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Background The advent of novel therapeutic agents has advanced biomarker characterization in non-small-cell lung cancer (NSCLC), driving increased adoption of next-generation sequencing (NGS) technologies for molecular testing. However, comprehensive data addressing the clinical utility of different NGS platforms for NSCLC remains limited. Methods This retrospective study analyzed real-world data from 478 Taiwanese NSCLC patients over five years, using the Oncomine Focus Assay (OFA) to assess genetic alterations. The evaluation focused on assay accuracy, limit of detection (LoD), sequencing performance, and the genetic landscape of NSCLC. Results The OFA achieved an NGS success rate of 80.5% (385/478), with tumor cell percentage, specimen source and FFPE block age identified as key factors affecting success. Quality metrics demonstrated robust sequencing performance, including 97.0 ± 9.6% on-target alignment, 94.7 ± 6.4% uniformity, and ≥ 500 × coverage for 98.0 ± 6.6% of amplicons. Among the 385 patients analyzed, 86.8% (334/385) were found to harbor pathogenic or likely pathogenic variants, of which 78.4% (262/334) were SNVs/Indels, 41.6% (139/334) were CNVs, 2.7% (9/334) were exon skipping alterations, and 10.2% (34/334) were gene fusions. Actionable driver mutations included EGFR mutations (46.2%, 178/385), KRAS mutations (9.4%, 36/385), ERBB2 mutations (6.8%, 26/385), ALK fusions (4.4%, 17/385), MET exon 14 skipping (2.3%, 9/385), BRAF mutations (2.3%, 9/385), ROS1 and RET fusions (1.8%, 7/385 each), and NTRK1 fusions (0.5%, 2/385). Notably, KRAS G12 C mutation was detected in 2.8% (11/385) of cases. Conclusions This study demonstrates the robust performance of the OFA in identifying clinically relevant genetic alterations in NSCLC. The findings support its clinical utility in precision oncology and provide valuable insights into the genetic landscape of Asian NSCLC, enhancing personalized treatment strategies for lung cancer patients.

Preclinical and clinical studies have offered evidence for protective effects of various polyphenol-rich foods against cardiovascular diseases, neurodegenerative diseases, and cancers. Resveratrol is among the most widely studied polyphenols. However, the preventive and treatment effectiveness of resveratrol in cancer remain controversial because of certain limitations in existing studies. For example, studies of the activity of resveratrol against cancer cell lines in vitro have often been conducted at concentrations in the low μM to mM range, whereas dietary resveratrol or resveratrol-containing wine rarely achieve nM concentrations in the clinic. While the mechanisms underlying the failure of resveratrol to inhibit cancer growth in the intact organism are not fully understood, the interference by thyroid hormones with the anticancer activity of resveratrol have been well documented in both in vitro and xenograft studies. Thus, endogenous thyroid hormones may explain the failure of anticancer actions of resveratrol in intact animals, or in the clinic. In this review, mechanisms involved in resveratrol-induced antiproliferation and effects of thyroid hormones on these mechanisms are discussed.

Ornithobacterium rhinotracheale (ORT) is a bacterium common to commercial poultry and wild birds throughout the world. It is also known as a causative agent of respiratory diseases. A total of 93 ORT isolates originating from chickens, pigeons, ostriches, quail, turkeys, and an Asian crested goshawk (Accipiter trivirgatus) in Taiwan, between 2004 and 2006, were used in this study. High genetic similarity (97%–100%) in 16S rRNA sequence was revealed among the 50 randomly selected isolates, in addition to a reference strain (ATCC-51464) and seven reference sequences from GenBank. In order to obtain a greater genetic discrimination among the ORT isolates, random amplified polymorphic DNA (RAPD) and single-enzyme amplified fragment length polymorphism (SE-AFLP) methods were further conducted. The results showed that both RAPD and SE-AFLP assays showed higher discriminatory abilities than the 16S rRNA sequence assay. Genetic clustering revealed that chicken- and quail-origin isolates were genetically distinct from those of the ostrich, pigeon, and Asian crested goshawk-origin isolates. However, among the two typing methods, the turkey-origin isolates showed diverse genetic characteristics to domestic avian species. With this information, ecologic and epidemiologic studies could be furthered for the reduction and control of ORT transmission in Taiwan.

MicroRNA399-mediated regulation of the ubiquitin-conjugating enzyme UBC24/PHOSPHATE2 (PHO2) is crucial for Pi acquisition and translocation in plants. Because of a potential role for PHO2 in protein degradation and its association with membranes, an iTRAQ (for isobaric tags for relative and absolute quantitation)- based quantitative membrane proteomic method was employed to search for components downstream of PHO2. A total of 7491 proteins were identified from Arabidopsis thaliana roots by mass spectrometry, 35.2% of which were predicted to contain at least one transmembrane helix. Among the quantifiable proteins, five were significantly differentially expressed between the wild type and pho2 mutant under two growth conditions. Using immunoblot analysis, we validated the upregulation of several members in PHOSPHATE TRANSPORTER1 (PHT1) family and PHOSPHATE TRANSPORTER TRAFFIC FACILITATOR1 (PHF1) in pho2 and demonstrated that PHO2 mediates the degradation of PHT1 proteins. Genetic evidence that loss of PHF1 or PHT1;1 alleviated Pi toxicity in pho2 further suggests that they play roles as downstream components of PHO2. Moreover, we showed that PHO2 interacts with PHT1s in the postendoplasmic reticulum compartments and mediates the ubiquitination of endomembrane-localized PHT1;1. This study not only uncovers a mechanism by which PHO2 modulates Pi acquisition by regulating the abundance of PHT1s in the secretory pathway destined for plasma membranes, but also provides a database of the membrane proteome that will be widely applicable in root biology research.

Phytoplasma SAP11 effectors acquired fundamental activity in destabilizing TB/CYC-TCPs, the key factors controlling axillary meristem development, and serve as core virulence factors responsible for the witches' broom symptom. Abstract As key mediators linking developmental processes with plant immunity, TCP (TEOSINTE-BRANCHED, CYCLOIDEA, PROLIFERATION FACTOR 1 and 2) transcription factors have been increasingly shown to be targets of pathogenic effectors. We report here that TB/CYC (TEOSINTE-BRANCHED/CYCLOIDEA)-TCPs are destabilized by phytoplasma SAP11 effectors, leading to the proliferation of axillary meristems. Although a high degree of sequence diversity was observed among putative SAP11 effectors identified from evolutionarily distinct clusters of phytoplasmas, these effectors acquired fundamental activity in destabilizing TB/CYC-TCPs. In addition, we demonstrate that miR156/SPLs and miR172/AP2 modules, which represent key regulatory hubs involved in plant phase transition, were modulated by Aster Yellows phytoplasma strain Witches' Broom (AY-WB) protein SAP11. A late-flowering phenotype with significant changes in the expression of flowering-related genes was observed in transgenic Arabidopsis plants expressing SAP11AYWB. These morphological and molecular alterations were correlated with the ability of SAP11 effectors to destabilize CIN (CINCINNATA)-TCPs. Although not all putative SAP11 effectors display broad-spectrum activities in modulating morphological and physiological changes in host plants, they serve as core virulence factors responsible for the witches' broom symptom caused by phytoplasmas.

Pancreatic cancer is usually asymptomatic in the early stages; the 5-y survival rate is around 9%; and there is a lack of effective treatment. Here we show that SSEA-4 is more expressed in all pancreatic cancer cell lines examined but not detectable in normal pancreatic cells; and high expression of SSEA-4 or the key enzymes B3GALT5 + ST3GAL2 associated with SSEA-4 biosynthesis significantly lowers the overall survival rate. To evaluate potential new treatments for pancreatic cancer, homogeneous antibodies with a well-defined Fc glycan for optimal effector functions and CAR-T cells with scFv construct designed to target SSEA-4 were shown highly effective against pancreatic cancer in vitro and in vivo. This was further supported by the finding that a subpopulation of natural killer (NK) cells isolated by the homogeneous antibody exhibited enhancement in cancer-cell killing activity compared to the unseparated NK cells. These results indicate that targeting SSEA-4 by homologous antibodies or CAR-T strategies can effectively inhibit cancer growth, suggesting SSEA-4 as a potential immunotherapy target for treating pancreatic disease.

The impact of film thickness and annealing temperature on the structural, electrical, magnetic, and mechanical properties of cobalt–iron–dysprosium (Co40Fe40Dy20 ) thin films deposited on Si(100) substrates have been investigated. X-ray diffraction (XRD) analysis confirmed the film's crystalline microstructure, featuring dysprosium oxide, Dy2O3(440), and cobalt oxide, Co2O3(422) and Co2O3(511), crystallographic phases. Surface energy measurements indicated a noticeable reduction in surface energy following annealing treatments, which could be ascribed to the alleviation of residual stress and enhanced atomic arrangement, resulting in a more stable film structure with reduced surface energy. The film exhibited a decreasing trend in hardness with increasing thickness, and film resistivity was significantly responsive to alterations in thickness and annealing temperature. Notably, the Co40Fe40Dy20 film demonstrated exceptional characteristics, featuring a high saturation magnetization (Ms) of 675 emu/cm3 and a low coercivity (Hc) of 9.5 Oe. Further analysis of magnetic domains and hysteresis loops revealed that larger and brighter domains were associated with higher Hc. To sum up, the surface roughness of CoFeDy films under various annealing temperatures played a pivotal role in shaping their magnetic, electrical, adhesive, and optical characteristics. An improved low-frequency alternating current magnetic susceptibility (χac) value was achieved by minimizing the pinning effect on domain walls through surface smoothing. Moreover, smoother surfaces displayed heightened carrier conductivity, resulting in a decrease in electrical resistance. On the whole, Co40Fe40Dy20 films exhibited outstanding soft magnetic properties, encompassing high saturation magnetization, low coercivity, exceptional mechanical attributes, and decreased surface energy.

Purpose - Creditor reliance on accounting-based numbers as a persistent and traditional standard to assess a firm's financial soundness and viability suggests that the integrity of financial statements is essential to credit decisions. The purpose of this paper is to provide an approach to explore fraudulent financial reporting (FFR) via growing hierarchical self-organizing map (GHSOM), an unsupervised neural network tool, to help capital providers evaluate the integrity of financial statements, and to facilitate analysis further to reach prudent credit decisions.Design methodology approach - This paper develops a two-stage approach: a classification stage that well trains the GHSOM to cluster the sample into subgroups with hierarchical relationship, and a pattern-disclosure stage that uncovers patterns of the common FFR techniques and relevant risk indicators of each subgroup.Findings - An application is conducted and its results show that the proposed two-stage approach can help capital providers evaluate the reliability of financial statements and accounting numbers-based decisions.Practical implications - Following the SOM theories, it seems that common FFR techniques and relevant risk indicators extracted from the GHSOM clustering result are applicable to all samples clustered in the same leaf node (subgroup). This principle and any pre-warning signal derived from the identified indicators can be applied to assessing the reliability of financial statements and forming a basis for further analysis in order to reach prudent decisions. The limitation of this paper is the subjective parameter setting of GHSOM.Originality value - This is the first application of GHSOM to financial data and demonstrates an alternative way to help capital providers such as lenders to evaluate the integrity of financial statements, a basis for further analysis to reach prudent decisions. The proposed approach could be applied to other scenarios that rely on accounting numbers as a basis for decisions.

The objective of this study is to apply an unsupervised neural network tool to analyze fraudulent financial reporting (FFR) by extracting distinguishing features from samples of groups of companies and converting them into useful information for FFR detection. This methodology can be used as a decision support tool to help build an FFR identification model or other financial fraud or financial distress scenarios. The three stages of the proposed quantitative analysis approach are as follows: the data-preprocessing stage; the clustering stage, which uses an unsupervised neural network tool known as a growing hierarchical self-organizing map (GHSOM) to cluster sample observations into subgroups with hierarchical relationships; and the feature-extraction stage, which uncovers common features of each subgroup via principle component analysis. This study uses the hierarchal topology mapping ability of a GHSOM to cluster financial data, and it adopts principal component analysis to determine common embedded features and fraud patterns. The results show that the proposed three-stage approach is helpful in revealing embedded features and fraud patterns, using a set of significant explanatory financial indicators and the proportion of fraud. The revealed features can be used to distinguish distinctive groups.

Emotion dysregulation is one of the challenges that children with autism spectrum disorder (ASD) and their families face. It is unclear whether emotion dysregulation plays a mediating role in the relationship between sensory processing patterns and problem behaviors among these children. This study examined the relations between emotion dysregulation, behavioral problems, and sensory processing patterns among fifty-seven young children with ASD. Behavioral problems and sensory processing patterns were moderately to strongly correlated with emotion dysregulation. The relationship between sensory processing patterns and behavioral problems was significant with emotion dysregulation as a mediator. These findings help identify the relationship between emotion dysregulation, sensory processing patterns, and behavioral problems to facilitate the planning of intervention strategies for young children with ASD.