-nitrogen-carbon (Fe-N-C) catalysts derived by sacrificial support method (SSM). These nanomaterials present a carbonaceous matrix with nitrogen-doped sites and atomically dispersed and; in some cases; iron and nanoparticles embedded in the carbonaceous matrix. Fe-N-C oxygen reduction reaction electrocatalysts were synthesized by varying several synthetic parameters to obtain nanomaterials with different composition and morphology. Combining spectroscopy, microscopy and electrochemical reactivity allowed the building of structure-to-properties correlations which demonstrate the contributions of these moieties to the catalyst activity, and mechanistically assign the active sites to individual reaction steps. Associated with Fe-Nx motive and the presence of Fe metallic particles in the electrocatalysts showed the clear differences in the variation of composition; processing and treatment conditions of SSM. From the results of material characterization; catalytic activity and theoretical studies; Fe metallic particles (coated with carbon) are main contributors into the HO₂- generation.

Author(s): Yoshiaki Nakamura [sup.1] [sup.2] , Wataru Okamoto [sup.1] [sup.2] [sup.3] , Takeshi Kato [sup.4] , Taito Esaki [sup.5] , Ken Kato [sup.6] , Yoshito Komatsu [sup.7] , Satoshi Yuki [...], The applicability of circulating tumor DNA (ctDNA) genotyping to inform enrollment of patients with cancer in clinical trials has not been established. We conducted a phase 2 trial to evaluate the efficacy of pertuzumab plus trastuzumab for metastatic colorectal cancer (mCRC), with human epidermal growth factor receptor 2 (HER2) amplification prospectively confirmed by tumor tissue or ctDNA analysis (UMIN000027887). HER2 amplification was confirmed in tissue and/or ctDNA in 30 patients with mCRC. The study met the primary endpoint with a confirmed objective response rate of 30% in 27 tissue-positive patients and 28% in 25 ctDNA-positive patients, as compared to an objective response rate of 0% in a matched real-world reference population treated with standard-of-care salvage therapy. Post hoc exploratory analyses revealed that baseline ctDNA genotyping of HER2 copy number and concurrent oncogenic alterations adjusted for tumor fraction stratified patients according to efficacy with similar accuracy to tissue genotyping. Decreased ctDNA fraction 3 weeks after treatment initiation associated with therapeutic response. Pertuzumab plus trastuzumab showed similar efficacy in patients with mCRC with HER2 amplification in tissue or ctDNA, showing that ctDNA genotyping can identify patients who benefit from dual-HER2 blockade as well as monitor treatment response. These findings warrant further use of ctDNA genotyping in clinical trials for HER2-amplified mCRC, which might especially benefit patients in first-line treatment. The multicenter phase 2 TRIUMPH trial shows the utility of ctDNA genotyping as a screening platform to select patients with HER2-amplified metastatic colorectal cancer who benefit from dual-HER2 blockade with trastuzumab and pertuzumab