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Osteosarcoma(OS) is a highly aggressive bone cancer for which treatment has remained essentially unchanged for decades. Although OS is characterized by extensive genomic heterogeneity and instability, RB1 and TP53 have been shown to be the most commonly inactivated tumor suppressors in OS. We previously generated a mouse model with a double knockout (DKO) of Rb1 and Trp53 within cells of the osteoblastic lineage, which largely recapitulates human OS with nearly complete penetrance. SKP2 is a repression target of pRb and serves as a substrate recruiting subunit of the SCFSKP2 complex. In addition, SKP2 plays a central role in regulating the cell cycle by ubiquitinating and promoting the degradation of p27. We previously reported the DKOAA transgenic model, which harbored a knock-in mutation in p27 that impaired its binding to SKP2. Here, we generated a novel p53-Rb1-SKP2 triple-knockout model (TKO) to examine SKP2 function and its potential as a therapeutic target in OS. First, we observed that OS tumorigenesis was significantly delayed in TKO mice and their overall survival was markedly improved. In addition, the loss of SKP2 also promoted an apoptotic microenvironment and reduced the stemness of DKO tumors. Furthermore, we found that small-molecule inhibitors of SKP2 exhibited anti-tumor activities in vivo and in OS organoids as well as synergistic effects when combined with a standard chemotherapeutic agent. Taken together, our results suggest that SKP2 inhibitors may reduce the stemness plasticity of OS and should be leveraged as next-generation adjuvants in this cancer.

Objective: Nutrition and physical activity are key components of daily diabetes care in young children with type I diabetes (T1D). Normative developmental behavioral challenges related to nutrition and physical activity complicate management of T1D. The current pilot study evaluated the feasibility, acceptability, and indications of behavior change of an intervention aimed at improving nutrition and physical activity in young children with T1D. Method: Thirty-6 parents of young children (ages 2-5 years, M - 4.2) with T1D from 2 clinics in the Washington, DC area were randomized to receive the type One Training (TOTs) program or Usual Care (UC). Assessments included recruitment and completion rates, participant acceptability, and outcomes including glycemic variability via continuous glucose monitoring, nutritional intake via remote food photography, physical activity via accelerometers, and parental report on behavior and psychosocial functioning. Results: Despite recruitment challenges, the TOTs program was feasible to administer, with high program and assessment completion rates. Acceptability ratings were very high but differed by recruitment site. Participants randomized to TOTs had an increase in percent of time in target glycemic range and reduction in behavioral feeding problems between baseline and follow-up while those randomized to UC did not. Participants in UC demonstrated a decrease in in moderate to vigorous physical activity at follow-up. Conclusions: The TOTs program demonstrated preliminary feasibility and acceptability. Future research will examine components of treatment for evidence of efficacy and target the intervention to those most likely to benefit. Keywords: type 1 diabetes, young children, parents, eating, Type I diabetes (T1D) occurs in 1 in 500-600 children and incidence is increasing annually, with higher growth in young children ages 0-9 years (Dabelea et al., 2014; Mayer-Davis et [...]

Synovial sarcoma (SS) is an aggressive soft tissue sarcoma with poor prognosis due to late recurrence and metastasis. Metastasis is an important prognostic factor of SS. This study aimed to identify the core genes and mechanisms associated with SS metastasis. Microarray data for GSE40021 and GSE40018 were obtained from the Gene Expression Omnibus database. 186 differentially expressed genes (DEGs) were identified. The biological functions and signalling pathways closely associated with SS metastasis included extracellular matrix (ECM) organization and ECM‐receptor interaction. Gene set enrichment analysis showed that the terms cell cycle, DNA replication, homologous recombination and mismatch repair were significantly enriched in the metastasis group. Weighted gene co‐expression network analysis identified the most relevant module and 133 hub genes, and 31 crossover genes were identified by combining DEGs. Subsequently, four characteristic genes, EXO1, NCAPG, POLQ and UHRF1, were identified as potential biomarkers associated with SS metastasis using the least absolute shrinkage and selection operator algorithm and validation dataset verification analysis. Immunohistochemistry results from our cohort of 49 patients revealed visible differences in the expression of characteristic genes between the non‐metastatic and metastatic groups. Survival analysis indicated that high expression of characteristic genes predicted poor prognosis. Our data revealed that primary SS samples from patients who developed metastasis showed activated homologous recombination and mismatch repair compared to samples from patients without metastasis. Furthermore, EXO1, NCAPG, POLQ and UHRF1 were identified as potential candidate metastasis‐associated genes. This study provides further research insights and helps explore the mechanisms of SS metastasis. [ABSTRACT FROM AUTHOR]

Purpose: The purpose of this review is to summarize the impact of the multidisciplinary tumor board as a tool or mechanism for orthopedic oncology care, to highlight its evolution and changing role over time, to assess its strengths and weaknesses, and to report our institutional experience as an NCI-Designated Comprehensive Cancer Center. Methods: We reviewed the relevant literature about multidisciplinary tumor boards in orthopedic oncology, and summarized the articles to provide a summary of the topic. Additionally, we retrospectively reviewed our electronic medical records to analyze the distribution, characteristics, and numbers of the cases that were discussed. Results: Our retrospective institutional review revealed a total of 1178 individual patients discussed between August 2018 and August 2023. There was an even distribution of patients by sex, with 549 female (50.2%) patients and 544 male (49.8%). Diagnoses peaked in the second and sixth decades of life (189 and 175 patients, respectively). The majority of patients were discussed once (55%) or twice (21%). The most common neoplastic diagnosis that was presented in these meetings was giant cell tumor of bone (n = 51). Osteosarcoma (n = 41) was the most common diagnosis among the primary malignant bone tumors, and liposarcomas (n = 41) were the most frequently discussed soft tissue sarcoma histology. Conclusion: Tumor boards have played a central role in cancer care for almost a century. Our experience at an NCI-designated comprehensive cancer center has yielded a review of over a thousand individual cases in only a 5-year span of time. [ABSTRACT FROM AUTHOR]

In order to study the effects of different irrigation amounts on the root characteristics and yield of cotton without film mulching (abbreviated as filmless cotton) under drip irrigation in Southern Xinjiang, five irrigation amounts of filmless cotton (300, 375, 450, 525 and 600 mm, represented by W1, W2, W3, W4 and W5) and one irrigation amount of cotton with film mulching (abbreviated as filmed cotton) (450 mm, represented by WCK) were set. The effects of irrigation amount on root length density (RLD), root surface area (RSA), root average diameter (RAD), root volume (RV), root weight density (RED) and yield of filmless cotton were analyzed. The results of the two-year experiment showed the following: (1) The indexes of cotton root growth reached the maximum at the flowering and bolling stage, and the growth of soil root in the periphery (30 cm from the main root) and the lower layer (40–60 cm soil layer) reached the peak at the flowering and bolling stages, respectively; (2) The average value of root growth index of film-free cotton in each treatment was W2 > W3 > W4 > W5 and W1. The RLD of W2 and W3 increased by 19.41–106.67% and 13.66–84.22% in the peripheral and lower soil layer, and the proportion of RSA in the peripheral and middle soil layer (20–40 cm soil layer) increased by 1.64–3.41% and 0.49–4.09% compared with other treatments. The RAD, RV and RWD after W2 treatment were relatively large at various distribution points in the soil, followed by W3 treatment; (3) The average root indexes of WCK were not significantly different from those of W3, but the indexes of the lower soil layer were the smallest, at only 29.18–66.84% of the average value of the non-film mulching treatment, while the root indexes of the surface layer (0–20 cm soil layer) and the surrounding soil were larger, with an increase of 11.43–102.17% and 29.60–111.57%, respectively, compared with the non-film mulching treatment; (4) The seed cotton yield of W3 was the highest in the non-film mulching treatment, reaching 4833.25 kg·hm−2, but was still lower than that of WCK by 27.79%. Conclusion: An appropriate water deficit is conducive to root growth and increases the uniformity of its distribution in the soil layer. The irrigation amount of 375–450 mm for filmless cotton in Southern Xinjiang can promote root growth, prevent senescence and increase yield, which can be used as a reference in production. [ABSTRACT FROM AUTHOR]

The weak signals of artificial seismic records contain the subsurface medium information that is required in the inversion. But in the full waveform inversion (FWI), the weak signals contribute less to the objective functions. Therefore, how to improve the contribution of the weak signals in the objective functions of FWI is the problem that needs to be solved urgently. The research shows (Ren, D. 1980. Preliminary research on seismic record and instantaneous frequency. Oil Geophysical Prospecting 15 no. 1: 7–21) that instantaneous frequency attributes, which are very sensitive to the changes in subsurface velocity, have the potential to extract the weak signals from the seismic records. However, this frequency can only be estimated from the complex seismic signals. Empirical mode decomposition (EMD) method has been widely used in signal analysis so as to estimate the instantaneous frequency, but it is difficult to be applied in FWI due to the huge computation. In order to solve this problem, the instantaneous frequency is replaced with the first-order approximation of the exponential frequency in FWI. In this paper, the objective functions of the first-order approximate exponential frequency FWI (FRE-EFWI) in elastic waves and the source terms of its back propagation formula were derived. Besides, the FRE-EFWI method was proved to improve the contribution of the weak signals in the objective functions of FWI. In addition, the correctness and effectiveness of the method were demonstrated by the examples of FWI. [ABSTRACT FROM AUTHOR]

Breastfeeding is a health promoting social behavior but statistics suggest a persistent disparity of lower rates among African American mothers. The Theory of Normative Social Behavior (TNSB) explains when and how norms influence behaviors, but has produced inconsistent results with respect to proposed moderators group identity and injunctive norms (IN), limiting its predictive value in diverse cultural groups. Cultural norms are one of many influences on breastfeeding behaviors, yet little is known about their mechanisms of influence. The TNSB has not been tested in the breastfeeding context or within an exclusively African American cultural group. Given this knowledge gap, a survey of 528 African American mothers in the Washington, D.C. area was conducted to test the moderating effects of IN and subjective norms (SN) and social identity on the descriptive norms (DN) to intentions relationship as predicted by the TNSB. Structural equation modeling was used to show that when controlling for education and breastfeeding history, norms significantly predicted 26.4% of the variance in breastfeeding intentions. SN and DN interacted negatively to enhance breastfeeding intentions. Latent profile analysis using ethnic pride, collectivism, and religiosity scales detected four profiles of African American social identity. Social identity profile membership was a significant moderator on the DN to intentions pathway in the structural equation model. Profiles with the highest ethnic pride were significantly influenced by DN to intend to breastfeed. Implications from this study for public health intervention and communication messaging are discussed. [ABSTRACT FROM AUTHOR]