DeCiFering the elusive cancer cell fraction in tumor heterogeneity and evolution

The cancer cell fraction (CCF), or proportion of cancerous cells in a tumor containing a single-nucleotide variant (SNV), is a fundamental statistic used to quantify tumor heterogeneity and evolution. Existing CCF estimation methods from bulk DNA sequencing data assume that every cell with an SNV contains the same number of copies of the SNV. This assumption is unrealistic in tumors with copy-number aberrations that alter SNV multiplicities. Furthermore, the CCF does not account for SNV losses due to copy-number aberrations, confounding downstream phylogenetic analyses. We introduce DeCiFer, an algorithm that overcomes these limitations by clustering SNVs using a novel statistic, the descendant cell fraction (DCF). The DCF quantifies both the prevalence of an SNV at the present time and its past evolutionary history using an evolutionary model that allows mutation losses. We show that DeCiFer yields more parsimonious reconstructions of tumor evolution than previously reported for 49 prostate cancer samples

Photoinduced transient symmetry breaking in plasmonic structures for ultrafast nanophotonics

We study the spatio-temporal evolution of hot electrons generated in plasmonic nanostructures under resonant excitation with fs-laser pulses. A spatially inhomogeneous version of the Three-Temperature Model for hot-electrons dynamics, coupled to semiclassical calculations of third-order optical nonlinearity in gold, enabled us to engineer a transient symmetry breaking of the optical properties at the nanoscale. This effect is exploited to achieve all-optical control of light with unprecedented speed. For instance, a photoinduced broadband dichroism, fully reversible and transiently vanishing in less than 1 picoseconds (overcoming the speed bottleneck caused by slower, electron-phonon and phonon-phonon relaxation processes), has been experimentally demonstrated in plasmonic metasurfaces with nanocross metaatoms. Also, we designed a nonlinear plasmonic metagrating (based on cross-polarized gold nanostrip dimer metaatoms), where the nanoscale symmetry breaking enables ultrafast reconfiguration of diffraction orders via control laser pulses. The photoinduced power imbalance between symmetrical diffraction orders is calculated to exceed 20% under moderate (similar to 2 mJ/cm(2)) laser fluence, and returns to the balanced diffraction in about 2 ps. Our design has been developed for gold nanomaterials, but the concept of ultrafast all-optical symmetry breaking can be exploited beyond plasmonics (e.g. in semiconductor nanostructures), with potential impact on a broad range of applications in nanophotonics

Synthesis of stabilized analogues of fragments of Neisseria meningitidis type A capsular polysaccharide

The resistance to Neisseria meningitidis (N. m.), a gram-negative bacterium causing meningitis, is mediated by the presence of antibodies directed against its capsular polysaccharides (CPS), which are associated with different serogroups. One of the most virulent is serotype A (Men A), whose CPS is constituted of (\uf0ae6)-N-acetylmannosamine \uf061-1-O-Phosphate as a repeating unit. The already existing vaccines against N.m. give a T-cell independent immune response, therefore inefficient in infants. The response can be improved by conjugation of the saccharidic portion to a protein carrier, which invokes T-cell involvement. In addition, anomeric phosphodiester bridges are chemically labile and therefore not appropriate for a vaccine. To overcome these problems, phosphonate 4 and its oligomers 5 and 7 have been synthesised as stable analogues of the repeating unit of Men A CPS. Key steps of the synthetic strategy are: a) Synthesis of building blocks 3 and 4, the latter bearing a spacer at the reducing end suitable for conjugation to a proper protein carrier; b) Coupling of 3 with 4 via Mitsunobu reaction providing 5, followed by 6'-O-deacetylation and a second Mitsunobu coupling to give trimer 7. After removal of the protecting groups, the synthesized compounds have been evaluated through a competitive ELISA assay (IC50 values) by use of Men A antiserum. Moreover, preliminary approaches towards the carba-analogue 8 of N-acetylmannosamine 1-O-phosphate, a key building block for the synthesis of a new type of Men A analogues, will be also discussed

Obturator nerve split for gracilis free-flap double reinnervation in facial paralysis

The use of a double-powered free muscle transfer for facial reanimation has been reported by several authors with different types of nerve coaptation. A new nerve coaptation strategy is presented herein. We performed a 1-stage double-powered free gracilis muscle flap transfer in a patient with long-standing facial paralysis by splitting the obturator nerve and anastomosing the 2 free ends to the contralateral facial nerve (through a sural graft) and to the masseteric nerve. Voluntary movement of the transferred muscle with teeth clenching was observed at 6 months after the operation and a symmetric smile with bilateral elevation of the mouth angle at 10 months. Our limited experience suggests that in case of a large cross-section of the obturator nerve, the latter can be split and sutured to the ipsilateral masseteric nerve and to the contralateral facial nerve with a sural graft by double end-to-end anastomosis

Heart Rate Turbulence Predicts Survival Independently From Severity of Liver Dysfunction in Patients With Cirrhosis

Background: Reduced heart rate variability (HRV) is an independent predictor of mortality in patients with cirrhosis. However, conventional HRV indices can only be interpreted in individuals with normal sinus rhythm. In patients with recurrent premature ventricular complexes (PVCs), the predictive capacity of conventional HRV indices is compromised. Heart Rate Turbulence (HRT) represents the biphasic change of the heart rate after PVCs. This study was aimed to define whether HRT parameters could predict mortality in cirrhotic patients. Materials and Methods: 24 h electrocardiogram recordings were collected from 40 cirrhotic patients. Turbulence Onset was calculated as HRT indices. The enrolled patients were followed up for 12 months after the recruitment in relation to survival and/or transplantation. Results: During the follow-up period, 21 patients (52.5%) survived, 12 patients (30%) died and 7 patients (17.5%) had liver transplantation. Turbulence Onset was found to be strongly linked with mortality on Cox regression (Hazard ratio = 1.351, p < 0.05). Moreover, Turbulence Onset predicted mortality independently of MELD and Child-Pugh's Score. Conclusion: This study provides further evidence of autonomic dysfunction in cirrhosis and suggests that HRT is reliable alternative to HRV in patients with PVCs

Non-invasive tool to assess heart rhythm in Zebrafish embryos

In the last years the zebrafish (Danio rerio) has emerged as model organism for cardiac research, in spite of the morphological differences with the human heart. In consequence of the similarity to humans in the early function, the zebrafish embryo has been suggested as an ideal model i) to study the molecular mechanism of cardiac development, and ii) to identify genes related to congenital cardiac defects in human [1]. The overall similarity of zebrafish embryos and human, in responses to human cardiotoxic drugs, was demonstrated, for example, in drug-induced cardiac arrhythmia [2]. For this reason, several methods have been developed to assess cardiac functions in zebrafish embryos [3,4]. Unfortunately, all these techniques suffer from drawbacks (time consuming, skillful operator are ended to perform the experiments) which limit their applications for large scale studies. The development in digital imaging has recently made analysis of cardiac functions in genetically modified transparent zebrafish embryos easier. This allowed to assess non-invasively heart rate variability in zebrafish embryos from videos of beating heart, but without measuring heartbeat rhythm, an important indicator of the cardiac function (heartbeat regularity is associated with cardiotoxicity in humans [1]), from power spectrum of heart signal. In the present study, we present a simple, non-invasive method that, by video-recording embryo images using confocal microscopy, and integrating image processing and power spectral analysis, allows to measure the heartbeat rhythm in zebrafish embryos heart chambers (atrium, ventricle, bulb) (Figure 1). The reliability of the herein proposed method was verified. Some embryos undergone treatment by tricaine, a cardiac anaesthetizing drug, in consequence of which a decrease of the heart rate is expected: the heartbeat regularity in tricaine- treated embryos determined from power spectral analysis decreased as compared to no-treated embryos. The results demonstrated that our method is able to assess the cardiac physiology, in term of heart rhythm, in zebrafish embryos

Exercise prescription to improve clinical practice on cancer patients suffering chemotherapy-induced peripheral neuropathy undergoing treatment: a systematic review

This document aims to summarize and analyze systematically the current body of evidence about the effects of specific exercise proto- cols on physical function, balance control and quality of life in patients with peripheral neuropathy (PNP) induced by chemotherapy. Methods: Systematic Review, Literature survey Specific terms were identified for the literature research in MEDLINE, Scopus, Bandolier, PEDro, and Web of Science. Only studies pub- lished in peer-reviewed journals written in English language were considered. Four manuscripts were classified as eligible with 88 total participants, with an average of 57.1 years old. Quality appraisal classified two studies as high quality investigations while two with low quality. Results were summarized in the following domains: \u201cCIPN symptoms\u201d, \u201cStatic balance control\u201d, \u201cDynamic balance control\u201d, \u201cQuali- ty of life and Physical function\u201d. Results Specific exercise protocols were able to counteract common symptoms of chemotherapy-induced peripheral neuropathy (CIPN) during chemotherapy treatments. Significant improvements were detected on postural control. Additionally, patients\u2019 quality of life and inde- pendence were found ameliorated after exercise sessions, together with reductions on altered sensations and in other peripheral neu- ropathy symptoms. Combined exercise protocols including endurance, strength and sensorimotor training showed larger improvements. Conclusions Exercise prescriptions for cancer patients undergoing chemotherapy with CIPN symptoms should be recommended since these exercise interventions appeared as feasible and have been demonstrated as useful tools to counteract some common side effects of chemother- apeutic agents