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  • Huffman posted an update 10 months, 3 weeks ago

    (151/150).Brain metastases are refractory to therapies that control systemic disease in patients with human epidermal growth factor receptor 2 (HER2+) breast cancer, and the brain microenvironment contributes to this therapy resistance. Nutrient availability can vary across tissues, therefore metabolic adaptations required for brain metastatic breast cancer growth may introduce liabilities that can be exploited for therapy. Here, we assessed how metabolism differs between breast tumors in brain versus extracranial sites and found that fatty acid synthesis is elevated in breast tumors growing in brain. We determine that this phenotype is an adaptation to decreased lipid availability in brain relative to other tissues, resulting in a site-specific dependency on fatty acid synthesis for breast tumors growing at this site. Genetic or pharmacological inhibition of fatty acid synthase (FASN) reduces HER2+ breast tumor growth in the brain, demonstrating that differences in nutrient availability across metastatic sites can result in targetable metabolic dependencies.While T-cell responses to cancer immunotherapy have been avidly studied, long-lived memory has been poorly characterized. In a cohort of metastatic melanoma survivors with exceptional responses to immunotherapy, we probed memory CD8+ T-cell responses across tissues, and across several years. Single-cell RNA sequencing revealed three subsets of resident memory T (TRM) cells shared between tumors and distant vitiligo-affected skin. Paired T-cell receptor sequencing further identified clonotypes in tumors that co-existed as TRM in skin and as effector memory T (TEM) cells in blood. Clonotypes that dispersed throughout tumor, skin, and blood preferentially expressed a IFNG / TNF-high signature, which had a strong prognostic value for melanoma patients. Remarkably, clonotypes from tumors were found in patient skin and blood up to nine years later, with skin maintaining the most focused tumor-associated clonal repertoire. CPTinhibitor These studies reveal that cancer survivors can maintain durable memory as functional, broadly-distributed TRM and TEM compartments.

    We compare the repeatability and accuracy of ultrasound shear wave elastography (USE) and transient optical coherence elastography (OCE).

    Elastic wave speed in gelatin phantoms and chicken breast was measured with USE and OCE and compared with uniaxial mechanical compression testing. Intra- and Inter-repeatability were analyzed using Bland-Altman plots and intraclass correlation coefficients (ICC).

    OCE and USE differed from uniaxial testing by a mean absolute percent error of 8.92% and 16.9%, respectively, across eight phantoms of varying stiffness. Upper and lower limits of agreement for intrasample repeatability for USE and OCE were ±0.075 m/s and -0.14 m/s and 0.13 m/s, respectively. OCE and USE both had ICCs of 0.9991. In chicken breast, ICC for USE was 0.9385 and for OCE was 0.9924.

    OCE and USE can detect small speed changes and give comparable measurements. These measurements correspond well with uniaxial testing.

    OCE and USE can detect small speed changes and give comparable measurements. These measurements correspond well with uniaxial testing.African Americans are at higher risk of multiple myeloma (MM) yet underrepresented in clinical trials and reap less benefits from novel therapies of the disease. To improve representation of African Americans in MM clinical trials, researchers, providers, patients, industry partners and regulators at the FDA-AACR workshop developed recommendations to all stakeholders. The outlined principles offer a roadmap to addressing disparities broadly in clinical trials.

    The field of dentistry has been revolutionized by various concepts. Minimal invasive dentistry is the preferred treatment approach in the present era; therefore, various techniques have been advocated to arrest caries lesions at an early stage on the grounds of better understanding of the dynamic nature of dental caries. Thus, study was conducted to compare and evaluate the penetration depth and enamel microhardness of Resin Infiltrant, CPP-ACPF and Novamin on artificial demineralized enamel surface after orthodontic banding.

    Eighty extracted sound premolars were banded. The bands were cemented with type 1 GIC and further divided into – Group I Resin Infiltrant, Group II CCP-ACPF, Group III Novamin and Group IV Control. The samples were incubated for 30 days and then thermocycled. A window of 4 mm × 4 mm was prepared on the buccal surface of samples and artificially demineralized for 4 weeks. A single application was made for Resin Infiltrant, while Novamin and CCP-ACPF were applied twice daily. These samavitated lesions approaching the outer layer dentine which are too advanced for remineralizing agents but do not necessarily require any drilling of tooth.

    Resin Infiltrant exhibited the highest potential to impede caries and constitutes a competent aerosol free micro-invasive strategy for combating non cavitated lesions approaching the outer layer dentine which are too advanced for remineralizing agents but do not necessarily require any drilling of tooth.Specimens of Tripylina gorganensis, collected from a natural beech forest in Slovak Republic, are described and illustrated. These nematodes were initially identified as an undescribed species, morphologically similar to Tripylina gorganensis described from Iran. An important feature distinguishing both species was the presence of post-vulval uterine sac (PUS) in specimens from Slovak Republic, which, according to the original description (Asghari et al., 2012), was absent in Tripylina gorganensis. However, a careful re-examination of type specimens performed in this study revealed that T. gorganensis also has the post-vulval uterine sac. Consequently, the findings of the morphological and molecular studies performed on the Slovak population and observations on the type material contribute to the redescription of T. gorganensis.Survival prediction aims to predict the time of occurrence of a particular event of interest, such as the time until a patient dies. The main challenge in survival prediction is the presence of incomplete observations due to censoring. The classical formulation for survival prediction treats the survival time as a continuous outcome, which leads to a censored regression problem. Recent work has reformulated the survival prediction problem by discretizing time into a finite number of bins and then applying multi-task binary classification. While the discrete-time formulation is convenient and potentially requires less assumptions than the continuous-time approach, it also loses information by discretizing time. In this paper, we empirically investigate continuous and discrete-time representations for survival prediction to try to quantify the trade-offs between the two formulations. We find that discretizing time does not necessarily decrease prediction accuracy. Furthermore, discrete-time models can result in even more accurate predictors than continuous-time models, but the number of time bins used for discretization has a significant effect on accuracy and should thus be tuned as a hyperparameter rather than specified for convenience.

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