Assessments included: single cell gel electrophoresis assay (COMET assay) to confirm lack of genetic toxicology, magnetic resonance imaging (MRI) for tumorigenicity, and body, muscle and organ weights. Human DEC biodistribution to the target  and non-target  organs was detected by flow cytometry assessment of HLA-ABC markers. Human origin of dystrophin was verified by co-localization of dystrophin and human spectrin by immunofluorescence. No complications were observed after intraosseous transplant of human DEC. COMET assay of donors and fused DEC cells confirmed lack of DNA damage. Biodistribution analysis of HLA-ABC expression revealed dose-dependent presence of human DEC cells in target organs, whereas negligible presence was detected in non-target organs. Human origin of dystrophin in the heart, diaphragm and gastrocnemius muscle was confirmed by co-localization of dystrophin expression with human spectrin. MRI revealed no evidence of tumor formation. Body mass and muscle and organ weights were stable and comparable to vehicle controls, further confirming DEC safety at 180 days post- transplant. This preclinical study confirmed long-term local and systemic safety of human DEC therapy at 180 days after intraosseous administration. Thus, DEC can be considered as a novel myoblast based advanced therapy medicinal product for DMD patients.Duchenne muscular dystrophy (DMD) is a lethal disease caused by X-linked mutations in the dystrophin gene. Dystrophin deficiency results in progressive degeneration of cardiac, respiratory and skeletal muscles leading to premature death due to cardiopulmonary complications. Currently, no cure exists for DMD. Based on our previous reports confirming a protective effect of human dystrophin expressing chimeric (DEC) cell therapy on cardiac, respiratory, and skeletal muscle function after intraosseous administration, now we assessed long-term safety and biodistribution of human DEC therapy for potential clinical applications in DMD patients. Safety of different DEC doses (1 × 10 Duchenne muscular dystrophy (DMD) is a lethal X-linked recessive genetic disease, characterized by mutations of the dystrophin gene leading to fibrosis, inflammation and progressive weakness and degeneration of cardiac, respiratory and skeletal muscles resulting in premature death of DMD patients.Currently, there is no cure for DMD and the recommended supportive therapies include corticosteroid and physical therapy with a focus on amelioration of symptoms and improvement of quality of life of DMD patients , and at the autopsy. The effect of DEC therapy on the animal’s well-being was assessed weekly by experienced veterinarians and body and organ weights were taken to further assess DEC therapy safety.In summary, in this study we confirmed long-term safety of dystrophin expressing chimeric cell therapy as confirmed by the lack of DNA damage after DEC fusion, lack of local toxicity at the DEC injection site, lack of tumor formation by MRI and at the autopsy, biodistribution of DEC to the selected target organs and negligible presence in the non-target organs. Moreover, the muscle and organ weights were comparable with the vehicle-injected controls, further confirming DEC safety. This encouraging safety data introduces DEC as a novel therapeutic modality of advanced therapy medicinal product (ATMP) to the armamentarium of therapeutic options for DMD patients.mdx/scid mice—the animal model for Duchenne muscular dystrophy  were purchased from Jackson Laboratories. Animals were kept in a pathogen-free environment on a light/dark cycle. Prior to study initiation, aged matched male mdx/scid mice were ear tagged and randomized into experimental groups: vehicle-injected animals with 60 µl phosphate-buffered saline—PBS (n = 4), animals injected with 1 × 106 DEC cells suspended in 60 µl PBS (n = 5), and animals injected with 5 × 106 DEC cells suspended in 60 µl PBS (n = 5). All treated animals were observed daily after injection of the DEC cells or saline for any local signs of infection, edema or hematoma or animal distress for the first week. No signs of local changes were observed, and treatment had no effect on general animal conditions, food consumption and coat changes. Animal observations were carried out up to 180 days after administration of DEC therapy and there were no acute or delayed signs of immune response  observed.This study was approved by the Institutional Animal Care and Use Committee (IACUC) of University of Illinois at Chicago, which is approved by the American Association for the Accreditation of Laboratory Animal Care (AAALAC). All animals received humane care in compliance with the “Principles of Laboratory Animal Care” formulated by the National Society for Medical Research and the “Guide for the Care and Use of Laboratory Animal Resources”. Six- to 8 week-old male Normal human myoblasts were purchased from Lonza Bioscience , and DMD-affected myoblasts were purchased from Creative Bioarray Ltd. . Myoblasts (MB) were cultured in Skeletal Muscle Cell Growth Medium-2  supplemented with: human epidermal growth factor; fetal bovine serum (FBS); Dexamethasone; Gentamicin/Amphotericin B from Lonza Clonetics. Upon reaching 60–70% confluence, myoblasts were harvested using 0.25% trypsin/EDTA . Enzymatic activity was inhibited with 10% serum-supplemented culture media. Human MBs were harvested between passages 3–7, which is optimal for an ex vivo cell fusion procedure.N and MBDMD) were washed in serum-free media supplemented with antibiotics . Then, our standard cell fusion procedure was performed. As previously described  were fluorescently labeled using PKH26 or PKH67  membrane dyes according to the manufacturer’s instructions. Parent cells were mixed and washed, then fusion was performed using a 1.46 g/mL PEG solution  containing 16% DMSO .After harvesting, cell viability was assessed with 0.4% Trypan Blue staining , parent myoblasts  markers and staining efficacy. After sorting, DEC cells were suspended in 10% serum-supplemented with culture media. DEC cells were further propagated in Lonza Clonetics supplemented with FBS to achieve an optimal number of cells for transplantation.Fused cells were transferred to the fluorescently activated cells sorting (FACS) buffers containing 5% HEPES, 1% EDTA and 5% FBS. Cells presenting double positive (PKH26/PKH67) staining were selected via FACS  and used for in vitro analysis in preparation for transplantation to 6 and 5 × 106 of DEC cells were suspended in 60 μl of PBS and transferred into the tuberculin syringe with 25G needle . The same volume of 60 μl of PBS without DEC cells was injected into the vehicle control group.DEC cells were harvested between passages 3 and 7 after cell fusion, which is the optimal number of passages to receive a sufficient number of cells for intraosseous administration to the recipient mice. Next, DEC cells were counted and viability of cells was evaluated, then two doses of 1 × 10Mice were anesthetized with 2% isoflurane inhalation along with 1 ml/kg buprenorphine subcutaneous injection. DEC intraosseous transplant was performed as previously reported , and immediately layered onto microscope slides. Cells were assessed at different passages to confirm DNA stability and compared to the positive control with induced DNA-damage . After standard single cell electrophoresis , DNA was visualized using Vista Green dye diluted in TE buffer  and samples were examined immediately using LSM 710 fluorescence microscope Meta . Assessment of 50 cells randomly selected in images of therapy and control groups was performed by visual presence or lack of the “comet”-like tail and Comet Assay Software, CaspLab, to detect a “comet”-like tail which indicate the DNA damage.To ensure safety of the therapy, an analysis was performed using the alkaline single cell gel electrophoresis according to the manufacturer  instructions. Cells were resuspended at 1 × 10Following intraosseous DEC administration, the injection site was assessed daily for 2 weeks post-injection and on a monthly basis thereafter for any signs of bruising, redness, inflammation, infection or wound dehiscence. The analysis was performed by an experienced veterinarian from the College of Veterinary Medicine, University of Illinois at Chicago (USA).6 and 5 × 106 of human DEC cells suspended in 60 µl of saline and equivalent volume of saline in the control group, were injected via systemic intraosseous delivery route to the bone marrow compartment of the femoral bone. Animals were assessed during DEC therapy administration as well as for the following 72 h after DEC injection, for any signs of therapy related toxicity such as anaphylactic reaction, and local or systemic immune response. The analysis was performed by the experienced fellows and investigators from Siemionow Laboratory and by the experienced veterinarians from the College of Veterinary Medicine, University of Illinois at Chicago (USA).To assess potential dose-dependent toxicity of DEC therapy, two different doses of 1 × 102, matrix size 128 × 128, TR = 2000 ms, echo train length 16, effective echo time 28 ms. Scan parameters for T1 included: field of view 40 × 40 mm2, matrix size 128 × 128, TR = 550 ms, echo time 28 ms. MRI scanning was performed before treatment and at day 30, 90 and 180 days after DEC transplantation.In preparation for MRI imaging, mice were induced with 2% isoflurane, and then anesthesia was maintained with 1–1.5% in 100% oxygen throughout the experiment. A rectal probe was used to monitor body temperature, which was maintained at 37.5 °C by regulating the warm air flow into the scanner bore. Temperature and respiration rate were monitored using an MRI—compatible physiological monitoring system . MRI was carried out by an Agilent Varian 9.4 T preclinical scanner with a 39-mm proton volume coil. Each mouse was scanned in three sections: brain, chest, and pelvis. T2 weighted images were acquired for each section and T1 for brain and liver (greater soft-tissue resolution facilitates tumor detection in solid organs). Scan parameters for T2 weighted images included: field of view 40 × 40 mmAutopsy was performed at the study endpoint, at 180 days after systemic-intraosseous injection of DEC cells. The animals underwent euthanasia and were assessed by an experienced veterinarian for any signs of tumor or tumor-like formation, changes in organ size, texture or appearance, and presence of third-space body fluids.The baseline body mass of each animal was recorded at the beginning of the study and was then measured weekly after intraosseous DEC administration until the study endpoint at 180 days. In addition, at the study endpoint, the selected organs  and the skeletal muscles  were harvested after animal euthanasia, and dry weights of tissues of interest were recorded.Evaluation of human DEC cells biodistribution included assessment of the presence of human HLA-ABC (human leukocyte antigen) marker in the target organs  and non-target organs  analyzed by flow cytometry. Biodistribution of human DEC cells to the organs was evaluated by staining of the cell solution isolated from the respective organs with the anti-human mouse derived HLA-ABC antibody conjugated with allophycocyanin (APC)  for 40 min, in the dark, at 4 °C. Next, cells were washed with PBS supplemented with 1% BSA, then fixed using 4% paraformaldehyde, washed with PBS and assessed using flow cytometry  detecting the APC signal. Biodistribution studies were performed at the study endpoint of 180 days after DEC transplant, to assess cell migration and persistence of human DEC cells within the selected target organs.To assess the migration and check the presence of human DEC cells after 180 days, the staining for dystrophin and human spectrin was performed on optimal cutting temperature frozen sections of the heart, diaphragm and gastrocnemius muscle (GM) as described previously . GraphPad Prism (ver 9.2.1) software was used to perform statistical analysis. Two-tailed Student N and MBDMD) as well as passaged (P5) DEC (MBN /MBDMD) cells, revealed lack of DNA damage confirming lack of genotoxicity in cell culture up to passage 6 as confirmed by the lack of a “comet like tail” structures in the cultured DEC cells, whereas the “comets'' were observed in the positive control cells treated with hydrogen peroxide to induce DNA damage. These results confirmed DNA stability and safety of the cell fusion procedure, and safety of in vitro cells propagation before intraosseous administration of DEC to the mdx/scid mouse model  parent cells  administration and was euthanized before the study endpoint. The pathology assessment revealed sarcoma of mouse origin which is prevalent in the mdx/scid mice prone to tumor formation . Specifically, the injection site was assessed on a daily basis for 2 weeks post-transplantation and at a monthly basis thereafter and there were no signs of bruising, redness, inflammation, infection or wound dehiscence observed at the injection site or reported in the animal’s individual charts over the entire 180 day observation period. During routine animal control, one mouse developed a mass on the right hind limb at 90 days after DEC  performed by the experienced veterinarian and study investigators. There were no signs of organ enlargement or shrinkage, no signs of inflammation or presence of fluid within the abdominal cavity. In addition, the organs of animals treated with both doses of DEC therapy were harvested at the necropsy, weighed and compared with the organs of the control—saline injected animals and there were no abnormalities found in the organs size, appearance, texture or weight at 180 days after DEC administration confirming lack of toxicity after systemic-intraosseous administration of two different doses of DEC therapy.Assessment of animals during intraosseous administration of the lower DEC dose of 1 × 106 dose  as well as in the control vehicle-injected mice, over the long-term 180 day follow-up period. At the study baseline, the vehicle-injected mice weighed, on average, 24.66 ± 1.80 g and the body weight increased to 29.47 ± 0.77 g at the 180 day study endpoint. The baseline average weights for 1 × 106 and 5 × 106 DEC treatment groups were 22.84 ± 1.08 g and 24.20 ± 1.63 g respectively and increased to 31.18 ± 0.61 g and 30.33 ± 0.47 g, respectively, at the 180 day study endpoint. Overall, a normal physiological increase in the body weight was observed in both DEC injected and the vehicle-injected animals at 180 days after systemic-intraosseous administration of human DEC , except for left gluteus muscle, showing increased weight (0.276 ± 0.039 g) when compared with vehicle-injected controls  and was comparable with the vehicle-injected controls . In contrast, there were no cells of human origin in the vehicle-injected controls. Moreover, the presence of HLA-ABC positive cells in the heart, diaphragm and gastrocnemius revealed a dose-dependent effect  and high dose (5 × 106) of DEC therapy which was well tolerated both during intraosseous administration as well as over the entire study follow-up period of 26 weeks.Next, we confirmed the lack of local and systemic side effects pertinent to the procedure of intraosseous administration of DEC cells. Moreover, we confirmed lack of the local and/or systemic toxicity in response to the administration of the low  after intraosseous DEC injection. We observed a normal physiological weight gain throughout the study, both in the DEC injected mice as well as in the vehicle-injected controls. There was no weight loss observed in any animal, which might have suggested illness or poor therapy tolerance. Moreover, during autopsy at the study endpoint, we also weighed muscles and selected organs of both the vehicle-injected controls and DEC treated Furthermore, we have proven that intraosseous DEC transplant was corresponding with long-term engraftment and biodistribution of the human DEC cells from the injection site of the bone marrow compartment to the target organs of heart, diaphragm, and GM as confirmed by the presence of human HLA-ABC marker expression. Moreover, the lack of HLA-ABC marker in the non-target organs of blood, bone marrow, liver, lungs, and spleen confirmed safety of intraosseous DEC administration by the lack of evidence of DEC cell migration and lodging in the lungs. This supports the benefits of the intraosseous when compared to intravenous administration of cell-based therapies . However, there are some limitations of immunocompromised mouse models, including the risk and susceptibility of developing the spontaneous tumor formations as observed in one mouse in our study and also reported by other investigators (Santagostino et al. Advantage of using the Furthermore, in contrast to gene therapies targeting the specific dystrophin mutations, thus limiting their clinical applications to the restricted number of patients, our DEC therapy does not require genetic manipulation or application of viral vectors and as such is potentially safer and applicable to all muscular dystrophies regardless of gene mutation including the limb-girdle muscular dystrophies and others.In summary, long-term engraftment and biodistribution of DEC cells to the selected target organs of heart, diaphragm and GM was confirmed by presence of the human HLA-ABC antigen expression in the respective target organs at 180 days after systemic-intraosseous DEC administration. Moreover, there was negligible presence of human HLA-ABC markers in the non-target organs of lung, liver, and spleen, confirming safety of DEC therapy. In addition, we confirmed co-localization of dystrophin with human spectrin, in the heart, diaphragm and GM, further confirming migration of human DEC cells from the injection-site of bone marrow compartment into the target organs as well as human origin of the dystrophin at 180 days after systemic intraosseous DEC administration.mdx/scid mouse model. We confirmed lack of DNA damage before and after cell fusion procedure by COMET assay, confirming lack of genotoxicity and safety of human DEC therapy. Moreover, lack of abnormal growth and tumor formation was confirmed by weekly animal palpation and by MRI scanning of selected organs before and after DEC administration as well as at the study endpoint by autopsy. Assessment of body weight and selected muscle and organ weights revealed normal physiological growth of animals over the entire 26-week follow-up which was comparable with the assessments of the vehicle injected controls. Biodistribution of DEC to target and non-target organs assessed by expression of HLA-ABC antibody confirmed human DEC trafficking to the heart, diaphragm and GM of the mdx/scid host. Moreover, the negligible presence of DEC in the non-target organs further confirmed DEC therapy safety. Further assessment of biodistribution of DEC to the selected target organs after systemic administration was confirmed by co-localization of dystrophin with human spectrin at 26 weeks after administration. The long-term assessments of safety, toxicity and biodistribution performed in this study confirmed, both the safety as well as selectivity of DEC therapy in targeting the DMD- affected organs. Moreover, these findings correlated with lack of tumorigenicity, confirmed by MRI and preservation of normal physiological growth and wellbeing of the DEC-injected animals. Thus, to the best of our knowledge this is the first report on the long-term safety of DEC therapy for DMD. Our preclinical safety and tolerability data represent a valuable contribution towards the unmet medical needs and introduces DEC as a novel, efficient and safe therapy for Duchenne muscular dystrophy patients.In this study, we assessed long-term safety of DEC fusion protocol after systemic-intraosseous administration to the


The coexistence of glioblastoma multiforme (GBM) and arteriovenous malformation (AVM) is rarely reported in the literature. According to the present literature, these GBM or glioma-related vascular malformations may present simultaneously in distinct regions of the brain or occur in the same area but at different times. So far, these distinct hypervascular glioblastomas have been described but are not classified as a separate pathological entities. Considering their heterogeneity and complexity, all the above mentioned cases remain challenging in diagnosis and therapeutic modality. Likewise, there is a paucity of data surrounding the simultaneous presentation of GBM with intracranial aneurysms. In the literature, the independent concurrence of these three intracranial lesions has never been reported. In this article, we present a case who suffered from intermittent headaches and dizziness initially and further radiographic examination revealed an internal carotid artery (ICA) aneurysm that occurred in the patient with coexisting GBM and AVM. Surgical intervention for tumor and AVM removal was performed smoothly. This patient underwent endovascular coiling for the ICA aneurysm 4 months postoperatively. In addition, we also review the current literature relating to this rare combination of medical conditions. The coexistence of glioblastoma multiforme (GBM) and arteriovenous malformation (AVM) is rarely reported in the literature, and at times the term “angioglioma” is used to describe hypervascular glial cell tumors. Tunthanathip et al.  made a rRegarding the present case, the pathological entity may resemble the abovementioned “angiogliomas” to some degree although they are usually hypervascular low-grade lesions with a favorable prognosis. According to the present literature, these GBM or glioma-related vascular malformations may present simultaneously in distinct regions of the brain or occur in the same area but at different times. So far, these distinct hypervascular glioblastomas have been described but have not been classified as a separate pathological entities. Considering their heterogeneity and complexity, all the above mentioned cases remain challenging in diagnosis and therapeutic modality.In addition to the clinical illustration of the rare combination of GBM, AVM and ICA aneurysm, we also searched the literature focusing on pathogenesis, especially in molecular investigation, and discuss whether there is a correlation between these three distinct but simultaneously existing lesions.A 44-year-old female was presented to our hospital experiencing intermittent headaches and dizziness. Furthermore, she had experienced a change in consciousness three times in the previous month. Her neurological examination was normal except for slight paresthesia in her right hand. Computed tomography demonstrated enhancement with a peri-focal edema lesion over the right temporo-parietal area Magnetic resonance imaging (MRI) demonstrated a well enhanced mass, 1.1 cm × 2.3 cm in size, with a peri-focal edema in the right temporal lobe We arranged a navigation-guided right temporo-parieto-occipital craniotomy under general anesthesia. We planned to remove the AVM first and then remove the temporal lesion. We left the observed unruptured aneurysm since it was difficult to clip with the same approach. During the operation, the resection of the temporo-occipital AVM was performed first. Then, we aimed to achieve the gross resection of the temporal lesion. During the tumor removal procedure, the lesion was noted at the right temporal area with dural adhesion, while a cystic part with straw-colored contents was also noted. The patient recovered well and was discharged on the postoperative day 11.Histopathological analysis of the tumor revealed glioblastoma (WHO grade IV), with increased cellularity, cellular atypia, and frequent mitotic figures. Glomeruloid microvascular proliferation and tumor necrosis were also found 2 daily. Upon a follow-up visitation 6 months post-operation, apart from previous neurologic deficits, she remained in good condition. Surveillance imaging showed no disease progression in the past 18 months after the surgery. We performed digital subtraction angiography (DSA) 4 months later and found no evidence of AVM, but the ICA aneurysm revealed only a sparse change in size without a sign of rupture Following discharge, she underwent concurrent chemoradiotherapy with a total dose of 6900 cGy given in 30 fractions in conjunction with temozolomide (TMZ) at 75 mg/mSimultaneous presentation of vascular lesions and glioblastoma are rarely encountered, while the coexistence of AVM, glioblastoma and an intracranial aneurysm is never reported. Tunthanathip et al.  made a rThe term “angioglioma” was originally used by Russell and Rubinstein to describe a tumor possessing characteristics of angiogenic and glial origin, including gliomas in combination with either venous malformations, cavernous angioma or arteriovenous malformations ,3. TheseIn vascular malformation, it has been shown that VEGF expression plays a fundamental role in mediating angiogenesis and may also play an important role in both AVM development and progression. In the presence of VEGF, Angiopoietin-2 induces pericytes to dissociate themselves from existing vessels and facilitates the extravasation of other pro-angiogenic factors. These events finally result in the formation of new blood vessels . On the For the coexisting intracranial aneurysm, we have reviewed the current literature about the coexistence of aneurysms and glioma. Ali et al.  showed 1Regarding the present case, we expected that the supra-clinoid aneurysm would reduce in size after removal of the ipsilateral AVM and glioblastoma due to intracranial hemodynamic changes and fewer angiogenesis-stimulation factors such as VEGF from the tumor. A similar hypothesis was addressed in the current literature and demonstrated good outcomes in cases where intracranial aneurysms and brain tumors simultaneously coexisted ,14, but In hindsight, a pre-operative DSA or utilization of a hybrid operating room with intra-operative DSA might provide a safer strategy facing lesions with complex angioarchitecture. Secondly, more extensive genetic/biomolecular investigation should be performed. For example, the IHC stain could include HIF-1 and VEGF concerning the overexpression status. For the lesions with hypervascularity, these factors play important roles in angiogenesis mediation and the IHC stain data could provide us with a more apparent correlation between these coexisting lesions. Furthermore, an analysis of the methylation status of the O6-methylguanine-DNA methyl-transferase (MGMT) gene promoter might provide us with significant information in predicting patient survival and response to chemoradiotherapy with the alkylating agent ,16,17.The coexistence of vascular malformation, aneurysm, and malignant glioma has been rarely reported. The treatment plan is usually challenging and requires multiple modalities for the complexity of each lesion. The correlation between these lesions remains uncertain and needs more genetic and molecular studies. With regard to our case, the pre-surgical image survey provided us with much support towards making critical decisions. Surgery surrounding the removal of simultaneously coexisting AVM and GBM is always a challenging task due to the potential risk of massive intraoperative bleeding.


The MOF, MIL-101⊃{Mg(TFSI)2}1.6 (TFSI– = bis(trifluoromethanesulfonyl)imide),containing Mg2+ inside its pores, showed a superionic conductivityof 1.9 × 10–3 S cm–1 at roomtemperature (RT) (25 °C) under the optimal guest vapor (MeCN),which is the highest value among all Mg2+-containing crystallinecompounds. The Mg2+ conductivity in the MOF was estimatedto be 0.8 × 10–3 S cm–1 atRT, by determining the transport number of Mg2+ (t2+Mg = 0.41), which is the levelas high as practical use for secondary battery. Measurements of adsorptionisotherms, pressure dependence of ionic conductivity, and in situFourier transform infrared measurements revealed that the “superMg2+ conductivity” is caused by the efficient migrationof the Mg2+ carrier with the help of adsorbed guest molecules.We first report asolid-state crystalline “Mg Normally, the electrolyte of a secondary batteryrequires a practical conductivity of around 10–3 S cm–1 at operating temperatures.2 There are numerous reports of Li+ conductorsshowing superionic conductivity above 10–3 S cm–1 at room temperature (RT),4 whilewe found no report of such RT conductivity for Mg2+ conductionin crystalline solids. The main reason for the suppressed conductivityof Mg2+ in solids is the strong electrostatic interactionwith neighboring anions because conventional solid-state materialstend to have closely packed crystal structures with the included Mg2+ carrier.5Efficient magnesiumion (Mg+)7 and hydroxide ions,8 showing excellent conductivity at ambient temperatures.The porous structures of MOFs provide great opportunities for constructingefficient ion-conductive pathways inside the pores, which often consistof adsorbed guest molecules, called “conducting media”. However, in thecase of Mg2+,12 there is a lack of reports of high “Mg2+ conduction” inside the MOF pores, and thus, the creationof a highly Mg2+-conductive MOF is still a challengingissue. We recently reported on “Mg2+ conduction”with a conductivity of around 10–4 S cm–1 at RT inside the MOF pore, which is assisted by adsorbed guest moleculessuch as MeOH, introduced as anhydrous organic vapors.13 However, the conductivity is still insufficient for practicaluse.Recently, metal–organicframeworks (MOFs) have been widelystudied as novel ion-conductive materials with various ionic carrierssuch as protons 2}x) (TFSI– =bis(trifluoromethanesulfonyl)imide), and that the mobile Mg2+ carrier would be coordinated or solvated species formed in MOF pores.13 This suggested the efficient migration of acoordinated Mg2+ carrier, whose size is much larger thanthe lone Mg2+, as it requires a relatively large pore sizeof the mother framework as the optimal ion-conducting pathway. Inthis study, we used MIL-101, which has large three-dimensional (3-D)pores (maximum approximately 32 Å),14 as the mother framework and prepared MIL-101⊃{Mg(TFSI)2}x (MIL-101 = Cr3O(NO3)(H2O)2(bdc)3, where H2bdc is terephthalic acid, x = 0–1.7)that only includes Mg(TFSI)2 as the Mg2+ carrierin it. The samples showed a high ionic conductivity under anhydrousorganic vapors, and MIL-101⊃{Mg(TFSI)2}1.6 exhibited superionic conductivity of 1.9 × 10–3 S cm–1 under MeCN vapor at RT, which is the highestconductivity among all Mg2+-containing crystalline solid-statematerials. The transport number of Mg2+ (t2+Mg), that is, the direct evidence of Mg2+ transport, was determined to be t2+Mg = 0.41, confirming an Mg2+ conductivityof 0.8 × 10–3 S cm–1 at RTin the MOF. The role of the adsorbed guest molecules for the “Mg2+ conduction” in the MOF pores was also studied.Here, we demonstrate for the first time super Mg3)2·9H2O  and terephthalic acid (H2bdc)  were stirred in deionized water (150 mL)for several minutes at RT. The mixture was placed in a Teflon-linedautoclave and heated at 200 °C for 24 h. The precipitate wascollected by centrifugation. It was washed by repetition of immersionin dimethylformamide and centrifugation. After that, it was stirredin MeOH at 70 °C for 1 d (the solvent was replaced with freshMeOH two times during the day). The green powder was collected bycentrifugation and dried at 70 °C for 24 h .Elemental analysis. Calcd (for Cr3O(NO3)(H2O)2(C8O4H4)3(H2O)0.8(CH3OH)): C, 37.12%;H, 2.69%; N, 1.88%. Found: C, 37.34%; H, 2.75%; N, 1.88%.MIL-101 was synthesized usingthe solvothermal method. Cr(NO2 was introduced into MIL-101through slow evaporation of EtOH from a EtOH solution of Mg(TFSI)2. MIL-101  was soaked in EtOH solution(20 mL) of [Mg(H2O)6](TFSI)2·2H2O  in a test tube.It was then heated at 85 °C for 7 d.Mg(TFSI)2 (77 K) and MeCN vapor (298K) were measured using BELSORP-max . Before themeasurements, the samples were dried under vacuum at 130 °C fora night. Inductively coupled plasma atomic emission spectroscopy (ICP–AES)measurements were carried out using SPECTRO ARCOS (Hitachi High-TechScience Corporation). The sample (about 20 mg) was added with nitricacid (2 mL) and diluted to 50 mL with deionized water. The supernatantsolution was used for ICP–AES measurements to determine theconcentration of Mg.X-ray powder diffraction (XRPD)measurements were performed in air using Rigaku MiniFlex600 (Cu Kα).Adsorption isotherms for N13 The temperaturewas controlled in an incubator, SU-222 . The amountsof N2 gas flows were controlled by mass flow controllers.The samples were dried under N2 flow at 130 °C overnightto remove adsorbed water molecules before the measurements. Afterthat, ionic conductivity was measured under the dry N2 flowor various guest vapors of MeOH, EtOH, MeCN, tetrahydrofuran (THF),diethyl carbonate (DEC), and propylene carbonate (PC), produced bybubbling each anhydrous organic solvent with the dry N2 in the temperature range of 19–34 °C. The resistanceof the sample was estimated by a semicircle fitting . In the case of the sample underTHF, a typical equivalent circuit, as shown in Z′-axis intercept (for the sampleunder MeOH).The alternatingcurrent (ac)impedance measurements were carried out with the two-probe methodusing a Solartron 1260/1296A impedance analyzer for the frequencyrange of 1 Hz to 10 MHz. Two porous silver electrodes were attachedto the compacted pellet (3 mm ϕ) in a homemade sealed cell,as previously reported.16 the transport numberof Mg2+ in the sample was estimated by measuring the directcurrent (dc) of the cell, Mg|MIL-101⊃{Mg(TFSI)2}x(MeCN)n|Mg. The x = 1.6 sample was preliminarily dried at 130 °C undervacuum for a night. The cell was constructed using a sealed cell.All experimental manipulations for the construction of the cell wereperformed in a glove bag filled with Ar gas with MeCN vapor. The powderof the sample was sandwiched with metal Mg foil and pressed into apellet (5 mm ϕ) under MeCN vapor. The dc current was measuredusing a Vertex10A  potentiostat/galvanostatby applying 0.3 V at 60 °C. Before and after the polarization,ac impedance measurements were also performed using a Solartron 1260/1296Aimpedance analyzer for the frequency range of 1 Hz–10 MHz toestimate the resistance between the electrode and the sample. Thetransport number of Mg2+ was calculated with the Bruce–Vincentmethod17 using the following equationV, I0, Iss, R0, and Rss correspondto theapplied voltage, initial current, current at steady state, initialresistance, and resistance at steady state, respectively. We performedfour experiments with the same setup and estimated the final valueof t2+Mg as an average of thesefour experiments.Accordingto previous reports,2 windows connected to a conventional gasflow system. Prior to the measurement, the sample pellet was heatedunder He flow (100 cm3 min–1) at 130°C overnight. After cooling to 30 °C under the He flow,2 μL of MeCN was injected to the sample. Spectra were measuredaccumulating 20 scans at a resolution of 4 cm–1.A reference spectrum taken at 30 °C under He flow was subtractedfrom each spectrum.In situ Fourier transform infrared (FT-IR) spectrawere recordedat 30 °C using a JASCO FT/IR-4200 with an mercury–cadmium–telluridedetector. A sample (40 mg) was pressed to obtain a self-supportingpellet (ϕ = 2 cm). The obtained pellet was placed in the quartzIR cell with CaF2}x (x = 0–1.7) through slow impregnation with gradualevaporation of the EtOH solvent for several days, according to ourprevious report.13 The Mg content in thesample was quantified using ICP–AES. 2 contents (x =0–1.7). The peaks from bulk Mg(TFSI)2 crystals (accuratelydescribed as [Mg(H2O)6](TFSI)2·2H2O) were observed above the x = 1.7 sample,whereas the MIL-101 peaks were observed in all samples, indicatingthat MIL-101 could incorporate the Mg(TFSI)2 inside itspores below the molar amount of x = 1.6. Note that,we confirmed that the intensity of weakened peaks at low angle (below7°) in the samples above x = 1.1, recoveredby exclusion of the included salts through immersing the sample inthe pure solvent. This is indicative that the decrease in the peakintensity at the low angle was not due to decomposition of the frameworkbut derived from some other reasons such as change in electron densityin the pores or weakening of the long-range order of the frameworkoccurred by inclusion of the salts. The incorporation of Mg(TFSI)2 was confirmed by N2 adsorption measurements at77 K 2 inside the pores occurred below x = 1.6.The samples, MIL-101⊃{Mg(TFSI)= 0–1.7)2a, were  MIL-101 S1 throug MIL-101 S1 throug2 after completedehydration of the sample. Examples of the obtained Nyquist plotsare shown in Figure S2. In the case ofthe sample under THF vapor, a typical plot consisting of both a semicirclederived from the sample resistance and a part of increasing impedancedue to the huge resistance between the blocking electrode and thesample was observed. Thus, the sample resistance could be determinedby fitting with the equivalent circuit, as described above. The samplesunder DEC, PC, and N2 only showed a part of the semicirclefrom the sample resistance due to their high resistivity. In contrast,in the case of the samples under MeOH, EtOH, and MeCN, a part of theelectrode-sample impedance or the inflection point from the sampleimpedance to it was clearly observed because of the low resistivityof the sample, which is similar to the case of other highly ion-conductivematerials.18 It is clear that the drasticchange in the sample resistance was observed just by changing thevapor atmosphere around the sample, as is the case with our previousreport.13 Since we could not observe thedivided components of bulk and grain boundary contributions in theNyquist plots, it was difficult to be sure of whether the ionic conductivity is mainly derived from thebulk or grain boundary, only by the impedance measurements. However,several facts could confirm that the changes in the ionic conductivitycorrespond to the changes in the bulk conductivity. For example, aswe reported,13 Mg(TFSI)2 itselfdoes not show such a change in ionic conductivity under vapors, meaningthat there is no possibility that slight amount of Mg(TFSI)2 located on the outside of the pores make the ion-conducting pathwayin the grain boundary region. In addition, the clear relationshipbetween guest adsorption and ionic conductivity of the Mg-includedsample, as described below, cannot be explained by the hypothesisthat the ionic conductivity of the sample is derived from the grainboundary. Therefore, we could attribute the observed conductivityof the sample to the bulk conductivity. The temperature dependenceof ionic conductivity of MIL-101⊃{Mg(TFSI)2}1.6, in which the maximum amount of Mg2+ was incorporated,is shown in 13 Surprisingly,MIL-101⊃{Mg(TFSI)2}1.6 showed superionicconductivity (1.9 × 10–3 S cm–1) at RT under MeCN vapor, which was the highest value among all Mg2+-containing crystalline compounds (Table S1). Very high conductivity values were also observed at RTunder other small guest molecules such as MeOH (1.4 × 10–3 S cm–1) and EtOH (4.5 × 10–4 S cm–1), and moderate conductivitywas observed at RT under THF (4.5 × 10–7 Scm–1). In contrast, almost no enhancement in theionic conductivity was observed under DEC or PC vapor, and thus, thesample presented an insulating character (<10–8 S cm–1), which was similar to the dry N2 condition. Note that the dc conductivity of the samples (x = 0 and 1.6) was not observable (at least below 10–8 S cm–1), confirming that the effectof electron conduction of the MOF is negligible and that the conductivityobserved in the ac impedance measurements is derived from the ionicconductivity. The samples of x = 0, 0.5, 1.1, and1.6 showed ionic conductivity under MeCN . The conductivity increased almost monotonically with increasingMg(TFSI)2 content in the pores, indicating that the ionicconductivity of the x = 1.6 sample was derived fromthe included Mg(TFSI)2.Toenclose the ionic conductivityof the MOF under optimal conditions, we performed ac impedance measurementsunder various anhydrous guest vapors or dry N2+ and TFSI– in the pores, conducting ionic species should be identified to statethe “Mg2+ conduction” in the MOF. To quantifythe contribution of Mg2+ conduction to the ionic conductivity,we evaluated the transport number of Mg2+ (t2+Mg) through dc polarization measurementswith nonblocking electrodes, as we previously reported.13 The value for t2+Mg under MeCN vapor for the x = 1.6sample was estimated to be 0.41 (the average of four experiments)2}1.6 showed “superMg2+ conductivity” (σ2+Mg = 0.8 × 10–3 S cm–1), atRT under MeCN. This is the first crystalline solid showing a practicalMg2+ conductivity of around 10–3 S cm–1 at ambient temperature. The activation energy ofthe ionic conduction in the x = 1.6 sample underMeCN was estimated to be 0.18 eV, much lower than that of reportedMg2+-containing compounds (0.8–1.6 eV)23 and similar to MgSc2Se4 (0.2 eV),24 which is one of the best crystalline inorganicMg2+ conductors, suggesting that efficient ion-conductingpathways were formed inside the MOF pores.Because the sample included both Mgriments)4, which 2+ conduction insidethe MOF, we measured adsorption isothermsfor MeCN vapor (x = 0) showed a large amountof MeCN adsorption at the low-pressure region, confirming its largepore volume and high affinity for MeCN. When the Mg(TFSI)2 was incorporated into the MOF, the adsorption of MIL-101⊃{Mg(TFSI)2}1.6 at the low-pressure region (∼0.2 P/P0) was suppressed, and theshape of the isotherms was remarkably changed compared with x = 0. This change in adsorption isotherms was indicativethat the incorporation of Mg(TFSI)2 does not only leadto a decrease in pore volume but changes the affinity of the remainingpores for guest molecules, that is, causes changes in the host–guestinteraction. Because the x = 1.6 sample presentedtype II-like isotherms, different types of adsorption sites or adsorptionprocesses corresponding to the low- and high-pressure regions shouldexist. In the low-pressure region, the adsorption might be due tostrong interactions, such as chemisorption by Mg2+, withcoordination bonds or strong binding by the framework. Above thisregion, the adsorption might be due to weaker interactions such asthe guest–guest interaction with intermolecular forces. Theadsorption in the x = 1.6 sample at the low-pressureregion reached ∼10 MeCN molecules (9.5 at 0.1 P/P0) per formula , which is near the 9.6 that is in good agreementwith the amount to form hexa-coordinated Mg2+ species bychemisorption 6]2+)25 in MIL-101⊃{Mg(TFSI)2}1.6. This suggests that the superionic conduction occurs underthe presence of both the coordinated or solvated Mg2+ speciesand additional uncoordinated MeCN molecules adsorbed in the higher-pressureregion.To clarify the role ofthe guest molecules for the super MgCN vapor 5. The pr2+ carries in the MOF, we performed in situ FT-IR measurementsfor x = 0 and 1.6 under the MeCN vapor after completedehydration of the samples. As shown in x = 0 and 1.6 in the regionof 2250–2350 cm–1, which is attributableto the absorption by MeCN. According to the literature, a MeCN moleculegives two characteristic absorption bands, namely, ν2 (CN stretching) and ν3 + ν4 (combinationof CH3 bending and CC stretching), in this region.26 In pure MeCN liquid , the ν2 and ν3 + ν4 bands are observed at around 2253 and 2293 cm–1, respectively, while the MeCN coordinating to Mg2+ givesthe shifted bands at around 2287 (for ν2) and 2315cm–1 (for ν3 + ν4).26 In the case of the Mg2+-included MOF (x = 1.6), these two different statesof MeCN were clearly observed. The main strong peaks at 2293 and 2320cm–1 were attributable to the MeCN coordinatingto Mg2+, which clearly confirms that the coordinated species,such as [Mg(MeCN)6]2+, were formed in the x = 1.6 under the MeCN vapor. In contrast, the spectra ofthe pristine MOF (x = 0) was mainly composed of thefree MeCN [observed at 2265 cm–1 (for ν2)], while the shifted bands were slightly observed, whichmight be derived from the MeCN coordinating to some defects or openmetal sites on the MIL-101 framework. This result is consistent withour previously reported hypothesis that the migration of the coordinatedor solvated species occurs in the Mg2+-included MOF underguest vapors.13 According to these results,we think that the excellent ionic conductivity with the remarkablylow activation energy of the x = 1.6 under the guestwas caused due to the decreased electrostatic interaction  between the carrier and some of trapping sites and the loweredfriction between the migrating carrier and framework or surroundedguest molecules.To get the direct evidence of the presence of the coordinated MgP/P0 at RT, usinga homemade conductivity evaluation system including multiple gas flowlines . The ionic conductivityof the x = 1.6 sample drastically increased withincreasing MeCN partial pressure and finally reached above 10–3 S cm–1 2 salt, which showsthe negligible change in conductivity below 0.3 P/P0, and above 0.4 P/P0, it was impossible to measure theconductivity due to deliquesces. The different vapor response in ionicconductivity shows that the ionic conduction in the x = 1.6 sample was not derived from bulk Mg(TFSI)2 on thesurface of the MOF as a possible impurity, as mentioned above. Itis also important to note that the pristine MIL-101 (x = 0) did not show such high conductivity at any partial pressure.These results demonstrated that the superionic conduction in the x = 1.6 sample was indeed derived from the Mg(TFSI)2 salt incorporated into the MOF pores and the adsorbed MeCNmolecules.To obtain a more precise picture of the role ofadsorbed MeCN moleculesfor the ionic conduction, we measured the dependence of ionic conductivityunder the varied partial pressure of MeCN vapor in the range from0 to 1 owlines S5. The ix = 1.6 sample did not show the monotonic increase with the numberof adsorbed MeCN molecules but showed a drastic rise within a specificamount (approximately from 7 to 16) of MeCN molecules per formula,which corresponds to the region near the formation of coordinatedspecies of Mg2+ (9.6 MeCN molecules). This clearly indicatedthat the formation of coordinated Mg2+ and some additionalMeCN molecules adsorbed in the pores critically contribute to the“super Mg2+ conduction” in the MOF. It wasalso revealed that additional adsorption above 18 MeCN molecules,which corresponds to the MeCN molecules bound by a weak interactionsuch as the guest–guest interaction, does not strongly contributeto the enhancement of the ionic conductivity. The detailed studieson the dynamics of the superionic conduction in the MOF are stillundergoing, while we believe that the coordinated Mg2+ carrier,that is, [Mg(MeCN)6]2+ itself, could not migrateefficiently in the MOF because of the remaining electrostatic interactionwith the framework, and also some of additional MeCN molecules stronglybound to the framework allow the formed Mg2+ carriers tomigrate more freely . We also believethat the direct diffusion of the coordinated Mg2+ carriersassisted by some of the additional guest molecules is advantageouscompared to the hopping of naked Mg2+, which requires reformationof the coordination bonds around Mg2+.From the combination of the results of adsorptionisotherms andthe partial pressure dependence of ionic conductivity, we could clarifythe relationship between the ionic conductivity and the number ofadsorbed MeCN molecules 8. Notabl2+ conductivity of around 10–3 S cm–1 in a porous MOF at ambient temperature. MIL-101⊃{Mg(TFSI)2}1.6 showed 1.9 × 10–3 Scm–1 at RT under MeCN vapor. We also determinedthe transport number of Mg2+ (t2+Mg = 0.41), demonstrating that this is the first exampleof a solid-state crystalline super Mg2+ conductor witha practical conductivity of around 10–3 S cm–1 at RT (σ2+Mg = 0.8 ×10–3 S cm–1). In situ FT-IR measurements,adsorption measurements, and partial pressure dependence of the ionicconductivity revealed that this super Mg2+ conduction isderived from the migration of coordinated Mg2+ speciesin the MOF pores and that some additional MeCN molecules adsorbedon the framework play a critical role in the efficient migration ofthe Mg2+ carriers. These results would greatly contributeto the development of the novel solid-state Mg2+ conductorsoperating at ambient temperatures.In conclusion, this is the first demonstration of super Mg


Cerebellar arteriovenous malformations (AVMs) represent 10%–15% of all intracranial AVMs and are associated with a greater risk for hemorrhagic presentation compared with supratentorial AVMs. When they reach the cerebellopontine angle cistern, neurovascular compression syndromes, including trigeminal neuralgia and hemifacial spasm, can occur. Due to the aggressive natural history of cerebellar AVM, an effective treatment strategy is required. In this video, the authors demonstrate the technical nuances of microsurgical resection of an unruptured cerebellar AVM in a 24-year-old female presenting with trigeminal neuralgia. The patient underwent right retrosigmoid craniotomy and complete resection of the AVM with resolution of trigeminal neuralgia.https://youtu.be/6GmNjgFQwx8The video can be found here:  In this video, we will discuss the surgical treatment of posterior fossa arteriovenous malformation (AVM) in a young patient. The relevant anatomy and technical nuances will also be presented. This is a 24-year-old woman with right trigeminal neuralgia and right upper-limb ataxia associated with a Spetzler-Martin grade III unruptured AVM located in the right cerebellopontine angle (CPA). The trigeminal neuralgia did not improve after medical treatment. Patient refused radiosurgery and endovascular treatment and chose for surgical removal of the AVM.0:55 Preoperative Imaging. The preoperative angiogram demonstrated the main feeders coming from the superior cerebellar artery (SCA), anterior inferior cerebellar artery (AICA), and from the posterior inferior cerebellar artery (PICA). The venous drainage was in the right Rosenthal vein (through the right superior hemispheric vein), in the superior petrosal sinus , and in the transverse sinus (through the inferior vermian vein). No venous outflow stenosis nor flow-related aneurysms were demonstrated on preoperative DSA. The MRI with FIESTA sequences was useful to assess the relationship between the vascular structures and the cranial nerves, showing the compression and distortion of the right trigeminal nerve by the SCA. Reconstruction of the 4D computed tomography (CT) angiogram were used to assess the relationship with bony structures and planning the craniotomy. The surgical plan was to achieve early proximal control through temporary clipping of the main arterial feeders during subarachnoid dissection and to start the subpial dissection with reduced blood flow in the draining veins.2:10 Patient Position and Craniotomy. The patient was positioned in a park-bench position with the head fixed in a three-pin frame. The skin and subcutaneous tissues opening was performed in a layer-by-layer fashion until the asterion, digastric incisura, and condylar fossa were exposed. A right retrosigmoid craniotomy was performed in a standard fashion exposing the transverse-sigmoid junction and was enhanced by skeletonizing the entire sigmoid sinus. After craniotomy, the posteromedial surface of the occipital condyle was drilled until the exposure of the hypoglossal canal. Finally, the hypoglossal nerve was confirmed through direct electrical stimulation.3:00 AVM Dissection. The dura mater was opened in a C-fashion and reflected on the sigmoid sinus. It is possible to appreciate the superior hemispheric draining vein on the suboccipital surface of the cerebellum. The subarachnoid dissection was started to identify the main feeders and the cranial nerves. The subarachnoid dissection is of paramount importance for distinguishing the arterial and venous structures related with the AVM from the normal vessels, which should be preserved. At first, the fifth nerve was exposed, which was compressed and distorted by the right SCA.We perform the subarachnoid dissection under the highest magnification, which allows the identification of the correct plane of dissection. Sharp arachnoid dissection prevents the stretching and avulsion of the vascular structures and therefore minimizes complications during early stages of AVM surgery. The AICA was dissected and exposed. It was in close relationship with the seventh and eighth nerves. The facial nerve was confirmed through direct electrical stimulation. The intraoperative indocyanine green (ICG) angiogram showed the arterialized vein structures. Finally, the lower cranial nerves and PICA were dissected. The choroid plexus, protruding from the foramen of Luschka, is well visualized above the origin of the ninth cranial nerve. The sixth cranial nerve was also identified in its cisternal portion, going toward Dorello’s canal.5:05 AVM Removal. After the subarachnoid dissection and identification of the arteries, the main feeders were occluded with temporary clips in this order: SCA, PICA, and AICA. We perform temporary clipping in the early phase of AVM surgery because it allows the repositioning of the clip during the following steps of dissection, avoiding ischemia in the territory of a temporary occluded “en passage” artery. In our experience, temporary proximal artery clipping helps in safe AVM dissection by reducing intraoperative bleeding and resection time. The PICA was followed in its route to the tonsillar vallecula and then clipped, avoiding the occlusion of branches not related to the AVM. Finally, the AICA, which was directly feeding the AVM, was occluded. Afterwards, the ICG showed a reduction in the draining veins’ flow. After the exclusion of the main feeders, the subpial dissection was started. The subpial dissection was carried circumferentially around the AVM, disconnecting the malformation from the surrounding parenchyma. The bleeding from the deep perforators was controlled with bipolar coagulation and a single clip. An accurate arachnoid dissection allowed us to minimize the subpial dissection and therefore the transgression of normal cerebellar tissue. At the end of the pial dissection, the connections with the draining veins were coagulated and cut; then the AVM was resected. Finally, the drainage toward the superior petrosal vein was coagulated and cut. The last ICG showed no residual AVM with no arterialized veins. You can well appreciate how even the ectasic venous structures fill during the venous phase of the ICG. The dura mater was closed in a watertight fashion with an autologous graft.9:30 Postoperative Course. The postoperative 4D CT angiogram showed no remnants. The postoperative DWI MRI showed no hyperintensities signs. The patient woke up without any deficits and was discharged at home with modified Rankin score (mRS) 0 with full recovery of trigeminal neuralgia at the last follow-up.Primary surgeon: Tanikawa. Assistant surgeon: Tsuji, Noda, Kinoshita. Editing and drafting the video and abstract: Marani, Montemurro, Tsuji. Critically revising the work: Marani, Montemurro, Perrini, Kinoshita, Tanikawa. Reviewed submitted version of the work: Marani, Montemurro, Perrini, Ota, Tanikawa. Approved the final version of the work on behalf of all authors: Marani. Supervision: Kamiyama, Tanikawa.


Nowadays, with the increased numbers of video cameras, the amount of recorded video is growing. Efficient video browsing and retrieval are critical issues when considering the amount of raw video data to be condensed. Activity-based video synopsis is a popular approach to solving the video condensation problem. However, conventional synopsis methods always consists of complicated and pairwise energy terms that involve a time-consuming optimization problem. In this paper, we propose a simple online video synopsis framework in which the number of collisions of objects is classified first. Different optimization strategies are applied according to different collision situations to maintain a balance among the computational cost, condensation ratio, and collision cost. Secondly, tube-resizing coefficients that are dynamic in different frames are adaptively assigned to a newly generated tube. Therefore, a suitable mapping result can be obtained in order to represent the proper size of the activity in each frame of the synopsis video. The maximum number of activities can be displayed in one frame with minimal collisions. Finally, in order to remove motion anti-facts and improve the visual quality of the condensed video, a smooth term is introduced to constrain the resizing coefficients. Experimental results on extensive videos validate the efficiency of the proposed method. Nowadays, a huge number of video cameras are used for security purposes for 24 h per day. These cameras produce an enormous amount of video material. The power of video over still images is the ability to represent all sorts of dynamic activities. Although the captured videos contain useful information for applications in security monitoring and criminal evidence, the storage, management, and control of huge amounts of recorded video are becoming more and more difficult. Efficient video browsing and retrieval are time-consuming due to the inherent spatio-temporal redundancies ,2, whereFrame-based video condensation aims to generate a short video that contains useful information by selecting frames with important content . The generated video is usually composed of a set of representative video frames  or video fragments  that have been stitched together in chronological order to form a shorter video. While frame-based video condensation is straightforward to implement, its performance is quite limited. These techniques lose either the temporal or semantic context of activities in surveillance videos .Another popular approach to solving the video condensation problem is video synopsis. Unlike frame-based video condensation approaches, the activities of interest are shifted in the time domain to obtain a video representation that is more compact . While tPlacing different object tubes with the least collision in a limited video length is crucial to the performance of a video synopsis, as this can lead to the loss of important content and cause a chaotic viewing experience, which would decrease the efficiency and visual quality for surveillance applications. Displaying the maximum number of activities in one frame with minimal collisions means a greater computational complexity. Currently, the most common methods of online video synopsis are carried out by optimizing complicated energy functions , which hi. In order to display more activities in one frame with minimal collisions, the tube-resizing coefficients are changed at different time positions. Therefore, a suitable mapping result, which is determined adaptively in optimization procedure, can be obtained in order to represent the proper size of an activity in each frame of the condensed video. Moreover, in order to remove motion anti-facts and improve the visual quality of the synopsis video, a smooth term is adopted to constrain the resizing coefficients.In this paper, we propose a simple online video synopsis framework that considers collision reduction, tube resizing, and smooth stitching. The condensation ratio, collision cost, and visual quality of the condensed video are important in video synopsis technologies. In the proposed method, the number of collisions of objects is classified first; then, different optimization strategies can be applied according to different collision situations in order to maintain a balance among the computational cost, condensation ratio, and collision cost. If this is within an acceptable range, i.e., The rest of this paper is organized as follows. Video synopsis is a popular approach to solving the video condensation problem, and it provides activity-based video condensation instead of frame-based techniques, such as video fast-forward , video aThe purpose of video synopsis is to provide a short video representation while preserving the essential activities in the original video. Activity-based video condensation was first proposed by Rav-Acha et al. ,13,14 unOptimization of the energy function is the most important part of video synopsis, and it aims to find the best rearrangement of extracted tubes in order to display most of the activities in the shortest time period. In order to reduce collisions and increase the condensation ratio, tube rearrangement is decided by the optimization module, and it guarantees the minimal cost for each of the tubes considered. Many spatio-temporal analysis methods have been proposed. Optimization approaches can be further divided into two classes: online and offline. Most video synopsis methods employ offline optimization for all generated tubes in order to find the global optimum. Xu et al. formulated the optimization problem of activities in terms of set theory and adopted the mean shift to solve it. However, temporal consistency was not considered in the tube rearrangement in this study. It was found that the particle swarm algorithm (PSO) could reach the global minimum solution, but with a lower computational cost. The PSO was used to solve the energy minimization function and to generate a synopsis video . HoweverIn this section, we will introduce the proposed online video synopsis framework in detail, which considers various issues such as collision reduction, tube resizing, and smoothing. Using this framework, a suitable mapping result can be obtained in order to represent the proper position of a newly generated tube in the synopsis video. Meanwhile, the resizing coefficients of the corresponding tube, which are dynamic in different frames, can be adaptively determined.E be the energy function and let M represent the mapping from the original video to the condensed video. Then, the energy function in the framework can be defined asIn traditional offline video synopsis, objective functions always consist of complicated and pairwise energy terms that involve a time-consuming optimization procedure. Therefore, a simplified objective function according to the characteristics of online video synopsis is first defined. Let Collision Term  In the condensed video, when a collision occurs between two tubes, the collision term is used to calculate the sizes of the collision areas of the entire regions in which collisions occur. For example, when tube o and tube p collide in the synopsis video, according to their positions in the original video, we calculate the size of the area of the intersection between the circumscribed rectangles of the corresponding foreground regions. The collision term can be formulated asct(·) denotes the calculation of the size of the bounding rectangle’s area. O is the set of all current tubes and o.(1) Resizing Term  In order to reduce the effects of collisions in the synopsis video, scaling down every object in a scene before rearrangement is an effective treatment. However, a down-scaling operation for a tube with a constant metric may decrease the visual quality and introduce more anti-facts in the condensed video. Scene changes are obvious for a tube that is temporally shifted in a video synopsis. In this study, a resizing term is introduced in order to penalize the cost of scaling down an object, and this can prevent excessive shrinking through minimization. The resizing term can be defined aso, and it is modified in a specific interval given by X. In our experiments, the interval is between 0.4 and 1, i.e., M denotes the tube’s length. The component (2) Smooth Term  In order to avoid motion anti-facts in the generated short video, another smooth term (3) By incorporating object segmentation and tube extraction, a video synopsis framework that integrates the simplified energy function illustrated in Equation  is obtaiAlgorithm 1: Procedure of optimization.There are three variables to be determined when minimizing the energy function Equation  is a matT in the tube buffer  P. T appears in the synopsis video. When the time labels of each tube in the tubelet L and H, according to the number of collisions of a tube to choose a reasonable time label for the tube and a resizing factor for the object. A number of collisions that is less than L indicates that the collisions are within the acceptable range and that no adjustments are required. When the number of collisions is greater than L but less than H, we resize the corresponding object to avoid some of the collisions. The resizing coefficient H, we directly update the time label to be T remains the same as that of T will become very small and cause a significantly decreased visual quality in the synopsis video. In a word, there are three phases in the proposed online video synopsis algorithm, namely, the adjustment, addition, and subtraction phases.A time label Equation  is adaptAdjustment phase: As discussed previously, when the number of collisions according to the tube T in the container L and H, the dynamic resizing coefficients of the object in the temporal domain are determined and adopted to avoid collisions and have a guaranteed visual quality. The overview of the adjustment phase in the video synopsis is shown in Tube addition phase: When a new activity tube i. After that, the smallest index i in i such that i such that Algorithm 2: Pseudocode for the addition of new tubes.For the tubes in Tube subtraction phase. If the tubelet P, the tube with the smallest time tag in o and p in the t-th frame of the original video. The temporal consistency between o and p can be defined aso and p is defined aso and p, in the original video, respectively. Similarly, o and p do not start at the same frame, another relative temporal relationship o and p.Temporal consistency is another important problem in video synopsis; it aims to group related activities and display them together in the synopsis video in order to provide a better understanding of the scene for the user. In this work, a temporal consistency constraint was defined to maintain the time relationship between two moving objects. Let To evaluate the performance of the proposed video synopsis framework, many experiments were conducted on multiple surveillance videos. Firstly, a brief description of the surveillance video data used in our experiments is presented.Dataset: Five surveillance videos were used in our experiments. The first (4514 frames) and the second videos (3950 frames) were provided by Nie et al. in [t al. in  and Li et al. in , respectEvaluation Metrics: At present, there are three evaluation metrics that are used to measure the quality of video synopsis models. They are the metrics of collision cost (CC), temporal consistency (TC), and condensation ratio (CR). In this paper, we define another evaluation parameter in order to measure the spatial utilization of frames in the synopsis video and we called it the frame compact ratio (FCR).Collision Cost (CC): In a condensed video, when a collision occurs between two tubes, the collision cost is calculated by counting the number of pixels within the collision areas. Usually, the collision cost is an important component of the energy function in a video synopsis model, as illustrated in Equation : The temporal consistency metric is used to measure whether the correlations between activities in the original video are preserved in the condensed video [TC is defined as: ed video . TherefoCondensation Ratio (CR): The CR is expressed as the ratio of the total frames of the condensed video to the total frames of the original one, and it is used to measure the video compression efficiency by using the following formula:Frame Compact Ratio (FCR) FCR is defined as followsP, the upper bound H, and the lower bound L for the collision cost. As illustrated in P increased, the frame compact ratio (FCR) also increased because of the growth of the number of tubes that could be accommodated in the tube buffer and the range of time tags for the selected tubes. However, when P was too large  gradually decreased as the tubelet capacity P increased, since the tubes could be rearranged more sparsely.Experiments were conducted to evaluate the influences of parameters, such as the tubes’ container capacity L in Algorithm 2 increased. The reason for this was that a larger L meant that more tubes were classified into the case in which H on the frame compact ratio was not obvious, although the impact on the CC was similar to that of L because the change in H had little effect on whether a tube would be re-categorized as a case in which In order to evaluate the contribution of dynamic tube resizing in the online video synopsis, experiments were conducted by using the traditional online video synopsis method without a tube-resizing operation, and this was compared with our proposed condensation method via dynamic and adaptive online tube resizing. The images were both located in the 435th frame of the condensation videos from the two different methods. From The results of comparisons on the datasets with state-of-the-art methods are presented in As shown in Offline video synopsis methods always try to find the global optimum for all generated tubes. Hence, they can have the best rearrangement of the activities in order to display them in a short time period and easily achieve good performance in terms of the frame compact ratio (FCR) and collision cost (CC). It is noted the method proposed by Nie et al.  had the To analyze the condensation results of different synopsis methods more intuitively, we displayed some frames from the synopsis videos that were generated using the original In this study, a simple online video synopsis framework was formulated. The proposed framework does not require any user interaction or prior models; it can condense activities in an original video into a shorter period by simultaneously showing multiple actions, and it can do so in real time. Different optimization strategies are applied according to different collision situations in order to maintain a balance among the computational cost, condensation ratio, and collision cost. Resizing coefficients are determined adaptively and dynamically in the optimization procedure; then, a suitable mapping result can be obtained to represent the proper size of an activity in each frame of the short condensed video. Finally, the maximum number of activities can be displayed in one frame with minimal collisions. The proposed online video synopsis framework can achieve a condensed video with a low collision cost. However, collisions cannot be completely avoided, and this degrades the visual quality of some frames in the synopsis video. Meanwhile, temporal consistency will be considered in the tube rearrangement in a future study.


The referees achieved a maximal oxygen uptake (V̇O2max) of 44.6 ± 6.1 ml/kg/min, with a maximal HR of 187.2 ± 11.1 BPM  and a peak lactate of 9.2 ± 3.2 mmol/l at 557.1 ± 168.3 sec on our continuous speed, increasing slope treadmill protocol. Second division referees were younger, on a weekly average they trained more, achieved higher treadmill exercise time  and anaerobic threshold time , while the two different divisional referees had similar V̇O2max values. Regarding our physical fitness measurements, huge individual differences were observed between the referees . Since it can affect their performance as referees, individual training planning, regular physical fitness measurements, and strict selection methods are suggested.In various team sports, such as handball, referees work on the court by continuously moving with the players. Therefore, their physical fitness also has an impact on their reaction time, which could affect their professional decisions. The cardiorespiratory fitness status of healthy Hungarian elite handball referees was examined via body composition analysis and vita maxima cardiopulmonary exercise testing with lactate measurements. One hundred referees were examined . A resting heart rate (HR) of 79.0 ± 12.6 BPM was measured. On the basis of the body composition analysis the fat-free mass index proved to be 19.9 ± 2.6 kg/m At greater loads, inappropriate physical fitness could negatively influence cognitive functions, which is essential to referee in a fair way, always according to the official rules and regulations of the refereed game  = body weight [kg] / body height2[m2], and fat-free mass index (FFMI) as FFMI [kg/m2] = body fat-free weight [kg] / body height2[m2] [220-age [All measurements were performed at least 12 hours after the last training session or refereeing . To ensuht2[m2] . Cardiopht2[m2] . Breath-ht2[m2] . The ref[220-age . The HR 95%): lower-limit—upper-limit), comprehensive statistical analysis was carried out for continuous data with Wilcoxon rank sum test (Mann–Whitney U test) or two-tailed unpaired Student’s t-probe with equal or unequal variance form, depending on the normality of the valuables; and with Chi-square test for discrete data. The normality of the valuables was tested with the Shapiro–Wilk test, the homogeneity of variances was tested with F-test. The effect size analyses were carried out using Cohen’s d formula, Glass rank-biserial correlation or Phi coefficient in accordance with the statistical tests performed [Descriptive statistical values are shown as mean ± SD . On average, they trained 4.3 ± 2.0 hours/week , 39.0% were former elite handball players. At the time of the examinations, 51.0% were first and 49.0% were second division referees of the HNHL. A 16.0% of the referees also officiated games for either the International Handball Federation or the European Handball Federation. Data according to the level of refereeing can be found in We examined 100 Hungarian elite handball referees , with a maximal HR of 187.2 ± 11.1 BPM , which was 98.1 ± 4.6% of their calculated maximal values. The referees achieved a maximal ventilation of 128.1 ± 29.7 l/min , with V̇O2max of 44.6 ± 6.1 ml/kg/min  and a peak lactate level of 9.2 ± 3.2 mmol/l . On average, the referees achieved their anaerobic threshold at 56.1 ± 15.8% of the exercise time, with 91.5 ± 6.5% of their maximal HR and with 86.5 ± 8.2% of their V̇O2max. Data are shown in 2max proved to be higher in male referees ).On our running protocol, the average running time was 557.1 ± 168.3 sec for all referees  and FFMI , while negative correlation was revealed with body fat percentage . Correlating the maximal ventilation with body composition analysis parameters numerous relationships were found .Considering the body composition analysis results and the fitness markers measured during the CPET examinations, positive correlations were found between the V̇O2max values. The second division referees also reached their anaerobic threshold later. Data are shown in Compared to the first division referees, the second division referees reached higher exercise time, maximal HR and maximal ventilation values, with similar peak lactate and V̇OIn our study, cardiorespiratory fitness measurements of elite handball referees were studied. Our main aims were i) to determine the fitness status of the Hungarian elite handball referees and to provide their CPET results for the first time in the literature. Since, in Hungary, there is no sex differentiation for referees in the refereed games, data were first analyzed collectively. By our results, the referees had a satisfactory fitness status compared to athletes who do mixed sports; however, remarkable individual differences were found. Our study lays grounds for further scientific research and training optimization of handball referees. We also aimed to carry out subgroup analyses ii) to compare the fitness status of referees working in the different divisions, and iii) to learn about the sex differences among elite referees. Surprisingly, the referees working in the second division achieved longer exercise time, supposedly because they were younger. Male and female referees reached similar exercise times on the CPET, however, differences in fitness status were observed.According to previous literature data, handball referees perform at moderate intensity for most of the time during handball matches; however, in 3.6% of the game, they are exposed to heavy or severe load . During According to our results, the measured oxygen uptake and ventilation values surpassed the estimated non-athlete reference values specified by the manufacturer in most of the cases. However, great individual differences were found in weekly training time, treadmill exercise time, aerobic capacity and anaerobic threshold time. These results highlight the necessity of routine physical fitness measurements, individual training programs, and reconsideration of minimal standards mandatory to be met.The female referees achieved similar treadmill exercise times as the males, which is a welcome result, since they work in the same leagues. The referees from the second division achieved longer CPET examination times, anaerobic threshold times, and lower maximal ventilations. These results, as well as their higher HR, can be partially explained with their younger age .To the best of our knowledge, this is the first study examining elite handball referees with cardiopulmonary exercise testing, thus, we could only compare these results with similar measurements of handball players and referees from other sports only. Comparing the results of this study with a report on 291 male elite German handball players, we can state that our referee group had lower maximal aerobic capacity and similar peak lactate levels .2max was lower in our population [Comparing the results of our younger referee population with the values of a small group of Brazilian handball referees, the maximal HR of referees was similar, while the maximal aerobic capacity proved to be lower in our study . Also, cpulation . The abo2max at the anaerobic threshold in a Turkish study conducted on handball players [The anaerobic threshold was determined following the recommendations, through the complex analysis of several parameters measured during the CPET examinations. Different types of sports can highly influence the time spent in aerobic, mixed, and anaerobic phases during an incremental protocol CPET examination . As comm players . In anot players .2 values, which could mean that some of the referees could meet the criteria to maintain a high-quality refereeing during the whole game, while those who achieved worse results during testing could have difficulties with their physical status during games.In a Croatian study, no differences in maximal and average HR in referees between the two halves of a handball game were revealed . These dIn the current referee population, huge personal differences could be observed in the referees’ fitness status. However, better fitness status was not attached to refereeing in a higher division, possibly because previous experience and routine highly influences their assignments.To better understand the fitness demands of handball referees, further examinations are required. Few studies are available where the physical load of the referees was measured during matches, but in those cases, no previous CPET examinations were carried out. Beyond the physical load during matches, the actual accuracy of refereeing should also be measured, and the correctness of their decisions should be correlated with the fatigue level of the referee at the time the calls are made.With better training planning, improvements could be achieved in both aerobic and anaerobic fitness. As a result, match refereeing would be less physically demanding, resulting in better performance during the games. Individual training plans should be prescribed for the referees, containing both endurance and anaerobic components.This is a single-center study conducted solely on Hungarian referees. The examined population should be broadened by extending the study to higher numbers of referees from different countries and ethnicities. A long-term follow-up should also be performed to evaluate their improvement and progress in their carrier. For a better understanding of the physical requirements of the handball referees, further examinations are required using data collected during matches, and comparisons should be performed between the results of CPET examinations and field measurements.In conclusion, our data underline the great individual differences among elite Hungarian handball referees, as well as the remarkable differences in the amount of training regularly done by them. Therefore, although refereeing experience highly affects the quality of refereeing, individual training plans should be prescribed for referees to reduce the differences observed in their physical fitness levels.S1 Dataset(XLSX)Click here for additional data file.


The aim of this review was to collate current evidence wherein digitalisation, through the incorporation of video technology and artificial intelligence (AI), is being applied to the practice of surgery. Applications are vast, and the literature investigating the utility of surgical video and its synergy with AI has steadily increased over the last 2 decades. This type of technology is widespread in other industries, such as autonomy in transportation and manufacturing.Articles were identified primarily using the PubMed and MEDLINE databases. The MeSH terms used were “surgical education”, “surgical video”, “Three main themes were identified and analysed throughout this review, (1) the multifaceted utility of surgical video recording, (2) teleconferencing/telemedicine and (3) artificial intelligence in the operating room.Evidence suggests the routine collection of intraoperative data will be beneficial in the advancement of surgery, by driving standardised, evidence-based surgical care and personalised training of future surgeons. However, many barriers stand in the way of widespread implementation, necessitating close collaboration between surgeons, data scientists, medicolegal personnel and hospital policy makers. A consensus on the definition of digital surgery was reached in 2022 by Lam et al., defining ce harm” .Surgical adverse events remain a significant cause of mortality and morbidity in patients worldwide, with research suggesting that over 50% are preventable . Over haA significant challenge for the surgical community is the backlog of patients after the surges in the COVID-19 pandemic. In England and Wales, resource diversion resulted in a 33.6% reduction in surgical activity in 2020 . In the In recent years, the utility of technology in the surgical field has become increasingly evident. The COVID-19 pandemic made evident the value of online learning in the form of video, telementoring and teleconferences, which are likely to become more prevalent in the coming years with the rise of blended learning, where online resources complement traditional training methods , surgicaThis review will focus on how the stance of video technology and AI can augment current surgical practice and overcome these contemporary challenges; we discuss systematically the use of video in its basic form to its application as a source of data in AI Fig. .Fig. 1ThArticles were identified primarily using the PubMed and MEDLINE databases. The MeSH terms used were “surgical education”, “surgical video”, “Surgical video offers an abundance of data, capturing sources of variability which can be analysed for personalised training interventions and systematic quality improvement. Such applications are discussed in this section.Surgical video is an objective record of intraoperative events, enabling review and investigation of surgical performance and how intraoperative events correlate to patient outcomes. Birkmeyer et al. demonstrated that a surgeon’s skill, determined by peer review rating of video-recorded cases, has significant associations with operative time, length of stay and mortality for gastric bypass surgery . A studyThis can enhance surgical coaching through personalised training. The identification of optimal operative technique of the best performing surgeons and technical factors associated with operative complications presents an opportunity to bolster training.Recorded video repositories provide an objective record for factors relating to a patient’s postoperative course, eliminating subjective elements to surgery. A 2011 study examined whether operative notes accurately represent laparoscopic cholecystectomy, when compared to video recordings; the results showed significant omissions of procedural steps in numerous operative reports . Novel mSurgical video offers fine detail which can be analysed. Microanalysis of a video dataset identified human factors found to impact the surgical team’s performance and situational awareness . LinguisThe awareness by surgical staff of video recording in the surgical setting may also be inherently advantageous. A study in 2018 showed there was a significant decrease in irrelevant conversation time following the implementation of audio-visual recording in the surgical environment , though a link between irrelevant conversation times and adverse events was not established in this study .Remote video auditing (RVA) is the recording’s subsequent critique of behaviours to promote safety and efficacy in various settings. In a general healthcare setting, Amerllino et al. assessed hand hygiene rates before and following implementation of RVA; an improvement in hygiene rates from 10 to 81.6% was witnessed amongst healthcare workers. The increased hand hygiene ratings were sustained during the 75-week feedback period; prolonged studies investigating the impact of RVA on infection rates amongst patients may justify the installation of such systems .RVA in a surgical setting was conducted in 2016 to investigate compliance with the surgical safety checklist as well as case turnover times, the recording of the surgical environment and the auditing of the surgical footage with real-time feedback served to improve efficiency in scheduled surgery . FeedbacRetrospective RVA analysis includes event transcription and analysis by a multidisciplinary team, to help identify deviations that can be addressed such as poor organisation or suboptimal dynamics . Such crSystematic reviews on the effectiveness of video-based surgical education compared to conventional methods indicate the former as an effective and equivalent tool. This is based on outcome measures such as trainee satisfaction gauged by participant questionnaires and improved operative performance –25. SuchIn 2018, LAP-VEGaS guidelines on reporting laparoscopic videos for education were developed to ensure resources met adequate standards due to concerns about the quality of educational resources and the lack of peer review. Guidelines were developed based on a Delphi process amongst an international cohort of surgical training experts, to facilitate the improvement of video-based education and reduce variability in academic rigour, enabling peer review on established guidelines , 28. ThiIn 2017, Hu et al. compared teaching in the operating room to video-based coaching, which resulted in significantly more teaching points per hour (102.7 vs. 63.0), and greater insight into the learning needs of residents . OperatiMendez et al. demonstrated significant benefits of video-based coaching amongst senior otolaryngology trainees performing complex neck dissection. The use of a narrated instructional video the day prior to operating led to reduced surgical error and staff takeover events . For genBesides recorded surgical video, video technology is often utilised as a live collaborative tool in surgery. Technological advancements in recent years have broadened opportunities for collaboration between hospitals and facilitated the sharing of specialised knowledge virtually via telemedicine. Recent literature has indicated a rapid uptake of telemedicine since the start of the COVID-19 pandemic owing to increased travel restrictions and infection control measures , 36.Telemedicine is broadly defined as a subset of e-health which utilises communication networks to facilitate the delivery of medical expertise and services between remote sites . It is aAmongst surgeons, telemedicine is primarily applied in the form of teleconferencing and telementoring. However, it has also been successfully applied for surgical consultations during the pandemic period being favoured by patients when travel and infection control restrictions were implemented . NeverthDemartines et al. assessed the value of telemedicine as a collaborative tool for surgical education and patient care amongst six international university hospitals over 2 years. The consultations between these sites increased the rate of therapeutic advice from 55 to 95% due to interactivity between participating surgeons following case presentations. Eighty-six percent of the surgeons expressed satisfaction with the educational quality of teleconferences, which guided challenging patient cases contributing to case resolution .In medical students, teleconferencing was found to enable more open communication, with students asking four times as many questions than when in the operative environment; students also had fewer unanswered questions compared to the OR . Post-inA systematic review in 2018 assessing the value of telementoring in surgery suggested that educational outcomes with telementoring were equivalent/superior to in-person teaching in 67% of included studies . Amidst The opportunity for innovative remote hands-on surgical skill courses using telemedicine fulfils educational goals. In 2020, a hands-on hernia course was successfully conducted in this manner—the success in transitioning from an in-person course to a remote course demonstrates the ability of telementoring to bolster surgical training .In 2012, 312.9 million surgeries occurred with associated expected complication rates . LaparosBeyond the use of surgical video for apparent extractable metrics and live exchanges of knowledge is the ability for deeper analysis through AI and machine learning applications. Video labelling assigns meaningful information to different aspects of unedited video, including visual and temporal features. Through annotating video datasets and training AI, studies have demonstrated degrees of success in the automatic segmentation of surgical video into constituent steps in laparoscopic cholecystectomy and sigmoidectomy –53. ThisWork in this field enables the automated indexing of surgical video libraries, requiring minimal human intervention. Processing can also include the removal of irrelevant or patient-identifiable segments of surgical video to optimise storage and maintain patient confidentiality . The appThe legal frame of recording and storage are major considerations for video labelling. The potential utility of video labelling and recording in the healthcare context is promising, though lacking clarity and clear guidelines surrounding the use of video data in the healthcare context are limiting factors .Using labelled video and AI enables practical applications in day-to-day practice, which can standardise aspects of surgical assessment. Research conducted by Khalid et al. raised the issue of impracticality of reviewing all surgical videos due to the high caseload being performed daily, also highlighting the subjectivity of individual surgeon review. The study assessed the feasibility of deep learning models to classify surgical actions  and estimate technical skill scores from surgical video. Its results revealed a mean precision of 91% in detecting surgical actions and a mean precision of 77% in predicting the surgical skill level of operators providing performance data which can improve patient safety .A 2021 study assessing the feasibility of training an algorithm to automate the assessment of surgical skill in laparoscopic cholecystectomy demonstrated accuracy of 87 ± 0.2% for distinguishing good versus poor surgical skill . NumerouAs mentioned, the correlation between technical surgical skill and patient outcomes is well-established in the literature . ResearcThe unification of various data sources in the OR with technologies described above can serve towards developing algorithms with context awareness of the surgical environment.Algorithms have shown accurate recognition of the stage of a procedure from external footage via synchronised cameras in the OR, with 84.4% accuracy in laparoscopic cholecystectomy . In 2019Such work was done with the intent of improving awareness of activities occurring in the surgical environment and serving to enhance surgical workflows for all members of the team. Applications including predicting remaining time in any given procedure, automating surgical reporting and mitigating the risk of surgical errors with intraoperative decision support are likely to develop significantly over the next decade , 69, 70.Surgical data science refers to utilising data to extract valuable metrics and processing them to enhance an aspect of surgical practice. Maier-Hein et al. defined surgical data science, in part as “an emerging scientific field with the objective of improving the quality of interventional healthcare and its value through capturing, organization, analysis, and modelling of data” .In other healthcare domains, data science has led to significant benefits being successfully applied in the fields of medical imaging and mental health , 73. In The previous sections within this review discussed the numerous applications of video technology in surgery to date and the wealth of data contained in a surgical video recording. Video data is typically processed using convolutional neural networks (CNNs), a form of AI used primarily in the analysis of visual data . The praIf surgical data can be extracted from not only a single operating room but numerous operating rooms worldwide, multifaceted improvements may be witnessed in surgical workflow, performance, education and inevitably patient outcomes and hospital profitability , 76. TheThe recording of the surgical field and the operative environment is increasingly common, with the increase in minimally invasive and robotic surgery necessitating an endoscope. AI through data science has shown to be able to develop the ability to distinguish and diagnose pathology from medical imaging , to recoInnovation in surgical practices has led to the speciality’s advancement and the optimisation of patient care. Recent technological innovation offers the potential to identify factors conducive to optimal surgical practice, evolving surgical education and identifying the stance of data science in the field. The preliminary and early clinical research highlights the potential utility of surgical technology, artificial intelligence and the research applications which exist when data is collected from the OR, particularly operative video.However, the progression of this field is closely related to the availability of high-quality data libraries, in this case, surgical video. There exist publicly available datasets for use by research societies, such as the Cholec80 dataset , though Compiling sufficient volumes of surgical data can be problematic in the standard operating room, whereby infrastructure for collecting and sharing data still needs to be implemented. Nevertheless, Maier-Hein et al. have detailed an extensive roadmap identifying many barriers and their solutions to translate proven clinical concepts into surgical practice, making evident that the evolution of surgical practice will require significant cultural shifts amongst surgical societies and patient populations to increase awareness and acceptability of digital solutions . MoreoveTranslating novel solutions to clinical practice will require mass interdisciplinary collaboration, establishing an agreed roadmap to integrate data collection, processing and careful integration and trialling of digital solutions. Efforts should be made to increase acceptability of video recording in the OR by educating relevant parties on the future benefits and facilitating partnerships between surgical centres and commercial infrastructure providers. Furthermore, it is pertinent to continue establishing and growing collaborative networks of data scientists and surgical researchers to increase awareness of the benefits of sharing data with the development of standardised protocols and confidentiality measures. Surgeons should be mindful of ethical and legal procedures surrounding the utilisation of patient data and comprehensive guidelines should be established to ensure the protection of patient confidentiality.The OR has evolved throughout the decades. With the advent of smart technology, mass data storage and connectivity should be installed and capitalised globally to benefit health providers and patients.