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Introduction: The use of robotic systems in the surgical domain has become groundbreaking for patients and surgeons in the last decades. While the annual number of robotic surgical procedures continues to increase rapidly, it is essential to provide the surgeon with innovative training courses along with the standard specialization path. To this end, simulators play a fundamental role. Currently, the high cost of the leading VR simulators limits their accessibility to educational institutions. The challenge lies in balancing high-fidelity simulation with cost-effectiveness; however, few cost-effective options exist for robotic surgery training., Methods: This paper proposes the design, development and user-centered usability study of an affordable user interface to control a surgical robot simulator. It consists of a cart equipped with two haptic interfaces, a VR visor and two pedals. The simulations were created using Unity, which offers versatility for expanding the simulator to more complex scenes. An intuitive teleoperation control of the simulated robotic instruments is achieved through a high-level control strategy., Results and Discussion: Its affordability and resemblance to real surgeon consoles make it ideal for implementing robotic surgery training programs in medical schools, enhancing accessibility to a broader audience. This is demonstrated by the results of an usability study involving expert surgeons who use surgical robots regularly, expert surgeons without robotic surgery experience, and a control group. The results of the study, which was based on a traditional Peg-board exercise and Camera Control task, demonstrate the simulator's high usability and intuitive control across diverse user groups, including those with limited experience. This offers evidence that this affordable system is a promising solution for expanding robotic surgery training., Competing Interests: MP, ET, FB were employed by Fos SpA. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2024 Neri, Coduri, Penza, Santangelo, Oliveri, Turco, Pizzirani, Trinceri, Soriero, Boero, Ricci and Mattos.)

Sarcomas are a rare and highly diverse group of malignancies of mesenchymal origin. While sarcomas are generally considered resistant to immunotherapy, recent studies indicate subtype-specific differences in clinical response to checkpoint inhibitors (CPIs) that are associated with distinct immune phenotypes present in sarcoma subtypes. Oncolytic viruses (OVs) are designed to selectively infect and kill tumor cells and induce intratumoral immune infiltration, enhancing immunogenicity and thereby sensitizing tumors to immunotherapy. Herein we review the accumulated clinical data evaluating OVs in sarcoma. Small numbers of patients with sarcoma were enrolled in early-stage OV trials as part of larger solid tumor cohorts demonstrating safety but providing limited insight into the biological effects due to the low patient numbers and lack of histologic grouping. Several recent studies have investigated talimogene laherparepvec (T-VEC), an approved oncolytic herpes simplex virus (HSV-1), in combination therapy regimens in sarcoma patient cohorts. These studies have shown promising responses in heavily pre-treated and immunotherapy-resistant patients associated with increased intratumoral immune infiltration. As new and more potent OVs enter the clinical arena, prospective evaluation in subtype-specific cohorts with correlative studies to define biomarkers of response will be critical to advancing this promising approach for sarcoma therapy., Competing Interests: The authors declare no competing interests., (© 2024 Published by Elsevier Inc. on behalf of The American Society of Gene and Cell Therapy.)

Mengovirus is an oncolytic picornavirus whose broad host range allows for testing in immunocompetent cancer models. Two pathogenicity-ablating approaches, polycytidine (polyC) tract truncation and microRNA (miRNA) targets insertion, eliminated the risk of encephalomyocarditis. To investigate whether a polyC truncated, miRNA-detargeted oncolytic Mengovirus might be boosted, we partially or fully rebuilt the polyC tract into the 5' noncoding region (NCR) of polyC-deleted (MC 0 ) oncolytic constructs (NC) carrying miRNA target (miRT) insertions to eliminate cardiac/muscular (miR-133b and miR-208a) and neuronal (miR-124) tropisms. PolyC-reconstituted viruses (MC 24 -NC and MC 37 -NC) replicated in vitro and showed the expected tropism restrictions, but reduced cytotoxicity and miRT deletions were frequently observed. In the MPC-11 immune competent mouse plasmacytoma model, both intratumoral and systemic administration of MC 0 -NC led to faster tumor responses than MC 24 -NC or MC 37 -NC, with combined durable complete response rates of 75%, 0.5%, and 30%, respectively. Secondary viremia was higher following MC 0 -NC versus MC 24 -NC or MC 37 -NC therapy. Sequence analysis of virus progeny from treated mice revealed a high prevalence of miRT sequences loss among MC 24 - and MC 37 - viral genomes, but not in MC 0 -NC. Overall, MC 0 -NC was capable of stably retaining miRT sites and provided a more effective treatment and is therefore our lead Mengovirus candidate for clinical translation., Competing Interests: S.J.R. is chief executive officer at Vyriad, an oncolytic virus company. S.J.R. and Mayo Clinic hold equity in Vyriad., (© 2022 The Authors.)

When planning an operation, surgeons usually rely on traditional 2D imaging. Moreover, colon neoplastic lesions are not always easy to locate macroscopically, even during surgery. A 3D virtual model may allow surgeons to localize lesions with more precision and to better visualize the anatomy. In this study, we primary analyzed and discussed the clinical impact of using such 3D models in colorectal surgery. This is a monocentric prospective observational pilot study that includes 14 consecutive patients who presented colorectal lesions with indication for surgical therapy. A staging computed tomography (CT)/magnetic resonance imaging (MRI) scan and a colonoscopy were performed on each patient. The information gained from them was provided to obtain a 3D rendering. The 2D images were shown to the surgeon performing the operation, while the 3D reconstructions were shown to a second surgeon. Both of them had to locate the lesion and describe which procedure they would have performed; we then compared their answers with one another and with the intraoperative and histopathological findings. The lesion localizations based on the 3D models were accurate in 100% of cases, in contrast to conventional 2D CT scans, which could not detect the lesion in two patients (in these cases, lesion localization was based on colonoscopy). The 3D model reconstruction allowed an excellent concordance correlation between the estimated and the actual location of the lesion, allowing the surgeon to correctly plan the procedure with excellent results. Larger clinical studies are certainly required.

Laser microsurgery is the current gold standard surgical technique for the treatment of selected diseases in delicate organs such as the larynx. However, the operations require large surgical expertise and dexterity, and face significant limitations imposed by available technology, such as the requirement for direct line of sight to the surgical field, restricted access, and direct manual control of the surgical instruments. To change this status quo, the European project μRALP pioneered research towards a complete redesign of current laser microsurgery systems, focusing on the development of robotic micro-technologies to enable endoscopic operations. This has fostered awareness and interest in this field, which presents a unique set of needs, requirements and constraints, leading to research and technological developments beyond μRALP and its research consortium. This paper reviews the achievements and key contributions of such research, providing an overview of the current state of the art in robot-assisted endoscopic laser microsurgery. The primary target application considered is phonomicrosurgery, which is a representative use case involving highly challenging microsurgical techniques for the treatment of glottic diseases. The paper starts by presenting the motivations and rationale for endoscopic laser microsurgery, which leads to the introduction of robotics as an enabling technology for improved surgical field accessibility, visualization and management. Then, research goals, achievements, and current state of different technologies that can build-up to an effective robotic system for endoscopic laser microsurgery are presented. This includes research in micro-robotic laser steering, flexible robotic endoscopes, augmented imaging, assistive surgeon-robot interfaces, and cognitive surgical systems. Innovations in each of these areas are shown to provide sizable progress towards more precise, safer and higher quality endoscopic laser microsurgeries. Yet, major impact is really expected from the full integration of such individual contributions into a complete clinical surgical robotic system, as illustrated in the end of this paper with a description of preliminary cadaver trials conducted with the integrated μRALP system. Overall, the contribution of this paper lays in outlining the current state of the art and open challenges in the area of robot-assisted endoscopic laser microsurgery, which has important clinical applications even beyond laryngology., Competing Interests: Author AS was employed by the company Yuanda Robotics GmbH. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Mattos, Acemoglu, Geraldes, Laborai, Schoob, Tamadazte, Davies, Wacogne, Pieralli, Barbalata, Caldwell, Kundrat, Pardo, Grant, Mora, Barresi, Peretti, Ortiz, Rabenorosoa, Tavernier, Pazart, Fichera, Guastini, Kahrs, Rakotondrabe, Andreff, Deshpande, Gaiffe, Renevier, Moccia, Lescano, Ortmaier and Penza.)

Long polycytidine (polyC) tracts varying in length from 50 to 400 nucleotides were first described in the 5'-noncoding region (NCR) of genomes of picornaviruses belonging to the Cardio- and Aphthovirus genera over 50 years ago, but the molecular basis of their function is still unknown. Truncation or complete deletion of the polyC tracts in picornaviruses compromises virulence and pathogenicity but do not affect replicative fitness in vitro, suggesting a role as "viral security" RNA element. The evidence available suggests that the presence of a long polyC tract is required for replication in immune cells, which impacts viral distribution and targeting, and, consequently, pathogenic progression. Viral attenuation achieved by reduction of the polyC tract length has been successfully used for vaccine strategies. Further elucidation of the role of the polyC tract in viral replication cycle and its connection with replication in immune cells has the potential to expand the arsenal of tools in the fight against cancer in oncolytic virotherapy (OV). Here, we review the published data on the biological significance and mechanisms of action of the polyC tract in viral pathogenesis in Cardio- and Aphthoviruses., Competing Interests: The authors have declared that no competing interests exist.

Background: Unsafe surgical care has emerged as a significant public health concern, motivated by a high percentage of major complications happening during surgery, attributed to surgeons' skills and experience, and determined to be preventable., Methods: This article presents APSurg, an Abdominal Positioning Surgical system designed to improve awareness and safety during laparoscopic surgery. The proposed system behaves like a GPS, offering an additional dynamic virtual reality view of the surgical field., Results: This work presents an evaluation study in terms of accuracy, effectiveness, and usability. Tests were conducted performing a localization task on an abdomen phantom in a simulated scenario. Results show a navigation accuracy below 5 mm. The task execution time was reduced by a 15% and the performed incision dimension was reduced by a 46%, with respect to a standard setup. A custom questionnaire showed a significant positive impact in exploiting APSurg during the surgical task execution., (© 2020 John Wiley & Sons Ltd.)

The turbulent thermal convection on the Sun is an example of an irreversible non-equilibrium phenomenon in a quasi-steady state characterized by a continuous entropy production rate. Here, the statistical features of a proxy of the local entropy production rate, in solar quiet regions at different timescales, are investigated and compared with the symmetry conjecture of the steady-state fluctuation theorem by Gallavotti and Cohen. Our results show that solar turbulent convection satisfies the symmetries predicted by the fluctuation relation of the Gallavotti and Cohen theorem at a local level.

Virus-infected cells release type 1 interferons, which induce an antiviral state in neighboring cells. Naturally occurring viruses are therefore equipped with stealth replication strategies to limit virus sensing and/or with combat strategies to prevent or reverse the antiviral state. Here we show that oncolytic viruses with simple RNA genomes whose spread was suppressed in tumor cells pretreated with interferon were able to replicate efficiently when the cells were coinfected with a poxvirus known to encode a diversity of innate immune combat proteins. In vivo the poxvirus was shown to reverse the intratumoral antiviral state, rescuing RNA virus replication in an otherwise restrictive syngeneic mouse tumor model leading to antitumor efficacy. Pairing of complementary oncolytic viruses is a promising strategy to enhance the antitumor activity of this novel class of anticancer drugs., (© 2020 The Author(s).)

Several studies have demonstrated that training with a laparoscopic simulator improves laparoscopic technical skills. We describe how to build a homemade, low-cost laparoscopic training simulator (LABOT) and its validation as a training instrument. First, sixty surgeons filled out a survey characterized by 12 closed-answer questions about realism, ergonomics, and usefulness for surgical training (global scores ranged from 1-very insufficient to 5-very good). The results of the questionnaires showed a mean (±SD) rating score of 4.18 ± 0.65 for all users. Then, 15 students (group S) and 15 residents (group R) completed 3 different tasks (T1, T2, T3), which were repeated twice to evaluate the execution time and the number of users' procedural errors. For T1, the R group had a lower mean execution time and a lower rate of procedural errors than the S group; for T2, the R and S groups had a similar mean execution time, but the R group had a lower rate of errors; and for T3, the R and S groups had a similar mean execution time and rate of errors. On a second attempt, all the participants tended to improve their results in doing these surgical tasks; nevertheless, after subgroup analysis of the T1 results, the S group had a better improvement of both parameters. Our laparoscopic simulator is simple to build, low-cost, easy to use, and seems to be a suitable resource for improving laparoscopic skills. In the future, further studies should evaluate the potential of this laparoscopic box on long-term surgical training with more complex tasks and simulation attempts., Competing Interests: The authors declare no conflict of interest.

Background: 3D reconstruction algorithms are of fundamental importance for augmented reality applications in computer-assisted surgery. However, few datasets of endoscopic stereo images with associated 3D surface references are currently openly available, preventing the proper validation of such algorithms. This work presents a new and rich dataset of endoscopic stereo images (EndoAbS dataset)., Methods: The dataset includes (i) endoscopic stereo images of phantom abdominal organs, (ii) a 3D organ surface reference (RF) generated with a laser scanner and (iii) camera calibration parameters. A detailed description of the generation of the phantom and the camera-laser calibration method is also provided., Results: An estimation of the overall error in creation of the dataset is reported (camera-laser calibration error 0.43 mm) and the performance of a 3D reconstruction algorithm is evaluated using EndoAbS, resulting in an accuracy error in accordance with state-of-the-art results (<2 mm)., Conclusions: The EndoAbS dataset contributes to an increase the number and variety of openly available datasets of surgical stereo images, including a highly accurate RF and different surgical conditions., (© 2018 John Wiley & Sons, Ltd.)

Despite the benefits introduced by robotic systems in abdominal Minimally Invasive Surgery (MIS), major complications can still affect the outcome of the procedure, such as intra-operative bleeding. One of the causes is attributed to accidental damages to arteries or veins by the surgical tools, and some of the possible risk factors are related to the lack of sub-surface visibilty. Assistive tools guiding the surgical gestures to prevent these kind of injuries would represent a relevant step towards safer clinical procedures. However, it is still challenging to develop computer vision systems able to fulfill the main requirements: (i) long term robustness, (ii) adaptation to environment/object variation and (iii) real time processing. The purpose of this paper is to develop computer vision algorithms to robustly track soft tissue areas (Safety Area, SA), defined intra-operatively by the surgeon based on the real-time endoscopic images, or registered from a pre-operative surgical plan. We propose a framework to combine an optical flow algorithm with a tracking-by-detection approach in order to be robust against failures caused by: (i) partial occlusion, (ii) total occlusion, (iii) SA out of the field of view, (iv) deformation, (v) illumination changes, (vi) abrupt camera motion, (vii), blur and (viii) smoke. A Bayesian inference-based approach is used to detect the failure of the tracker, based on online context information. A Model Update Strategy (MUpS) is also proposed to improve the SA re-detection after failures, taking into account the changes of appearance of the SA model due to contact with instruments or image noise. The performance of the algorithm was assessed on two datasets, representing ex-vivo organs and in-vivo surgical scenarios. Results show that the proposed framework, enhanced with MUpS, is capable of maintain high tracking performance for extended periods of time ( ≃ 4 min - containing the aforementioned events) with high precision (0.7) and recall (0.8) values, and with a recovery time after a failure between 1 and 8 frames in the worst case., (Copyright © 2017 Elsevier B.V. All rights reserved.)

In narrow band (NB) laryngeal endoscopy, the clinician usually positions the endoscope near the tissue for a correct inspection of possible vascular pattern alterations, indicative of laryngeal malignancies. The video is usually reviewed many times to refine the diagnosis, resulting in loss of time since the salient frames of the video are mixed with blurred, noisy, and redundant frames caused by the endoscope movements. The aim of this work is to provide to the clinician a unique larynx panorama, obtained through an automatic frame selection strategy to discard non-informative frames. Anisotropic diffusion filtering was exploited to lower the noise level while encouraging the selection of meaningful image features, and a feature-based stitching approach was carried out to generate the panorama. The frame selection strategy, tested on on six pathological NB endoscopic videos, was compared with standard strategies, as uniform and random sampling, showing higher performance of the subsequent stitching procedure, both visually, in terms of vascular structure preservation, and numerically, through a blur estimation metric.

Purpose: Single-incision laparoscopic surgery decreases postoperative infections, but introduces limitations in the surgeon's maneuverability and in the surgical field of view. This work aims at enhancing intra-operative surgical visualization by exploiting the 3D information about the surgical site. An interactive guidance system is proposed wherein the pose of preoperative tissue models is updated online. A critical process involves the intra-operative acquisition of tissue surfaces. It can be achieved using stereoscopic imaging and 3D reconstruction techniques. This work contributes to this process by proposing new methods for improved dense 3D reconstruction of soft tissues, which allows a more accurate deformation identification and facilitates the registration process., Methods: Two methods for soft tissue 3D reconstruction are proposed: Method 1 follows the traditional approach of the block matching algorithm. Method 2 performs a nonparametric modified census transform to be more robust to illumination variation. The simple linear iterative clustering (SLIC) super-pixel algorithm is exploited for disparity refinement by filling holes in the disparity images., Results: The methods were validated using two video datasets from the Hamlyn Centre, achieving an accuracy of 2.95 and 1.66 mm, respectively. A comparison with ground-truth data demonstrated the disparity refinement procedure: (1) increases the number of reconstructed points by up to 43 % and (2) does not affect the accuracy of the 3D reconstructions significantly., Conclusion: Both methods give results that compare favorably with the state-of-the-art methods. The computational time constraints their applicability in real time, but can be greatly improved by using a GPU implementation.