The decrease in sequencing cost and increased sophistication of assembly algorithms for short-read platforms has resulted in a sharp increase in the number of species with genome assemblies. However, these assemblies are highly fragmented, with many gaps, ambiguities, and errors, impeding downstream applications. We demonstrate current state of the art for de novo assembly using the domestic goat (Capra hircus), based on long reads for contig formation, short reads for consensus validation, and scaffolding by optical and chromatin interaction mapping. These combined technologies produced the most continuous de novo mammalian assembly to date, with chromosome-length scaffolds and only 649 gaps. Our assembly represents a ~400-fold improvement in continuity due to properly assembled gaps compared to the previously published C. hircus assembly, and better resolves repetitive structures longer than 1 kb, representing the largest repeat family and immune gene complex ever produced for an individual of a ruminant species.
This study estimates the percentage of health care expenditures in the non-institutionalized United States (U.S.) adult population associated with levels of physical activity inadequate to meet current guidelines. Leisure-time physical activity data from the National Health Interview Survey (2004–2010) were merged with health care expenditure data from the Medical Expenditure Panel Survey (2006–2011). Health care expenditures for inactive (i.e., no physical activity) and insufficiently active adults (i.e., some physical activity but not enough to meet guidelines) were compared with active adults (i.e., ≥150 minutes/week moderate-intensity equivalent activity) using an econometric model. Overall, 11.1% (95% CI: 7.3, 14.9) of aggregate health care expenditures were associated with inadequate physical activity (i.e., inactive and insufficiently active levels). When adults with any reported difficulty walking due to a health problem were excluded, 8.7% (95% CI: 5.2, 12.3) of aggregate health care expenditures were associated with inadequate physical activity. Increasing adults' physical activity to meet guidelines may reduce U.S. health care expenditures.
Lung cancer continues to be a major global health problem; the disease is diagnosed in more than 1.6 million new patients each year. However, significant progress is underway in both the prevention and treatment of lung cancer. Lung cancer therapy has now emerged as a "role model" for precision cancer medicine, with several important therapeutic breakthroughs occurring during 2015. These advances have occurred primarily in the immunotherapy field and in treatments directed against tumors harboring specific oncogenic drivers. Our knowledge about molecular mechanisms for oncogene-driven tumors and about resistance to targeted therapies has increased quickly over the past year. As a result, several regulatory approvals of new agents that significantly improve survival and quality of life for patients with lung cancer who have advanced disease have occurred. The International Association for the Study of Lung Cancer has gathered experts in different areas of lung cancer research and management to summarize the most significant scientific advancements related to prevention and therapy of lung cancer during the past year.
Obesity is associated with a higher risk of breast cancer mortality. The gold standard approach to weight loss is in-person counseling, but telephone counseling may be more feasible. We examined the effect of in-person versus telephone weight loss counseling versus usual care on 6-month changes in body composition, physical activity, diet, and serum biomarkers.
MethodsOne hundred breast cancer survivors with a body mass index $ 25 kg/m 2 were randomly assigned to in-person counseling (n = 33), telephone counseling (n = 34), or usual care (UC) (n = 33). In-person and telephone counseling included 11 30-minute counseling sessions over 6 months. These focused on reducing caloric intake, increasing physical activity, and behavioral therapy. Body composition, physical activity, diet, and serum biomarkers were measured at baseline and 6 months.
ResultsThe mean age of participants was 59 6 7.5 years old, with a mean BMI of 33.1 6 6.6 kg/m 2 , and the mean time from diagnosis was 2.9 6 2.1 years. Fifty-one percent of the participants had stage I breast cancer. Average 6-month weight loss was 6.4%, 5.4%, and 2.0% for in-person, telephone, and UC groups, respectively (P = .004, P = .009, and P = .46 comparing in-person with UC, telephone with UC, and in-person with telephone, respectively). A significant 30% decrease in C-reactive protein levels was observed among women randomly assigned to the combined weight loss intervention groups compared with a 1% decrease among women randomly assigned to UC (P = .05).
ConclusionBoth in-person and telephone counseling were effective weight loss strategies, with favorable effects on C-reactive protein levels. Our findings may help guide the incorporation of weight loss counseling into breast cancer treatment and care.
The Lung Master Protocol (Lung-MAP, S1400) is a groundbreaking clinical trial designed to advance the efficient development of targeted therapies for squamous cell cancer (SCCA) of the lung. There are no approved targeted therapies specific to advanced lung SCCA, although The Cancer Genome Atlas (TCGA) project and similar studies have detected a significant number of somatic gene mutations/amplifications in lung SCCA, some of which are targetable by investigational agents. However, the frequency of these changes is low (5–20%), making recruitment and study conduct challenging in the traditional clinical trial setting. Here we describe our approach to development of a biomarker-driven phase 2/3 multi-substudy “Master Protocol,” employing a common platform (Next Generation DNA Sequencing) to identify actionable molecular abnormalities, followed by randomization to the relevant targeted therapy versus standard of care.
We report a new strategy for coupling chromone to Fe3O4 nanoparticles. The chromone-Fe3O4 NP conjugate shows a dramatic increase in chromone solubility in cell culture medium from less than 2.5 to 633 microg/ml, leading to the enhanced chromone uptake by HeLa cells. Chromone can be released at low pH and as a result, the chromone-Fe3O4 conjugate is much more efficient in inhibiting the HeLa cell proliferation. Such chromone-Fe3O4 NPs are promising as a powerful multifunctional delivery system for both chromone-based diagnostic and therapeutic applications.
Previous event-related potential (ERP) and brain imaging studies have suggested observer responses to others' pain are modulated by various bottom-up and top-down factors, including emotional primes. However, the temporal dynamics underlying the impact of emotional primes on responses to others' pain remains poorly understood. In the present study, we explored effects of negative, neutral, and positive emotional priming stimuli on behavioral and cortical responses to visual depictions of others in pain. ERPs were recorded from 20 healthy adults, who were presented with painful and non-painful target pictures following observation of negative, neutral, and positive emotional priming pictures. ERP analyses revealed that relative to non-painful pictures, differential P3 amplitudes for painful pictures were larger followed by negative primes than either neutral or positive primes. There were no significant differential P3 amplitudes for painful pictures relative to non-painful pictures were found followed neutral and positive emotional primes. These results suggest that negative emotional primes strengthen observers' attention toward others' pain. These results support the threat value of pain hypothesis.
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