Based on the molecular expression of cancer cells, molecular subtypes of breast cancer have been applied to classify patients for predicting clinical outcomes and prognosis. However, further evidence ...is needed regarding the influence of molecular subtypes on the efficacy of radiotherapy (RT) after breast-conserving surgery (BCS), particularly in a population-based context. Hence, the present study employed a propensity-score-matched cohort design to investigate the potential role of molecular subtypes in stratifying patient outcomes for post-BCS RT and to identify the specific clinical benefits that may emerge.
From 2006 to 2019, the present study included 59,502 breast cancer patients who underwent BCS from the Taiwan National Health Insurance Research Database. Propensity scores were utilized to match confounding variables between patients with and without RT within each subtype of breast cancer, namely luminal A, luminal B/HER2-negative, luminal B/HER2-positive, basal-like, and HER2-enriched ones. Several clinical outcomes were assessed, in terms of local recurrence (LR), regional recurrence (RR), distant metastasis (DM), disease-free survival (DFS), and overall survival (OS).
After post-BCS RT, patients with luminal A and luminal B/HER2-positive breast cancers exhibited a decrease in LR (adjusted hazard ratio aHR = 0.18, p < 0.0001; and, 0.24, p = 0.0049, respectively). Furthermore, reduced RR and improved DFS were observed in patients with luminal A (aHR = 0.15, p = 0.0004; and 0.29, p < 0.0001), luminal B/HER2-negative (aHR = 0.06, p = 0.0093; and, 0.46, p = 0.028), and luminal B/HER2-positive (aHR = 0.14, p = 0.01; and, 0.38, p < 0.0001) breast cancers. Notably, OS benefits were found in patients with luminal A (aHR = 0.62, p = 0.002), luminal B/HER2-negative (aHR = 0.30, p < 0.0001), basal-like (aHR = 0.40, p < 0.0001), and HER2-enriched (aHR = 0.50, p = 0.03), but not luminal B/HER2-positive diseases. Remarkably, when considering DM, luminal A patients who received RT demonstrated a lower cumulative incidence of DM than those without RT (p = 0.02).
In patients with luminal A breast cancer who undergo BCS, RT could decrease the likelihood of tumor metastasis. After RT, the tumor's hormone receptor status may predict tumor control regarding LR, RR, and DFS. Besides, the HER2 status of luminal breast cancer patients may serve as an additional predictor of OS after post-BCS RT. However, further prospective studies are required to validate these findings.
Aim
Biallelic loss‐of‐function FAM20A mutations cause amelogenesis imperfecta (AI) type IG, better known as enamel renal syndrome (ERS), characterized by severe enamel hypoplasia, delayed/failed ...tooth eruption, intrapulpal calcifications, gingival hyperplasia and nephrocalcinosis. FAM20A binds to FAM20C, the Golgi casein kinase (GCK) and potentiates its function to phosphorylate secreted proteins critical for biomineralization. While many FAM20A pathogenic mutations have been reported, the pathogeneses of orodental anomalies in ERS remain to be elucidated. This study aimed to identify disease‐causing mutations for patients with ERS phenotypes and to discern the molecular mechanism underlying ERS intrapulpal calcifications.
Methodology
Phenotypic characterization and whole exome analyses were conducted for 8 families and 2 sporadic cases with hypoplastic AI. A minigene assay was performed to investigate the molecular consequences of a FAM20A splice‐site variant. RNA sequencing followed by transcription profiling and gene ontology (GO) analyses were carried out for dental pulp tissues of ERS and the control.
Results
Biallelic FAM20A mutations were demonstrated for each affected individual, including 7 novel pathogenic variants: c.590‐5T>A, c.625T>A (p.Cys209Ser), c.771del (p.Gln258Argfs*28), c.832_835delinsTGTCCGACGGTGTCCGACGGTGTC CA (p.Val278Cysfs*29), c.1232G>A (p.Arg411Gln), c.1297A>G (p.Arg433Gly) and c.1351del (p.Gln451Serfs*4). The c.590‐5T>A splice‐site mutation caused Exon 3 skipping, which resulted in an in‐frame deletion of a unique region of the FAM20A protein, p.(Asp197_Ile214delinsVal). Analyses of differentially expressed genes in ERS pulp tissues demonstrated that genes involved in biomineralization, particularly dentinogenesis, were significantly upregulated, such as DSPP, MMP9, MMP20 and WNT10A. Enrichment analyses indicated overrepresentation of gene sets associated with BMP and SMAD signalling pathways. In contrast, GO terms related to inflammation and axon development were underrepresented. Among BMP signalling genes, BMP agonists GDF7, GDF15, BMP3, BMP8A, BMP8B, BMP4 and BMP6 were upregulated, while BMP antagonists GREM1, BMPER and VWC2 showed decreased expression in ERS dental pulp tissues.
Conclusions
Upregulation of BMP signalling underlies intrapulpal calcifications in ERS. FAM20A plays an essential role in pulp tissue homeostasis and prevention of ectopic mineralization in soft tissues. This critical function probably depends upon MGP (matrix Gla protein), a potent mineralization inhibitor that must be properly phosphorylated by FAM20A‐FAM20C kinase complex.
Opportunity identification, opportunity development, and evaluation studies are the main contents in the entrepreneurship literature, but there lacks in‐depth research on the decision‐making process ...of franchise entrepreneurship. Through case interviews and literature review, this paper presents the cases of four franchise entrepreneurs of convenience store chains in Taiwan as examples to develop a new model of a franchise entrepreneurship decision‐making process. In addition to the new model of this decision‐making process, the following key observations are made based on the case comparison analysis. (1) Franchise entrepreneurs with prior knowledge of relevant industries were all affected by prior knowledge in both industrial decision and organizational type (self‐employment/franchise/merger) decision. Franchise entrepreneurs without prior knowledge of related industries were influenced by social network in both industrial decision and organizational (self‐employment/franchise/merger) decision. (2) Franchise entrepreneurs with prior knowledge of related industries were influenced by prior knowledge and potential financial reward in brand decision. Franchise entrepreneurs without prior knowledge of related industries were influenced by social network and potential financial reward in brand decision. (3) Franchise entrepreneurs with prior knowledge of related industries were influenced by prior knowledge, potential financial reward, and financial resources of the franchise headquarters in the franchise type (franchising/commissioning) decision. Franchise entrepreneurs without prior knowledge of the relevant industry were influenced by the social network, potential financial reward, and financial resources of the franchise headquarters in the franchise type (franchise/authorized chain) decision. (4) Franchise entrepreneurs were influenced by potential financial reward and franchise headquarters management knowledge in the location decision of the start‐up process, regardless of having prior knowledge of the industry or not.
This research introduces Meta-Analysis Structural Equation Modeling (MASEM), a novel method that integrates meta-analysis (MA) and structural equation modeling (SEM). The method helps researchers to ...comprehensively understand issues in the strategic management field. Applying MASEM to analyze data from 112 papers, covering 101,981 observations, the results can be summarized as follows. (1) Entrepreneurial orientation (EO) is significantly positively correlated with firm performance (FP), which addresses the issue of inconsistency among prior studies’ findings. (2) There is a significantly positive correlation between EO and market orientation (MO) and a significantly positive relationship between MO and FP, indicating that MO is a mediator variable to the EO-FP. (3) Environmental dynamism (ED) increases a positive link exists between MO and FP; in other words, compared to low ED, the presence of high ED enhances the correlation between MO and FP significantly. (4) ED influences the slope of MO’s function as a mediator between EO and FP - that is, high ED increases the slope of the intermediary effect of MO on the MO-FP nexus, and low ED reduces the slope of the mediation effect of MO on the MO-FP nexus. These findings provide new thoughts and insights for studies on the correlation between EO and FP and offer substantial suggestions for enterprises. The aforementioned results indicate that besides providing deeper insights and a more comprehensive understanding, MASEM presents deeper insights for researchers and is more efficient than the traditional meta-analysis method. Moreover, MASEM can be applied to in other fields and used with other methods for greater in-depth analyses. Overall, the MASEM technique herein has high reliability and validity when utilized for discussing relationships among variables and gives more comprehensive and accurate conclusions in theoretical and practical aspects.
Plain Language Summary
The Relationship Between Entrepreneurial Orientation and Firm Performance From the perspective of MASEM
This research proposes meta-analysis structural equation modeling (MASEM), which combines meta-analysis and structural equation modeling. The method helps researchers to comprehensively understand issues in the strategic management field. Applying MASEM to analyze data from 112 papers, covering 101,981 observations. (1) There is a significantly positive relationship between entrepreneurial orientation (EO) and firm performance (FP), which addresses the issue of inconsistency among prior studies’ findings. (2) There is a significantly positive relationship between EO and market orientation (MO) and a significantly positive relationship between MO and FP, indicating that MO is a mediator variable to the EO-FP. (3) Environmental dynamism (ED) increases the positive relationship between MO and FP; compared to low ED, high ED has a greater impact on the relationship between MO and FP. (4) ED influences the slope of the mediation effect of MO on the relationship between EO and FP—that is, high ED increases the slope of the mediation effect of MO on the MO-FP nexus, and low ED reduces the slope of the mediation effect of MO on the MO-FP nexus. These findings provide new thoughts and insights for studies on the correlation between EO and FP and offer substantial suggestions for enterprises.
Background and objective
Biallelic loss‐of‐function mutations of human FAM20A have been known to cause enamel‐renal syndrome (ERS), featured by agenesis of dental enamel, nephrocalcinosis, and other ...orodental abnormalities, including gingival hyperplasia. However, while the histopathology of this gingival anomaly has been analyzed, its underlying molecular mechanism remains largely unknown. This study aimed to unravel the pathogenesis of gingival hyperplasia in ERS.
Methods
Whole‐exome sequencing was conducted for an ERS case. Transcriptome analyses, using RNA sequencing, of the patient's gingiva were performed to unravel dysregulated molecules and aberrant biological processes underlying the gingival pathology of ERS, which was further confirmed by histology and immunohistochemistry.
Results
Two novel frameshift FAM20A mutations in Exon 1 (g.5417delG; c.129delG; p.Cys44Alafs*101) and Exon 5 (g.62248_62249delAG; c.734_735delAG; p.Glu245Glyfs*11) were identified. Transcriptional profiling of patient's gingival tissue revealed a total of 1683 genes whose expression had increased (1129 genes) or decreased (554 genes) at least 2‐fold compared to control gingival tissues. There were 951 gene ontology (GO) terms of biological process being significantly over‐represented or under‐represented. While GOs involved in extracellular matrix organization, angiogenesis, biomineralization, and epithelial cell proliferation appeared to be activated in ERS gingiva, genes related to keratinocyte differentiation, epithelial development, and keratinization were of decreased expression. FAM20A immunohistochemistry revealed a strong reactivity at the suprabasal layers of epithelium in control gingiva but showed a significantly diminished and scattered signal in ERS tissues. For genes showing significant over‐expression in the transcriptome analyses, namely ALPL, SPARC, and ACTA2, an increased immunoreactivity was observed.
Conclusion
Our results unraveled a potential role for FAM20A in homeostasis of both gingival epithelium and connective tissues.
Background
The 23‐valent pneumococcal polysaccharide vaccine (PPSV23) is indicated for adults who have a high risk of pneumonia; however, its effectiveness in patients with prostate cancer who are at ...a risk of pneumonia because of age and cancer treatments, including androgen‐deprivation therapy, is unknown.
Methods
Between 2000 and 2010, 38,735 patients with prostate cancer were diagnosed in Taiwan. After exclusions and exact matching for age, previous pneumonia, and influenza vaccination, 2188 vaccinated patients and 2188 unvaccinated patients were recruited. The incidence density of all‐cause bacterial pneumonia hospitalizations was analyzed.
Results
Over 7 years of follow‐up, patients who received the PPSV23 had a significantly lower incidence density, with 142.8 per 1000 person‐years versus 162.0 per 1000 person‐years for unvaccinated patients. More patients in the vaccinated cohort were never hospitalized for pneumonia compared with those in the unvaccinated cohort (64.2% vs 62.2%, respectively). After adjusting for the Charlson comorbidity index, cancer treatment modalities, and socioeconomic levels, the risk of pneumonia‐related hospitalization in the PPSV23 vaccination cohort was 0.48 times lower than that in the unvaccinated cohort (adjusted incidence rate ratio, 0.48; P = .046). For patients who received the influenza vaccination, subgroup analysis demonstrated that PPSV23 vaccination significantly decreased the risk (adjusted incidence rate ratio, 0.45; P < .001). Compared with unvaccinated controls, PPSV23‐vaccinated patients had a lower cumulative incidence for the first occurrence of pneumonia‐related hospitalization (34.49% vs 36.36%; P = .178) and higher overall survival (47.5% and 42.3%, respectively; P < .001).
Conclusions
Vaccination of elderly patients who have prostate cancer with the relatively common and inexpensive PPSV23 can decrease the risk of pneumonia and prolong survival.
Elderly patients and those undergoing treatments for cancer, such as androgen‐deprivation therapy or chemotherapy, are at increased risk of developing pneumonia that requires hospitalization. In elderly patients who have prostate cancer, vaccination with the 23‐valent pneumococcal polysaccharide vaccine is associated with lower rates of pneumonia‐related hospitalization and better survival outcomes compared with unvaccinated patients.
The cyanobacteria-bloom in raw waters frequently causes an unpredictable chemical dosing of preoxidation and coagulation for an effective removal of algal cells in water treatment plants. This study ...investigated the effects of preoxidation with NaOCl and ClO_2 on the coagulation-flotation effectiveness in the removal of two commonly blooming cyanobacteria species, Microcystis aeruginosa（MA） and Cylindrospermopsis raciborskii（CR）, and their corresponding trihalomethane（THM） formation potential. The results showed that dual dosing with NaOCl plus ClO_2 was more effective in enhancing the deformation of cyanobacterial cells compared to single dosing with Na OCl, especially for CR-rich water.Both preoxidation approaches for CR-rich water effectively reduced the CR cell count with less remained dissolved organic carbon（DOC）, which benefited subsequent coagulation–flotation. However, preoxidation led to an adverse release of algogenic organic matter（AOM） in the case of MA-rich water. The release of AOM resulted in a poor removal in MA cells and a large amount of THM formation after oxidation-assisted coagulation-flotation process. The reduction in THM formation potential of CR-rich waters is responsible for effective algae and DOC removal by alum coagulation. It is concluded that the species-specific characteristic of cyanobacteria and their AOM released during chlorination significantly influences the performance of coagulation–flotation for AOM removal and corresponding THM formation.
Angle of arrival (AoA) for target echo signal detection is crucial in vehicular radar systems, where the estimation of signal parameters via rotational invariance (ESPRIT) provides a high-resolution ...estimation. A subarray decomposition strategy is presented in this article to create two ESPRIT antenna arrays with enhanced echo signal strengths, applicable to multi-input-multioutput (MIMO) operations for creating a large virtual array. The concept intends to maximize the echo signal's strength with minimum signal interferences by increasing the aperture sizes of the two ESPRIT antenna arrays. The decomposition produces two virtually overlapped subarrays to increase the subarray aperture sizes in the spatial or spectral representations. It is applied to the MIMO-based arrays for two-way radiation patterns for ESPRIT estimation of AoA. Numerical simulation examples are shown to validate the feasibility and demonstrate the applications.
The dose–response effect of proton pump inhibitors on colorectal cancer prognosis is still under exploration. This population-based study in Taiwan was designed to examine the effect of proton pump ...inhibitors on overall death, colorectal cancer-specific death, and recurrence in colorectal cancer patients with different cumulative proton pump inhibitor dose levels. This cohort study was based on the Taiwan Cancer Registry and Taiwan National Health Insurance Research Database from 2005 to 2020. After frequency matching with a 1:1 ratio, a total of 20,889 users with proton pump inhibitors and 20,889 without proton pump inhibitors were analyzed. The cumulative defined daily dose level of proton pump inhibitor was stratified to explore the dose–response relationship. A proton pump inhibitor exposure cumulative defined daily dose > 60 after colorectal cancer diagnosis had higher risk of all-cause death than non-proton pump inhibitor users with adjusted hazard ratios of 1.10 (95% CIs: 1.04–1.18). For recurrence, a proton pump inhibitor exposure cumulative defined daily dose > 60 had reduced recurrence risk with an adjusted hazard ratio of 0.84 (95% CIs: 0.76–0.93). This study demonstrated that the long-term use of proton pump inhibitors in patients with colorectal cancer was associated with an increased risk of death that related to the proton pump inhibitor exposure cumulative defined daily dose > 60 and had different dose–response effect in various dose level.
The research nature of this study is to examine the priority of English as a foreign language in many non-English speaking countries in the context of globalization with a focus on the importance of ...English for cross-linguistic communication and interpersonal communication. The research purpose is to understand the effects of language picture books applied to interactive teaching methods on English language learning motivation, learning performance, and language and reading ability of elementary school students in southern Taiwan. The research method used herein is an experimental design model. In total, 192 students in eight classes in Grade Six of two elementary schools in southern Taiwan, each with four classes of 24 students, who used the same picture book materials are taken as the research subjects for an experimental study. The research method includes the application of language picture books to interactive teaching methods, combined with a variety of teaching activities, to create a fun and enjoyable learning atmosphere. The study observes students’ active participation and learning performance in the classroom and evaluates the impacts of these activities on their learning motivation, language ability, and reading ability were evaluated. The findings of this study are as follows. 1) The use of the interactive teaching method with language picture books has a significant effect on students’ motivation to learn English, by observing students’ active participation in the classroom. 2) The English picture books inspire children’s curiosity and interest in reading, increase their motivation for English learning, and make them quite interested in reading. 3) The course incorporated a variety of teaching activities to create a happy learning atmosphere, so that students can continue to work toward their English learning goals after the course is over. We also present the conclusions and discussions based on the results in the hope that language picture books can develop students’ capacity for listening and concentration and contribute to the development and improvement of their language ability and reading ability.
Plain Language Summary
The Impact of Interactive Picture Book Teaching Methods
This study aims to understand the effects of applying language picture books to interactive teaching methods on the English learning motivation, performance, and language and reading abilities of elementary school students in southern Taiwan. The research method employed is an experimental design model. In total, 192 students from eight Grade Six classes across two elementary schools in southern Taiwan, each class consisting of 24 students, utilized the same picture book materials for this experimental study. The methodology integrates language picture books with interactive teaching methods, combined with various teaching activities, to create a fun and enjoyable learning environment. This study observes students’ active participation and performance in the classroom and evaluates the impact of these activities on their learning motivation, language proficiency, and reading skills. The findings of this study are as follows: 1) The use of interactive teaching methods with language picture books significantly enhances students’ motivation to learn English, as evidenced by their active participation in class. 2) English picture books ignite children’s curiosity and interest in reading, boosting their motivation to learn English and fostering a profound interest in reading. 3) The curriculum, enriched with diverse teaching activities, establishes a joyful learning atmosphere, motivating students to continue their English learning journey even after the course concludes. Based on the results, we also present conclusions and discussions, hoping that language picture books can cultivate students’ listening and concentration abilities and contribute to the growth and enhancement of their language and reading skills.
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