Ethical considerations regarding classroom use of personal genomic information.

Rapidly decreasing costs of genetic technologies-especially next-generation sequencing-and intensifying need for a clinical workforce trained in genomic medicine have increased interest in having students use personal genomic information to motivate and enhance genomics education. Numerous ethical issues attend classroom/pedagogical use of students' personal genomic information, including their informed decision to participate, pressures to participate, privacy concerns, and psychosocial sequelae of learning genomic information. This paper addresses these issues, advocates explicit discussion of these issues to cultivate students' ethical reasoning skills, suggests ways to mitigate potential harms, and recommends collection of ethically relevant data regarding pedagogical use of personal genomic information

Complete Genomic Sequences of Three Salmonella enterica subsp. enterica Serovar Muenchen Strains from an Orchard in San Joaquin County, California.

We present here the complete genome sequences of three Salmonella enterica subsp. enterica serovar Muenchen strains, LG24, LG25, and LG26. All three strains were isolated from almond drupes grown in an orchard in San Joaquin County, California, in 2016. These genomic sequences are nonidentical and will contribute to our understanding of S. enterica genomics

The impact of the skim milk powder manufacturing process on the flavor of model white chocolate

Milk powder is an important ingredient in the confectionary industry but its variable nature has consequences for the quality of the final confectionary product. This paper demonstrates that skim milk powders (SMP) produced using different (but typical) manufacturing processes, when used as ingredients in the manufacture of model white chocolates, had a significant impact on the sensory and volatile profiles of the chocolate. SMP was produced from raw bovine milk using either low or high heat treatment, and a model white chocolate was prepared from each SMP. A directional discrimination test with naïve panellists showed that the chocolate prepared from the high heat SMP had more caramel/fudge character (p<0.0001), and sensory profiling with an expert panel showed an increase in both fudge (p<0.05) and condensed milk (p<0.05) flavor. GC-MS and GC-Olfactometry of both the SMPs and the model chocolates showed a concomitant increase in Maillard-derived volatiles which are likely to account for this change in flavor

Meeting the Emerging Public Health Needs of Persons With Blood Disorders

In its decades-long history, the Division of Blood Disorders (DBD) at CDC has evolved from a patient-focused, services-supporting entity at inception, to one of the world leaders in the practice of public health to improve the lives of people at risk for or affected by nonmalignant blood disorders. The DBD’s earliest public health activities consisted of working with care providers in a network of hemophilia treatment centers to provide AIDS risk reduction services to people with hemophilia. Because this infectious disease threat has been reduced over time as a result of the development of safer treatment products, the DBD—under the auspices of congressional appropriations guidance—has expanded its core activities to encompass blood disorders other than hemophilia, including hemoglobinopathies such as thalassemia and sickle cell disease, and Diamond Blackfan anemia. Simultaneously, in transitioning to a greater public health role, the DBD has expanded its network of partners to new consumer and professional organizations, as well as state and other federal health agencies. The DBD has also developed and maintains many surveillance and registry activities beyond the Universal Data Collection system aimed at providing a better understanding of the health status, health needs, and health-related quality of life of people with nonmalignant blood disorders. The DBD has integrated applicable components of the Essential Services of Public Health successfully to promote and advance the agenda of blood disorders in public health

Genomic analysis identifies unique signatures predictive of brain, lung, and liver relapse

The ability to predict metastatic potential could be of great clinical importance, however, it is uncertain if predicting metastasis to specific vital organs is feasible. As a first step in evaluating metastatic predictions, we analyzed multiple primary tumors and metastasis pairs and determined that >90% of 298 gene expression signatures were found to be similarly expressed between matched pairs of tumors and metastases; therefore, primary tumors may be a good predictor of metastatic propensity. Next, using a dataset of >1,000 human breast tumor gene expression microarrays we determined that HER2-enriched subtype tumors aggressively spread to the liver, while basal-like and claudin-low subtypes colonize the brain and lung. Correspondingly, brain and lung metastasis signatures, along with embryonic stem cell, tumor initiating cell, and hypoxia signatures, were also strongly expressed in the basal-like and claudin-low tumors. Interestingly, low “Differentiation Scores,” or high expression of the aforementioned signatures, further predicted for brain and lung metastases. In total, these data identify that depending upon the organ of relapse, a combination of gene expression signatures most accurately predicts metastatic behavior

Promoting Entrepreneurship amid Youth in Windhoek’s Informal Settlements: A Namibian Case

Considering the high unemployment rate among Namibian youth and a lack of job opportunities, the promotion of entrepreneurship has gained wider attention in the country. A number of initiatives have been started such as entrepreneurship trainings and workshops, business idea competitions, etc. All these aim to inspire young people to think of alternative income sources. As part of a two-year funded community outreach research and development (R&D) project, we have investigated participatory approaches to engage marginalized youth into conceptualizing their own context, imparting skills, and deriving new career paths. This article reports and reflects on one of the interventions we have recently concluded with a group of youth in Havana, an informal settlement in the outskirts of Windhoek. We conducted what we entitled “The Havana Entrepreneur”, a series of interactions inspired upon the model of the American reality game show “The Apprentice”. Over a number of weeks two youth groups were given challenges to tackle by means of competing against one another. After completion of each challenge, groups were rated by a number of judges on skills demonstrated such as marketing, presentation, reflection and creativity among others. We observed an increase in, and improvement of skills revealed along tasks’ completion, besides an openly expressed self-realization and discovery of abilities by participants. Moreover, the youth are currently engaged in the continuation of activities beyond the initial entrepreneurial interactions. Thus we suggest replicating “The Havana Entrepreneur”, including the recording on camera of it by the youth themselves as a new mode to instigating a wider entrepreneurial spirit in informal settlements

Integrated DNA and RNA Sequencing Reveals Drivers of Endocrine Resistance in Estrogen Receptor Positive Breast Cancer

PURPOSE: Endocrine therapy resistance (ETR) remains the greatest challenge in treating patients with hormone receptor–positive breast cancer. We set out to identify molecular mechanisms underlying ETR through in-depth genomic analysis of breast tumors. EXPERIMENTAL DESIGN: We collected pre-treatment and sequential on-treatment tumor samples from 35 patients with estrogen receptor–positive breast cancer treated with neoadjuvant then adjuvant endocrine therapy; 3 had intrinsic resistance, 19 acquired resistance, and 13 remained sensitive. Response was determined by changes in tumor volume neoadjuvantly and by monitoring for adjuvant recurrence. Twelve patients received two or more lines of endocrine therapy, with subsequent treatment lines being initiated at the time of development of resistance to the previous endocrine therapy. DNA whole-exome sequencing and RNA sequencing were performed on all samples, totalling 169 unique specimens. DNA mutations, copy-number alterations, and gene expression data were analyzed through unsupervised and supervised analyses to identify molecular features related to ETR. RESULTS: Mutations enriched in ETR included ESR1 and GATA3. The known ESR1 D538G variant conferring ETR was identified, as was a rarer E380Q variant that confers endocrine hypersensitivity. Resistant tumors which acquired resistance had distinct gene expression profiles compared with paired sensitive tumors, showing elevated pathways including ER, HER2, GATA3, AKT, RAS, and p63 signaling. Integrated analysis in individual patients highlighted the diversity of ETR mechanisms. CONCLUSIONS: The mechanisms underlying ETR are multiple and characterized by diverse changes in both somatic genetic and transcriptomic profiles; to overcome resistance will require an individualized approach utilizing genomic and genetic biomarkers and drugs tailored to each patient

Treg depletion potentiates checkpoint inhibition in claudin-low breast cancer

Claudin-low breast cancer is an aggressive subtype that confers poor prognosis and is found largely within the clinical triple-negative group of breast cancer patients. Here, we have shown that intrinsic and immune cell gene signatures distinguish the claudin-low subtype clinically as well as in mouse models of other breast cancer subtypes. Despite adaptive immune cell infiltration in claudin-low tumors, treatment with immune checkpoint inhibitory antibodies against cytotoxic T lymphocyte–associated protein 4 (CTLA-4) and programmed death receptor 1 (PD-1) were ineffective in controlling tumor growth. CD4+FoxP3+ Tregs represented a large proportion of the tumor-infiltrating lymphocytes (TILs) in claudin-low tumors, and Tregs isolated from tumor-bearing mice were able to suppress effector T cell responses. Tregs in the tumor microenvironment highly expressed PD-1 and were recruited partly through tumor generation of the chemokine CXCL12. Antitumor efficacy required stringent Treg depletion combined with checkpoint inhibition; delays in tumor growth were not observed using therapies that modestly diminished the number of Tregs in the tumor microenvironment. This study provides evidence that the recruitment of Tregs to the tumor microenvironment inhibits an effective antitumor immune response and highlights early Treg recruitment as a possible mechanism for the lack of response to immune checkpoint blockade antibodies in specific subtypes of cancer that are heavily infiltrated with adaptive immune cells