103 research outputs found
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Prognostic factors in post-prostatectomy salvage radiotherapy setting with and without hormonotherapy: An individual patient data analysis of randomized trials from ICECaP database
Background: Early salvage radiotherapy (SRT) is the standard of care for biochemical recurrence post-prostatectomy but outcomes are heterogeneous. Objective: To develop a risk scoring system based on relevant standard-of-care clinico-pathological prognostic factors for patients treated with SRT with and without hormonal therapy (HT). Design, setting, and participants: The Intermediate Clinical Endpoints in Cancer of the Prostate (ICECaP) database included three randomized trials (Individual patients' data from 1647 subjects) assessing SRT (GETUG-AFU-16; NRG/RTOG-9601, and a subset of EORTC-22911). Outcome measurements and statistical analysis: Outcomes were clinical progression (CP). metastasis free-survival (MFS) and overall survival (OS). Clinico-pathological factors, including pathological Gleason Score (GS), PSA at SRT start, margin status, persistent PSA post-RP and time from RP to SRT were evaluated by multivariable models stratified by type of treatment. Results and limitations: On multivariable analysis PSA ≥ 0.5 ng/mL at SRT start, GS ≥ 8 and negative margin status were the three strongest prognostic factors. Three prognostic groups defined by number of these risk features (high risk: 2 or 3; intermediate risk: 1 and low risk: 0) were strongly associated with OS, MFS and CP outcomes with SRT alone or with HT. This prognostic group definition was also relevant for patients with persistent PSA post RP and for patients treated Conclusion: A risk score for patients receiving SRT with or without HT, using three standard-of-care clinico-pathological risk factors provides refined prognostic information for individual patient counselling. Patient summary: By using a composite score of pathology grading (Gleason Score), PSA at start of salvage radiation and margin status data, physicians can provide patients with more refined information on the risk of a second relapse after receiving radiation to the prostate bed after a prostatectomy for a rising or persistent PSA, both with and without hormonal therapy.</p
Role of brachytherapy in the treatment of cancers of the anal canal: Long-term follow-up and multivariate analysis of a large monocentric retrospective series
Background and purpose: There are few data on long-term clinical results and tolerance of brachytherapy in anal canal cancer. We present one of the largest retrospective analyses of anal canal cancers treated with external beam radiotherapy with/without (±) chemotherapy followed by a brachytherapy boost. Materials and methods: We performed a retrospective analysis of clinical results in terms of efficacy and toxicity. The impact of different clinical and therapeutic variables on these outcomes was studied. Results: From May 1992 to December 2009, 209 patients received brachytherapy after external beam radiotherapy ± chemotherapy. Of these patients, 163 were stage II or stage IIIA (UICC 2002) and 58 were N1-3. According to age, ECOG performance status (PS), and comorbidities, patients received either radiotherapy alone (58/209) or radiochemotherapy (151/209). The median follow-up was 72.8months. The 5- and 10-year local control rates were 78.6 and 73.9 %, respectively. Globally, severe acute and late G3-4 reactions (NCI-CTC scale v. 4.0) occurred in 11.2 and 6.3 % of patients, respectively. Univariate analysis showed the statistical impact of the pelvic treatment volume (p = 0.046) and of the total dose (p = 0.02) on the risk of severe acute and late toxicities, respectively. Only six patients required permanent colostomy because of severe late anorectal toxicities. Conclusion: After a long follow-up time, brachytherapy showed an acceptable toxicity profile and high local control rates in patients with anal canal cancer
Adaptation of topoisomerase I paralogs to nuclear and mitochondrial DNA
Topoisomerase I is essential for DNA metabolism in nuclei and mitochondria. In yeast, a single topoisomerase I gene provides for both organelles. In vertebrates, topoisomerase I is divided into nuclear and mitochondrial paralogs (Top1 and Top1mt). To assess the meaning of this gene duplication, we targeted Top1 to mitochondria or Top1mt to nuclei. Overexpression in the fitting organelle served as control. Targeting of Top1 to mitochondria blocked transcription and depleted mitochondrial DNA. This was also seen with catalytically inactive Top1 mutants, but not with Top1mt overexpressed in mitochondria. Targeting of Top1mt to the nucleus revealed that it was much less able to interact with mitotic chromosomes than Top1 overexpressed in the nucleus. Similar experiments with Top1/Top1mt hybrids assigned these functional differences to structural divergences in the DNA-binding core domains. We propose that adaptation of this domain to different chromatin environments in nuclei and mitochondria has driven evolutional development and conservation of organelle-restricted topoisomerase I paralogs in vertebrates
GeneFarm, structural and functional annotation of Arabidopsis gene and protein families by a network of experts
Genomic projects heavily depend on genome annotations and are limited by the current deficiencies in the published predictions of gene structure and function. It follows that, improved annotation will allow better data mining of genomes, and more secure planning and design of experiments. The purpose of the GeneFarm project is to obtain homogeneous, reliable, documented and traceable annotations for Arabidopsis nuclear genes and gene products, and to enter them into an added-value database. This re-annotation project is being performed exhaustively on every member of each gene family. Performing a family-wide annotation makes the task easier and more efficient than a gene-by-gene approach since many features obtained for one gene can be extrapolated to some or all the other genes of a family. A complete annotation procedure based on the most efficient prediction tools available is being used by 16 partner laboratories, each contributing annotated families from its field of expertise. A database, named GeneFarm, and an associated user-friendly interface to query the annotations have been developed. More than 3000 genes distributed over 300 families have been annotated and are available at http://genoplante-info.infobiogen.fr/Genefarm/. Furthermore, collaboration with the Swiss Institute of Bioinformatics is underway to integrate the GeneFarm data into the protein knowledgebase Swiss-Prot
GeneFarm, structural and functional annotation of Arabidopsis gene and protein families by a network of experts
Genomic projects heavily depend on genome annotations and are limited by the current deficiencies in the published predictions of gene structure and function. It follows that, improved annotation will allow better data mining of genomes, and more secure planning and design of experiments. The purpose of the GeneFarm project is to obtain homogeneous, reliable, documented and traceable annotations for Arabidopsis nuclear genes and gene products, and to enter them into an added-value database. This re-annotation project is being performed exhaustively on every member of each gene family. Performing a family-wide annotation makes the task easier and more efficient than a gene-by-gene approach since many features obtained for one gene can be extrapolated to some or all the other genes of a family. A complete annotation procedure based on the most efficient prediction tools available is being used by 16 partner laboratories, each contributing annotated families from its field of expertise. A database, named GeneFarm, and an associated user-friendly interface to query the annotations have been developed. More than 3000 genes distributed over 300 families have been annotated and are available at http://genoplante-info.infobiogen.fr/Genefarm/. Furthermore, collaboration with the Swiss Institute of Bioinformatics is underway to integrate the GeneFarm data into the protein knowledgebase Swiss-Pro
Requirements for measurement and validation of biochemical methane potential (BMP).
This document presents the minimal requirements for measurement and validation of biochemical methane potential (also called biomethane potential) (BMP) in batch tests. It represents the consensus of more than 50 biogas researchers. The list of requirements is the same as in the open-access commentary by Holliger et al. [2021]. For details on development of these requirements see the open-access papers Holliger et al. [2016] and Hafner et al. [2020c]
Probing atmospheric electric fields in thunderstorms through radio emission from cosmic-ray-induced air showers
We present measurements of radio emission from cosmic ray air showers that took place during thunderstorms. The intensity and polarization patterns of these air showers are radically different from those measured during fair-weather conditions. With the use of a simple two-layer model for the atmospheric electric field, these patterns can be well reproduced by state-of-the-art simulation codes. This in turn provides a novel way to study atmospheric electric fields
Measures for interoperability of phenotypic data: minimum information requirements and formatting
BackgroundPlant phenotypic data shrouds a wealth of information which, when accurately analysed and linked to other data types, brings to light the knowledge about the mechanisms of life. As phenotyping is a field of research comprising manifold, diverse and time-consuming experiments, the findings can be fostered by reusing and combining existing datasets. Their correct interpretation, and thus replicability, comparability and interoperability, is possible provided that the collected observations are equipped with an adequate set of metadata. So far there have been no common standards governing phenotypic data description, which hampered data exchange and reuse.ResultsIn this paper we propose the guidelines for proper handling of the information about plant phenotyping experiments, in terms of both the recommended content of the description and its formatting. We provide a document called “Minimum Information About a Plant Phenotyping Experiment”, which specifies what information about each experiment should be given, and a Phenotyping Configuration for the ISA-Tab format, which allows to practically organise this information within a dataset. We provide examples of ISA-Tab-formatted phenotypic data, and a general description of a few systems where the recommendations have been implemented.ConclusionsAcceptance of the rules described in this paper by the plant phenotyping community will help to achieve findable, accessible, interoperable and reusable data
Extracorporeal Membrane Oxygenation for Severe Acute Respiratory Distress Syndrome associated with COVID-19: An Emulated Target Trial Analysis.
RATIONALE: Whether COVID patients may benefit from extracorporeal membrane oxygenation (ECMO) compared with conventional invasive mechanical ventilation (IMV) remains unknown. OBJECTIVES: To estimate the effect of ECMO on 90-Day mortality vs IMV only Methods: Among 4,244 critically ill adult patients with COVID-19 included in a multicenter cohort study, we emulated a target trial comparing the treatment strategies of initiating ECMO vs. no ECMO within 7 days of IMV in patients with severe acute respiratory distress syndrome (PaO2/FiO2 <80 or PaCO2 ≥60 mmHg). We controlled for confounding using a multivariable Cox model based on predefined variables. MAIN RESULTS: 1,235 patients met the full eligibility criteria for the emulated trial, among whom 164 patients initiated ECMO. The ECMO strategy had a higher survival probability at Day-7 from the onset of eligibility criteria (87% vs 83%, risk difference: 4%, 95% CI 0;9%) which decreased during follow-up (survival at Day-90: 63% vs 65%, risk difference: -2%, 95% CI -10;5%). However, ECMO was associated with higher survival when performed in high-volume ECMO centers or in regions where a specific ECMO network organization was set up to handle high demand, and when initiated within the first 4 days of MV and in profoundly hypoxemic patients. CONCLUSIONS: In an emulated trial based on a nationwide COVID-19 cohort, we found differential survival over time of an ECMO compared with a no-ECMO strategy. However, ECMO was consistently associated with better outcomes when performed in high-volume centers and in regions with ECMO capacities specifically organized to handle high demand. This article is open access and distributed under the terms of the Creative Commons Attribution Non-Commercial No Derivatives License 4.0 (http://creativecommons.org/licenses/by-nc-nd/4.0/)
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