Supersensitive PSA-Monitored neoadjuvant hormone treatment of clinically localized prostate cancer: Effects on positive margins, tumor detection and epithelial cells in bone marrow

Objective: The present study was done to investigate the effects of supersensitive PSA-controlled inductive treatment on positive margins, detection of tumor and epithelial cells in bone marrow of 101 patients with untreated and clinically localized prostatic carcinoma (cT1-3N0M0). Methods: Hormonal treatment was given until PSA (DPD Immulite(R) third-generation assay) reached 0.3 ng/ml in only 1 case. Of the 101 patients, 82 had a measurable hypoic lesion on initial transrectal ultrasound. 84% of these became smaller, 7.5% remained unchanged and 8.5% increased. Of the 101 prostatectomy specimens, 20 (20%) were margin-positive. The incidence of affected margins was relatively high (35% from 55 patients) with cT3 tumors, but almost negligible (2% from 46 patients) in cT1-2 tumor. Our pathologists, despite their great experience in evaluating hormonally treated prostates (>500 cases) and using immunohistochemical staining, were unable to detect carcinoma in 15 (15%) specimens. Whereas only 2 (4%) of the 55 cT3 specimens were without detectable tumor, this incidence rised to 28% (13 of 46 prostates) in patients with cT1-2 tumors. Of the initial 29 patients with epithelial cells in bone marrow, only 4 (14%) remained positive after controlled induction and all of them had fewer cells than before. Conclusion: Endocrine induction controlled by a supersensitive PSA assay and continued until reaching PSA nadir is highly effective in clearing surgical margins and eliminating tumor cells from bone marrow. It seems to be clearly superior to the conventional 3 months of pretreatment at least in cT1-2 tumors in respect to surgical margins and detectability of tumor in the resected prostate. A definitive statement about the value of endocrine induction can only be given by prospective randomized studies, with optimal drugs, doses and treatment time. But the conventional 3 months of pretreatment are far from exploiting the possibilities of this therapeutic option

Direct Type I IFN but Not MDA5/TLR3 Activation of Dendritic Cells Is Required for Maturation and Metabolic Shift to Glycolysis after Poly IC Stimulation

Type I interferons (IFNs) play an important role in direct antiviral defense as well as linking the innate and adaptive immune responses. On dendritic cells (DCs), IFNs facilitate their activation and contribute to CD8+ and CD4+ T cell priming. However, the precise molecular mechanism by which IFNs regulate maturation and immunogenicity of DCs in vivo has not been studied in depth. Here we show that, after in vivo stimulation with the TLR ligand poly IC, IFNs dominate transcriptional changes in DCs. In contrast to direct TLR3/mda5 signaling, IFNs are required for upregulation of all pathways associated with DC immunogenicity. In addition, metabolic pathways, particularly the switch from oxidative phosphorylation to glycolysis, are also regulated by IFNs and required for DC maturation. These data provide evidence for a metabolic reprogramming concomitant with DC maturation and offer a novel mechanism by which IFNs modulate DC maturation

Mild Cognitive Impairment in the Elderly is Associated with Volume Loss of the Cholinergic Basal Forebrain Region

Background Cholinergic neurons within the basal forebrain are assumed to be an early (preclinical) manifestation site of pathological changes in Alzheimer's disease (AD). Methods We used morphometric magnetic resonance imaging (MRI) to detect and quantify atrophic changes in the basal forebrain of subjects suffering from amnestic mild cognitive impairment (aMCI). Three Tesla magnetic resonance (MR) data of 26 aMCI patients, 46 cognitively normal elderly control subjects (CO), and 12 patients suffering from Alzheimer's dementia were analyzed, including segmentation and quantification of brain tissue as well as a segmentation of basal forebrain structures (substantia innominata [SI]). Results We found the volume of the SI to be significantly different between groups in that control subjects showed the largest SI volumes, followed by aMCI and AD patients. Conclusions These results are in line with the hypothesis that cell loss within the cholinergic basal forebrain regions occurs already in the early (predementia) stage of AD. In vivo quantification of these changes might be of use as a novel neuroimaging marker of cholinergic neurodegeneration in AD

Document Filtering for Long-tail Entities

Filtering relevant documents with respect to entities is an essential task in the context of knowledge base construction and maintenance. It entails processing a time-ordered stream of documents that might be relevant to an entity in order to select only those that contain vital information. State-of-the-art approaches to document filtering for popular entities are entity-dependent: they rely on and are also trained on the specifics of differentiating features for each specific entity. Moreover, these approaches tend to use so-called extrinsic information such as Wikipedia page views and related entities which is typically only available only for popular head entities. Entity-dependent approaches based on such signals are therefore ill-suited as filtering methods for long-tail entities. In this paper we propose a document filtering method for long-tail entities that is entity-independent and thus also generalizes to unseen or rarely seen entities. It is based on intrinsic features, i.e., features that are derived from the documents in which the entities are mentioned. We propose a set of features that capture informativeness, entity-saliency, and timeliness. In particular, we introduce features based on entity aspect similarities, relation patterns, and temporal expressions and combine these with standard features for document filtering. Experiments following the TREC KBA 2014 setup on a publicly available dataset show that our model is able to improve the filtering performance for long-tail entities over several baselines. Results of applying the model to unseen entities are promising, indicating that the model is able to learn the general characteristics of a vital document. The overall performance across all entities---i.e., not just long-tail entities---improves upon the state-of-the-art without depending on any entity-specific training data.Comment: CIKM2016, Proceedings of the 25th ACM International Conference on Information and Knowledge Management. 201

A versatile microarray platform for capturing rare cells

Analyses of rare events occurring at extremely low frequencies in body fluids are still challenging. We established a versatile microarray-based platform able to capture single target cells from large background populations. As use case we chose the challenging application of detecting circulating tumor cells (CTCs) - about one cell in a billion normal blood cells. After incubation with an antibody cocktail, targeted cells are extracted on a microarray in a microfluidic chip. The accessibility of our platform allows for subsequent recovery of targets for further analysis. The microarray facilitates exclusion of false positive capture events by co-localization allowing for detection without fluorescent labelling. Analyzing blood samples from cancer patients with our platform reached and partly outreached gold standard performance, demonstrating feasibility for clinical application. Clinical researchers free choice of antibody cocktail without need for altered chip manufacturing or incubation protocol, allows virtual arbitrary targeting of capture species and therefore wide spread applications in biomedical sciences

Factors Identified by Lapsed Donors that Might Influence Donor Return

Introduction: The Burlington Chapter of the American Red Cross estimates that 8,000 donors a year become lapsed, or fail to return for further donation. To better target this population and retain current donors, it is essential to identify reasons for lapsed donation. Several studies have been conducted on the barriers to retaining blood donors, revealing these common factors: past physical reactions, convenience, previous deferrals, lack of awareness, medical reasons, time, satisfaction with the experience, too impersonal, and personal benefit. While many studies have identified reasons for lapsed donation, the majority have not used free text as their data source, have been conducted in a wide range of geographic locations not specific to Vermont residents, and have focused on reasons for discontinuing donations, rather than positive factors. Using free text limits the question bias and eliminates constraints that predefined answers enforce. In 2007, Balderama et alconducted a study identifying common motivations for donating blood, which included an unanalyzed free text portion. We used this free text to answer the question, “What factors identified by lapsed donors might influence donor return?”https://scholarworks.uvm.edu/comphp_gallery/1047/thumbnail.jp

Circulating tumor cells detection has independent prognostic impact in high-risk non-muscle invasive bladder cancer

High-risk non-muscle invasive bladder cancer (NMIBC) progresses to metastatic disease in 10–15% of cases, suggesting that micrometastases may be present at first diagnosis. The prediction of risks of progression relies upon EORTC scoring systems, based on clinical and pathological parameters, which do not accurately identify which patients will progress. Aim of the study was to investigate whether the presence of CTC may improve prognostication in a large population of patients with Stage I bladder cancer who were all candidate to conservative surgery. A prospective single center trial was designed to correlate the presence of CTC to local recurrence and progression of disease in high-risk T1G3 bladder cancer. One hundred two patients were found eligible, all candidate to transurethral resection of the tumor followed by endovesical adjuvant immunotherapy with BCG. Median follow-up was 24.3 months (minimum–maximum: 4–36). The FDA-approved CellSearch System was used to enumerate CTC. Kaplan–Meier methods, log-rank test and multivariable Cox proportional hazard analysis was applied to establish the association of circulating tumor cells with time to first recurrence (TFR) and progression-free survival. CTC were detected in 20% of patients and predicted both decreased TFR (log-rank p < 0.001; multivariable adjusted hazard ratio [HR] 2.92 [95% confidence interval: 1.38–6.18], p 5 0.005), and time to progression (log-rank p < 0.001; HR 7.17 [1.89–27.21], p 5 0.004). The present findings provide evidence that CTC analyses can identify patients with Stage I bladder cancer who have already a systemic disease at diagnosis and might, therefore, potentially benefit from systemic treatment