Tumour stroma ratio is a potential predictor for 5-year disease-free survival in breast cancer.

BACKGROUND: The tumour-stroma ratio (TSR) is identified as a promising prognostic parameter for breast cancer, but the cutoff TSR value is mostly assessed by visual assessment, which lacks objective measurement. The aims of this study were to optimize the cutoff TSR value, and evaluate its prognosis value in patients with breast cancer both as continuous and categorical variables. METHODS: Major clinicopathological and follow-up data were collected for a series of patients with breast cancer. Tissue microarray images stained with cytokeratin immunohistochemistry were evaluated by automated quantitative image analysis algorithms to assess TSR. The potential cutoff point for TSR was optimized using maximally selected rank statistics. The association between TSR and 5-year disease-free survival (5-DFS) was assessed by Cox regression analysis. Kaplan-Meier analysis and log-rank test were used to assess the significance in survival analysis. RESULTS: The optimal cut-off TSR value was 33.5%. Using this cut-off point, categorical variable analysis found that low TSR (i.e., high stroma, TSR ≤ 33.5%) predicts poor outcomes for 5-DFS (hazard ratio [HR] = 2.82, 95% confidence interval [CI] = 1.81-4.40, P = 0.000). When TSR was considered as a continuous parameter, results showed that increased stroma content was associated with worse 5-DFS (HR = 1.71, 95% CI = 1.34-2.18, P = 0.000). Similar results were also obtained in three molecular subtypes in continuous and categorical variable analyses. Moreover, in the Kaplan-Meier analysis, log-rank test showed that low TSR displayed a worse 5-DFS than high TSR (P = 0.000). Similar results were also obtained in patients with triple-negative breast cancer, human epidermal growth factor receptor 2 (HER2)-positive breast cancer, and luminal-HER2-negative breast cancer. CONCLUSION: TSR is an independent predictor for 5-DFS in breast cancer with worse survival outcomes in low TSR. The prognostic value of TSR was also observed in other three molecular subtypes.

Epstein-Barr virus-positive inflammatory follicular dendritic cell sarcoma presenting as a solitary colonic mass: two rare cases and a literature review.

AIMS: Follicular dendritic cell (FDC) sarcoma is a rare neoplasm originating from follicular dendritic cells in germinal centres. It is classified as conventional and Epstein-Barr virus (EBV)-positive inflammatory FDC sarcoma according to the 2019 World Health Organization classification of digestive system tumours; the latter is rarer. So in view of the rarity and difficulty in diagnosis, the aim of the manuscript is to share our experience of diagnosing EBV-positive inflammatory FDC sarcoma. METHODS AND RESULTS: Here, we describe the clinicopathological features, gross description, histomorphology, immunophenotype, EBV-encoded mRNA (EBER) in-situ hybridisation, gene rearrangement and clinical follow-up of two patients with EBV-positive inflammatory FDC sarcoma in the colon, and review the relevant literature. The tumours were found in two males, aged 53 and 48 years, respectively, with a tumour diameter between 10 and 45 mm. Both cases occurred in the colon and presented as pedunculated colonic masses. Microscopically, scanty atypical ovoid to spindle neoplastic cells were mixed in a background of florid lymphoplasmacytic infiltration. The nuclei of these atypical cells showed vesicular chromatin and small, distinct nucleoli. Immunohistochemistry demonstrated that the atypical stromal cells were positive for CD21, CD23, CD35, and D2-40. EBER in-situ hybridisation also gave positive results in two cases. There was a mean follow-up of 9 months (range, 7-11 months). CONCLUSION: EBV-positive inflammatory FDC sarcoma is an extremely rare tumour with a distinct morphology and phenotype. Therefore, it is very important to recognise it particularly for correct diagnosis and prevention of misdiagnosis and mistreatment.

Combined high expression of CD47 and CD68 is a novel prognostic factor for breast cancer patients.

BACKGROUND: Avoiding the phagocytosis by tumor-associated macrophages (TAMs) is necessary for the growth and metastasis of solid tumors. CD47 binds to the receptor signal-regulatory protein-α (SIRP-α) on the macrophages to avoid normal phagocytosis. In this study, we evaluated the expression and prognostic significance of CD47 and CD68-labeled TAMs in breast cancer solid tumors. METHODS: Two hundred seventeen cases of breast cancer tissues and 40 cases of benign breast lesions were collected for immunohistochemical staining of CD47 and CD68. RESULTS: Both of the CD47 and CD68 expression were significantly higher in breast cancer tissues (P < 0.001), and associated with multiple clinicopathological parameters in breast cancer (P < 0.05). However, CD47 or CD68 expression alone was not an independent predictor of poor DFS in multivariate survival analysis (P > 0.05). Interestingly, combined high expression of CD47 and CD68 (CD47highCD68high) not only had a significant association with advanced TNM stage, histological grade, LNM, ER status, PR status and recurrence (P < 0.05), but also displayed a poorer 5-DFS (P = 0.011). Strikingly, CD47highCD68high served as a novel independent prognostic factor for poor DFS compared to the expression of CD47 or CD68 alone (P = 0.045). Furthermore, our study also showed for the first time that the prognostic significance of CD47highCD68high not only in breast cancer in general, but also in hormone receptor-negative breast cancer in particular. CONCLUSIONS: Combined detection of CD47 and CD68 may provide guidance for the prognosis of breast cancer, especially hormone receptor-negative breast cancer.

CIC::NUTM1 sarcomas occurred in soft tissues of upper limbs : a rare case report and literature review.

BACKGROUND: CIC-rearranged sarcomas (CRS) represent a new entity of undifferentiated small round cell sarcoma belonging to the Ewing-like sarcomas family. CRS are the most common type. Fusion partners for the CIC gene include DUX4, FOXO4, and the recently recognizedNUTM1. Rare cases of CIC::NUTM1 sarcoma in pediatric patients have recently been reported in brain, kidney, bone, and soft tissues. However, such cases have not been identified in the soft tissues of the limbs. CASE PRESENTATION: We reported a case of CIC::NUTM1 sarcoma located in the right upper limb of an 18-year-old man. The tumor displayed morphologic features typical of CIC::DUX4 sarcomas, with small- to medium-sized round cells, a lobular pattern, focal spindling, myxoid stroma, and patchy necrosis. The tumor diffusely expressed NUTM1, was positive for WT1cter at weak to moderate intensity, and was focally positive for CD99, while it was negative for keratins, EMA, P40, MyoD1, myogenin, NKX2.2, BCOR, and pan-TRK. Fluorescence in situ hybridization analyses revealed cleavage of the CIC and NUTM1 genes. CONCLUSION: CIC::NUTM1 sarcomas represent a novel molecular variant of CRS with a preference for the central nervous system and younger pediatric persons. Its morphology and phenotype may be mistaken for NUT carcinomas, and the behavior is more progressive than other forms of CRS. For this rare and newly discovered gene fusion variant, it is necessary to integrate molecular and immunohistochemical findings with morphologic features in the diagnosis of undifferentiated neoplasms.

Epithelioid solitary fibrous tumors from CNS and soft tissues: an unusual morphologic variant.

BACKGROUND: Solitary fibroous tumors (SFTs) are distinctive soft tissue tumors characterized by rearrangements of NAB2-STAT6 gene, which are associated with thin-walled, branching, "staghorn"-shaped vessels. SFTs are originally classified as a type of hemangiopericytoma (HPC). Classical SFTs are composed of spindle to ovoid cells arranged haphazardly or in fascicles. Rarely, SFTs exhibit unusual morphological variants such as fat formation, giant cells, dedifferentiation, or epithelioid variant. The epithelioid cell variant, which is composed almost entirely of epithelioid cells and arranged in solid or nest patterns, is extremely rare and frequently malignant. CASE PRESENTATION: In this study, we reported three cases of epithelioid SFTs (ESFTs) located in extrathoracic sites (right lateral ventricle, right lumbar, left pelvis). All the subjects in this study were elderly, with a predominance of female patients, accounting for two out of the three cases, and only one case involved a male patient. The tumor cells were entirely composed of epithelioid cells and exhibited positive for CD34 and STAT-6 markers. Ultimately, the majority of cases (two out of three) were diagnosed as malignant SFTs. CONCLUSION: This study aims to enhance the awareness of ESFTs. In these cases, irrespective of the onset location, the arrangement patterns of tumor cells, such as papillary structures and the morphology of epithelial-like cells, conspicuously lack the hallmark histological characteristics of Solitary Fibrous Tumors (SFTs). Consequently, it requires differential diagnosis from a plethora of malignant neoplasms. Moreover, the elevated malignancy level of this cohort of cases poses substantial diagnostic challenges to pathologists, compounding the complexity of accurate interpretation.

Chinese Private Preschool Teachers' Teaching Readiness and Teacher-Child Relationships: The Chain Mediation Effects of Motivation to Teach and Self-Efficacy.

The teacher-child relationship is a key element in measuring the quality of childcare institutions and is essential to the current and future physical and mental developmental outcomes of children. The purpose of this study is to investigate the role of private preschool teachers' readiness to teach in influencing the teacher-child relationship, and to explore the mechanisms by which teachers' motivation and self-efficacy mediate their readiness to teach and the teacher-child relationship. Online questionnaires were administered to 289 early-childhood teachers in Shanghai, China. The findings of the study indicated a significant and positive correlation between early-childhood teachers' readiness to teach and the quality of the teacher-child relationship. In addition, early-childhood teachers' internal motivation to teach and self-efficacy mediated their readiness to teach and the teacher-child relationship, respectively. However, teachers' external motivation did not mediate the effect of teaching readiness on the quality of the teacher-child relationship. Moreover, teachers' motivation to teach (encompassing both internal and external factors) and their self-efficacy played chained roles in mediating the relationships between teaching readiness and the teacher-child relationship. This study highlights the significant roles of teaching readiness and instructional motivation, along with self-efficacy, in cultivating positive teacher-child relationships within early-childhood education settings.

Lightweight dense video captioning with cross-modal attention and knowledge-enhanced unbiased scene graph.

Dense video captioning (DVC) aims at generating description for each scene in a video. Despite attractive progress for this task, previous works usually only concentrate on exploiting visual features while neglecting audio information in the video, resulting in inaccurate scene event location. In this article, we propose a novel DVC model named CMCR, which is mainly composed of a cross-modal processing (CM) module and a commonsense reasoning (CR) module. CM utilizes a cross-modal attention mechanism to encode data in different modalities. An event refactoring algorithm is proposed to deal with inaccurate event localization caused by overlapping events. Besides, a shared encoder is utilized to reduce model redundancy. CR optimizes the logic of generated captions with both heterogeneous prior knowledge and entities' association reasoning achieved by building a knowledge-enhanced unbiased scene graph. Extensive experiments are conducted on ActivityNet Captions dataset, the results demonstrate that our model achieves better performance than state-of-the-art methods. To better understand the performance achieved by CMCR, we also apply ablation experiments to analyze the contributions of different modules.

Case Report: Gastric cancer with chondromyxoid matrix similar matrix-producing metaplastic breast carcinoma: report of an undescribed entity.

Gastric cancer is a malignant epithelial neoplasm of the stomach, including adenocarcinoma, squamous cell carcinoma, adenosquamous carcinoma, undifferentiated carcinoma, gastroblastoma and neuroendocrine neoplasms, without gastric metaplastic carcinoma. We describe a 69-year-old male patient with gastric cancer who presented with a novel, biphasic histologic morphology with one component consisting of poorly differentiated adenocarcinoma and the other component consisting of chondromyxoid matrix with adenocarcinoma transition to, between the two components without a spindle cell component. The histological morphology of this case is similar to matrix-producing metaplastic breast carcinoma. Therefore, we diagnose this case as gastric carcinoma with chondromyxoid matrix similar matrix-producing metaplastic breast carcinoma.

Posterior choroidal leiomyoma: new findings from a case and literature review.

Posterior choroidal leiomyoma is a sporadic, rare benign tumor that is always confused with anaplastic melanoma. Here we report a case and provide a review. Most of the preoperative findings in our case were suggestive of malignant choroidal melanoma. However, the contrast enhanced ultrasound (CEUS) suggested a benign hemangioma. In summary, the posterior choroidal leiomyomas were yellowish-white in color and most commonly located in the temporal quadrant of the fundus (11/15). They were more frequent in Asians (13/16), the prevalence was almost equal in males and females (9:7), with a mean age of 35y. Microscopically, the tumor typically showed spindle cell bundles and nonmitotic ovoid nuclei arranged in intersecting fascicles. Vitrectomy is now a popular treatment option and definitive diagnosis can be made after immunohistochemistry. Finally, some summarized features of this tumor differ from those previously described. These may help in the diagnosis of posterior choroidal leiomyoma and differentiation from malignant melanoma.

Indolent T-cell lymphoproliferative disorder of gastrointestinal tract with unusual clinical courses: report of 6 cases and literature review.

Indolent T-cell lymphoproliferative disorder of the gastrointestinal tract (iTLPD-GI) is a rare neoplasm usually having an indolent clinical course and easily misdiagnosed as inflammatory bowel disease or other T-cell lymphomas. A subset of the disorders that progressed to overt peripheral T-cell lymphoma have been reported, and the etiology and pathogenesis are poorly understood. The current study retrospectively examined the pathological, molecular, and clinical features of 6 cases of iTLPD-GI. Hematoxylin and eosin staining, immunohistochemistry, in situ hybridization, T-cell receptor gene rearrangement, and next-generation sequencing (NGS) were performed with the diseased tissues. All the 6 patients were immunocompetent Chinese men, who presented with recurrent abdominal pain and diarrhea for 4 to 13 years. Histologically, the intestinal tissue was expanded by lymphoid infiltration, composed of small-to-medium-sized lymphocytes with gland intact. The neoplastic cells were CD4 - /CD8 + with expression of TIA1 and variable granzyme B in five cases, and the other one was CD4 + /CD8 - . Two of the 5 patients progressed to more aggressive T-cell lymphoma and died of disease with complications. NGS identified TET2 and DDX3X mutations in patient 1, and BIRC6 and REV3L mutations in patient 2. Literature review indicated that iTLPD-GI with CD4 - /CD8 + immunophenotype was more commonly reported in Chinese cases. Our limited data indicated CD4-/CD8 + iTLPD-GI have similar potential to progress to more aggressive T-cell lymphoma as that of CD4 + /CD8 - , and gradually increased expression of granzyme B and Ki-67 may be early signs of the disease progression. Gain of novel gene mutations may be indicators of the pathogenesis.

Association of Parental Screen Addiction with Young Children's Screen Addiction: A Chain-Mediating Model.

Preschool children are immersed in screen media, yet little study has been conducted on screen addiction among them. This study aimed to investigate the relationship between parental screen addiction and young children's screen addiction and to verify factors that mediate this relationship. A total of 477 parents of kindergarteners (3-6 years old) were recruited via six kindergartens in Henan province, China. They completed the Problematic Media Use Measure Short Form of Children, the Self-Rating Anxiety Scale, the Child-Parent Relationship Scale, and the Parental Screen Addiction Scale. The results showed that the relationships between each pair of parental screen addiction, parental anxiety, and children's screen addiction were significantly positive, but the parent-child relationship was negatively correlated with the other variables. Parental screen addiction can directly and indirectly affect children's screen addiction through parental anxiety and the parent-child relationship. The findings contribute to the development of family protection mechanisms against screen addiction in children.

Cultural Roots of Parenting: Mothers' Parental Social Cognitions and Practices From Western US and Shanghai/China.

Cultural values can be considered as important factors that impact parents' social cognitions and parenting practices. However, few studies compare specific cultural values of parents and the relationships between cultural values and parenting processes in eastern and western contexts. This study examined the ethnicity differences in mothers' cultural values, parental social cognitions (child-rearing ideologies and goals), and parenting practices between Mainland Chinese and European American contexts. Predictors of parenting goals and parenting practices were also investigated. Mothers of 4-6 years old children from the western United States (N = 78) and Shanghai/China (N = 96) participated in this study. The results suggested that mothers from Shanghai/China were both more collectivistic and individualistic than mothers from the western United States. Chinese mothers more strongly endorsed training and collectivistic parenting goals, while European American mothers more strongly endorsed individualistic parenting goals for their children. However, no significant difference was found in parenting practices for both groups of mothers. For both ethnic groups, in general, mothers' cultural values have small but significant impact on their parenting processes. The prediction of cultural values and parenting goals on parenting practices were also different for both ethnicity groups. Although Chinese mothers were higher on both individualism and collectivism, their collectivistic values were more important in predicting parental social cognitions.

Methylated markers accurately distinguish primary central nervous system lymphomas (PCNSL) from other CNS tumors.

BACKGROUND: Definitive diagnosis of primary central nervous system lymphoma (PCNSL) requires invasive surgical brain biopsy, causing treatment delays. In this paper, we identified and validated tumor-specific markers that can distinguish PCNSL from other CNS tumors in tissues. In a pilot study, we tested these newly identified markers in plasma. RESULTS: The Methylation Outlier Detector program was used to identify markers in TCGA dataset of 48 diffuse large B-cell lymphoma (DLBCL) and 656 glioblastomas and lower-grade gliomas. Eight methylated markers clearly distinguished DLBCL from gliomas. Marker performance was verified (ROC-AUC of ≥ 0.989) in samples from several GEO datasets (95 PCNSL; 2112 other primary CNS tumors of 11 types). Next, we developed a novel, efficient assay called Tailed Amplicon Multiplexed-Methylation-Specific PCR (TAM-MSP), which uses two of the methylation markers, cg0504 and SCG3 triplexed with ACTB. FFPE tissue sections (25 cases each) of PCNSL and eight types of other primary CNS tumors were analyzed using TAM-MSP. TAM-MSP distinguished PCNSL from the other primary CNS tumors with 100% accuracy (AUC = 1.00, 95% CI 0.95-1.00, P < 0.001). The TAM-MSP assay also detected as few as 5 copies of fully methylated plasma DNA spiked into 0.5 ml of healthy plasma. In a pilot study of plasma from 15 PCNSL, 5 other CNS tumors and 6 healthy individuals, methylation in cg0504 and SCG3 was detectable in 3/15 PCNSL samples (20%). CONCLUSION: The Methylation Outlier Detector program identified methylated markers that distinguish PCNSL from other CNS tumors with accuracy. The high level of accuracy achieved by these markers was validated in tissues by a novel method, TAM-MSP. These studies lay a strong foundation for a liquid biopsy-based test to detect PCNSL-specific circulating tumor DNA.

High expression of CD47 in triple negative breast cancer is associated with epithelial-mesenchymal transition and poor prognosis.

CD47 functions as a dominant anti-engulfment signal on tumour cells and is overexpressed in various malignant tumours. However, the expression and functional significance of CD47 in triple-negative breast cancer (TNBC) is not completely understood. In the present study, CD47 was demonstrated to be overexpressed in TNBC solid tumours. Moreover, increased CD47 expression was significantly associated with an advanced tumour-node-metastasis stage, lymph node involvement and recurrence. Moreover, CD47 was an unfavourable and independent prognostic factor for 5-year disease-free survival in patients with TNBC. In addition, the expression of CD47 was associated with several markers of epithelial-mesenchymal transition (EMT). The present study was the first to demonstrate an association between increased expression of CD47 with EMT and poor prognosis of TNBC. Thus, CD47 may be a potential prognostic biomarker and therapeutic target for TNBC.

[The role of myocardin in hypoxia-induced transdifferentiation of pulmonary artery endothelial cells into smooth muscle-like cells].

OBJECTIVE: To investigate the transdifferentiation of pulmonary artery endothelial cells (PAECs) into smooth muscle-like cells under hypoxia and the role of myocardin therein. METHODS: Recombinant plasmid psimyocardin (pSi), capable of silencing the expression of myocardin gene, was constructed by RNAi to be used to transfect the PAECs. Endothelial cells of adult pig pulmonary small arteries were purified by immunomagnetic purification technique, and divided into 4 groups: normoxia group (to be cultured in normoxic cell culture box containing 21% O(2), 5% CO2, and 74% N(2)), normoxia + pSi group, hypoxia group (to be cultured in cell box containing 1% O(2), 5% CO2, and 74% N(2)), and hypoxia + pSi group to be cultured for 1, 4, and 7 days respectively. Indirect fluorescence technique and morphological examination were used to identify the smooth muscle (SM) -like cells and the alpha-SM-actin positive cell ratio. RT-PCR was used to detect the mRNA expression of myocardin. RESULTS: Alpha-SM-actin positive cell could not be seen in the normoxia group and hypoxia 1 d group. The alpha-SM-actin positive cell rate of the hypoxia 7 days group was 2.07% +/- 0.06%, significantly higher than that of the hypoxia 4 d group (0.96% +/- 0.08%, P < 0.01). mRNA expression of myocardin gene could not be seen in the normoxia, normoxia + pSi, hypoxia 1 days, and hypoxia + pSi 1 days groups. The mRNA expression of myocardin gene of the hypoxia 7 days group was 0.23 +/- 0.03, significantly higher than that of the hypoxia 4 days group (0.14 +/- 0.01, P < 0.01). The mRNA expression levels of myocardin gene of the hypoxia + pSi 4 days and 7 days groups 0.03 +/- 0.02 and 0.05 +/- 0.01, both significantly lower than those of the hypoxia 4 days and 7 days groups respectively (0.14 +/- 0.01 and 0.23 +/- 0.03, both P < 0.01). The SM-like cell transdifferentiation rates of the hypoxia + pSi 4 days and 7 days groups were 0.19% +/- 0.07% and 0.21% +/- 0.04% respectively, both significantly lower than those of the corresponding hypoxia groups (0.96% +/- 0.08 and 2.07% +/- 0.06% respectively, both P < 0.01). CONCLUSION: Some PAECs have the potential to transdifferentiate into SM-like cells and may be one of the resources of muscularization of peripheral small vessels. Hypoxia remarkably promotes this transdifferentiation and myocardin may play an important role in this process.