The effect of immediate breast reconstruction on the timing of adjuvant chemotherapy: a systematic review

Adjuvant chemotherapy is often needed to achieve adequate breast cancer control. The increasing popularity of immediate breast reconstruction (IBR) raises concerns that this procedure may delay the time to adjuvant chemotherapy (TTC), which may negatively impact oncological outcome. The current systematic review aims to investigate this effect. During October 2014, a systematic search for clinical studies was performed in six databases with keywords related to breast reconstruction and chemotherapy. Eligible studies met the following inclusion criteria: (1) research population consisted of women receiving therapeutic mastectomy, (2) comparison of IBR with mastectomy only groups, (3) TTC was clearly presented and mentioned as outcome measure, and (4) original studies only (e.g., cohort study, randomized controlled trial, case–control). Fourteen studies were included, representing 5270 patients who had received adjuvant chemotherapy, of whom 1942 had undergone IBR and 3328 mastectomy only. One study found a significantly shorter mean TTC of 12.6 days after IBR, four studies found a significant delay after IBR averaging 6.6–16.8 days, seven studies found no significant difference in TTC between IBR and mastectomy only, and two studies did not perform statistical analyses for comparison. In studies that measured TTC from surgery, mean TTC varied from 29 to 61 days for IBR and from 21 to 60 days for mastectomy only. This systematic review of the current literature showed that IBR does not necessarily delay the start of adjuvant chemotherapy to a clinically relevant extent, suggesting that in general IBR is a valid option for non-metastatic breast cancer patients

Par1b induces asymmetric inheritance of plasma membrane domains via LGN-dependent mitotic spindle orientation in proliferating hepatocytes

The development and maintenance of polarized epithelial tissue requires a tightly controlled orientation of mitotic cell division relative to the apical polarity axis. Hepatocytes display a unique polarized architecture. We demonstrate that mitotic hepatocytes asymmetrically segregate their apical plasma membrane domain to the nascent daughter cells. The non-polarized nascent daughter cell can form a de novo apical domain with its new neighbor. This asymmetric segregation of apical domains is facilitated by a geometrically distinct “apicolateral” subdomain of the lateral surface present in hepatocytes. The polarity protein partitioning-defective 1/microtubule-affinity regulating kinase 2 (Par1b/MARK2) translates this positional landmark to cortical polarity by promoting the apicolateral accumulation of Leu-Gly-Asn repeat-enriched protein (LGN) and the capture of nuclear mitotic apparatus protein (NuMA)–positive astral microtubules to orientate the mitotic spindle. Proliferating hepatocytes thus display an asymmetric inheritance of their apical domains via a mechanism that involves Par1b and LGN, which we postulate serves the unique tissue architecture of the developing liver parenchyma

A Balkán és az Oszmán Birodalom III. : Társadalmi és gazdasági átalakulások a 18. század végétől a 20. század közepéig : Szerbia, Macedónia, Bosznia

High-throughput molecular profiling techniques are routinely generating vast amounts of data for translational medicine studies. Secure access controlled systems are needed to manage, store, transfer and distribute these data due to its personally identifiable nature. The European Genome-phenome Archive (EGA) was created to facilitate access and management to long-term archival of bio-molecular data. Each data provider is responsible for ensuring a Data Access Committee is in place to grant access to data stored in the EGA. Moreover, the transfer of data during upload and download is encrypted. ELIXIR, a European research infrastructure for life-science data, initiated a project (2016 Human Data Implementation Study) to understand and document the ELIXIR requirements for secure management of controlled-access data. As part of this project, a full ecosystem was designed to connect archived raw experimental molecular profiling data with interpreted data and the computational workflows, using the CTMM Translational Research IT (CTMM-TraIT) infrastructure http://www.ctmm-trait.nl as an example. Here we present the first outcomes of this project, a framework to enable the download of EGA data to a Galaxy server in a secure way. Galaxy provides an intuitive user interface for molecular biologists and bioinformaticians to run and design data analysis workflows. More specifically, we developed a tool -- ega_download_streamer - that can download data securely from EGA into a Galaxy server, which can subsequently be further processed. This tool will allow a user within the browser to run an entire analysis containing sensitive data from EGA, and to make this analysis available for other researchers in a reproducible manner, as shown with a proof of concept study. The tool ega_download_streamer is available in the Galaxy tool shed: https://toolshed.g2.bx.psu.edu/view/yhoogstrate/ega_download_streamer

Coarse-grained versus atomistic simulations: realistic interaction free energies for real proteins

MOTIVATION: To assess whether two proteins will interact under physiological conditions, information on the interaction free energy is needed. Statistical learning techniques and docking methods for predicting protein-protein interactions cannot quantitatively estimate binding free energies. Full atomistic molecular simulation methods do have this potential, but are completely unfeasible for large-scale applications in terms of computational cost required. Here we investigate whether applying coarse-grained (CG) molecular dynamics simulations is a viable alternative for complexes of known structure. RESULTS: We calculate the free energy barrier with respect to the bound state based on molecular dynamics simulations using both a full atomistic and a CG force field for the TCR-pMHC complex and the MP1-p14 scaffolding complex. We find that the free energy barriers from the CG simulations are of similar accuracy as those from the full atomistic ones, while achieving a speedup of >500-fold. We also observe that extensive sampling is extremely important to obtain accurate free energy barriers, which is only within reach for the CG models. Finally, we show that the CG model preserves biological relevance of the interactions: (i) we observe a strong correlation between evolutionary likelihood of mutations and the impact on the free energy barrier with respect to the bound state; and (ii) we confirm the dominant role of the interface core in these interactions. Therefore, our results suggest that CG molecular simulations can realistically be used for the accurate prediction of protein-protein interaction strength. Availability and implementation: The python analysis framework and data files are available for download at http://www.ibi.vu.nl/downloads/bioinformatics-2013-btt675.tgz

Direct numerical simulation analysis of local flow topology in a particle-laden turbulent channel flow

The results of point-particle Eulerian–Lagrangian direct numerical simulation (DNS) calculations of dilute particle-laden turbulent channel flow are used to study the effect of the particles on the local flow topology. It is found that in the viscous sublayer, the flow becomes increasingly more two-dimensional as the two-way coupling effect (due to interaction between particles and fluid flow) increases with increasing particle load. Beyond the viscous sublayer the modifications in flow topology are not strongly related to the preferential concentration of particles in the flow field, which is in contrast to previous channel flow simulations. The effect of particles on the turbulent flow beyond the viscous sublayer is mostly a result of the overall changing near-wall dynamics of the fluid flow.Aerodynamics & Wind EnergyAerospace Engineerin

Optimal High-Dose-Rate Brachytherapy Fractionation Scheme After Keloid Excision: A Retrospective Multicenter Comparison of Recurrence Rates and Complications

Purpose: To determine the optimal brachytherapy dose and fractionation scheme for keloid treatment. Methods and Materials: Patient cohorts from 3 centers treated with keloid excision followed by 2 × 9 Gy, 3 × 6 Gy, or 2 × 6 Gy high-dose-rate brachytherapy were retrospectively compared regarding recurrence (after at least 12 months' follow-up) and complications (after at least 1 month's follow-up), using logistic regression analyses. Results: A total of 238 keloids were treated. An overall full recurrence rate of 8.3% was found. After correction for confounders (sex, skin color, keloid location, keloid duration) no statistically significant differences in recurrence rates could be discerned between fractionation schemes. There were 12.8% major and 45.6% minor complication rates. Lower radiation dose resulted in significantly fewer complications (odds ratio 0.35, P=.015). Conclusions: After excision of resistant keloids, high-dose-rate brachytherapy with a biological equivalent dose of approximately 20 Gy is recommended, on the basis of low recurrence and complication rates