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[en] EWSR1-SMAD3 fibroblastic tumour is a recently described soft tissue lesion. To date, eight cases have been reported, all sited in superficial soft tissue, typically occurring in the hands and feet with a tendency for local recurrence if incompletely excised. No metastatic spread has been reported, and hence, these tumours are currently considered benign. Herein, we present the radiological and histological features of the first reported occurrence of this entity in bone: a 44-year-old man with a tumour in the right tibia, treated with en bloc resection and showing no signs of relapse at 7 years. This tumour should be added to the differential diagnosis of bone lesions which harbour EWSR1 gene rearrangement.
[en] A tenosynovial giant cell tumor is a benign proliferative disease, mostly arising from the synovial membrane of tendon sheaths, bursae, and joints. Axial skeleton involvement is very rare, but it is often found in the cervical spine. Spinal tenosynovial giant cell tumors often arise at the facet joints; a completely extra-articular spinal tenosynovial giant cell tumor is rare. We report an extremely rare case of tenosynovial giant cell tumor in the upper cervical spine that extended from the posterior atlanto-occipital membrane rather than the facet joint. Herein, the clinical and radiological findings will be reviewed to better our understanding of the characteristics of spinal tenosynovial giant cell tumors, and to help improve their diagnosis despite their non-typical locations of origin.
[en] Non-small-cell lung cancer (NSCLC) is a major cause of cancer-related death globally. Endothelial PAS domain-containing protein 1 (EPAS1) is a homolog of the hypoxia-inducible factor 1α and has been reported to confer tyrosine kinase inhibitor (TKI) resistance in NSCLC, but its role in peritoneal carcinomatosis of NSCLC is unknown. PC14HM, a high metastatic potential subline of NSCLC cell line PC14, was derived. Stable shRNA knockdown of EPAS1 was then established in PC14HM cells and subjected to assessment regarding the effects on proliferation and viability, xenograft tumor growth, metastatic potential, mesothelial–mesenchymal transition (MMT)-related characteristics and peritoneal carcinomatosis in a mouse model. EPAS1 expression was elevated in PC14HM cells. Knockdown of EPAS1 inhibited the proliferation and viability of PC14HM cells in vitro and suppressed tumorigenesis in vivo. In addition, the metastatic features and in vitro productions of MMT-inducing factors in PC14HM cells was also associated with EPAS1. More importantly, knockdown of EPAS1 drastically suppressed peritoneal carcinomatosis of PC14HM cells in vivo. EPAS1 promotes peritoneal carcinomatosis of NSCLC through enhancement of MMT and could therefore serve as a prognostic marker or a therapeutic target in treating NSCLC, particularly in patients with peritoneal carcinomatosis.
[en] The UAE was the first Newcomer country to start building a large nuclear power plant in three decades: The Nuclear Construction of four units of the Barakah Nuclear Power Plant started simultaneously in 2012 - Sets a role model globally by achieving in a record time requirements needed to ensure its nuclear infrastructure was capable to support the programme through the highest levels on nuclear safety, security and non proliferation; The FANR issued also regulations for onsite as well as offsite nuclear emergency preparedness and response, and the combined onsite and offsite arrangements were put in place. EPREV including the follow up done; The country builds its national capacity for a sustainable operation simultaneously. Simulators in FANR and at site. Online monitoring of plant parameters are available at FANR as well as laboratories and monitoring systems; Highly experienced regulatory experts support the program in headquarter in Abu Dhabi and at site office in Barakah. Steps taken by FANR - Initial phase: The creation of the necessary skills and legally binding requirements for the safe siting, construction and design of the reactors to be built as well as for the needed security and non-proliferation arrangements; Evaluation: FANR evaluated the project based on a two step process, first construction license and then the operating license. This included further innovative design enhancements to address extreme conditions related to severe phenomena inside and outside the reactors. Systematic documentation and knowledge management built at FANR; Enhancement: Environmental effects on the reactors, as well as additional cooling and power supply measures enhanced. UAE specific factors and Fukushima impact. Making the most of synergy: The government signed international agreements & conventions supporting the programme developments; The agreements with the country of origin regulatory bodies which allowed FANR to leverage the work of the Korean regulators to license the reference plant in Korea, the Shin Kori 3 and 4 reactors; Support of the IAEA was instrumental in ensuring that the FANR approach to regulation kept with the best international practices; A pool of international experienced experts work hand in hand with local staff to develop regulations, conduct assessments and do inspections. Also the competence based framework for training and mentoring is essential for sustainability of FANR as a recognized nuclear regulator worldwide; FANR has over 30 agreements with international organizations & other regulatory bodies to exchange technical knowledge & build national capacity.
[en] Proliferating cell nuclear antigen-associated factor (PAF) is involved in cancer cell growth and associated with cell death induced by ultraviolet (UV) radiation. However, the contribution of PAF to radiotherapy sensitivity in non-small cell lung cancer (NSCLC) is unknown. The aim of this study was to investigate the relationship between PAF expression and radiotherapy response in NSCLC. Associations between PAF expression and patient survival outcomes were evaluated using publicly available online gene expression datasets. RNA interference was performed to knockdown PAF expression in the NSCLC cells. The effects of PAF knockdown on cell proliferation, migration, apoptosis, DNA damage, and activation of MEK/ERK and Wnt/β-catenin signaling pathways following X‑ray irradiation were evaluated in vitro. PAF was found to be overexpressed in lung cancer tissues compared with normal samples, and elevated PAF expression was significantly correlated with inferior patient survival. In vitro, knockdown of PAF inhibited cell proliferation, cell apoptosis, and migration induced by X‑ray irradiation. Moreover, X‑ray-induced intracellular DNA strand damage was more obvious following PAF knockdown. Additionally, PAF knockdown inhibited activation of the MEK/ERK and Wnt/β-catenin signaling pathways in X‑ray-irradiated A549 cells. These data demonstrate that reduced expression of PAF enhances radiosensitivity in NSCLC cells. Mechanistically, inhibition of the MEK/ERK and Wnt/β-catenin signaling pathways caused by PAF interference may lead to impaired cell function and enhance sensitivity to X‑rays. Targeting PAF may therefore serve as a potential therapeutic strategy to increase the efficiency of radiotherapy in NSCLC patients, ultimately improving patient survival.
[en] Regulatory Framework - National Regulations: Decree on licensing of nuclear facilities; About 40 regulation 25 of which are related to the nuclear facilities and activities; All regulations are under revision to ensure conformance with new regulatory infrastructure and framework and to update in accordance with latest IAEA requirements; Five Guidelines for the applicants; About 25 internal procedures, including review and assessment guidelines and Project Management Plans for ongoing authorization projects. Safety Regime - Bilateral Peaceful Use: USA, Canada, France, South Korea, Russia, Argentine, Germany, China, Jordan, Japan. Multilateral Safety Related: Nuclear Safety Convention; Paris Convention on Liability; Joint Protocol Relating to the Application of the Vienna Convention and the Paris Convention; Convention on Assistance in the Case of a Nuclear Accident or Radiological Emergency; Convention on Early Notification of a Nuclear Accident; Joint Convention on Management of Spent Fuel and Management of Radioactive Waste (signed but not ratified yet non technical reason). Multilateral Security Related: Treaty on the Non proliferation of Nuclear Weapons; Convention on The Physical Protection of Nuclear Material (ratification of Amendment to CPPNM is in - Comprehensive Nuclear Test Ban Treaty - International Convention for the Suppression of Acts of Nuclear Terrorism. Safeguards: Agreement Between the Government of the Republic of Turkey and the IAEA for the Application of Safeguards in Connection with NPT; Protocol Additional to the Agreement Between the Government of the Republic of Turkey and the IAEA for the Application of Safeguards in Connection with NPT.
[en] Full text: Every Non-Nuclear Weapons State (NNWS) party to the Non-Proliferation Treaty (NPT) is required to conclude a safeguards agreement with the International Atomic Energy Agency (IAEA), accepting safeguards on all nuclear material in the State in order to verify non-diversion of this material to a clandestine weapons program. “Safeguards by design” (SBD) is a concept that encourages the integration of these safeguards requirements and objectives into the design process of a nuclear facility, from initial planning through design, construction, operation and decommissioning. SBD doesn’t introduce any new requirements for the State (beyond those in its existing safeguards agreement with the IAEA), but rather presents an opportunity to engage voluntarily earlier than might be required in order to reduce project risk associated with scope, schedule, budget and licensing. Other benefits include reduction of cost of safeguards implementation to the operator, the IAEA, and State regulators, and improving safeguards assurances to the international community and general public. The SBD process is a cooperative effort involving the designer, the State authorities, and the IAEA. Whereas effective cooperation depends upon all parties understanding the respective requirements, resources, and limitations of each participant, this can be a challenge for SBD since awareness of international safeguards is not high amongst the nuclear design community. This presentation will outline the objectives, benefits, and challenges of SBD, and provide an overview of information available to the nuclear design community that can inform its effective participation in the SBD process. (author)
[en] Magnetic resonance imaging (MRI) plays a critical role in disease characterization of intra-articular tenosynovial giant cell tumor. To characterize the MRI features of intra-articular tenosynovial giant cell tumor in children with respect to disease subtype and anatomical location. This retrospective study included children with tenosynovial giant cell tumor who underwent preoperative MRI between January 2006 and May 2020. Two radiologists reviewed each examination to determine disease subtype, signal intensities and the presence of an effusion, osseous changes, chondromalacia, juxtacapsular disease and concomitant joint involvement. Fisher exact, Mann-Whitney U, and Kruskal-Wallis H tests were used to compare findings between subtypes and locations. Twenty-four children (16 girls, 8 boys; mean age: 13.1±3.8 years) with 19 knee and 5 ankle-hindfoot tenosynovial giant cell tumor had either diffuse (n=15) or localized (n=9) disease. An effusion (P=0.004) was significantly more common with diffuse than localized disease. There was no significant difference in MRI signal (P-range: 0.09–1) or other imaging findings (P-range: 0.12–0.67) between subtypes. Children with knee involvement were significantly more likely to present with diffuse disease while those with ankle-hindfoot involvement all presented with focal disease (P=0.004). Juxtacapsular (n=4) and concomitant proximal tibiofibular joint involvement (n=5) were observed with diffuse disease in the knee. Erosions (P=0.01) were significantly more common in the ankle than in the knee. In our study, diffuse tenosynovial giant cell tumor was more common than localized disease, particularly in the knee where juxtacapsular and concomitant proximal tibiofibular joint disease can occur.
[en] Breast lesions classified as of “uncertain malignant potential” represent a heterogeneous group of abnormalities with an increased risk of associated malignancy. Clinical management of B3 lesions diagnosed on vacuum-assisted breast biopsy (VABB) is still challenging: surgical excision is no longer the only available treatment and VABB may be sufficient for therapeutic excision. The aim of the present study is to evaluate the positive predictive value (PPV) for malignancy in B3 lesions that underwent surgical excision, identifying possible upgrading predictive factors and characterizing the malignant lesions eventually diagnosed. These results are compared with a subset of patients with B3 lesions who underwent follow-up. A total of 1250 VABBs were performed between January 2006 and December 2017 at our center. In total, 150 B3 cases were diagnosed and 68 of them underwent surgical excision. VABB findings were correlated with excision histology. A PPV for malignancy for each B3 subtype was derived. The overall PPV rate was 28%, with the highest upgrade rate for atypical ductal hyperplasia (41%), followed by classical lobular neoplasia (29%) and flat epithelial atypia (11%). Only two cases of carcinoma were detected in the follow-up cohort, both associated with atypical ductal hyperplasia at VABB. Open surgery is recommended in case of atypical ductal hyperplasia while, for other B3 lesions, excision with VABB only may be an acceptable alternative if radio-pathological correlation is assessed, if all microcalcifications have been removed by VABB, and if the lesion lacks high-risk cytological features.