Multi-cancer early detection test sensitivity for cancers with and without current population-level screening options

There are four solid tumors with common screening options in the average-risk population aged 21 to 75 years (breast, cervical, colorectal, and, based on personalized risk assessment, prostate), but many cancers lack recommended population screening and are often detected at advanced stages when mortality is high. Blood-based multi-cancer early detection tests have the potential to improve cancer mortality through additional population screening. Reported here is a post-hoc analysis from the third Circulating Cell-free Genome Atlas substudy to examine multi-cancer early detection test performance in solid tumors with and without population screening recommendations and in hematologic malignancies. Participants with cancer in the third Circulating Cell-free Genome Atlas substudy analysis were split into three subgroups: solid screened tumors (breast, cervical, colorectal, prostate), solid unscreened tumors, and hematologic malignancies. In this post hoc analysis, sensitivity is reported for each subgroup across all ages and those aged ⩾50 years overall, by cancer, and by clinical cancer stage. Aggregate sensitivity in the solid screened, solid unscreened, and hematologic malignancy subgroups was 34%, 66%, and 55% across all cancer stages, respectively; restricting to participants aged ⩾50 years showed similar aggregate sensitivity. Aggregate sensitivity was 27%, 53%, and 60% across stages I to III, respectively. Within the solid unscreened subgroup, aggregate sensitivity was >75% in 8/18 cancers (44%) and >50% in 13/18 (72%). This multi-cancer early detection test detected cancer signals at high (>75%) sensitivity for multiple cancers without existing population screening recommendations, suggesting its potential to complement recommended screening programs. Clinical trial identifier: NCT02889978

Revisiting Date and Party Hubs: Novel Approaches to Role Assignment in Protein Interaction Networks

The idea of 'date' and 'party' hubs has been influential in the study of protein-protein interaction networks. Date hubs display low co-expression with their partners, whilst party hubs have high co-expression. It was proposed that party hubs are local coordinators whereas date hubs are global connectors. Here we show that the reported importance of date hubs to network connectivity can in fact be attributed to a tiny subset of them. Crucially, these few, extremely central, hubs do not display particularly low expression correlation, undermining the idea of a link between this quantity and hub function. The date/party distinction was originally motivated by an approximately bimodal distribution of hub co-expression; we show that this feature is not always robust to methodological changes. Additionally, topological properties of hubs do not in general correlate with co-expression. Thus, we suggest that a date/party dichotomy is not meaningful and it might be more useful to conceive of roles for protein-protein interactions rather than individual proteins. We find significant correlations between interaction centrality and the functional similarity of the interacting proteins.Comment: 27 pages, 5 main figures, 4 supplementary figure

The inhibitory effect of an RGD-human chitin-binding domain fusion protein on the adhesion of fibroblasts to reacetylated chitosan films

Biomaterials used for tissue engineering applications must provide a structural support for the tissue development and also actively interact with cells, promoting adhesion, proliferation, and differentiation. To achieve this goal, adhesion molecules may be used, such as the tripeptide Arg-Gly-Asp (RGD). A method based on the use of a carbohydrate-binding module, with affinity for chitin, was tested as an alternative approach to the chemical grafting of bioactive peptides. This approach would simultaneously allow the production of recombinant peptides (alternatively to peptide synthesis) and provide a simple way for the specific and strong adsorption of the peptides to the biomaterial. A fusion recombinant protein, containing the RGD sequence fused to a human chitin-binding module (ChBM), was expressed in E. coli. The adhesion of fibroblasts to reacetylated chitosan (RC) films was the model system selected to analyze the properties of the obtained proteins. Thus, the evaluation of cell attachment and proliferation on polystyrene surfaces and reacetylated chitosan films, coated with the recombinant proteins, was performed using mouse embryo fibroblasts 3T3. The results show that the recombinant proteins affect negatively fibroblasts anchorage to the materials surface, inhibiting its adhesion and proliferation. We also conclude that this negative effect is fundamentally due to the human chitin-binding domain.Fundação para a Ciência e a Tecnologia (FCT) - SFRH/BD/27359/2006, POCTI/BIO/45356/200

Future Prospects for Periodontal Bioengineering Using Growth Factors

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/142015/1/cap0088.pd

Osteoinduction of Human Mesenchymal Stem Cells by Bioactive Composite Scaffolds without Supplemental Osteogenic Growth Factors

The development of a new family of implantable bioinspired materials is a focal point of bone tissue engineering. Implant surfaces that better mimic the natural bone extracellular matrix, a naturally nano-composite tissue, can stimulate stem cell differentiation towards osteogenic lineages in the absence of specific chemical treatments. Herein we describe a bioactive composite nanofibrous scaffold, composed of poly-caprolactone (PCL) and nano-sized hydroxyapatite (HA) or beta-tricalcium phosphate (TCP), which was able to support the growth of human bone marrow mesenchymal stem cells (hMSCs) and guide their osteogenic differentiation at the same time. Morphological and physical/chemical investigations were carried out by scanning, transmission electron microscopy, Fourier-transform infrared (FTIR) spectroscopy, mechanical and wettability analysis. Upon culturing hMSCs on composite nanofibers, we found that the incorporation of either HA or TCP into the PCL nanofibers did not affect cell viability, meanwhile the presence of the mineral phase increases the activity of alkaline phosphatase (ALP), an early marker of bone formation, and mRNA expression levels of osteoblast-related genes, such as the Runt-related transcription factor 2 (Runx-2) and bone sialoprotein (BSP), in total absence of osteogenic supplements. These results suggest that both the nanofibrous structure and the chemical composition of the scaffolds play a role in regulating the osteogenic differentiation of hMSCs

Variations in Healthcare Access and Utilization Among Mexican Immigrants: The Role of Documentation Status

The objective of this study is to identify differences in healthcare access and utilization among Mexican immigrants by documentation status. Cross-sectional survey data are analyzed to identify differences in healthcare access and utilization across Mexican immigrant categories. Multivariable logistic regression and the Blinder-Oaxaca decomposition are used to parse out differences into observed and unobserved components. Mexican immigrants ages 18 and above who are immigrants of California households and responded to the 2007 California Health Interview Survey (2,600 documented and 1,038 undocumented immigrants). Undocumented immigrants from Mexico are 27% less likely to have a doctor visit in the previous year and 35% less likely to have a usual source of care compared to documented Mexican immigrants after controlling for confounding variables. Approximately 88% of these disparities can be attributed to predisposing, enabling and need determinants in our model. The remaining disparities are attributed to unobserved heterogeneity. This study shows that undocumented immigrants from Mexico are much less likely to have a physician visit in the previous year and a usual source of care compared to documented immigrants from Mexico. The recently approved Patient Protection and Affordable Care Act will not reduce these disparities unless undocumented immigrants are granted some form of legal status

Regional Environmental Breadth Predicts Geographic Range and Longevity in Fossil Marine Genera

Geographic range is a good indicator of extinction susceptibility in fossil marine species and higher taxa. The widely-recognized positive correlation between geographic range and taxonomic duration is typically attributed to either accumulating geographic range with age or an extinction buffering effect, whereby cosmopolitan taxa persist longer because they are reintroduced by dispersal from remote source populations after local extinction. The former hypothesis predicts that all taxa within a region should have equal probabilities of extinction regardless of global distributions while the latter predicts that cosmopolitan genera will have greater survivorship within a region than endemics within the same region. Here we test the assumption that all taxa within a region have equal likelihoods of extinction.We use North American and European occurrences of marine genera from the Paleobiology Database and the areal extent of marine sedimentary cover in North America to show that endemic and cosmopolitan fossil marine genera have significantly different range-duration relationships and that broad geographic range and longevity are both predicted by regional environmental breadth. Specifically, genera that occur outside of the focal region are significantly longer lived and have larger geographic ranges and environmental breadths within the focal region than do their endemic counterparts, even after controlling for differences in sampling intensity. Analyses of the number of paleoenvironmental zones occupied by endemic and cosmopolitan genera suggest that the number of paleoenvironmental zones occupied is a key factor of geographic range that promotes genus survivorship.Wide environmental tolerances within a single region predict both broad geographic range and increased longevity in marine genera over evolutionary time. This result provides a specific driving mechanism for the spatial and temporal distributions of marine genera at regional and global scales and is consistent with the niche-breadth hypothesis operating on macroevolutionary timescales

Estimating the Effects of Immigration Status on Mental Health Care Utilizations in the United States

Immigration status is a likely deterrent of mental health care utilization in the United States. Using the Medical Expenditure Panel Survey and National Health Interview survey from 2002 to 2006, multivariable logistic regressions were used to estimate the effects of immigration status on mental health care utilization among patients with depression or anxiety disorders. Multivariate regressions showed that immigrants were significantly less likely to take any prescription drugs, but not significantly less likely to have any physician visits compared to US-born citizens. Results also showed that improving immigrants’ health care access and health insurance coverage could potentially reduce disparities between US-born citizens and immigrants by 14–29% and 9–28% respectively. Policy makers should focus on expanding the availability of regular sources of health care and immigrant health coverage to reduce disparities on mental health care utilization. Targeted interventions should also focus on addressing immigrants’ language barriers, and providing culturally appropriate services

Leaf Trait-Environment Relationships in a Subtropical Broadleaved Forest in South-East China

Although trait analyses have become more important in community ecology, trait-environment correlations have rarely been studied along successional gradients. We asked which environmental variables had the strongest impact on intraspecific and interspecific trait variation in the community and which traits were most responsive to the environment. We established a series of plots in a secondary forest in the Chinese subtropics, stratified by successional stages that were defined by the time elapsed since the last logging activities. On a total of 27 plots all woody plants were recorded and a set of individuals of every species was analysed for leaf traits, resulting in a trait matrix of 26 leaf traits for 122 species. A Fourth Corner Analysis revealed that the mean values of many leaf traits were tightly related to the successional gradient. Most shifts in traits followed the leaf economics spectrum with decreasing specific leaf area and leaf nutrient contents with successional time. Beside succession, few additional environmental variables resulted in significant trait relationships, such as soil moisture and soil C and N content as well as topographical variables. Not all traits were related to the leaf economics spectrum, and thus, to the successional gradient, such as stomata size and density. By comparing different permutation models in the Fourth Corner Analysis, we found that the trait-environment link was based more on the association of species with the environment than of the communities with species traits. The strong species-environment association was brought about by a clear gradient in species composition along the succession series, while communities were not well differentiated in mean trait composition. In contrast, intraspecific trait variation did not show close environmental relationships. The study confirmed the role of environmental trait filtering in subtropical forests, with traits associated with the leaf economics spectrum being the most responsive ones