Image-guided selection of Gd@C-dots as sensitizers to improve radiotherapy of non-small cell lung cancer.

Background: Recently, gadolinium-intercalated carbon dots (Gd@C-dots) have demonstrated potential advantages over traditional high-Z nanoparticles (HZNPs) as radiosensitizers due to their high stability, minimal metal leakage, and remarkable efficacy.

Results: In this work, two Gd@C-dots formulations were fabricated which bore carboxylic acid (CA-Gd@C-dots) or amino group (pPD-Gd@C-dots), respectively, on the carbon shell. While it is critical to develop innovative nanomateirals for cancer therapy, determining their tumor accumulation and retention is equally important.

Obesity and altered angiogenic-related gene expression in endometrial cancer.

Objectives: Evaluate association between obesity and angiogenic-related gene expression in endometrial cancer (EC). Evaluate interaction between diet and metformin on angiogenic-related gene expression.

Methods: We evaluated the association between 168 human angiogenic-related genes and body mass index (BMI) in the TCGA Uterine Corpus Endometrial Carcinoma cohort (endometrioid endometrial cancer (EEC) cohort n = 290, and copy number high cohort n = 55), an independent validation cohort from Gynecologic Cancer Center of Excellence (GYN-COE) (n = 62) and corresponding 185 homologous mouse genes in an LKB1p53 mouse model of EC (n = 20).

Filopodia powered by class x myosin promote fusion of mammalian myoblasts.

Skeletal muscle fibers are multinucleated cellular giants formed by the fusion of mononuclear myoblasts. Several molecules involved in myoblast fusion have been discovered, and finger-like projections coincident with myoblast fusion have also been implicated in the fusion process. The role of these cellular projections in muscle cell fusion was investigated herein.

The CRCbiome study: a large prospective cohort study examining the role of lifestyle and the gut microbiome in colorectal cancer screening participants.

Background: Colorectal cancer (CRC) screening reduces CRC incidence and mortality. However, current screening methods are either hampered by invasiveness or suboptimal performance, limiting their effectiveness as primary screening methods. To aid in the development of a non-invasive screening test with improved sensitivity and specificity, we have initiated a prospective biomarker study (CRCbiome), nested within a large randomized CRC screening trial in Norway.

New insight into the role of MDMX in MDM2-mediated p53 degradation and anti-cancer drug development.

Inactivation of the tumor suppressor p53 has been generally accepted as a hallmark of tumor. MDM2 and MDMX, the two closely related proteins are considered to be critical for negatively regulating p53 activity through inhibitory binding to and post-translational modification of the p53 protein. We have demonstrated that MDMX facilitates MDM2-mediated p53 ubiquitination and degradation via recruitment of the ubiquitin-conjugating enzyme UbcH5c to the MDM2-MDMX heterooligomers.

A p53/CPEB2 negative feedback loop regulates renal cancer cell proliferation and migration.

The tumor suppressor p53 transactivates the expression of multiple genes to exert its multifaceted functions and ultimately maintains genome stability. Thus, cancer cells develop various mechanisms to diminish p53 expression and bypass the cell cycle checkpoint. In this study, we identified the gene encoding RNA-binding protein cytoplasmic polyadenylation element-binding protein 2 (CPEB2) as a p53 target.

Divergent Mechanisms Activating RAS and Small GTPases Through Post-translational Modification.

RAS is a founding member of the RAS superfamily of GTPases. These small 21 kDa proteins function as molecular switches to initialize signaling cascades involved in various cellular processes, including gene expression, cell growth, and differentiation. RAS is activated by GTP loading and deactivated upon GTP hydrolysis to GDP.

Combined Inhibition of Akt and mTOR Is Effective Against Non-Hodgkin Lymphomas.

Non-Hodgkin lymphoma (NHL) are a diverse group of hematological malignancies comprised of over 60 subtypes. These subtypes range from indolent to aggressive. The PI3K/Akt/mTOR pathway has been shown to contribute to cell survival and proliferation and is constitutively active in most NHL.

A Pilot Study of Preoperative Vandetanib on Markers of Proliferation and Apoptosis in Breast Cancer.

Introduction: Preclinical data supports antitumor activity of tyrosine kinase inhibitor vandetanib with Ret as the therapeutic target in breast cancer. We investigated the effect of preoperative vandetanib on markers of proliferation and apoptosis in breast cancer.

Methods: Patients with invasive breast cancer were randomly assigned vandetanib 300 mg or placebo PO daily for 2 weeks before operative resection from January 2014 to June 2017.

A guide to setting up and managing a lab at a research-intensive institution.

Postdocs who land faculty jobs at research-intensive institutions need to juggle several new large-scale tasks: identifying space and equipment needs for their lab, negotiating the hiring package, outfitting the lab with supplies, building a team, and learning to manage time in ways that can promote productivity and happiness. Here we share tips to help new hires think clearly about each of these tasks.

The Ends Dictate the Means: Promoter Switching in Herpesvirus Gene Expression.

Herpesvirus gene expression is dynamic and complex, with distinct complements of viral genes expressed at specific times in different infection contexts. These complex patterns of viral gene expression arise in part from the integration of multiple cellular and viral signals that affect the transcription of viral genes. The use of alternative promoters provides an increased level of control, allowing different promoters to direct the transcription of the same gene in response to distinct temporal and contextual cues.

Association between PEG3 DNA methylation and high-grade cervical intraepithelial neoplasia.

Background: Epigenetic mechanisms are hypothesized to contribute substantially to the progression of cervical intraepithelial neoplasia (CIN) to cervical cancer, although empirical data are limited.

Methods: Women (n = 419) were enrolled at colposcopic evaluation at Duke Medical Center in Durham, North Carolina. Human papillomavirus (HPV) was genotyped by HPV linear array and CIN grade was ascertained by biopsy pathologic review.

Waterpipe Tobacco Warnings: An Experimental Study Among a Nationally Representative Sample of US Young Adults.

Background: Waterpipe tobacco (WT) smoking by young adults remains high and misperceptions are common. Product warnings can increase knowledge of harms and reduce use. The goal of this study was to test warning statements, including the FDA-required nicotine warning (prior to implementation), on young adults' thinking about harms of and discouragement from WT smoking.

A critical review of measures of childhood vaccine confidence.

The World Health Organization and global partners sought to identify existing measures of confidence in childhood vaccines, as part of a broader effort to measure the range of behavioural and social drivers of vaccination. We identified 14 confidence measures applicable to childhood vaccination in general, all published between 2010 and 2019. The measures examined 1-5 constructs and included a mean of 12 items.

Genetics of HLA Peptide Presentation and Impact on Outcomes in HLA-Matched Allogeneic Hematopoietic Cell Transplantation.

Minor histocompatibility antigens (mHAs), recipient-derived peptide epitopes presented on the cell surface, are known to mediate graft-versus-host disease (GVHD); however, there are no current methods to associate mHA features with GVHD risk. This deficiency is due in part to the lack of technological means to accurately predict, let alone confirm, the tremendous number of potential mHAs in each individual transplant. Previous studies have shown that different HLA molecules present varying fractions of candidate peptide epitopes; however, the genetic "distance" between HLA-matched donors and recipients is relatively constrained.

Single enzyme electroanalysis.

Traditional studies of enzymatic activity rely on the combined kinetics of millions of enzyme molecules to produce a product, an experimental approach that may wash out heterogeneities that exist between individual enzymes. Evaluating these properties on an enzyme-by-enzyme basis represents an unambiguous means of elucidating heterogeneities; however, the quantification of enzymatic activity at the single-enzyme level is fundamentally limited by the maximum catalytic rate, k, inherent to a given enzyme. For electrochemical methods measuring current, single enzymes must turn over greater than 10 molecules per second to produce a measurable signal on the order of 10 A.

The control of polycomb repressive complexes by long noncoding RNAs.

The polycomb repressive complexes 1 and 2 (PRCs; PRC1 and PRC2) are conserved histone-modifying enzymes that often function cooperatively to repress gene expression. The PRCs are regulated by long noncoding RNAs (lncRNAs) in complex ways. On the one hand, specific lncRNAs cause the PRCs to engage with chromatin and repress gene expression over genomic regions that can span megabases.

Estimation of the binomial probabilities in a two-stage phase II clinical trial with two co-primary endpoints.

In cancer research, two-stage designs are usually used to assess the effect of a new agent in phase II clinical trials. Optimal two-stage designs with two co-primary endpoints have been proposed to assess the effects of new cancer treatments, such as cytostatic or molecularly targeted agents (MTAs), based on both response rate and early progression rate. Accurate estimation of response and early progression rates based on the data from the phase II trials conducted according to the optimal two-stage designs would be very useful for further testing of the agents in phase II trials.

Primary Hypothyroidism in Childhood Cancer Survivors Treated With Radiation Therapy: A PENTEC Comprehensive Review.

Purpose: From the Pediatric Normal Tissue Effects in the Clinic (PENTEC) initiative, a systematic review and meta-analysis of publications reporting on radiation dose-volume effects for risk of primary hypothyroidism after radiation therapy for pediatric malignancies was performed.

Methods And Materials: All studies included childhood cancer survivors, diagnosed at age <21 years, whose radiation therapy fields exposed the thyroid gland and who were followed for primary hypothyroidism. Children who received pituitary-hypothalamic or total-body irradiation were excluded.

Initial Data Pooling for Radiation Dose-Volume Tolerance for Carotid Artery Blowout and Other Bleeding Events in Hypofractionated Head and Neck Retreatments.

Purpose: Dose-volume data for injury to carotid artery and other major vessels in stereotactic body radiation therapy (SBRT)/SABR head and neck reirradiation were reviewed, modeled, and summarized.

Methods And Materials: A PubMed search of the English-language literature (stereotactic and carotid and radiation) in April 2018 found 238 major vessel maximum point doses in 6 articles that were pooled for logistic modeling. Two subsequent studies with dose-volume major vessel data were modeled separately for comparison.

Low-Se Diet Can Affect Sperm Quality and Testicular Glutathione Peroxidase-4 activity in Rats.

This study aimed to observe the influence of selenium (Se) deficiency on sperm quality and selenoprotein expression in rats. Four-week male Wista rats were randomly divided into three groups: Se-A, Se-L, and Se-D (respectively for Se- adequate, low, and deficient group). After 9 weeks, the rats were sacrificed by anesthesia, with the cauda epididymidis quickly fetched for sperm count, motility, and deformity.

Identifying Heterogeneous Effect using Latent Supervised Clustering with Adaptive Fusion.

Precision medicine is an important area of research with the goal of identifying the optimal treatment for each individual patient. In the literature, various methods are proposed to divide the population into subgroups according to the heterogeneous effects of individuals. In this paper, a new exploratory machine learning tool, named latent supervised clustering, is proposed to identify the heterogeneous subpopulations.

What Works in Implementing Patient Decision Aids in Routine Clinical Settings? A Rapid Realist Review and Update from the International Patient Decision Aid Standards Collaboration.

Background: Decades of effectiveness research has established the benefits of using patient decision aids (PtDAs), yet broad clinical implementation has not yet occurred. Evidence to date is mainly derived from highly controlled settings; if clinicians and health care organizations are expected to embed PtDAs as a means to support person-centered care, we need to better understand what this might look like outside of a research setting.

Aim: This review was conducted in response to the IPDAS Collaboration's evidence update process, which informs their published standards for PtDA quality and effectiveness.