This Article aims to ascertain the role of the Charter of Fundamental Rights in promoting economic and social rights within the internal market through an analysis of its applicability in horizontal ...disputes. Recognition of the horizontal effects of fundamental rights can ensure a minimum level of social justice in relations between individuals, help overturn the division between political and social rights in the Charter and promote an appropriate balance between the market and the social. In a series of rulings in 2018 on paid annual leave, the Court of Justice of the European Union attempted to clarify the legal relationship between the rights enshrined in the Charter and the directives on which those rights are based, and admitted the possibility of relying on certain rights conferred by the Charter in disputes between private parties. In particular, in Bauer and Max-Planck, the Court argued that art. 31(2) of the Charter, is of a mandatory and unconditional character and sufficient in itself to confer on workers a right to be invoked in horizontal disputes in a field covered by EU law. Recent CJEU case law has recognised horizontal direct effects to a Charter's right outside the scope of the principle of non-discrimination, thus opening a new path to enforcement of the economic and social rights in the internal market and to shaping the future of the European Union through reiteration of its social values and objectives.
Abstract Background The introduction of robotics revolutionized prostate cancer surgery because the magnified three-dimensional vision system and wristed instruments allow microsurgery to be ...performed. The advantages of robotic surgery could lead to improved continence outcomes in terms of early recovery compared with the traditional surgical methods. Objective To describe the total anatomical reconstruction (TAR) technique during robot-assisted radical prostatectomy (RARP). Primary endpoint: evaluation of the continence rate at different time points. Secondary endpoint: evaluation of urine leakage and anastomosis stenosis rates related to the technique. Design, setting, and participants June, 2013 to November, 2014; prospective consecutive series of patients with localized prostate cancer (cT1-3, cN0, cM0). Surgical procedure RARP with TAR was performed in all cases. Lymph node dissection was performed if the risk of lymph nodal metastasis was over 5%, according to the Briganti updated nomogram. Measurements Preoperative, intraoperative, postoperative, and pathological variables were analyzed. Enrolled patients were arbitrarily divided into three groups according to a time criterion. The relationships between the learning curve and the trend of the above-mentioned variables were analyzed using LOESS analysis. Continence was rigorously analyzed preoperatively and at 24 h, 1 wk, 4 wk, 12 wk, and 24 wk after catheter removal. Results and limitations In total, 252 patients were analyzed. The continence rates immediately after catheter removal and at 1 wk, 4 wk, 12 wk, and 24 wk after RARP were 71.8%, 77.8%, 89.3%, 94.4%, and 98.0%, respectively. Multivariate analysis revealed that the nerve sparing technique, D’Amico risk groups, lymph node dissection, and prostate volume were involved in the early recovery of urinary continence. One ileal perforation requiring reoperation was recorded. The transfusion rate was 0.8%. Thirty-one (12.3%) postoperative complications were recorded up to 6 mo after surgery. Among these, eight acute urinary retentions (3.2%) and three urine leakages (1.2%) were recorded. There was a lack of randomization and comparison with other techniques. Both anatomical dissection of the prostatic apex and TAR were used. The results may not be generalized to low-volume centers. Conclusions The TAR technique showed promising results in the early recovery of urinary continence, as well as watertight anastomosis and a low rate of urine leakage. The oncologic results were not affected. Comparative studies are needed to support the quality of reported results. Patient summary On the basis of our findings, it seems that the risk of urinary incontinence following radical prostatectomy can be lowered via meticulous anatomical reconstruction using a robotic system. Comparative studies are required to support the reported results.
Solvent accessibility (SASA) is a key feature of proteins for determining their folding and stability. SASA is computed from protein structures with different algorithms, and from protein sequences ...with machine-learning based approaches trained on solved structures. Here we ask the question as to which extent solvent exposure of residues can be associated to the pathogenicity of the variation. By this, SASA of the wild-type residue acquires a role in the context of functional annotation of protein single-residue variations (SRVs). By mapping variations on a curated database of human protein structures, we found that residues targeted by disease related SRVs are less accessible to solvent than residues involved in polymorphisms. The disease association is not evenly distributed among the different residue types: SRVs targeting glycine, tryptophan, tyrosine, and cysteine are more frequently disease associated than others. For all residues, the proportion of disease related SRVs largely increases when the wild-type residue is buried and decreases when it is exposed. The extent of the increase depends on the residue type. With the aid of an in house developed predictor, based on a deep learning procedure and performing at the state-of-the-art, we are able to confirm the above tendency by analyzing a large data set of residues subjected to variations and occurring in some 12,494 human protein sequences still lacking three-dimensional structure (derived from HUMSAVAR). Our data support the notion that surface accessible area is a distinguished property of residues that undergo variation and that pathogenicity is more frequently associated to the buried property than to the exposed one.
Purpose We evaluated the minimum core number for better index tumor detection to determine the best core site as well as biopsy Gleason score heterogeneity in the same index lesion. The aim was to ...optimize the highest Gleason score detection. Materials and Methods A total of 327 patients with negative digital rectal examination underwent magnetic resonance imaging/transrectal ultrasound fusion targeted biopsy for elevated/rising prostate specific antigen and/or 1 or more detectable lesions on multiparametric magnetic resonance imaging after a previous negative standard biopsy. Depending on the diameter of each index lesion (8 or less, or greater than 8 mm) 4 or 6 cores, respectively, were taken according to a well determined sequence. Results Of the patients 166 (50.7%) had prostate cancer, including 79 (47.6%) with an 8 mm or less index lesion and 87 (52.4%) with a greater than 8 mm index lesion. Of patients with an index tumor 8 mm or less 7 (8.9%) had 1, 31 (39.2%) had 2, 27 (34.2%) had 3 and 14 (17.7%) had 4 positive cores. Similarly, of patients with a lesion greater than 8 mm 8 (9.2%) had 1, 30 (34.5%) had 2, 13 (14.9%) had 3, 14 (16.1%) had 4, 12 (13.8%) had 5 and 10 (11.5%) had 6 positive cores. The major prevalence of positive cores was observed in the center of the target. Gleason score heterogeneity was found in 12.6% of those with an 8 mm or less target vs 26.4% with a target greater than 8 mm. In the center of the target there was a slight prevalence of Gleason pattern 4 or greater, or a lesser pattern. Conclusions Approaching magnetic resonance imaging/transrectal ultrasound fusion targeted biopsy with a single core might be inadequate. Rather, taking 2 cores in the center of the index lesion may provide more accurate cancer detection and optimize the chances of finding the highest Gleason pattern.
Artificial intelligence (AI) is the field of computer science that aims to build smart devices performing tasks that currently require human intelligence. Through machine learning (ML), the deep ...learning (DL) model is teaching computers to learn by example, something that human beings are doing naturally. AI is revolutionizing healthcare. Digital pathology is becoming highly assisted by AI to help researchers in analyzing larger data sets and providing faster and more accurate diagnoses of prostate cancer lesions. When applied to diagnostic imaging, AI has shown excellent accuracy in the detection of prostate lesions as well as in the prediction of patient outcomes in terms of survival and treatment response. The enormous quantity of data coming from the prostate tumor genome requires fast, reliable and accurate computing power provided by machine learning algorithms. Radiotherapy is an essential part of the treatment of prostate cancer and it is often difficult to predict its toxicity for the patients. Artificial intelligence could have a future potential role in predicting how a patient will react to the therapy side effects. These technologies could provide doctors with better insights on how to plan radiotherapy treatment. The extension of the capabilities of surgical robots for more autonomous tasks will allow them to use information from the surgical field, recognize issues and implement the proper actions without the need for human intervention.
Context
Despite the current era of precision surgery in robotics, an unmet need still remains for optimal surgical planning and navigation for most genitourinary diseases. 3D virtual reconstruction ...of 2D cross-sectional imaging has been increasingly adopted to help surgeons better understand the surgical anatomy.
Objectives
To provide a short overview of the most recent evidence on current applications of 3D imaging in robotic urologic surgery.
Evidence acquisition
A non-systematic review of the literature was performed. Medline, PubMed, the Cochrane Database and Embase were screened for studies regarding the use of 3D models in robotic urology.
Evidence synthesis
3D reconstruction technology creates 3D virtual and printed models that first appeared in urology to aid surgical planning and intraoperative navigation, especially in the treatment of oncological diseases of the prostate and kidneys. The latest revolution in the field involves models overlapping onto the real anatomy and performing augmented reality procedures.
Conclusion
3D virtual/printing technology has entered daily practice in some tertiary centres, especially for the management of urological tumours. The 3D models can be virtual or printed, and can help the surgeon in surgical planning, physician education and training, and patient counselling. Moreover, integration of robotic platforms with the 3D models and the possibility of performing augmented reality surgeries increase the surgeon’s confidence with the pathology, with potential benefits in precision and tailoring of the procedures.
Objective
To evaluate the feasibility and the safety of applying chitosan membrane (ChiMe) on the neurovascular bundles (NVBs) after nerve‐sparing robot‐assisted radical prostatectomy (NS‐RARP). The ...secondary aim of the study was to report preliminary data and in particular potency recovery data.
Patients and Methods
This was a single‐centre, single‐arm prospective study, enrolling all patients with localised prostate cancer scheduled for RARP with five‐item version of the International Index of Erectile Function scores of >17, from July 2015 to September 2016. All patients underwent NS‐RARP with ChiMe applied on the NVBs. The demographics, perioperative, postoperative and complications data were evaluated. Potency recovery data were evaluated in particular and any sign/symptom of local allergy/intolerance to the ChiMe was recorded and evaluated.
Results
In all, 140 patients underwent NS‐RARP with ChiMe applied on the NVBs. Applying the ChiMe was easy in almost all the cases, and did not compromise the safety of the procedure. None of the patients reported signs of intolerance/allergy attributable to the ChiMe and potency recovery data were encouraging.
Conclusion
In our experience, ChiMe applied on the NVBs after NS‐RARP was feasible and safe, without compromising the duration, difficulty or complication rate of the ‘standard’ procedure. No patients had signs of intolerance/allergy attributable to the ChiMe and potency recovery data were encouraging. A comparative cohort would have added value to the study. The present paper was performed before Conformité Européene (CE)‐mark achievement.
Context
The development of a tailored, patient-specific medical and surgical approach is becoming object of intense research. In kidney oncologic surgery, where a clear understanding of case-specific ...surgical anatomy is considered a key point to optimize the perioperative outcomes, such philosophy gained increasing importance. Recently, important advances in 3D virtual modeling technologies have fueled the interest for their application in the field of robotic minimally invasive surgery for kidney tumors.
Objective
To provide a synthesis of current applications of 3D virtual models for robot-assisted partial nephrectomy.
Evidence acquisition
Medline, PubMed, the Cochrane Database, and Embase were screened for Literature regarding the use of 3D virtual models for robot-assisted partial nephrectomy (RAPN).
Evidence synthesis
The use of 3D virtual models for RAPN has been tested in different settings, including surgical indication and planning, intraoperative guidance, and training. Currently, several studies are available on the application of this technology for surgical planning, demonstrating impact on clinical outcomes such as renal function recovery, whilst experiences concerning their intraoperative application for navigation are still experimental. One of the latest innovations in this field is represented by the development of dedicated softwares able to automatically overlap the 3D virtual models to the real anatomy, to perform augmented reality procedures.
Conclusions
The available Literature suggests a potentially crucial role of 3D virtual reconstructions during RAPN. Encouraging results concerning surgical planning and indication, intraoperative navigation, and surgical training are available. In the future, artificial intelligence may represent the key to further improve the 3D virtual modeling technology during RAPN.
Coiled-coil domains (CCDs) are structural motifs observed in proteins in all organisms that perform several crucial functions. The computational identification of CCD segments over a protein sequence ...is of great importance for its functional characterization. This task can essentially be divided into three separate steps: the detection of segment boundaries, the annotation of the heptad repeat pattern along the segment, and the classification of its oligomerization state. Several methods have been proposed over the years addressing one or more of these predictive steps. In this protocol, we illustrate how to make use of CoCoNat, a novel approach based on protein language models, to characterize CCDs. CoCoNat is, at its release (August 2023), the state of the art for CCD detection. The web server allows users to submit input protein sequences and visualize the predicted domains after a few minutes. Optionally, precomputed segments can be provided to the model, which will predict the oligomerization state for each of them. CoCoNat can be easily integrated into biological pipelines by downloading the standalone version, which provides a single executable script to produce the output. Key features • Web server for the prediction of coiled-coil segments from a protein sequence. • Three different predictions from a single tool (segment position, heptad repeat annotation, oligomerization state). • Possibility to visualize the results online or to download the predictions in different formats for further processing. • Easy integration in automated pipelines with the local version of the tool.
In the last years, the widespread use of the prostate-specific antigen (PSA) blood examination to triage patients who will enter the diagnostic/therapeutic path for prostate cancer (PCa) has almost ...halved PCa-specific mortality. As a counterpart, millions of men with clinically insignificant cancer not destined to cause death are treated, with no beneficial impact on overall survival. Therefore, there is a compelling need to develop tools that can help in stratifying patients according to their risk, to support physicians in the selection of the most appropriate treatment option for each individual patient. The aim of this study was to develop and validate on multivendor data a fully automated computer-aided diagnosis (CAD) system to detect and characterize PCas according to their aggressiveness. We propose a CAD system based on artificial intelligence algorithms that a) registers all images coming from different MRI sequences, b) provides candidates suspicious to be tumor, and c) provides an aggressiveness score of each candidate based on the results of a support vector machine classifier fed with radiomics features. The dataset was composed of 131 patients (149 tumors) from two different institutions that were divided in a training set, a narrow validation set, and an external validation set. The algorithm reached an area under the receiver operating characteristic (ROC) curve in distinguishing between low and high aggressive tumors of 0.96 and 0.81 on the training and validation sets, respectively. Moreover, when the output of the classifier was divided into three classes of risk, i.e., indolent, indeterminate, and aggressive, our method did not classify any aggressive tumor as indolent, meaning that, according to our score, all aggressive tumors would undergo treatment or further investigations. Our CAD performance is superior to that of previous studies and overcomes some of their limitations, such as the need to perform manual segmentation of the tumor or the fact that analysis is limited to single-center datasets. The results of this study are promising and could pave the way to a prediction tool for personalized decision making in patients harboring PCa.
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