The effect of signal acquisition and processing choices on ApEn values: Towards a “gold standard” for distinguishing effort levels from isometric force records

Approximate Entropy (ApEn) is frequently used to identify changes in the complexity of isometric force records with ageing and disease. Different signal acquisition and processing parameters have been used, making comparison or confirmation of results difficult. This study determined the effect of sampling and parameter choices by examining changes in ApEn values across a range of submaximal isometric contractions of the First Dorsal Interosseus. Reducing the sample rate by decimation changed both the value and pattern of ApEn values dramatically. The pattern of ApEn values across the range of effort levels was not sensitive to the filter cut-off frequency, or the criterion used to extract the section of data for analysis. The complexity increased with increasing effort levels using a fixed ‘r’ value (which accounts for measurement noise) but decreased with increasing effort level when ‘r’ was set to 0.1 of the standard deviation of force. It is recommended isometric force records are sampled at frequencies >200 Hz, template length (‘m’) is set to 2, and 'r' set to measurement system noise or 0.1 SD depending on physiological process to be distinguished. It is demonstrated that changes in ApEn across effort levels are related to changes in force gradation strategy

Critical appraisal of the role of volumetric modulated arc therapy in the radiation therapy management of breast cancer

Background: The aim of this review is the critical appraisal of the current use of volumetric modulated arc therapy for the radiation therapy management of breast cancer. Both clinical and treatment planning studies were investigated. Material and methods: A Pubmed/MEDLINE search of the National Library of Medicine was performed to identify VMAT and breast related articles. After a first order rejection of the irrelevant findings, the remaining articles were grouped according to two main categories: clinical vs. planning studies and to some sub-categories (pointing to significant technical features). Main areas of application, dosimetric and clinical findings as well as areas of innovations were defined. Results: A total of 131 articles were identified and of these, 67 passed a first order selection. Six studies reported clinical results while 61 treatment dealed with treatment planning investigations. Among the innovation lines, the use of high intensity photon beams (flattening filter free), altered fractionation schemes (simultaneous integrated boost, accelerated partial breast irradiation, single fraction), prone positioning and modification of standard VMAT (use of dynamic trajectories or hybrid VMAT methods) resulted among the main relevant fields of interest. Approximately 10% of the publications reported upon respiratory gating in conjunction with VMAT. Conclusions: The role of VMAT in the radiation treatment of breast cancer seems to be consolidated in the in-silico arena while still limited evidence and only one phase II trial appeared in literature from the clinical viewpoint. More clinical reports are needed to fully proove the expected dosimetric benefits demonstrated in the planning investigations

An intra-population analysis of the indris' song dissimilarity in the light of genetic distance

Abstract The increasing interest in the evolution of human language has led several fields of research to focus on primate vocal communication. The ‘singing primates’, which produce elaborated and complex sequences of vocalizations, are of particular interest for this topic. Indris (Indri indri) are the only singing lemurs and emit songs whose most distinctive portions are “descending phrases” consisting of 2-5 units. We examined how the structure of the indris’ phrases varied with genetic relatedness among individuals. We tested whether the acoustic structure could provide conspecifics with information about individual identity and group membership. When analyzing phrase dissimilarity and genetic distance of both sexes, we found significant results for males but not for females. We found that similarity of male song-phrases correlates with kin in both time and frequency parameters, while, for females, this information is encoded only in the frequency of a single type. Song phrases have consistent individual-specific features, but we did not find any potential for advertising group membership. We emphasize the fact that genetic and social factors may play a role in the acoustic plasticity of female indris. Altogether, these findings open a new perspective for future research on the possibility of vocal production learning in these primates

Adipocyte-derived extracellular vesicles promote breast cancer cell malignancy through HIF-1α activity.

Abstract Extracellular vesicles (EVs) are emerging key protagonists in intercellular communication between adipocytes and breast cancer (BC) cells. Here, we described a new mechanism by which EVs released by mature adipocytes promoted breast cancer cell malignancy "in vitro" and "in vivo". We found that adipocyte-derived EVs enhanced growth, motility and invasion, stem cell-like properties, as well as specific traits of epithelial-to-mesenchymal transition in both estrogen receptor positive and triple negative BC cells. Of note, adipocyte-derived EVs aid breast tumor cells in lung metastatic colonization after tail-vein injection in mice. These EV-mediated effects occur via the induction of HIF-1α activity, since they were abrogated by the use of the HIF-1α inhibitor KC7F2 or in cells silenced for HIF-1α expression. Moreover, using an "ex vivo" model of obese adipocytes we found that the depletion of EVs counteracted the ability of obese adipocytes to sustain pro-invasive phenotype in BC cells. Interestingly, EVs released by undifferentiated adipocytes failed to induce aggressiveness and HIF-1α expression. These findings shed new light on the role of adipocyte-derived EVs in breast cancer progression, suggesting the possibility to target HIF-1α activity to block the harmful adipocyte-tumor cell dialogue, especially in obese settings

Stereotactic Ablative Radiotherapy (SABR) in inoperable oligometastatic disease from colorectal cancer: a safe and effective approach

Background: To assess the safety and efficacy of Stereotactic Ablative Radiotherapy (SABR) in oligometastatic patients from colorectal cancer. Methods: 82 patients with 1-3 inoperable metastases confined to one organ (liver or lung), were treated with SABR for a total of 112 lesions in an observational study. Prescription dose ranged between 48 and 75Gy in 3 or 4 consecutive fractions. Primary end-points were local control (LC), overall survival (OS) and progression-free survival (PFS). Secondary end-point was toxicity. Results: Median follow-up was 24 months (range 3-47). One, two and three years LC rate was 90%,80% and 75% (85%,75% and 70% for lung and 95%, 90% and 85% for liver metastases; no statistically significance was found). The difference in LC between the subgroup of lesions treated with >= 60 Gy (n = 58) and those irradiated with 3 cm (p 3 toxicity. Conclusions: SABR is a safe and feasible alternative treatment of oligometastatic colorectal liver and lung metastases in patients not amenable to surgery or other ablative treatments

Erythropoietin (EPO) haplotype associated with all-cause mortality in a cohort of Italian patients with Type-2 Diabetes

Type-2 Diabetes (T2D), diabetic complications, and their clinical risk factors harbor a substantial genetic component but the genetic factors contributing to overall diabetes mortality remain unknown. Here, we examined the association between genetic variants at 21 T2D-susceptibility loci and all-cause mortality in an elderly cohort of 542 Italian diabetic patients who were followed for an average of 12.08 years. Univariate Cox regression analyses detected age, waist-to-hip ratio (WHR), glycosylated haemoglobin (HbA1c), diabetes duration, retinopathy, nephropathy, chronic kidney disease (CKD), and anaemia as predictors of all-cause mortality. When Cox proportional hazards multivariate models adjusted for these factors were run, three erythropoietin (EPO) genetic variants in linkage disequilibrium (LD) with each other (rs1617640-T/G, rs507392-T/C and rs551238-A/C) were significantly (False Discovery Rate < 0.1) associated with mortality. Haplotype multivariate analysis revealed that patients carrying the G-C-C haplotype have an increased probability of survival, while an opposite effect was observed among subjects carrying the T-T-A haplotype. Our findings provide evidence that the EPO gene is an independent predictor of mortality in patients with T2D. Thus, understanding the mechanisms by which the genetic variability of EPO affects the mortality of T2D patients may provide potential targets for therapeutic interventions to improve the survival of these patients

Gut microbiota regulation of P-glycoprotein in the intestinal epithelium in maintenance of homeostasis

BACKGROUND: P-glycoprotein (P-gp) plays a critical role in protection of the intestinal epithelia by mediating efflux of drugs/xenobiotics from the intestinal mucosa into the gut lumen. Recent studies bring to light that P-gp also confers a critical link in communication between intestinal mucosal barrier function and the innate immune system. Yet, despite knowledge for over 10 years that P-gp plays a central role in gastrointestinal homeostasis, the precise molecular mechanism that controls its functional expression and regulation remains unclear. Here, we assessed how the intestinal microbiome drives P-gp expression and function. RESULTS: We have identified a functional core microbiome of the intestinal gut community, specifically genera within the Clostridia and Bacilli classes, that is necessary and sufficient for P-gp induction in the intestinal epithelium in mouse models. Metagenomic analysis of this core microbial community revealed that short-chain fatty acid and secondary bile acid production positively associate with P-gp expression. We have further shown these two classes of microbiota-derived metabolites synergistically upregulate P-gp expression and function in vitro and in vivo. Moreover, in patients suffering from ulcerative colitis (UC), we find diminished P-gp expression coupled to the reduction of epithelial-derived anti-inflammatory endocannabinoids and luminal content (e.g., microbes or their metabolites) with a reduced capability to induce P-gp expression. CONCLUSION: Overall, by means of both in vitro and in vivo studies as well as human subject sample analysis, we identify a mechanistic link between cooperative functional outputs of the complex microbial community and modulation of P-gp, an epithelial component, that functions to suppress overactive inflammation to maintain intestinal homeostasis. Hence, our data support a new cross-talk paradigm in microbiome regulation of mucosal inflammation. Video abstract

Multimodality therapy approaches, local and systemic treatment, compared with chemotherapy alone in recurrent glioblastoma

BACKGROUND: Long-term local control in Glioblastoma is rarely achieved and nearly all patients relapse. In this study we evaluated the clinical effect of different treatment approaches in recurrent patients. METHODS: Forty-three patients, with median age of 51 years were evaluated for salvage treatment: re-resection and/or re-irradiation plus chemotherapy or chemotherapy alone. Response was recorded using the Response Assessment in Neuro-Oncology criteria. Hematologic and non-hematologic toxicities were graded according to Common Terminology Criteria for Adverse Events 4.0. Twenty-one patients underwent chemotherapy combined with local treatment, surgery and/or radiation therapy, and 22 underwent chemotherapy only. RESULTS: The median follow up was 7 months (range 3–28 months). The 1 and 2-years Progression Free Survival was 65 and 10 % for combined treatment and 22 and 0 % for chemotherapy alone (p < 0.01). The 1 and 2-years overall survival was 69 and 29 % for combined and 26 and 0 % for chemotherapy alone (p < 0.01). No toxicity greater than grade 2 was recorded. CONCLUSION: These data showed that in glioblastoma recurrence the combination of several approaches in a limited group of patients is more effective than a single treatment alone. This stress the importance of multimodality treatment whenever clinically feasible