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Detection of cytokine biomarkers has the potential to aid in diagnosis and treatment of different diseases. Here, the authors report on the creation of an asymmetric geometry MoS2 diode-based biosensor for the detection of TNF-α as a model biomarker in a proof of concept study.

BACKGROUND The aberrant activation of the PI3K/mTOR signaling circuitry is one of the most frequently dysregulated signaling events in head and neck squamous cell carcinoma (HNSCC). Here, we conducted a single-arm, open-label phase IIa clinical trial in individuals with oral premalignant lesions (OPLs) to explore the potential of metformin to target PI3K/mTOR signaling for HNSCC prevention.METHODS Individuals with OPLs, but who were otherwise healthy and without diabetes, underwent pretreatment and posttreatment clinical exam and biopsy. Participants received metformin for 12 weeks (week 1, 500 mg; week 2, 1000 mg; weeks 3–12, 2000 mg daily). Pretreatment and posttreatment biopsies, saliva, and blood were obtained for biomarker analysis, including IHC assessment of mTOR signaling and exome sequencing.RESULTS Twenty-three participants were evaluable for response. The clinical response rate (defined as a ≥50% reduction in lesion size) was 17%. Although lower than the proposed threshold for favorable clinical response, the histological response rate (improvement in histological grade) was 60%, including 17% complete responses and 43% partial responses. Logistic regression analysis revealed that when compared with never smokers, current and former smokers had statistically significantly increased histological responses (P = 0.016). Remarkably, a significant correlation existed between decreased mTOR activity (pS6 IHC staining) in the basal epithelial layers of OPLs and the histological (P = 0.04) and clinical (P = 0.01) responses.CONCLUSION To our knowledge this is the first phase II trial of metformin in individuals with OPLs, providing evidence that metformin administration results in encouraging histological responses and mTOR pathway modulation, thus supporting its further investigation as a chemopreventive agent.TRIAL REGISTRATION NCT02581137FUNDING NIH contract HHSN261201200031I, grants R01DE026644 and R01DE026870

Risk assessment and follow-up of oral potentially malignant disorders in patients with mild or moderate oral epithelial dysplasia is an ongoing challenge for improved oral cancer prevention. Part of the challenge is a lack of understanding of how observable features of such dysplasia, gathered as data by clinicians during follow-up, relate to underlying biological processes driving progression. Current research is at an exploratory phase where the precise questions to ask are not known. While traditional statistical and the newer machine learning and artificial intelligence methods are effective in well-defined problem spaces with large datasets, these are not the circumstances we face currently. We argue that the field is in need of exploratory methods that can better integrate clinical and scientific knowledge into analysis to iteratively generate viable hypotheses. In this perspective, we propose that visual analytics presents a set of methods well-suited to these needs. We illustrate how visual analytics excels at generating viable research hypotheses by describing our experiences using visual analytics to explore temporal shifts in the clinical presentation of epithelial dysplasia. Visual analytics complements existing methods and fulfills a critical and at-present neglected need in the formative stages of inquiry we are facing.

South Asian children and parents have been shown to have a higher risk for cardiovascular disease (CVD) relative to white individuals. To design interventions aimed at addressing the comparatively higher burden in South Asians, a better understanding of attitudes and perspectives regarding CVD-associated behaviors is needed. As a result, we sought to understand knowledge about CVD risk in both children and parents, and attitudes toward physical activity and diet in both the children and parents, including potential cultural influences. In-depth interviews were conducted with 13 South Asian child-and-parent dyads representing a range of child body mass index (BMI) levels, ages, and with both sexes. South Asian children and parents demonstrated good knowledge about CVD prevention; however, knowledge did not always translate into behavior. The influence of social and cultural dynamics on behavior was also highlighted. To ensure that interventions aimed at this population are effective, an understanding of the unique social dynamics that influence diet and physical activity–related behaviors is needed.

To identify reliable biomarkers of age-related changes in chronic inflammation and responsiveness to bacterial and viral challenges, we evaluated endogenous and ex vivo stimulated levels of 18 inflammatory markers, using whole blood collected in EDTA and sodium heparin tubes from 41 healthy volunteers, i.e., 11 men + 10 women aged 20-35 and 10 men + 10 women aged 50-77. These studies revealed significant differences in the levels of inflammatory markers when blood was collected in EDTA versus sodium heparin and age related differences in these biomarkers were confirmed with blood collected in EDTA from 120 healthy volunteers in 3 age categories, ie, 20 men + 20 women, aged 20-35, 36-49 and 50-77. Studies with unstimulated blood samples, to measure levels of chronic inflammation, revealed a significant increase with age in IL-12p70, CRP and PGE2, consistent with the concept of "inflammaging", and a decrease in G-CSF in both men and women. Interestingly, in response to E. coli stimulation, PGE2 levels were markedly reduced in the 50-77 year old cohort while they were increased following Herpes Simplex virus-1 (HSV-1) stimulation, along with IL-8. In addition, unlike E. coli, HSV-1 potently stimulated IFNα production, but levels were dramatically reduced in the older cohort, consistent with a reduced ability to generate an anti-viral response. We also found platelets and CD8+ T cells were reduced with age while CD4+ T cells were significantly increased, resulting in a substantially higher CD4/CD8 ratio in the older cohort. Surprisingly, however, we found that the older cohort exhibited more T cell proliferation and IFNγ production in response to anti-CD3+anti-CD28 stimulation. Importantly, there was considerable person-to-person variation in these inflammatory markers in all age groups, making possible comparisons between a person's "inflammage" and chronological age. These assays should help to identify individuals at high risk of autoimmune disorders and cancer.

For the first time, we present co-registered autofluorescence imaging and optical coherence tomography (AF/OCT) of excised human palatine tonsils to evaluate the capabilities of OCT to visualize tonsil tissue components. Despite limited penetration depth, OCT can provide detailed structural information about tonsil tissue with much higher resolution than that of computed tomography, magnetic resonance imaging, and Ultrasound. Different tonsil tissue components such as epithelium, dense connective tissue, lymphoid nodules, and crypts can be visualized by OCT. The co-registered AF imaging can provide matching biochemical information. AF/OCT scans may provide a non-invasive tool for detecting tonsillar cancers and for studying the natural history of their development.