Predicting interactions between proteins and other biomolecules solely based on structure remains a challenge in biology. A high-level representation of protein structure, the molecular surface, ...displays patterns of chemical and geometric features that fingerprint a protein's modes of interactions with other biomolecules. We hypothesize that proteins participating in similar interactions may share common fingerprints, independent of their evolutionary history. Fingerprints may be difficult to grasp by visual analysis but could be learned from large-scale datasets. We present MaSIF (molecular surface interaction fingerprinting), a conceptual framework based on a geometric deep learning method to capture fingerprints that are important for specific biomolecular interactions. We showcase MaSIF with three prediction challenges: protein pocket-ligand prediction, protein-protein interaction site prediction and ultrafast scanning of protein surfaces for prediction of protein-protein complexes. We anticipate that our conceptual framework will lead to improvements in our understanding of protein function and design.
•On-line, time resolved volumetric detection of hydrogen during electrochemical experiments reported for the first time.•Simultaneous measurement of partial elementary dissolution rates by ...AESEC.•Excellent agreement between the quantity of dissolved zinc and evolved hydrogen for Zn in HCl solution.•Clear evidence for negative difference effect (NDE) for anodized Mg in dilute NaCl solution.•Results indicate an electrochemical dissolution of Mg with n=2 occurs independently from the NDE mechanism which involves rapid spontaneous dissolution.
Gas evolution at the surface of a dissolving material plays an important role in the overall dissolution process. In order to measure the kinetics of the gas evolution as a function of time (time resolved volumetry, TRV), a microfluidic system was constructed combined with high speed camera and a dedicated image analysis algorithm to measure the volume of gas as a function of time. This instrumental set up was added to an existing coupling between an electrochemical cell and a time resolved atomic emission spectroscopic detection. This article presents the instrumental development and first results concerning the spontaneous dissolution of zinc in a dilute HCl solution, the spontaneous dissolution of Mg in 0.01M NaCl at open circuit potential and under an applied anodic potential. For Zn dissolution, an excellent correlation was obtained between the quantity of hydrogen measured and the quantity of zinc dissolved, with average accuracy of 5%. For Mg however, the anomalous production of hydrogen was observed attributed to the negative difference effect. A steady Mg dissolution was observed correlating with the electrochemical current for an n=2 dissolution mechanism with superimposed bursts of Mg dissolution and hydrogen release corresponding to the anomalous dissolution mechanism.
•The GHG identified an unmet need for standardized OAR contouring guidance.•AAPM TG 263 recommendations exist for all but 10 OAR structures.•Here we present consensus guidance on 73 OARs with ...nomenclature and peer-reviewed descriptions.
The Global Quality Assurance of Radiation Therapy Clinical Trials Harmonization Group (GHG) is a collaborative group of Radiation Therapy Quality Assurance (RTQA) Groups harmonizing and improving RTQA for multi-institutional clinical trials. The objective of the GHG OAR Working Group was to unify OAR contouring guidance across RTQA groups by compiling a single reference list of OARs in line with AAPM TG 263 and ASTRO, together with peer-reviewed, anatomically defined contouring guidance for integration into clinical trial protocols independent of the radiation therapy delivery technique.
The GHG OAR Working Group comprised of 22 multi-professional members from 6 international RTQA Groups and affiliated organizations conducted the work in 3 stages: (1) Clinical trial documentation review and identification of structures of interest (2) Review of existing contouring guidance and survey of proposed OAR contouring guidance (3) Review of survey feedback with recommendations for contouring guidance with standardized OAR nomenclature.
157 clinical trials were examined; 222 OAR structures were identified. Duplicates, non-anatomical, non-specific, structures with more specific alternative nomenclature, and structures identified by one RTQA group were excluded leaving 58 structures of interest. 6 OAR descriptions were accepted with no amendments, 41 required minor amendments, 6 major amendments, 20 developed as a result of feedback, and 5 structures excluded in response to feedback. The final GHG consensus guidance includes 73 OARs with peer-reviewed descriptions (Appendix A).
We provide OAR descriptions with standardized nomenclature for use in clinical trials. A more uniform dataset supports the delivery of clinically relevant and valid conclusions from clinical trials.
Abstract Background Chemotherapy with lomustine is widely considered as standard treatment option for progressive glioblastoma. The value of adding radiotherapy to second-line chemotherapy is not ...known. Methods EORTC-2227-BTG (LEGATO, NCT05904119) is an investigator-initiated, pragmatic (PRECIS-2 score: 34 out of 45), randomized, multicenter phase III trial in patients with first progression of glioblastoma. A total of 411 patients will be randomized in a 1:1 ratio to lomustine (110 mg/m 2 every 6 weeks) or lomustine (110 mg/m 2 every 6weeks) plus radiotherapy (35 Gy in 10 fractions). Main eligibility criteria include histologic confirmation of glioblastoma, isocitrate dehydrogenase gene ( IDH ) wild-type per WHO 2021 classification, first progression at least 6 months after the end of prior radiotherapy, radiologically measurable disease according to RANO criteria with a maximum tumor diameter of 5 cm, and WHO performance status of 0–2. The primary efficacy endpoint is overall survival (OS) and secondary endpoints include progression-free survival, response rate, neurocognitive function, health-related quality of life, and health economic parameters. LEGATO is funded by the European Union’s Horizon Europe Research program, was activated in March 2024 and will enroll patients in 43 sites in 11 countries across Europe with study completion projected in 2028. Discussion EORTC-2227-BTG (LEGATO) is a publicly funded pragmatic phase III trial designed to clarify the efficacy of adding reirradiation to chemotherapy with lomustine for the treatment of patients with first progression of glioblastoma. Trial registration ClinicalTrials.gov NCT05904119. Registered before start of inclusion, 23 May 2023
Abstract
The greatest part of the documents concerning the last reclamation scheme of the Pontine Plain is now stored in a section of the state archive and in the archive of the Consorzio di Bonifica ...dell’Agro Pontino, both located in Latina (Italy). Detailed plans of the realised buildings, infrastructures as well as thousands of pictures of the environments before the reclamation scheme are available to the public. These data can be used to reconstruct the ancient landscape before the major changes which occurred after the spread of mechanical vehicles for earthmoving in the 1970s. The reconstruction maps can be used to set the proper background for the archaeological research in the area.
Abstract Background and purpose The phase III EORTC 1219-DAHANCA 29 intergroup trial evaluates the influence of nimorazole in patients with locally advanced head and neck cancer when treated with ...accelerated radiotherapy (RT) in combination with chemotherapy. This article describes the results of the RT Benchmark Case (BC) performed before patient inclusion. Materials and methods The participating centers were asked to perform a 2-step BC, consisting of (1) a delineation and (2) a planning exercise according to the protocol guidelines. Submissions were prospectively centrally reviewed and feedback was given to the submitting centers. Sørensen–Dice similarity index (DSI) and the 95th percentile Hausdorff distance (HD) were retrospectively used to evaluate the agreement between the centers and the expert contours. Results Fifty-four submissions (34 delineation and 20 planning exercises) from 19 centers were reviewed. Nine (47%) centers needed to perform the delineation step twice and three (16%) centers 3 times before receiving an approval. An increase in DSI-value and a decrease in HD, in particular for the prophylactic Clinical Target Volume (pCTV), could be found for the resubmitted cases. No unacceptable variations could be found for the planning exercise. Conclusions These BC-results highlight the need for effective and prospective RTQA in clinical trials. Even with clearly defined protocol guidelines, delineation and not planning remain the main reason for unacceptable protocol variations. The introduction of more objective quantitative analysis methods, such as the HD and DSI, in future trials might strengthen the evaluation by experts.
Time is a transversal topic that plays a fundamental role in our every-day experience and represents a natural conceptual bridge between common sense ideas and scientific knowledge. Two classes of ...Prospective Primary Teachers (PPTs) at the Universities of Udine and Verona were introduced to the theme of Time in a formative intervention organized into a) the discussion of various educational and multidisciplinary approaches aimed to deal with different aspects of Time and b) the exploration/experimentation of various instruments for time measurement. In this work, we study and compare the learning outcomes in terms of planning and implementation of educational projects built by PPTs following two different Rubrics.
Quality assurance (QA) for clinical trials is important. Lack of compliance can affect trial outcome. Clinical trial QA groups have different methods of dose distribution verification and analysis, ...all with the ultimate aim of ensuring trial compliance. The aim of this study was to gain a better understanding of different processes to inform future dosimetry audit reciprocity.
Six clinical trial QA groups participated. Intensity modulated treatment plans were generated for three different cases. A range of 17 virtual ‘measurements’ were generated by introducing a variety of simulated perturbations (such as MLC position deviations, dose differences, gantry rotation errors, Gaussian noise) to three different treatment plan cases. Participants were blinded to the ‘measured’ data details. Each group analysed the datasets using their own gamma index (γ) technique and using standardised parameters for passing criteria, lower dose threshold, γ normalisation and global γ.
For the same virtual ‘measured’ datasets, different results were observed using local techniques. For the standardised γ, differences in the percentage of points passing with γ < 1 were also found, however these differences were less pronounced than for each clinical trial QA group’s analysis. These variations may be due to different software implementations of γ.
This virtual dosimetry audit has been an informative step in understanding differences in the verification of measured dose distributions between different clinical trial QA groups. This work lays the foundations for audit reciprocity between groups, particularly with more clinical trials being open to international recruitment.
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